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29 pages, 9744 KiB  
Article
A Novel Method for Estimating the Thermal Performance of Multi-Block Wall Systems Using Thermal Impedance Z-Value under Transient Uncontrolled Heat Transfer Conditions
by Payal Ashish Modi, Bu Kwan Kee, Abdelgadir Mohamed Mahmoud and Yousif Abdalla Abakr
Buildings 2024, 14(9), 2833; https://doi.org/10.3390/buildings14092833 - 9 Sep 2024
Viewed by 290
Abstract
Climate change is one of the biggest challenges today. An increasing population accelerates the construction of concrete houses and the use of air conditioners, thereby leading to an increase in energy consumption. When the walls of buildings are well-designed and insulated, energy consumption [...] Read more.
Climate change is one of the biggest challenges today. An increasing population accelerates the construction of concrete houses and the use of air conditioners, thereby leading to an increase in energy consumption. When the walls of buildings are well-designed and insulated, energy consumption can be reduced. Therefore, it is important to measure the thermal performance of wall systems accurately. The existing traditional methods of measuring R- and U-values provide acceptable solutions for steady-state controlled, uncontrolled or transient state-controlled conditions. However, a need to develop a novel approach for transient state-uncontrolled realistic conditions has been identified. The present study involves both experimental and numerical investigations. An in situ model room with dimensions of 1.60 m × 1.73 m × 1.50 m was built for the experimental work, and a series of experiments were conducted. For numerical work, two models using Ansys Fluent 2021/2022 and MATLAB Simulink 2021/2022 were developed. The real-time experimental data were fed into numerical models to predict the thermal behavior of the wall system. The results include the evaluation of a concept called ‘Time-Lag’ for all three models. ‘Time-Lag’ is the time taken for the heat energy to flow across the wall system. The Time-Lag for the experimental model was 8 h 45 min, while for MATLAB and Ansys models, it was 8 h 22 min. (average) and 7 h 30 min, respectively. Minor variations validate the accuracy of the numerical models. Further, a novel method using a new parameter in building systems called ‘thermal impedance Z-value’ was developed to estimate the real-time thermal performance of walls using MATLAB Simulink. The Z-value measures the ability of a wall system to resist the flow of heat (thermal resistance, R-value) combined with its ability to store heat energy (thermal capacitance, Cth-value). It is evaluated for steady-state and dynamic (transient) systems. For the steady-state system, the Z-values on the outer and inner walls were 18.2683 K/W and 18.6761 K/W, respectively with a minor difference of 0.4078 K/W at the end of 72 h. For the dynamic system, the Z-value did not reach a constant value and fluctuated in a particular pattern during 24 h of the solar cycle with average values of 3.2969 K/W on the outer and 1.2886 K/W on the inner walls at the end of 72 h, thus presenting more accurate and realistic thermal performance results of a wall system. Full article
(This article belongs to the Section Building Energy, Physics, Environment, and Systems)
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Figure 1
<p>Development and description: In situ experimental model. (<b>a</b>) Concrete foundation. (<b>b</b>) Walls of model room using IMSI blocks. (<b>c</b>) Slab. (<b>d</b>) Application of 20 mm plaster on inner and outer wall surfaces. (<b>e</b>) Piping (blue) for wires on three walls. (<b>f</b>) Overall view of the room from the inner side with three walls and roof insulated using polystyrene sheets. (<b>g</b>) Model room with door. (<b>h</b>) Thermocouple mounted on outer side of east wall to measure the outer air temperature (yellow). Pipe is sealed with insulation (orange) to prevent escape of room air to the surroundings. (<b>i</b>) Pyranometer mounted on outer side of east wall to measure the incident solar radiations (yellow). Thermocouple (orange) mounted on east wall to measure the outer side wall temperature. (<b>j</b>) Thermocouples mounted on inner side of east wall to measure the inner air (yellow) and inner surface (orange) temperatures. (<b>k</b>) PicoLog data logger placed inside the room to log the data of the temperatures on the inner and outer sides of east wall and inner and outer air temperatures. (<b>l</b>) Pyranometer is connected to a laptop (placed inside the room) to collect data of the solar radiations through software every 15 min. PicoLog data logger is also connected to laptop to collect data of wall surfaces and air temperatures every 15 min. (<b>m</b>) Door sealed with polystyrene sheets to prevent heat loss. Final overall view of the model room during the experimentation period. (<b>n</b>) Final outer view of model room with required labelling. (<b>o</b>) Final inner view of model room with required labelling.</p>
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<p>Development and description: In situ experimental model. (<b>a</b>) Concrete foundation. (<b>b</b>) Walls of model room using IMSI blocks. (<b>c</b>) Slab. (<b>d</b>) Application of 20 mm plaster on inner and outer wall surfaces. (<b>e</b>) Piping (blue) for wires on three walls. (<b>f</b>) Overall view of the room from the inner side with three walls and roof insulated using polystyrene sheets. (<b>g</b>) Model room with door. (<b>h</b>) Thermocouple mounted on outer side of east wall to measure the outer air temperature (yellow). Pipe is sealed with insulation (orange) to prevent escape of room air to the surroundings. (<b>i</b>) Pyranometer mounted on outer side of east wall to measure the incident solar radiations (yellow). Thermocouple (orange) mounted on east wall to measure the outer side wall temperature. (<b>j</b>) Thermocouples mounted on inner side of east wall to measure the inner air (yellow) and inner surface (orange) temperatures. (<b>k</b>) PicoLog data logger placed inside the room to log the data of the temperatures on the inner and outer sides of east wall and inner and outer air temperatures. (<b>l</b>) Pyranometer is connected to a laptop (placed inside the room) to collect data of the solar radiations through software every 15 min. PicoLog data logger is also connected to laptop to collect data of wall surfaces and air temperatures every 15 min. (<b>m</b>) Door sealed with polystyrene sheets to prevent heat loss. Final overall view of the model room during the experimentation period. (<b>n</b>) Final outer view of model room with required labelling. (<b>o</b>) Final inner view of model room with required labelling.</p>
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<p>IMSI block assembly with neglected complicated features (circled in red) of the insulation parts.</p>
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<p>Simplied geometry of the block showing concrete and insulation parts.</p>
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<p>Breakdown of the block geometry and direction of heat flow.</p>
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<p>Symmetry and modeled geometry of the block.</p>
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<p>Layers of model for MATLAB simulation.</p>
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<p>Simulink model for the wall.</p>
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<p>Variation in inner wall surface temperature with respect to time.</p>
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<p>Variation in outer wall surface temperature with respect to time.</p>
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<p>Variation in inner and outer wall surface temperature with respect to time for Ansys Simulation.</p>
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<p>Variation in inner and outer wall surface temperature with respect to time for MATLAB Simulink Simulation.</p>
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<p>Solar radiation incident on east wall of the model room with respect to time.</p>
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<p>Heat flux at inner and outer walls with respect to time.</p>
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<p>Variation in steady state heat flux on inner and outer sides of wall with respect to time.</p>
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<p>Variation in steady-state thermal impedance on inner and outer sides of the wall with respect to time.</p>
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<p>Variation in dynamic state thermal impedance on inner and outer sides of the wall with respect to time.</p>
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<p>Numerical model of IMSI building block using SolidWorks design software: concrete part.</p>
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<p>Numerical model of IMSI building block using SolidWorks design software: front insulation.</p>
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<p>Numerical model of IMSI building block using SolidWorks design software: rear insulation.</p>
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<p>Ansys Fluent simulation: geometry and mesh.</p>
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<p>Ansys Fluent simulation: material properties.</p>
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<p>Ansys Fluent simulation settings.</p>
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<p>Panel in MATLAB Simulink simulation: example of material thermal mass and thermal resistance.</p>
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<p>MATLAB Simulink model for the inner side of the wall.</p>
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<p>MATLAB Simulink model for the outer side of the wall.</p>
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<p>Specifications and calibration details of Pyranometer SP-420 [<a href="#B44-buildings-14-02833" class="html-bibr">44</a>].</p>
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<p>Specifications and Calibration details of data logger: Pico Log TC-08 [<a href="#B35-buildings-14-02833" class="html-bibr">35</a>].</p>
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<p>Graph for the valuation of heat transfer coefficient hc out of air on outer side and hc in of air, respectively, on the outer and inner sides of the wall System.</p>
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22 pages, 3833 KiB  
Article
Viral Vector-Based Chlamydia trachomatis Vaccines Encoding CTH522 Induce Distinct Immune Responses in C57BL/6J and HLA Transgenic Mice
by Giuseppe Andreacchio, Ylenia Longo, Sara Moreno Mascaraque, Kartikan Anandasothy, Sarah Tofan, Esma Özün, Lena Wilschrey, Johannes Ptok, Dung T. Huynh, Joen Luirink and Ingo Drexler
Vaccines 2024, 12(8), 944; https://doi.org/10.3390/vaccines12080944 - 22 Aug 2024
Viewed by 662
Abstract
Chlamydia trachomatis remains a major global health problem with increasing infection rates, requiring innovative vaccine solutions. Modified Vaccinia Virus Ankara (MVA) is a well-established, safe and highly immunogenic vaccine vector, making it a promising candidate for C. trachomatis vaccine development. In this study, [...] Read more.
Chlamydia trachomatis remains a major global health problem with increasing infection rates, requiring innovative vaccine solutions. Modified Vaccinia Virus Ankara (MVA) is a well-established, safe and highly immunogenic vaccine vector, making it a promising candidate for C. trachomatis vaccine development. In this study, we evaluated two novel MVA-based recombinant vaccines expressing spCTH522 and CTH522:B7 antigens. Our results show that while both vaccines induced CD4+ T-cell responses in C57BL/6J mice, they failed to generate antigen-specific systemic CD8+ T cells. Only the membrane-anchored CTH522 elicited strong IgG2b and IgG2c antibody responses. In an HLA transgenic mouse model, both recombinant MVAs induced Th1-directed CD4+ T cell and multifunctional CD8+ T cells, while only the CTH522:B7 vaccine generated antibody responses, underscoring the importance of antigen localization. Collectively, our data indicate that distinct antigen formulations can induce different immune responses depending on the mouse strain used. This research contributes to the development of effective vaccines by highlighting the importance of careful antigen design and the selection of appropriate animal models to study specific vaccine-induced immune responses. Future studies should investigate whether these immune responses provide protection in humans and should explore different routes of immunization, including mucosal and systemic immunization. Full article
(This article belongs to the Special Issue Strategies of Viral Vectors for Vaccine Development)
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<p>Construction, genetic characterization, recombinant antigen expression and localization of MVA-spCTH522 and MVA-CTH522:B7 (<b>A</b>) Schematic representation of MVA-spCTH522 (<b>left</b>) and MVA-CTH522:B7 (<b>right</b>) genomes. The location of the respective expression cassettes in the major deletion site VI (del VI) of the MVA genome is shown at the top. PmH5, modified early late H5 vaccinia virus promoter (<b>B</b>) Viral genomic DNA was extracted from stocks of non-recombinant MVA (MVA-WT), MVA-spCTH522 and MVA-CTH522:B7 and analyzed by PCR using delVI-specific primers. The PCR fragments obtained for the respective expression cassettes are expected to be 2151 bp in size for spCTH522 and 2256 bp for CTH522:B7 (<b>C</b>) HeLa cells were mock-infected or infected with MVA-WT, MVA-spCTH522 or MVA-CTH522:B7 (MOI = 5). Cells were lysed at 0, 24 or 48 hpi (MVA-spCTH522 and MVA-CTH522:B7) or at 48 hpi (mock and MVA-WT). Whole cell lysates were analyzed by Western blotting with antibodies against MOMP-SvD, displaying recombinant proteins with an expected size of ~57.4 kDa for spCTH522 and ~63.9 kDa for CTH522:B7. Vaccinia virus H3 protein and b-actin were used as infection and loading controls, respectively (<b>D</b>) CTH522:B7 is located at the cell membrane. Confocal laser microscopy immunofluorescence analysis (CLSM) to determine the location of spCTH522 and CTH522:B7 proteins in the infected cells. HeLa cells infected with MVA-spCTH522, MVA-CTH522:B7, or MVA-WT at MOI of 5 were fixed 6 h after infection, and non-permeabilized cells were stained with WGA probe conjugated to Alexa Fluor 594 (red) and a mouse monoclonal anti-MOMP antibody. Bound anti-MOMP was visualized using a mouse secondary antibody conjugated to Alexa Fluor 488 (green). Nuclei were stained with DAPI (blue). Scale bars: 10 µm.</p>
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<p>MVA-spCTH522 and MVA-CTH522:B7 induced CTH522-specific CD4<sup>+</sup> but not CD8<sup>+</sup> T-cell responses in C57BL/6J mice (<b>A</b>) Schematic representation of the experimental setting. C57BL/6J mice were immunized intraperitoneally with MVA-WT, MVA-spCTH522 or MVA-CTH522:B7 (n = 5 per group) on days 0 and boosted on day 28. Spleens were harvested on day 56 and splenocytes were restimulated with a pool of overlapping peptides spanning the full spCTH522 sequence. OVA-specific (OVA<sub>257–264</sub>, OVA<sub>323–339</sub>) and MVA-specific (B8<sub>20−27</sub>, B5<sub>46–60</sub>) peptides were used as negative and positive controls, respectively (<b>B</b>) Representative flow cytometry gates of cytokine-producing CD4<sup>+</sup> (upper gates) and CD8<sup>+</sup> T cells (lower gates) from the spleens of MVA-WT, MVA-spCTH522 or MVA-CTH522:B7 immunized mice (<b>C</b>) Frequencies of CD8<sup>+</sup> T cells and CD4<sup>+</sup> T cells producing IFNγ or TNFα were measured by flow cytometry. Each data point represents one mouse, and short horizontal lines geometrical mean. Kruskal–Wallis test followed by Dunn’s multiple comparisons was used to compare groups (ns, non-significant, * <span class="html-italic">p</span> &lt; 0.05).</p>
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<p>MVA-CTH522:B7 but not MVA-spCTH522 induced humoral responses in C57BL/6J mice. C57BL/6J mice (n = 9 per group) were immunized as shown in <a href="#vaccines-12-00944-f002" class="html-fig">Figure 2</a>A (<b>A</b>) Serum samples from MVA-spCTH522 (<b>left</b>) and MVA-CTH522:B7 (<b>right</b>) immunized mice were serially diluted and added to CTH522-coated plates. Antigen-specific IgG was analyzed by enzyme-linked immunosorbent assay (ELISA). Single thin lines represent each individual mouse, thick lines represent the geometrical mean of the optical density values at each dilution step (<b>B</b>) Individual OD405 values for IgG obtained at a serum dilution of 1:100 for CTH522-specific antibodies (<b>left</b>) and at a dilution of 1:500 for MVA-specific antibodies (<b>right</b>). For statistical analysis, Kruskal–Wallis test followed by Dunn’s multiple comparisons was used to compare CTH522-specific antibodies between groups (ns, non-significant, ** <span class="html-italic">p</span> &lt; 0.005) (<b>C</b>) Levels of CTH522-specific IgG subtypes (IgG1, IgG2b, IgG2c and IgG3) in serum were determined by ELISA from mice immunized with either MVA-CTH522:B7 or MVA-WT. Single thin lines represent each individual mouse, thick lines represent the geometrical mean of the optical density values at each dilution step (<b>D</b>) Ratio of OD405 values were calculated at 1:100 dilution for IgG2b, IgG2c or IgG3 to IgG1. Values are shown as geometric mean with geometric SD (<b>E</b>) Levels of CTH522-specific IgG and IgA antibodies were determined by ELISA in serum or vaginal washes from mice immunized with MVA-CTH522:B7 or MVA-WT.</p>
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<p>A single dose of MVA-spCTH522 and MVA-CTH522:B7 induces MOMP-specific CD8<sup>+</sup> T cell immune responses in HLA transgenic mice (<b>A</b>) Schematic representation of the experimental setting. A2.DR1 mice were immunized intraperitoneally with MVA-WT (n = 6), MVA-spCTH522 (n = 7), or MVA-CTH522:B7 (n = 7) on days 0. Spleens were harvested on day 7 and splenocytes were restimulated with a pool of overlapping peptides spanning the full spCTH522 sequence to determine CD4<sup>+</sup> T-cell responses or pulsed with MOMP<sub>282–290</sub> or MOMP<sub>200–209</sub> peptides to determine CD8<sup>+</sup> T-cell responses by ICS assay (<b>B</b>) Representative flow cytometry gates of cytokine-producing CD4<sup>+</sup> (upper gates) and CD8<sup>+</sup> T cells (lower gates) from the spleens of MVA-WT, MVA-spCTH522 or MVA-CTH522:B7 immunized mice (<b>C</b>) Total percentage of CTH522-specific CD4<sup>+</sup> T cells (upper graphs), MOMP<sub>282–290</sub>- (middle graphs) and MOMP<sub>200–209</sub>- (lower graphs) specific CD8<sup>+</sup> T cells producing IFNγ or TNFα. Each data point represents one mouse, and short horizontal lines geometrical mean. Kruskal–Wallis test followed by Dunn’s multiple comparisons was used to compare groups (ns, non-significant, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.005).</p>
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<p>A boosting dose of MVA-spCTH522 or MVA-CTH522:B7 enhanced the magnitude of T-cell responses in HLA transgenic mice (<b>A</b>) Schematic representation of the experimental setting. A2.DR1 mice were immunized intraperitoneally with MVA-WT (n = 5), MVA-spCTH522 (n = 9) or MVA-CTH522:B7 (n = 11) on days 0 and boosted at day 28. Spleens were harvested on day 56 and splenocytes were restimulated with either a pool of overlapping peptides spanning the full spCTH522 sequence or HLA-A*0201-restricted MOMP<sub>282–290</sub> or MOMP<sub>200–209</sub> peptides. Activation of CD4<sup>+</sup> and CD8<sup>+</sup> T cells was measured by ICS assay (<b>B</b>) Representative flow cytometry gates of cytokine-producing CD4<sup>+</sup> (upper gates) and CD8<sup>+</sup> T cells (lower gates) from the spleens of MVA-WT, MVA-spCTH522 or MVA-CTH522:B7 immunized mice (<b>C</b>) Overall percentage of CTH522-specific CD4<sup>+</sup> T cells producing IFNγ or TNFα (upper graphs) after stimulation with the peptide pool and percentage of MOMP<sub>282–290</sub>- and MOMP<sub>200–209</sub>- specific CD8<sup>+</sup> T cells (lower graphs) producing IFNγ, TNFα, CD107 and IL2 (cytokines). For statistical analysis, Kruskal–Wallis test followed by Dunn’s multiple comparisons was used to compare groups (<b>D</b>) Comparison of the CD8<sup>+</sup> and CD4<sup>+</sup> T cells at 7 days after prime (see <a href="#vaccines-12-00944-f004" class="html-fig">Figure 4</a>C) or 28 days after boost (see <a href="#vaccines-12-00944-f005" class="html-fig">Figure 5</a>C) with MVA-spCTH522 or MVA-CTH522:B7. Statistical analysis was performed using unpaired <span class="html-italic">t</span> test with Welch’s correction (<b>E</b>) A2.DR1 mice were immunized as shown in <a href="#vaccines-12-00944-f005" class="html-fig">Figure 5</a>A with MVA-WT, MVA-spCTH522, or MVA-CTH522:B7, and antigen-specific total IgG was analyzed by enzyme-linked immunosorbent assay (ELISA). Individual OD405 values for IgG were obtained at a serum dilution of 1:100 for CTH522-specific antibodies (<b>left</b>) and MVA-specific antibodies (<b>right</b>). For statistical analysis, Kruskal–Wallis test followed by Dunn’s multiple comparisons was used to compare CTH522-specific antibodies between groups (ns, non-significant, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.005, *** <span class="html-italic">p</span> &lt; 0.0005).</p>
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<p>MVA-spCTH522 and MVA-CTH522:B7 elicit multifunctional CD8<sup>+</sup> T-cell responses. Splenocytes from A2.DR1 mice immunized intraperitoneally with MVA-spCTH522 or MVA-CTH522:B7 (<a href="#vaccines-12-00944-f005" class="html-fig">Figure 5</a>A) were incubated with either the HLA-A*02:01-restricted MOMP<sub>282–290</sub> or MOMP<sub>200–209</sub> peptides (<b>A</b>) Polyfunctional profiles of MOMP<sub>282–290</sub>- and MOMP<sub>200–209</sub>-specific CD8<sup>+</sup> T cells in MVA-spCTH522 (<b>left</b> graphs) and MVA-CTH522:B7 (<b>right</b> graphs) immunized mice. All possible combinations of cytokines tested are plotted on the x-axis, while the percentage of T cells expressing such combinations of CD107a, IFNγ, TNFα and IL2 in their response against MOMP<sub>282–290</sub> (<b>upper</b> graphs) and MOMP<sub>200–209</sub> (<b>lower</b> graphs) peptides are plotted on the y-axis. Responses are grouped and color-coded according to the number of functions (1, 2, 3, or 4 cytokines co-expressed). Results are presented as box and whisker plots. Each point represents one mouse, the boxes represent the interquartile range, the center line in the box represents the median, and the whiskers extend to the minimum and maximum data values (<b>B</b>) Individual multifunctional CD8<sup>+</sup> T cell populations specific to MOMP<sub>282–290</sub> (upper graphs) and MOMP<sub>200–209</sub> (lower graphs) were plotted to compare the difference in CD8<sup>+</sup> T cell magnitude between MVA-spCTH522 and MVA-CTH522:B7 immunized mice. For statistical analysis, Mann–Whitney test was used for comparing the multifunctional CD8<sup>+</sup> T-cell populations (ns, non-significant, * <span class="html-italic">p</span> &lt; 0.05).</p>
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17 pages, 778 KiB  
Review
An Update on Polyphosphate In Vivo Activities
by Robert Schoeppe, Moritz Waldmann, Henning J. Jessen and Thomas Renné
Biomolecules 2024, 14(8), 937; https://doi.org/10.3390/biom14080937 - 2 Aug 2024
Viewed by 619
Abstract
Polyphosphate (polyP) is an evolutionary ancient inorganic molecule widespread in biology, exerting a broad range of biological activities. The intracellular polymer serves as an energy storage pool and phosphate/calcium ion reservoir with implications for basal cellular functions. Metabolisms of the polymer are well [...] Read more.
Polyphosphate (polyP) is an evolutionary ancient inorganic molecule widespread in biology, exerting a broad range of biological activities. The intracellular polymer serves as an energy storage pool and phosphate/calcium ion reservoir with implications for basal cellular functions. Metabolisms of the polymer are well understood in procaryotes and unicellular eukaryotic cells. However, functions, regulation, and association with disease states of the polymer in higher eukaryotic species such as mammalians are just beginning to emerge. The review summarises our current understanding of polyP metabolism, the polymer’s functions, and methods for polyP analysis. In-depth knowledge of the pathways that control polyP turnover will open future perspectives for selective targeting of the polymer. Full article
(This article belongs to the Special Issue Inorganic Polyphosphate: A Multifaceted Biomolecule)
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<p>Gross structures of natural polyP. (<b>A</b>): PolyP is a polymer consisting of 3–1000 tetrahedral phosphate subunits linked to each other via a shared oxygen atom. Most polyP is linear; however, branched forms exist. (<b>B</b>): PolyP binds Ca<sup>2+</sup>, which binds further polyP and lines up, presumably in a helical secondary structure [<a href="#B27-biomolecules-14-00937" class="html-bibr">27</a>]. (<b>C</b>): Aggregated Ca<sup>2+</sup> polyP forms nanoparticles that, in turn, form microsomes within cells.</p>
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10 pages, 1345 KiB  
Review
Polyploid Giant Cancer Cells: A Distinctive Feature in the Transformation of Epithelial Cells by High-Risk Oncogenic HCMV Strains
by Georges Herbein and Ranim El Baba
Viruses 2024, 16(8), 1225; https://doi.org/10.3390/v16081225 - 31 Jul 2024
Viewed by 654
Abstract
Human cytomegalovirus (HCMV) infection is common in tumor tissues across different types of cancer. While HCMV has not been recognized as a cancer-causing virus, numerous studies hint at its potential role in cancer development where its presence in various cancers corresponds with the [...] Read more.
Human cytomegalovirus (HCMV) infection is common in tumor tissues across different types of cancer. While HCMV has not been recognized as a cancer-causing virus, numerous studies hint at its potential role in cancer development where its presence in various cancers corresponds with the hallmarks of cancer. Herein, we discuss and demonstrate that high-risk HCMV-DB and BL strains have the potential to trigger transformation in epithelial cells, including human mammary epithelial cells (HMECs), ovarian epithelial cells (OECs), and prostate epithelial cells (PECs), through the generation of polyploid giant cancer cells (PGCCs). A discussion is provided on how HCMV infection creates a cellular environment that promotes oncogenesis, supporting the continuous growth of CMV-transformed cells. The aforementioned transformed cells, named CTH, CTO, and CTP cells, underwent giant cell cycling with PGCC generation parallel to dedifferentiation, displaying stem-like characteristics and an epithelial–mesenchymal transition (EMT) phenotype. Furthermore, we propose that giant cell cycling through PGCCs, increased EZH2 expression, EMT, and the acquisition of malignant traits represent a deleterious response to the cellular stress induced by high-risk oncogenic HCMV strains, the latter being the origin of the transformation process in epithelial cells upon HCMV infection and leading to adenocarcinoma of poor prognosis. Full article
(This article belongs to the Special Issue 65-Year Anniversary of the Discovery of Cytomegalovirus)
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<p>PGCC detection in CMV-transformed cells generated from HR-HCMV infection of HMECs, OECs, and PECs. (<b>A</b>). White light images of PGCCs generated in CTH, CTO, and CTP cultures. (<b>B</b>). Confocal microscopic images of IE1 and DAPI staining in CTH, CTO, and CTP cells. Magnification ×63; scale bar 10 μm. Red arrows represent the heterogeneous cellular morphologies detected in CTH, CTO, and CTP cell population.</p>
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<p>IE1 expression in CTH, CTO, and CTP cells. Confocal microscopic images of IE1 and DAPI staining in CTH, CTO, and CTP cells (two stained cells per image). Magnification ×63; scale bar 10 μm.</p>
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<p>Stemness traits in PGCCs elicited from HR-HCMV infection of HMECs, OECs, and PECs. (<b>A</b>) Spheroids in CTH, CTO, and CTP cultures. As specified, the size of a CTO spheroid is approximately 100 μm. (<b>B</b>) EZH2 and Nanog expression by confocal microscopy in CTH, CTO, and CTP cells. Magnification ×63; scale bar 10 μm. (<b>C</b>). Confocal microscopy images showing IE1/Nanog co-staining for CTH cells, IE1/Myc co-staining for CTO cells, and IE1/Nestin co-staining for CTP cells. Uninfected HMECs, OECs, and PECs were used as controls; magnification ×63 and scale bar 10 μm.</p>
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16 pages, 3291 KiB  
Article
Effect of Support Functionalization on Catalytic Direct Hydrogenation and Catalytic Transfer Hydrogenation of Muconic Acid to Adipic Acid
by Elisa Zanella, Stefano Franchi, Narmin Jabbarli, Ilaria Barlocco, Marta Stucchi and Carlo Pirola
Catalysts 2024, 14(7), 465; https://doi.org/10.3390/catal14070465 - 19 Jul 2024
Viewed by 531
Abstract
The liquid-phase hydrogenation of muconic acid (MA) to produce bio-adipic acid (AdA) is a prominent environmentally friendly chemical process, that can be achieved through two distinct methodologies: catalytic direct hydrogenation using molecular hydrogen (H2), or catalytic transfer hydrogenation utilizing a hydrogen [...] Read more.
The liquid-phase hydrogenation of muconic acid (MA) to produce bio-adipic acid (AdA) is a prominent environmentally friendly chemical process, that can be achieved through two distinct methodologies: catalytic direct hydrogenation using molecular hydrogen (H2), or catalytic transfer hydrogenation utilizing a hydrogen donor. In this study, both approaches were explored, with formic acid (FA) selected as the hydrogen source for the latter method. Palladium-based catalysts were chosen for these processes. Metal’s nanoparticles (NPs) were supported on high-temperature heat-treated carbon nanofibers (HHT-CNFs) due to their known ability to enhance the stability of this metal catalyst. To assess the impact of support functionalization on catalyst stability, the HHT-CNFs were further functionalized with phosphorus and oxygen to obtain HHT-P and HHT-O, respectively. In the hydrogenation reaction, catalysts supported on functionalized supports exhibited higher catalytic activity and stability compared to Pd/HHT, reaching an AdA yield of about 80% in less than 2 h in batch reactor. The hydrogen-transfer process also yielded promising results, particularly with the 1%Pd/HHT-P catalyst. This work highlights the efficacy of support functionalization in improving catalyst performance, particularly when formic acid is used as a safer and more cost-effective hydrogen donor in the hydrogen-transfer process. Full article
(This article belongs to the Section Catalytic Materials)
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<p>Reaction scheme for AdA production starting from different substrates: MA (<b>left</b>) and Na-Muc (<b>right</b>).</p>
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<p>Initial activity (h<sup>−1</sup>) of the three different catalysts for the CDH process calculated after 5 min of reaction using the Equation (5).</p>
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<p>Comparison of the reaction courses for the three different catalysts in the catalytic direct hydrogenation: (<b>a</b>) 1%Pd@HHT, (<b>b</b>) 1%Pd@HHT-O, (<b>c</b>) 1%Pd@HHT-P. Reaction conditions: MA concentration 0.05 M, temperature 70 °C, 3 bar pressure of H<sub>2</sub>, metal/substrate molar ratio 1/500, 1200 rpm.</p>
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<p>AdA Yield monitored along time in the catalytic direct hydrogenation of MA. Reaction conditions: MA concentration 0.05 M, temperature 70 °C, 3 bar pressure of H<sub>2</sub>, metal/substrate molar ratio 1/500, 1200 rpm.</p>
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<p>(<b>a</b>) MA conversion and (<b>b</b>) Yield of AdA after 120 min during recycling tests in the catalytic direct hydrogenation of MA. Reaction conditions: MA concentration 0.05 M, temperature 70 °C, 3 bar pressure of H<sub>2</sub>, metal/substrate molar ratio 1/500, 1200 rpm.</p>
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<p>Comparison of the reaction courses for the three different catalysts in the catalytic transfer hydrogenation: (<b>a</b>) 1%Pd@HHT, (<b>b</b>) 1%Pd@HHT-O, (<b>c</b>) 1%Pd@HHT-P. Reaction conditions: MA concentration 0.005 M, metal/substrate molar ratio 1/65, temperature 70 °C, pressure of N<sub>2</sub> 3 bar, MA/FA ratio 1/10, 1200 rpm.</p>
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<p>Study of the influence of the metal/substrate ratio: 1/65, 1/100 and 1/125 in the catalytic transfer hydrogenation: (<b>a</b>) MA conversion and (<b>b</b>) AdA Yield monitored along time. Reaction conditions: MA concentration 0.005 M, temperature 70 °C, pressure of N<sub>2</sub> 3 bar, MA/FA ratio 1/10, 1200 rpm.</p>
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<p>Study of the influence of the temperature. (<b>a</b>) MA conversion and (<b>b</b>) AdA Yield monitored along time. Reaction conditions: MA concentration 0.005 M, metal substrate molar ratio 1/100, pressure of N<sub>2</sub> 3 bar, MA/FA ratio 1/10, 1200 rpm.</p>
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<p>Representative HR-STEM images of. (<b>a</b>,<b>b</b>) 1wt%Pd@HHT, (<b>c</b>,<b>d</b>) 1wt%Pd@P-HHT and (<b>e</b>,<b>f</b>) 1wt%Pd@O-HHT.</p>
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17 pages, 8501 KiB  
Article
Exploring the Mechanism of H2S Synthesis in Male Bactrian Camel Poll Glands Based on Data Independent Acquisition Proteomics and Non-Targeted Metabolomics
by Bao Yuan, Quanwei Zhang, Bohao Zhang, Jianfu Li, Wenli Chen, Yu Zhao, Weitao Dong, Yong Zhang, Xingxu Zhao and Yuan Gao
Int. J. Mol. Sci. 2024, 25(14), 7700; https://doi.org/10.3390/ijms25147700 - 13 Jul 2024
Viewed by 668
Abstract
During estrus, the poll glands of male Bactrian Camels (Camelus Bactrianus) become slightly raised, exuding a large amount of pale yellow watery secretion with a characteristic odor that may contain hydrogen sulfide (H2S). However, whether H2S can [...] Read more.
During estrus, the poll glands of male Bactrian Camels (Camelus Bactrianus) become slightly raised, exuding a large amount of pale yellow watery secretion with a characteristic odor that may contain hydrogen sulfide (H2S). However, whether H2S can be synthesized in the poll glands of male Bactrian Camels and its role in inducing camel estrus remains unclear. This study aimed to identify differentially expressed proteins (DEPs) and signaling pathways in the poll gland tissues of male Bactrian Camels using data independent acquisition (DIA) proteomics. Additionally, gas chromatography–mass spectrometry (GC-MS) was performed to identify differentially expressed metabolites (DEMs) in the neck hair containing secretions during estrus in male Bactrian Camels, to explore the specific expression patterns and mechanisms in the poll glands of camels during estrus. The results showed that cystathionine-γ-lyase (CTH) and cystathionine-β-synthase (CBS), which are closely related to H2S synthesis in camel poll glands during estrus, were mainly enriched in glycine, serine, and threonine metabolism, amino acid biosynthesis, and metabolic pathways. In addition, both enzymes were widely distributed and highly expressed in the acinar cells of poll gland tissues in camels during estrus. Meanwhile, the neck hair secretion contains high levels of amino acids, especially glycine, serine, threonine, and cystathionine, which are precursors for H2S biosynthesis. These results demonstrate that the poll glands of male Bactrian Camels can synthesize and secrete H2S during estrus. This study provides a basis for exploring the function and mechanism of H2S in the estrus of Bactrian Camels. Full article
(This article belongs to the Section Molecular Informatics)
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<p>Identification and annotation of DEPs based on DIA proteomic data in poll glands during estrus. (<b>A</b>) Number of recognized precursors, peptides, and proteins. (<b>B</b>) Peptide number distribution and proportion of proteins. (<b>C</b>) The number of significantly upregulated and downregulated proteins in poll glands during vigorous estrus. (<b>D</b>) GO annotation and pathways of the 1703 DEPs. BP: biological process. MF: molecular function. CC: cellular component. (<b>E</b>) The top 50 enriched biological processes in GO annotations of the DEPs. (<b>F</b>) Top 20 enriched signaling pathways of the DEPs. Con: Poll glands group during indistinct estrus. Exp: Poll glands group during vigorous estrus. Statistical analyses: Wilcoxon rank sum test, α = 0.05.</p>
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<p>Identification of candidate DEPs related to H<sub>2</sub>S production. Red font indicates GO terms related to sulfur metabolism, while orange font indicates GO terms associated with sulfur-containing amino acidsz. (<b>A</b>,<b>B</b>). Screen of molecular function term and biological processes terms associated with sulfur and sulfur-containing amino acid metabolism under GO annotation. (<b>C</b>) Venn diagram shows differential genes in sulfur metabolism and sulfur amino acid metabolism, respectively. (<b>D</b>) Cluster analysis and heat map of these 76 differentially expressed proteins. Red font highlights key enzymes involved in H<sub>2</sub>S synthesis, including CTH and CBS. (<b>E</b>) Analysis of 34 upregulated genes by constructing a protein–protein interaction network (PPI). Orange represents sulfur-containing amino acid metabolism processes, red represents sulfur metabolism processes, blue represents cellular amino acid metabolism processes, green represents α- amino acid metabolism processes, and gold and light orange represent small molecule metabolism and serine metabolism processes, respectively. Con: Poll glands group during indistinct estrus. Exp: Poll glands group during vigorous estrus. Statistical analyses: Wilcoxon rank sum test, α = 0.05. Data are presented as median (rank). * Represents <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Screening the metabolic pathways involved in CTH and CBS based on KEGG pathway. (<b>A</b>) Candidate pathways for CTH and CBS; both involvements were selected from 45 significantly different pathways from KEGG annotation. (<b>B</b>) Seven genes were screened to be significantly regulated in all three pathways. (<b>C</b>) Volcano plot shows the positions of the 7 genes significantly regulated. Vertical dashed lines are drawn at log<sub>2</sub>(fold change) = −2 and 2, representing the thresholds for significantly down-regulated and up-regulated genes, respectively; The horizontal dashed line is positioned at −log<sub>10</sub>(FDR) = 1.3, indicating the significance threshold of FDR = 0.05. (<b>D</b>) Heatmap shows the clustering of the 7 significantly regulated genes. Red font highlights key enzymes involved in H<sub>2</sub>S synthesis, including CTH and CBS. (<b>E</b>) The PPI network of DEPs’ interaction with CTH and CBS in three pathways. Yellow represents proteins that interact with CBS or CTH, respectively. Blue represents 12 proteins that interact with both CTH and CBS. Con: Poll glands group during indistinct estrus. Exp: Poll glands group during vigorous estrus. Data are presented as median (rank). * Represents <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Identification of factors and pathways involved in sulfur metabolism and sulfur-containing amino acid metabolism. (<b>A</b>) Venn diagram of DEPs selected from GO terms and KEGG pathways associated with sulfur metabolism and sulfur-containing amino acid metabolism. (<b>B</b>) Volcano plot shows the distribution of 79 gene expression levels screened from (<b>A</b>). (<b>C</b>) Protein–protein interaction (PPI) network construction for the 79 proteins identified in panel (<b>A</b>). Orange nodes represent proteins interacting with both CTH and CBS, while green nodes represent proteins interacting with either CTH or CBS. Red nodes denote the key enzymes for H<sub>2</sub>S synthesis, CTH and CBS. (<b>D</b>) Heatmap showing the clustering of 16 significantly differentially expressed proteins from 79 proteins. (<b>E</b>) Sankey diagram illustrating the relationship between DEPs and three pathways and 16 biological processes related to sulfur metabolism and sulfur-containing amino acid metabolism. Red font highlights key enzymes involved in H<sub>2</sub>S synthesis, including CTH and CBS. Statistical analyses: Wilcoxon rank sum test, α = 0.05. Data are presented as median (rank). * Represents <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Identification of differentially expressed metabolites (DEMs) involved in H<sub>2</sub>S synthesis based on GC-MS analysis. (<b>A</b>) The number of DEMs identified in neck hair of male Bactrian Camels during estrus compared to ventral hair using non-targeted metabolomics analysis via the GC-MS method. (<b>B</b>) The number of DEMs enriched in metabolic pathways using KEGG annotation. (<b>C</b>) The number of pathways to which DEMs were mapped and enriched (<span class="html-italic">p</span> &lt; 0.05) using KEGG annotation. (<b>D</b>) The top 20 enriched pathways in (<b>C</b>). (<b>E</b>) Heatmap showing the differential content of 26 amino acids using GC-MS analysis. NM: neck hair; VH: ventral hair. Red font indicates important DEMs in the glycine, serine, and threonine metabolic pathways, which are significant in relation to H<sub>2</sub>S synthesis. (<b>F</b>) The changes in cystathionine, glycine, serine, and threonine levels, related to H<sub>2</sub>S synthesis, in neck hair compared to ventral hair. (<b>G</b>) Venn diagram showing that CBS, CTH and cystathionine, glycine, serine, and threonine share the same metabolic pathway. Data are presented as median (rank).</p>
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<p>Concentration of H<sub>2</sub>S and the expression and distribution of CTH and CBS in poll gland tissues. (<b>A</b>) Detection of H<sub>2</sub>S content in poll gland tissues. (<b>B</b>,<b>C</b>) The mRNA levels of <span class="html-italic">CBS</span> and <span class="html-italic">CTH</span> monitored by qRT-PCR assays. (<b>D</b>–<b>F</b>) The protein expression levels of CTH and CBS monitored by Western blot assay and the optical density of bands. (<b>G1</b>,<b>H1</b>) Histological staining of poll glands using the H&amp;E method. (<b>G2</b>–<b>G4</b>,<b>H2</b>–<b>H4</b>) The IHC staining of poll glands against CBS and CTH, respectively. (<b>G5</b>,<b>H5</b>) The gray values of positive expression of CTH and CBS proteins with IHC sections were scanned and quantified. (<b>I1</b>,<b>J1</b>) DAPI-labeled nuclei of cells from various cell types in cervical gland tissues of groups Con and Exp. (<b>I2</b>,<b>J2</b>) Epithelial cell-specific marker CK-18 observed in the cytoplasm of poll glands epithelial cells. (<b>I3</b>,<b>I4</b>,<b>J3</b>,<b>J4</b>) Cellular localization of CTH and CBS. (<b>I5</b>,<b>J5</b>) Co-localization analysis showing CK-18, CTH, and CBS in the cytoplasm of poll glands epithelial cells. Con: Poll glands group during indistinct estrus. Exp: Poll glands group during vigorous estrus. NC: negative control. AI: acinar. Sd: secretory duct. Se: secretions. Mf: muscle fibers. Fb: Fibroblasts. Data are presented as means  ±  SEM. * represents <span class="html-italic">p</span> &lt; 0.05 and ** represents <span class="html-italic">p</span> &lt; 0.01.</p>
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<p>Potential molecular mechanism of H<sub>2</sub>S synthesis mediated by CTH and CBS in the poll glands of male Bactrian Camels. ** represents <span class="html-italic">p</span> &lt; 0.01.</p>
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14 pages, 3171 KiB  
Article
Comparative Analysis of Mitochondria Surrounding the Intercalated Discs in Heart Diseases—An Ultrastructural Pilot Study
by Rebecca Schönmehl, Daniel H. Mendelsohn, Lina Winter, Steffen Pabel, Tanja Niedermair, Katja Evert, Wing-Hoi Cheung, Ronald Man Yeung Wong, Volker H. Schmitt, Karsten Keller, Friedrich Barsch, Alexander Dietl, Jan F. Gummert, René Schramm, Samuel Sossalla and Christoph Brochhausen
Int. J. Mol. Sci. 2024, 25(14), 7644; https://doi.org/10.3390/ijms25147644 - 12 Jul 2024
Viewed by 728
Abstract
Background: Mitochondria play a crucial role in adapting to fluctuating energy demands, particularly in various heart diseases. This study investigates mitochondrial morphology near intercalated discs in left ventricular (LV) heart tissues, comparing samples from patients with sinus rhythm (SR), atrial fibrillation (AF), dilated [...] Read more.
Background: Mitochondria play a crucial role in adapting to fluctuating energy demands, particularly in various heart diseases. This study investigates mitochondrial morphology near intercalated discs in left ventricular (LV) heart tissues, comparing samples from patients with sinus rhythm (SR), atrial fibrillation (AF), dilated cardiomyopathy (DCM), and ischemic cardiomyopathy (ICM). Methods: Transmission electron microscopy was used to analyze mitochondria within 0–3.5 μm and 3.5–7 μm of intercalated discs in 9 SR, 10 AF, 9 DCM, and 8 ICM patient samples. Parameters included mean size in µm2 and elongation, count, percental mitochondrial area in the measuring frame, and a conglomeration score. Results: AF patients exhibited higher counts of small mitochondria in the LV myocardium, resembling SR. DCM and ICM groups had fewer, larger, and often hydropic mitochondria. Accumulation rates and percental mitochondrial area were similar across groups. Significant positive correlations existed between other defects/size and hydropic mitochondria and between count/area and conglomeration score, while negative correlations between count and size/other defects and between hydropic mitochondria and count could be seen as well. Conclusion: Mitochondrial parameters in the LV myocardium of AF patients were similar to those of SR patients, while DCM and ICM displayed distinct changes, including a decrease in number, an increase in size, and compromised mitochondrial morphology. Further research is needed to fully elucidate the pathophysiological role of mitochondrial morphology in different heart diseases, providing deeper insights into potential therapeutic targets and interventions. Full article
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<p>Comparison of the mitochondrial population between patients with SR, AF, DCM, and ICM in 0–3.5 μm (<b>A</b>,<b>C</b>) and 3.5–7 μm (<b>B</b>,<b>D</b>) distance from the intercalated discs. (<b>A</b>,<b>B</b>) Percental mitochondrial area in the measuring frame. (<b>C</b>,<b>D</b>) Number of mitochondria counted. * indicates statistical significance (* for <span class="html-italic">p</span> &lt; 0.05, ** for <span class="html-italic">p</span> &lt; 0.01, and *** for <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Comparison of the mitochondrial population between patients with SR, AF, DCM, and ICM in 0–3.5 μm (<b>A</b>,<b>C</b>) and 3.5–7 μm (<b>B</b>,<b>D</b>) distance from the intercalated discs. (<b>A</b>,<b>B</b>) Mitochondria size in µm<sup>2</sup>. (<b>C</b>,<b>D</b>) Mitochondria elongation. * indicates statistical significance (* for <span class="html-italic">p</span> &lt; 0.05, and *** for <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Comparison of the mitochondrial population between patients with SR, AF, DCM, and ICM in 0–3.5 μm (<b>A</b>,<b>C</b>,<b>E</b>) and 3.5–7 μm (<b>B</b>,<b>D</b>,<b>F</b>) distance from the intercalated discs. (<b>A</b>,<b>B</b>) Conglomeration score. (<b>C</b>,<b>D</b>) Percentage of hydropic mitochondria. (<b>E</b>,<b>F</b>) Percentage of otherwise defective mitochondria. * indicates statistical significance (* for <span class="html-italic">p</span> &lt; 0.05, ** for <span class="html-italic">p</span> &lt; 0.01, and *** for <span class="html-italic">p</span> &lt; 0.001).</p>
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<p>Workflow diagram of sample preparation from acquisition to embedding.</p>
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<p>Comparison of mitochondrial ultrastructure. (<b>A</b>,<b>B</b>) Healthy mitochondria (electron-dense with regular cristae structure). (<b>C</b>,<b>D</b>) Hydropic mitochondria marked with red arrows (reduced matrix density). (<b>E</b>,<b>F</b>) Otherwise defective mitochondria marked with red arrows (lamellar structures arising from mitochondria, loss of cristae without the loss of matrix density); pink-labeled mitochondria are adjacent and green-labeled mitochondria are proximate to the intercalated disc.</p>
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<p>Measuring frames adjacent at 0–3.5 µm and 3.5–7 µm distance to the intercalated disc (1) with regular interfibrillar (2) and conglomerated (3) mitochondria; pink-labeled mitochondria are adjacent and green-labeled mitochondria are proximate to the intercalated disc.</p>
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19 pages, 8018 KiB  
Article
Characteristics of Yellow Sea Fog under the Influence of Eastern China Aerosol Plumes
by Jiakun Liang and Jennifer D. Small Griswold
Remote Sens. 2024, 16(13), 2262; https://doi.org/10.3390/rs16132262 - 21 Jun 2024
Viewed by 518
Abstract
Sea fog is a societally relevant phenomenon that occurs under the influence of specific oceanic and atmospheric conditions including aerosol conditions. The Yellow Sea region in China regularly experiences sea fog events, of varying intensity, that impact coastal regions and maritime activities. The [...] Read more.
Sea fog is a societally relevant phenomenon that occurs under the influence of specific oceanic and atmospheric conditions including aerosol conditions. The Yellow Sea region in China regularly experiences sea fog events, of varying intensity, that impact coastal regions and maritime activities. The occurrence and structure of fog are impacted by the concentration of aerosols in the air where the fog forms. Along with industrial development, air pollution has become a serious environmental problem in Northeastern China. These higher pollution levels are confirmed by various satellite remote sensing instruments including the Moderate Resolution Imaging Spectroradiometer (MODIS) aboard the Aqua satellite that observes aerosol and cloud properties. These observations show a clear influence of aerosol loading over the Yellow Sea region, which can impact regional sea fog. In this study, high-resolution data sets from MODIS Aqua L2 are used to investigate the relationships between cloud properties and aerosol features. Using a bi-variate comparison method, we find that, for most cases, larger values of COT (cloud optical thickness) are related to both a smaller DER (droplet effective radius) and higher CTH (cloud top height). However, in the cases where fog is thinner with many zero values in CTH, the larger COT is related to both a smaller DER and CTH. For fog cases where the aerosol type is dominated by smoke (e.g., confirmed fire activities in the East China Plain), the semi-direct effect is indicated and may play a role in determining fog structure such that a smaller DER corresponds with thinner fog and smaller COT values. Full article
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<p>MODIS Aqua L1B Granule Images highlighting different fog case scenarios. (<b>a</b>) Fog case on 2 May 2020, red box: “incomplete” fog area, the upper portion of the Yellow Sea is not included in the MODIS granule. (<b>b</b>) Fog case on 31 July 2020, cyan box: fog area covered by high cloud. (<b>c</b>) Fog case on 28 March 2012, yellow box: pollution (aerosol) band visible on and offshore.</p>
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<p>An example of CTH modification for the fog case was on 13 May 2018. (<b>a</b>) The original CTH of 5 km resolution from MODIS Aqua L2 cloud data product, (<b>b</b>) the modified CTH.</p>
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<p>MODIS Aqua L1B Granule Image of a fog case on 13 May 2018 (<b>a</b>), and CTH of (<b>b</b>) mean temperature inversion height 633 m, (<b>c</b>) 700 m, (<b>d</b>) 800 m. (<b>e</b>) DER at 1 km resolution from MODIS Aqua L2 cloud data product, (<b>f</b>) result of the CTH for the selected fog area after applying the DER mask and land-sea mask.</p>
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<p>Terrestrial aerosol types surrounding the Yellow Sea region from the MODIS Aqua L2 aerosol data product. (<b>a</b>) Fog case on 23 May 2006, main aerosol type: sulfate and dust. (<b>b</b>) Fog case on 8 June 2007, main aerosol type: heavy absorbing smoke and sulfate. (<b>c</b>) Fog case on 2 May 2008, main aerosol type: sulfate. (<b>d</b>) Fog case on 3 May 2009, main aerosol type: sulfate and dust. (<b>e</b>) Fog case on 4 May 2009, main aerosol type: sulfate and dust. (<b>f</b>) Fog case on 17 May 2011, main aerosol type: sulfate. (<b>g</b>) Fog case on 1 June 2011, main aerosol type: heavy absorbing smoke, dust, and sulfate. (<b>h</b>) Fog case on 28 March 2012, main aerosol type: sulfate. (<b>i</b>) Fog case on 8 April 2014, main aerosol type: sulfate. (<b>j</b>) Fog case on 9 April 2014, main aerosol type: sulfate and dust. (<b>k</b>) Fog case on 10 April 2016, main aerosol type: sulfate and dust. (<b>l</b>) Fog case on 13 April 2016, main aerosol type: sulfate and dust. (<b>m</b>) Fog case on 14 April 2016, main aerosol type: sulfate and dust. (<b>n</b>) Fog case on 13 May 2018, main aerosol type: sulfate and dust. (<b>o</b>) Fog case on 6 June 2018, main aerosol type: heavy absorbing smoke and sulfate.</p>
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<p>Fog cases with fire occurrences around the Shandong Peninsula on 8 June 2007 (the first column, (<b>a</b>,<b>d</b>,<b>g</b>,<b>j</b>,<b>m</b>)), 1 June 2011 (the second column (<b>b</b>,<b>e</b>,<b>h</b>,<b>k</b>,<b>n</b>)), and 6 June 2018 (the third column (<b>c</b>,<b>f</b>,<b>i</b>,<b>l</b>,<b>o</b>)). (<b>a</b>–<b>c</b>) Satellite RGB visible image from MODIS L2B Granule Image, red box: pollution band. (<b>d</b>–<b>f</b>) Thermal indicators of fire from NASA World View. (<b>g</b>–<b>i</b>) Vertical structures of air temperature (blue line) and dew point temperature (red line) from Sounding files at Qingdao Station. (<b>j</b>–<b>l</b>) Temperature advection calculated from the NECP/NCAR reanalysis data. The black line indicates the geopotential height at 1000 mb, the black arrows indicate the wind direction at the speed of 10 m/s unit, and the red (blue) areas indicate the warm (cold) temperature advection. (<b>m</b>–<b>o</b>) AOD from MODIS Aqua L2 aerosol data product.</p>
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<p>Bi-variate comparison for 15 fog cases. Diagonal Pattern (<b>a</b>,<b>d</b>–<b>j</b>,<b>l</b>–<b>n</b>) refers to distributions with larger COT values corresponding to smaller DER values and larger CTH values. Left-Right Pattern (<b>c</b>,<b>k</b>) refers to distributions with larger COT values corresponding to larger DER values and smaller CTH values. Inverse-Diagonal Pattern (<b>b</b>,<b>o</b>) refers to distributions with larger COT values corresponding to both larger DER values and larger CTH values.</p>
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<p>Aerosol, wind conditions, and cloud properties for the sea fog case on 28 March 2012, from MODIS Aqua L2 cloud data. (<b>a</b>) AOD form MODIS Aqua L2 aerosol data product. (<b>b</b>) Surface wind from NCEP/NCAR reanalysis dataset. (<b>c</b>) DER. (<b>d</b>) CTH. (<b>e</b>) COT.</p>
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<p>CTH from the MODIS Aqua L2 cloud data product. (<b>a</b>) Fog case on 2 May 2008. (<b>b</b>) Fog case on 10 April 2016.</p>
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<p>Cloud properties and aerosol for the sea fog case on 8 June 2007, from the MODIS Aqua L2 cloud data. (<b>a</b>) DER. (<b>b</b>) CTH. (<b>c</b>) COT.</p>
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<p>The sum bi-variate comparison of the 15 fog cases.</p>
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17 pages, 2912 KiB  
Article
Cloud Top Height Retrieval from FY-4A Data: A Residual Module and Genetic Algorithm Approach
by Tao Li, Niantai Chen, Fa Tao, Shuzhen Hu, Jianjun Xue, Rui Han and Di Wu
Atmosphere 2024, 15(6), 643; https://doi.org/10.3390/atmos15060643 - 27 May 2024
Viewed by 655
Abstract
This paper proposes a ResGA-Net algorithm for cloud top height (CTH) retrieval using FY-4A satellite data. The algorithm utilizes genetic algorithms for data selection and employs a residual module-based neural network for modeling. It takes the spectral channel data from the FY-4A satellite [...] Read more.
This paper proposes a ResGA-Net algorithm for cloud top height (CTH) retrieval using FY-4A satellite data. The algorithm utilizes genetic algorithms for data selection and employs a residual module-based neural network for modeling. It takes the spectral channel data from the FY-4A satellite as input features and uses CTH extracted from ground-based millimeter-wave cloud radar reflectivity as the target. By combining the large observation scale of the FY-4A satellite and the high accuracy of ground-based cloud radar observations, the model can generate satellite CTH products with higher precision. To validate the effectiveness of the algorithm, experiments were conducted using data from the Beijing area spanning from January 2020 to January 2022. The experimental results show that the metrics of the proposed ResGA-Net outperform those of various contrastive algorithms, and compared to the original FY-4A CTH product, the RMSE and MAE have decreased by 37.89% and 34.77%, while the PCC and SRCC have increased by 11.17% and 9.47%, respectively, demonstrating the superiority of the proposed method presented in this paper. Full article
(This article belongs to the Section Atmospheric Techniques, Instruments, and Modeling)
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<p>Overall structure of ResGA-Net. It mainly consists of two modules: (i) a genetic algorithm module used to enhance the quality of the training dataset and (ii) a residual-enhanced NN that is used to train neural networks from the selected training data and evaluate them using the testing dataset.</p>
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<p>Chromosome encoding schematic. This is an example of chromosome gene encoding corresponding to the dataset samples. Each gene in the chromosome represents whether a sample is retained, encoded as 1 for retention and 0 for discard (denoted by a red “X” in the figure). The dataset formed by the retained samples is used for the subsequent residual-enhanced NN modeling.</p>
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<p>Schematic diagrams of randomly divided data (<b>a</b>) and compute temporary fitness (<b>b</b>). (<b>a</b>) The random division of the dataset corresponding to the chromosomes into three groups for the fitness calculation in (<b>b</b>). (<b>b</b>) The establishment of a BP neural network using the data divided in (<b>a</b>) to calculate the fitness of the chromosomes.</p>
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<p>Overall structure of the residual-enhanced NN. The entire network consists of six layers, including input and output layers, as well as four hidden layers. In the diagram, yellow shapes represent the batch normalization (BN) layer, blue shapes represent the fully connected layer, and red shapes represent the sigmoid activation layer. The green arrow indicates the data flow direction.</p>
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<p>Scatter plots of various algorithms with cloud radar data. The vertical axis represents the CTH values obtained from cloud radar, while the horizontal axis represents the predicted results of various algorithms. The closer the points are to the central dividing line (representing y = x), the closer the predicted results are to the radar data. The comparison methods are (<b>a</b>) FY-4A CTH, (<b>b</b>) LightGBM, (<b>c</b>) Random Forest, (<b>d</b>) CatBoost, (<b>e</b>) SVR_rbf, (<b>f</b>) ANN, and (<b>g</b>) ResGA-Net (ours).</p>
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<p>The histogram of errors between the predicted results of various algorithms and the cloud radar data, with a bin width of 600 m. The vertical axis of each subplot represents the number of samples, while the horizontal axis represents the errors between the algorithm’s predicted results and the radar data. The comparison methods are (<b>a</b>) FY-4A CTH, (<b>b</b>) LightGBM, (<b>c</b>) Random Forest, (<b>d</b>) CatBoost, (<b>e</b>) SVR_rbf, (<b>f</b>) ANN, and (<b>g</b>) ResGA-Net (ours).</p>
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<p>The example of a cloud radar reflectivity factor map at Beijing Nanjiao Station selected from the four seasons of the year. To enhance clarity, a portion of the reflectivity factor map containing clouds was selected, and areas without clouds at certain time intervals and height levels were discarded. In the figure, the black circles represent the cloud top heights measured by the cloud radar. The purple squares, yellow triangles, orange diamonds, pink inverted triangles, green pentagons, blue hexagons, and red pentagrams, respectively, represent the CTH product data from FY-4A and the predicted results from LightGBM, Random Forest, CatBoost, SVR (rbf), ANN, and ResGA-Net.</p>
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<p>The example of a cloud radar reflectivity factor map at Beijing Fangshan Station selected from the four seasons of the year. To validate the model’s cross-regional capability, models trained with data from the Nanjiao Station were utilized to test the Fangshan Station. For clarity, the figure still cropped out the cloud-free areas of the reflectivity factor map along the time axis and height layers. The legend is consistent with that in <a href="#atmosphere-15-00643-f007" class="html-fig">Figure 7</a>.</p>
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24 pages, 8560 KiB  
Article
Hybrid Caffeic Acid-Based DHFR Inhibitors as Novel Antimicrobial and Anticancer Agents
by Renu Sehrawat, Ritu Pasrija, Priyanka Rathee, Deepika Kumari, Anurag Khatkar, Esra Küpeli Akkol and Eduardo Sobarzo-Sánchez
Antibiotics 2024, 13(6), 479; https://doi.org/10.3390/antibiotics13060479 - 23 May 2024
Viewed by 966
Abstract
A novel series of 1,2,4-triazole analogues of caffeic acid was designed, synthesized, characterized, and assessed for their capacity to inhibit DHFR, as well as their anticancer and antimicrobial properties. A molecular docking analysis was conducted on DHFR, utilizing PDB IDs 1U72 and 2W9S, [...] Read more.
A novel series of 1,2,4-triazole analogues of caffeic acid was designed, synthesized, characterized, and assessed for their capacity to inhibit DHFR, as well as their anticancer and antimicrobial properties. A molecular docking analysis was conducted on DHFR, utilizing PDB IDs 1U72 and 2W9S, aiming to design anticancer and antimicrobial drugs, respectively. Among all the synthesized derivatives, compound CTh7 demonstrated the highest potency as a DHFR inhibitor, with an IC50 value of 0.15 μM. Additionally, it exhibited significant cytotoxic properties, with an IC50 value of 8.53 µM. The molecular docking analysis of the CTh7 compound revealed that it forms strong interactions with key residues of homo sapiens DHFR such as Glu30, Phe34, Tyr121, Ile16, Val115, and Phe31 within the target protein binding site and displayed excellent docking scores and binding energy (−9.9; −70.38 kcal/mol). Additionally, synthesized compounds were screened for antimicrobial properties, revealing significant antimicrobial potential against bacterial strains and moderate effects against fungal strains. Specifically, compound CTh3 exhibited notable antibacterial efficacy against Staphylococcus aureus (MIC = 5 µM). Similarly, compound CTh4 demonstrated significant antibacterial activity against both Escherichia coli and Pseudomonas aeruginosa, with MIC values of 5 µM for each. A docking analysis of the most active antimicrobial compound CTh3 revealed that it forms hydrogen bonds with Thr121 and Asn18, a π–cation bond with Phe92, and a salt bridge with the polar residue Asp27. Full article
(This article belongs to the Special Issue Microbial Natural Products as a Source of Novel Antimicrobials)
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<p>(<b>a</b>) 2D model illustrating the interaction between compound CTh7 and active site amino acids, highlighting various types of bonds. (<b>b</b>) A three-dimensional representation of CTh7 within the active pocket of the DHFR (PDB ID 1U72) receptor, highlighting amino acid residues in close proximity to the active site.</p>
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<p>(<b>a</b>) Depicts a 2D interaction perspective of methotrexate with PDB ID 1U72. (<b>b</b>) Superimposed image of CTh7 (magenta) and MTX (green) in the binding pocket of the DHFR (1U72) receptor with amino acid residues present in proximity of the active site.</p>
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<p>(<b>a</b>) RMSD relative to the initially minimized complex of the molecule during MD simulations {protein (PDB ID 1U72): left <span class="html-italic">Y</span>-axis and ligand CTh7: right <span class="html-italic">Y</span>-axis}. (<b>b</b>) A schematic of detailed ligand CTh7 atom interactions with the protein residues (interactions that occur more than <b>30.0%</b> of the simulation time in the selected trajectory). (<b>c</b>) A timeline representation of the interactions and contacts between protein and ligand CTh7. (<b>d</b>) Protein interaction with ligand (green: hydrogen bond; purple: hydrophobic; blue: water bridges). (<b>e</b>) Root mean square deviation of a ligand with respect to the reference conformation.</p>
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<p>(<b>a</b>) 2D model illustrating the interaction between compound CTh3 and active site amino acids, highlighting various types of bonds. (<b>b</b>) A three-dimensional representation of CTh3 within the active pocket of the DHFR (2W9S) receptor, highlighting amino acid residues in close proximity to the active site.</p>
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<p>(<b>a</b>) 2D model illustrating the interaction between trimethoprim and binding site amino acids, highlighting various types of bonds. (<b>b</b>) A three-dimensional representation of TMP within the active pocket of the DHFR (2W9S) receptor, highlighting amino acid residues in close proximity to the active site.</p>
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<p>(<b>a</b>) 2D model illustrating the interaction between compound CTh4 and active site amino acids, highlighting various types of bonds. (<b>b</b>) A three-dimensional representation of CTh4 within the active pocket of the DHFR (2W9S) receptor, highlighting amino acid residues in close proximity to the active site.</p>
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<p>Superimposed image of CTh4 (green) and TMP (white) in the pocket of the DHFR (2W9S) receptor active site with amino acid residues present in proximity to the active site.</p>
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<p>(<b>a</b>) 2D model illustrating the interaction between compound CTh6 and active site amino acids, highlighting various types of bonds. (<b>b</b>) Three-dimensional representation of CTh6 within the active pocket of the DHFR (2W9S) receptor, highlighting amino acid residues in close proximity to the active site.</p>
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<p>Explication of SAR of newly synthesized caffeic acid derivatives.</p>
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<p>General synthetic scheme to synthesize caffeic acid derivatives.</p>
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16 pages, 784 KiB  
Article
Outcome of Pulmonary Embolism with and without Ischemic Stroke
by Karsten Keller, Volker H. Schmitt, Omar Hahad and Lukas Hobohm
J. Clin. Med. 2024, 13(10), 2730; https://doi.org/10.3390/jcm13102730 - 7 May 2024
Viewed by 998
Abstract
Background: Ischemic stroke is the second, and pulmonary embolism (PE) is the third most common cardiovascular cause of death after myocardial infarction. Data regarding risk factors for ischemic stroke in patients with acute PE are limited. Methods: Patients were selected by screening the [...] Read more.
Background: Ischemic stroke is the second, and pulmonary embolism (PE) is the third most common cardiovascular cause of death after myocardial infarction. Data regarding risk factors for ischemic stroke in patients with acute PE are limited. Methods: Patients were selected by screening the German nationwide in-patient sample for PE (ICD-code I26) and were stratified by ischemic stroke (ICD code I63) and compared. Results: The nationwide in-patient sample comprised 346,586 hospitalized PE patients (53.3% females) in Germany from 2011 to 2014; among these, 6704 (1.9%) patients had additionally an ischemic stroke. PE patients with ischemic stroke had a higher in-hospital mortality rate than those without (28.9% vs. 14.5%, p < 0.001). Ischemic stroke was independently associated with in-hospital death (OR 2.424, 95%CI 2.278–2.579, p < 0.001). Deep venous thrombosis and/or thrombophlebitis (DVT) combined with heart septal defect (OR 24.714 [95%CI 20.693–29.517], p < 0.001) as well as atrial fibrillation/flutter (OR 2.060 [95%CI 1.943–2.183], p < 0.001) were independent risk factors for stroke in PE patients. Systemic thrombolysis was associated with a better survival in PE patients with ischemic thrombolysis who underwent cardio-pulmonary resuscitation (CPR, OR 0.55 [95%CI 0.36–0.84], p = 0.006). Conclusions: Ischemic stroke did negatively affect the survival of PE. Combination of DVT and heart septal defect and atrial fibrillation/flutter were strong and independent risk factors for ischemic stroke in PE patients. In PE patients with ischemic stroke, who had to underwent CPR, systemic thrombolysis was associated with improved survival. Full article
(This article belongs to the Special Issue Targeted Therapies and Clinical Outcomes for Ischemic Stroke)
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<p>Risk factors, comorbidities, risk stratification markers, systemic thrombolysis, and adverse events in stroke with additionally diagnosed PE stratified by age groups. (<b>A</b>) Risk factors and comorbidities stratified by age groups. (<b>B</b>) Risk stratification markers, systemic thrombolysis, and adverse events stratified by age groups.</p>
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<p>(<b>A</b>) Kaplan–Meier plot for the in-hospital mortality of PE patients with additionally coded ischemic stroke (green line) and without (blue line) related to the in-hospital stay. (<b>B</b>) Kaplan–Meier plot for the in-hospital mortality of PE patients with additionally diagnosed ischemic stroke stratified by the comorbidity of atrial fibrillation/flutter related to the in-hospital stay (blue line: patients without AF; green line: patients with AF).</p>
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11 pages, 1779 KiB  
Article
Injection Site Matters: A Comparative Analysis of Transpulmonary Thermodilution via Simultaneous Femoral and Jugular Indicator Injections under Veno-Venous Extracorporeal Membrane Oxygenation Therapy
by Sabrina Kopp, Johannes Windschmitt, Lena Schnauder, Thomas Münzel, Karsten Keller, Susanne Karbach, Lukas Hobohm, Philipp Lurz, Ingo Sagoschen and Johannes Wild
J. Clin. Med. 2024, 13(8), 2334; https://doi.org/10.3390/jcm13082334 - 17 Apr 2024
Viewed by 1066
Abstract
Background: The use of veno-venous extracorporeal membrane oxygenation (vv-ECMO) in acute lung failure has witnessed a notable increase. The PiCCO system is frequently used for advanced hemodynamic monitoring in this cohort. Our study aimed to investigate whether the choice of indicator injection site [...] Read more.
Background: The use of veno-venous extracorporeal membrane oxygenation (vv-ECMO) in acute lung failure has witnessed a notable increase. The PiCCO system is frequently used for advanced hemodynamic monitoring in this cohort. Our study aimed to investigate whether the choice of indicator injection site (jugular vs. femoral) in patients undergoing vv-ECMO therapy affects transpulmonary thermodilution (TPTD) measurements using the PiCCO® device (Pulsion Medical Systems SE, Munich, Germany). Methods: In a retrospective single-center analysis, we compared thermodilution-derived hemodynamic parameters after simultaneous jugular and femoral injections in 28 measurements obtained in two patients with respiratory failure who were undergoing vv-ECMO therapy. Results: Elevated values of the extravascular lung water index (EVLWI), intrathoracic blood volume index (ITBVI) and global end-diastolic volume index (GEDVI) were observed following femoral indicator injection compared to jugular indicator injection (EVLWI: 29.3 ± 10.9 mL/kg vs. 18.3 ± 6.71 mL/kg, p = 0.0003; ITBVI: 2163 ± 631 mL/m2 vs. 806 ± 125 mL/m2, p < 0.0001; GEDVI: 1731 ± 505 mL/m2 vs. 687 ± 141 mL/m2, p < 0.0001). The discrepancy between femoral and jugular measurements exhibited a linear correlation with extracorporeal blood flow (ECBF). Conclusions: In a PiCCO®-derived hemodynamic assessment of patients on vv-ECMO, the femoral indicator injection, as opposed to the jugular injection, resulted in an overestimation of all index parameters. This discrepancy can be attributed to mean transit time (MTt) and downslope time-dependent (DSt) variations in GEDVI and cardiac function index and is correlated with ECBF. Full article
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<p>Comparison of TPTD-derived parameters from jugular or femoral indicator injections. (<b>A</b>) Cardiac index (CI, n = 23), (<b>B</b>) cardiac function index (CFI, n = 21), (<b>C</b>) extravascular lung water index (EVLWI, n = 21), (<b>D</b>) global end-diastolic volume index (GEDVI, n = 21), (<b>E</b>) mean transit time (MTt, n = 20), and (<b>F</b>) downslope time (DSt, n = 20) and paired <span class="html-italic">t</span>-tests. Data are reported as single values with median and SEM; <span class="html-italic">p</span>-values are shown above the brackets.</p>
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<p>Simple linear regression model (n = 28) of the PiCCO®-derived jugular measurements as a function of the extracorporeal blood flow indexed to body surface area. (<b>A</b>) Downslope time, (<b>B</b>) mean transit time, (<b>C</b>) extravascular lung water index derived by jugular injection as a function of the extracorporeal blood flow indexed to body surface area, and (<b>D</b>) cardiac function index as a function of the extracorporeal blood flow indexed to body surface area.</p>
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<p>Simple linear regression model of the PiCCO-derived femoral deviations (as a percentage) from the PiCCO-derived jugular measurements as a function of the extracorporeal blood flow. (<b>A</b>) Deviation of CFI<sub>fem</sub> (n = 21), (<b>B</b>) deviation of EVLWI<sub>fem</sub> (n = 21), (<b>C</b>) deviation of MTt<sub>fem</sub> (n = 20), and (<b>D</b>) deviation of DSt<sub>fem</sub> (n = 20).</p>
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<p>Simple linear regression between the femoral and jugular TPTD-derived cardiac index. (<b>A</b>) Simple linear regression (n = 23) between the femoral and jugular TPTD-derived cardiac index and (<b>B</b>) simple linear regression (n = 23) between the femoral and jugular TPTD-derived cardiac index plus extracorporeal blood flow indexed to body surface area.</p>
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16 pages, 7952 KiB  
Article
Cloud Characteristics in South China Using Ka-Band Millimeter Cloud Radar Datasets
by Haowen Li, Chengyan Mao, Huaiyu Li, Jieyi Li, Binghong Chen, Lin Zeng, Jiawen Zheng and Mingtuan Liu
Atmosphere 2024, 15(4), 486; https://doi.org/10.3390/atmos15040486 - 15 Apr 2024
Viewed by 1028
Abstract
In this study, we investigate the seasonal and diurnal variations in cloud occurrence frequency, as well as cloud vertical structure (CVS) characteristics under different seasons and precipitation intensities over the Guangzhou region in South China, based on the analysis of millimeter-wave cloud radar [...] Read more.
In this study, we investigate the seasonal and diurnal variations in cloud occurrence frequency, as well as cloud vertical structure (CVS) characteristics under different seasons and precipitation intensities over the Guangzhou region in South China, based on the analysis of millimeter-wave cloud radar (MMCR) and ground automatic weather station rainfall observations from May 2019 to August 2021. The results showed that the occurrence frequency of clouds exhibits a bimodal distribution throughout the year, with peaks in March to June and October, reaching its highest occurrence in May at approximately 80% and its lowest from December to February at around 40%. Additionally, there are distinct diurnal variations in occurrence frequency, with the lowest rates occurring around 0005 LST, rapidly increasing after 0006 LST, and peaking during the afternoon to evening hours. Cloud top height (CTH) shows bimodal distributions during the pre-flood and post-flood seasons. The most frequently occurring range of CTH during the pre-flood season is below 3 km, accounting for approximately 43%, while during the post-flood season, it ranges from 11 to 14 km, constituting about 37%. For precipitation clouds, CTH can extend beyond 12 km, with the radar reflectivity decreasing gradually with increasing height. The highest frequencies of radar echoes are observed below 2 km and between 4 and 7 km, exhibiting clear diurnal variations, with echoes mainly below 2 km and between 4 to 6 km during the early morning, intensifying and shifting to higher altitudes during the day and reaching their maximum below 4 km during the afternoon to nighttime hours, while both the frequency and intensity increase in the height range of 4 to 12 km. Vertical profiles of radar reflectivity and cloud ice/liquid water content (IWC/LWC) exhibit similar trends under different precipitation intensities. The main differences are observed below 4 km, where both radar reflectivity and IWC/LWC generally increase with increasing precipitation intensity. These findings contribute to a better understanding of cloud characteristics in the South China region, enhance the accuracy of model simulations, and provide a scientific basis for accurate forecasting and warning of meteorological disasters. Full article
(This article belongs to the Special Issue Cloud Remote Sensing: Current Status and Perspective)
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<p>Experimental location of the Guangzhou Weather Observatory (GZWO; 113°19′12″ E, 23°0′36″ N, 42 m above sea level).</p>
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<p>The time-height cross section of MMCR-observed radar reflectivity before (<b>a</b>) and after (<b>b</b>) quality control at GZWO on 20 May 2020.</p>
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<p>Cloud occurrence frequency in each month, as observed by MMCR in GZWO during the observation period.</p>
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<p>Diurnal variation of cloud occurrence frequency in different seasons.</p>
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<p>Histogram of CTHs as observed by MMCR installed at GZWO for the period of 2019 to 2021 for (<b>a</b>) pre-flood season and (<b>b</b>) post-flood season.</p>
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<p>Normalized contoured frequency by altitude diagram (NCFAD) for precipitating clouds in (<b>a</b>) pre-flood season and (<b>b</b>) post-flood season.</p>
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<p>Normalized contoured frequency by altitude diagram (NCFAD) for precipitating clouds in pre-flood season during (<b>a</b>) 0000–0600 LST; (<b>b</b>) 0700–1200 LST; (<b>c)</b> 1300–1800 LST; (<b>d</b>) 1900–2400 LST.</p>
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<p>Normalized contoured frequency by altitude diagram (NCFAD) for precipitating clouds in post-flood season during (<b>a</b>) 0000–0600 LST; (<b>b</b>) 0700–1200 LST; (<b>c</b>) 1300–1800 LST; (<b>d</b>) 1900–2400 LST.</p>
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<p>Profiles of cloud radar reflectivity under different precipitation intensities: (<b>a</b>) 0.1–9.9 mm h<sup>−1</sup>; (<b>b</b>) 10–19.9 mm h<sup>−1</sup>; (<b>c</b>) 20–30 mm h<sup>−1</sup>.</p>
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<p>Profiles of cloud ice/liquid water content (IWC/LWC) under different precipitation intensities: (<b>a</b>) 0.1–9.9 mm h<sup>−1</sup>; (<b>b</b>) 10–19.9 mm h<sup>−1</sup>; (<b>c</b>) 20–30 mm h<sup>−1</sup>.</p>
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13 pages, 3866 KiB  
Article
Choroidal Changes in Patients with Diabetic Retinopathy: A Retrospective Study
by Shu-Yu Peng, Ta-Ching Chen, Yi-Ting Hsieh, Tzyy-Chang Ho, Chung-May Yang and Chang-Hao Yang
Diagnostics 2024, 14(5), 537; https://doi.org/10.3390/diagnostics14050537 - 3 Mar 2024
Viewed by 910
Abstract
This study aimed to investigate the characteristic choroidal changes in patients with diabetic retinopathy and identify factors affecting choroidal thickness (CTh), choroidal vascular index (CVI), and choriocapillaris flow. We retrospectively analyzed 79 eyes of 48 patients with diabetes between August 2021 and February [...] Read more.
This study aimed to investigate the characteristic choroidal changes in patients with diabetic retinopathy and identify factors affecting choroidal thickness (CTh), choroidal vascular index (CVI), and choriocapillaris flow. We retrospectively analyzed 79 eyes of 48 patients with diabetes between August 2021 and February 2022. We collected laboratory data, including HbA1c, serum creatinine, blood urea nitrogen, triglyceride, total cholesterol, high-density lipoprotein, and low-density lipoprotein (LDL) levels. Optical coherence tomography images of the foveal avascular zone, retinal vascular density, choroidal flow, retinal thickness, CTh, and CVI were analyzed. Possible determining factors affecting CTh, CVI, and choriocapillaris flow were analyzed using nonparametric multivariate analysis. LDL (p < 0.001) positively correlated with CTh, whereas CVI (p = 0.007) was negatively correlated with CTh in diabetic patients with diabetes. We also identified a negative correlation between choriocapillaris flow and deep parafoveal retinal vessel density in patients with low-grade diabetic retinopathy (DR), which diminished in those with more advanced DR. Our study provides further information on the changes in choroidal structure and blood flow in patients with diabetes. Full article
(This article belongs to the Section Medical Imaging and Theranostics)
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<p>Measurement of choroidal thickness by the AngioVue Imaging System. The distance from the fovea, indicated by orange double-headed arrows, and the choroidal thickness of a certain distance, indicated by green double-headed arrows, were measured.</p>
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<p>Measurement of central 500 µm (<b>left</b>) and 3000 µm (<b>right</b>) choriocapillaris flow. The area of measurement is indicated by the yellow circle. The red circle in the middle of the yellow circle is the center of the fovea. The boxes at the bottom left of both subfigures indicate that the scanning layer is located in the choroid layer.</p>
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<p>Measurement of the choroidal vascular index. The area of the analysis is marked in yellow.</p>
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<p>Flow diagram of study participants.</p>
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<p>The relationship between the retinal vessel densities and severity of diabetic retinopathy. Univariate regression analysis is performed to assess the association between DR severity and retinal vessel densities. The <span class="html-italic">p</span>-values are shown in parentheses. SVD: superficial parafoveal retinal vessel density, DVD: deep parafoveal retinal vessel density, RPC: radial peripapillary capillary density.</p>
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<p>The relationship between the choroidal vessel and severity of diabetic retinopathy. Univariate regression analysis is performed to assess the association between DR severity and CVI/choroidal flow. The <span class="html-italic">p</span>-values are shown in parentheses. (<b>A</b>) The trend of the choroidal vascular index (CVI); (<b>B</b>) the trend of central 500 and 3000 µm choroidal flow.</p>
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14 pages, 2706 KiB  
Article
Establishment and Validation of a Transdermal Drug Delivery System for the Anti-Depressant Drug Citalopram Hydrobromide
by Yi-yang Sun, Ya-jing Ni, Run-jia Wang, Zi-cheng Qin, Zhao Liu, Li-hui Xiao and Yan-qiang Liu
Molecules 2024, 29(4), 767; https://doi.org/10.3390/molecules29040767 - 7 Feb 2024
Cited by 1 | Viewed by 1102
Abstract
To enhance the bioavailability and antihypertensive effect of the anti-depressant drug citalopram hydrobromide (CTH) we developed a sustained-release transdermal delivery system containing CTH. A transdermal diffusion meter was first used to determine the optimal formulation of the CTH transdermal drug delivery system (TDDS). [...] Read more.
To enhance the bioavailability and antihypertensive effect of the anti-depressant drug citalopram hydrobromide (CTH) we developed a sustained-release transdermal delivery system containing CTH. A transdermal diffusion meter was first used to determine the optimal formulation of the CTH transdermal drug delivery system (TDDS). Then, based on the determined formulation, a sustained-release patch was prepared; its physical characteristics, including quality, stickiness, and appearance, were evaluated, and its pharmacokinetics and irritation to the skin were evaluated by applying it to rabbits and rats. The optimal formulation of the CTH TDDS was 49.2% hydroxypropyl methyl cellulose K100M, 32.8% polyvinylpyrrolidone K30, 16% oleic acid-azone, and 2% polyacrylic acid resin II. The system continuously released an effective dose of CTH for 24 h and significantly enhanced its bioavailability, with a higher area under the curve, good stability, and no skin irritation. The developed CTH TDDS possessed a sustained-release effect and good characteristics and pharmacokinetics; therefore, it has the potential for clinical application as an antidepressant. Full article
(This article belongs to the Section Macromolecular Chemistry)
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<p>Effect of the excipient material ratio on the in vitro release of CTH from the transdermal drug delivery system. Data are presented as the mean ± standard deviation (SD; n = 3). The marked different letters indicate significant difference among treatments. CTH, citalopram hydrobromide.</p>
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<p>Effect of the penetration enhancer concentration on the in vitro release of CTH from the transdermal drug delivery system. Data are presented as the mean ± SD (n = 3). The marked different letters indicate significant difference between treatments, and the same letters indicate no significant difference between treatments.</p>
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<p>Effect of polyacrylic acid resin II on the in vitro release of CTH from the transdermal drug delivery system. Data are presented as the mean ± SD (n = 3). The marked different letters indicate significant difference between treatments, and the same letters indicate no significant difference between treatments.</p>
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<p>SEM image of the CTH transdermal drug delivery system. SEM: scanning electron microscopy. The images showed that the patch had good integrity and the drugs were evenly distributed in the polymer matrix.</p>
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<p>Plasma drug concentration–time curve analysis in rabbits after the administration of CTH via the transdermal drug delivery system and oral application. Data are presented as the mean ± SD (n = 6). * <span class="html-italic">p</span> &lt; 0.05, vs. the oral administration group.</p>
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<p>Skin irritation study of the CTH transdermal drug delivery system. (<b>A1</b>–<b>F1</b>): Before application of the patch; (<b>A2</b>–<b>F2</b>): after removal of the patch.</p>
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<p>SEM images of the skin after transdermal administration of CTH. (<b>A1</b>–<b>C1</b>): Before application of the patch; (<b>A2</b>–<b>C2</b>): after removal of the patch. Images showed that the surface structure and morphology of the skin did not significantly change after the transdermal administration of CTH.</p>
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