Search Results (1,301)

In the present study, a series of coumarins, including eight undescribed bis-isoprenylated ones Spinifoliumin A-H, were isolated and identified from the aerial parts of Zanthoxylum dimorphophyllum var. spinifolium (ZDS), a plant revered in traditional Chinese medicine, particularly for treating rheumatoid arthritis (RA). The structures of the compounds were elucidated using 1D and 2D NMR spectroscopy, complemented by ECD, [Rh₂(OCOCF₃)₄]-induced ECD, Mo₂(OAc)₄ induced ECD, IR, and HR-ESI-MS mass spectrometry. A network pharmacology approach allowed for predicting their anti-RA mechanisms and identifying the MAPK and PI3K-Akt signaling pathways, with EGFR as a critical gene target. A CCK-8 method was used to evaluate the inhibition activities on HFLS-RA cells of these compounds. The results demonstrated that Spinifoliumin A, B, and D-H are effective at preventing the abnormal proliferation of LPS-induced HFLS-RA cells. The results showed that compounds Spinifoliumin A, D, and G can significantly suppress the levels of IL-1β, IL-6, and TNF-α. Moreover, molecular docking methods were utilized to confirm the high affinity between Spinifoliumin A, D, and G and EGFR, SRC, and JUN, which were consistent with the results of network pharmacology. This study provides basic scientific evidence to support ZDS’s traditional use and potential clinical application. Full article

Background: The objective of this study was to evaluate how effectively the bioelectric toothbrush can alleviate dentin hypersensitivity (DHS) by using electrostatic forces to remove biofilm from the tooth surface. Methods: This study divided inpatients of a preventative dental clinic between March and October 2023 into the following two groups: a bioelectric toothbrush group (BET, n = 25) and a non-bioelectric toothbrush group (NBET, n = 18) as a control group. This was a randomized double-blind, placebo-controlled trial study. A survey, the number of hypersensitive teeth, the O’Leary index, the visual analogue scale (VAS), and the Schiff Cold Air Sensitivity Scale (SCASS) were also investigated. Results: When fluoride toothpaste was applied with a bioelectric toothbrush, the subjects’ VAS and SCASS scores reflecting symptoms of hyperesthesia significantly decreased over time, as did the number of hypersensitive teeth and the O’Leary index. Moreover, the bioelectric toothbrush was confirmed to be effective in removing dental plaque. Conclusions: Dental clinics must actively promote bioelectric toothbrushes and fluoride toothpaste for patients suffering from hyperesthesia and pain. Furthermore, these items can be suggested as preventative oral care products to patients with potential hyperesthesia. Full article

Nailfold capillaroscopy is a non-invasive investigation, which allows for the study of the microvasculature (anatomical and functional). Rheumatoid arthritis (RA) is associated with a high risk of cardiovascular atherosclerotic diseases, with endothelial dysfunction (macrovascular and microvascular) representing the first step in atherosclerosis development. The aim of this study is represented by the assessment of microvascular endothelial dysfunction in RA patients by means of nailfold capillaroscopy and to assess its evolution after a period of 12 months of anti TNF-alpha treatment. The study included 70 consecutive patients with RA and 70 healthy subjects, matched for age and gender, as the control group. Rheumatoid factor, anti-cyclic citrullinated peptide antibodies, serum TNF-α, C reactive protein, and erythrocytes sedimentation rate were evaluated in all patients, but in controls, only rheumatoid factor, serum TNF-α, C reactive protein, and erythrocytes sedimentation rate were measured. The RA activity was measured by DAS28. Nailfold capillaroscopy was carried out in all patients and controls, determining the baseline nailfold capillary density (Db), nailfold capillary density during reactive hyperemia (Dh), and nailfold capillary density after venous congestion (Dc). Data were presented as mean ± standard deviation. Statistical analysis was performed using ANOVA and Pearson’s correlation, with p < 0.05 being statistically significant. Db, Dh, and Dc were lower in RA patients than in controls (p < 0.0001), correlating with RA activity and TNF-α (p < 0.05). After 12 months of anti TNF-α treatment, microvascular endothelial dysfunction improved (p < 0.0001). Microvascular endothelial dysfunction can be assessed by nailfold capillaroscopy, with anti TNF-α medication contributing to its improvement. Full article

Coastal lagoons are important wetland sites for migratory species and the local flora and fauna population. The Stagnone Lagoon is a coastal lagoon located on the west edge of Sicily between the towns of Marsala and Trapani. The area is characterized by salt-harvesting plants and several archaeological sites and is affected by microtidal excursion. Two mouths allow exchange with the open sea: one smaller and shallower in the north and one larger and deeper in the south. This study aims to understand the lagoon’s hydrodynamics, in terms of circulation and involved forces. The circulation process appears to be dominated mainly by tide excursions and wind forces. Wind velocity, water levels, and water velocity were recorded during different field campaigns in order to obtain a benchmark value. The hydrodynamic circulation has been studied with a 2DH (two-dimensional in the horizontal plane) unstructured mesh model, calibrated with data collected during the 2006 field campaign and validated with the data of the 2007 campaign. Rapid changes in averaged velocity have been found both in Vx and Vy components, showing the strong dependence on seiches. This study tries to identify the main factor that domains the evolution of the water circulation. Sensitivity analyses were conducted to estimate the correct energy transfer between the forcing factors and dissipating ones. A Gauckler–Strickler roughness coefficient between 20 and 25 m^1/3/s is found to be the most representative in the lagoon. To enhance the knowledge of this peculiar lagoon, the MIKE 21 model has been used, reproducing all the external factors involved in the circulation process. Nash–Sutcliffe coefficient of efficiency (NSE) values up to 0.92 and 0.79 are reached with a Gauckler–Strickler coefficient equal to 20 m^1/3/s related to water depth and the Vy velocity component. The Vx velocity component NSE has never been satisfying, showing the limits of the 2D approach in reproducing the currents induced by local morphological peculiarities. Comparing the NSE value of water depth, there is a loss of up to 70% in model predictivity capability between the southern and the northern lagoon areas. This study aims to support the local decision-makers to improve the management of the lagoon itself. Full article

The prescription of a course of oral antibiotics following bone grafting procedures is a common practice in clinical periodontics to reduce surgical site infections. The goal of this study is to characterize the release profile of antibiotics via local delivery using dendrimer hydrogels (DH) and to analyze the effect of two different particulate bone allografts on the release of the antibiotics in vitro. DH were synthesized from polyamidoamine (PAMAM) dendrimer G5 and polyethylene glycol diacrylate, and cefazolin was chosen as the antibiotic. The antibiotic-loaded samples were bathed in PBS and incubated at 37 °C; aliquots were taken (1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 12 h, 24 h, 48 h, 72 h) and analyzed using HPLC to determine the amounts of released cefazolin. In samples with DH, the estimated maximum concentration of cefazolin was 36.97 ± 2.39 μg/mL (95% CI: 34.58–39.36) with 50% released in 4.17 h (95%: 3.26–5.07) and an estimated growth rate of 0.27 (95% CI: 0.17–0.37). For samples without DH, the estimated maximum concentration of cefazolin was 167.4 ± 7.0 μg/mL (95% CI: 160.4–174.4) with 50% released in 2.36 h (95% CI: 2.05–2.67) and an estimated growth rate of 0.70 (95% CI: 0.54–0.87). We conclude that DH are a promising platform for sustained antibiotic release and that the presence of bone grafts did not significantly affect their release. Full article

Microgel particles can play a key role, e.g., in drug delivery systems, tissue engineering, advanced (bio)sensors or (bio)catalysis. Amine-functionalized microgels are particularly interesting in many applications since they can provide pH responsiveness, chemical functionalities for, e.g., bioconjugation, unique binding characteristics for pollutants and interactions with cell surfaces. Since the incorporation of amine functionalities in controlled amounts with predefined architectures is still a challenge, here, we present a novel method for the synthesis of responsive core–shell nanogels (d_h < 100 nm) with a poly(N-isopropylacrylamide) (pNIPAm) core and a polyamine shell. To achieve this goal, a surface-functionalized pNIPAm nanogel was first prepared in a semi-batch precipitation polymerization reaction. Surface functionalization was achieved by adding acrylic acid to the reaction mixture in the final stage of the precipitation polymerization. Under these conditions, the carboxyl functionalities were confined to the outer shell of the nanogel particles, preserving the core’s temperature-responsive behavior and providing reactive functionalities on the nanogel surface. The polyamine shell was prepared by the chemical coupling of polyethyleneimine to the nanogel’s carboxyl functionalities using a water-soluble carbodiimide (EDC) to facilitate the coupling reaction. The efficiency of the coupling was assessed by varying the EDC concentration and reaction temperature. The molecular weight of PEI was also varied in a wide range (M_w = 0.6 to 750 kDa), and we found that it had a profound effect on how many polyamine repeat units could be immobilized in the nanogel shell. The swelling and the electrophoretic mobility of the prepared core–shell nanogels were also studied as a function of pH and temperature, demonstrating the successful formation of the polyamine shell on the nanogel core and its effect on the nanogel characteristics. This study provides a general framework for the controlled synthesis of core–shell nanogels with tunable surface properties, which can be applied in many potential applications. Full article

Cardiovascular disease is the first cause of death worldwide and kills more people each year than any other cause of death. N, N-dimethylaniline-heliamine (DH), a synthetic tetrahydroisoquinoline alkaloid, has shown notable antiarrhythmic activity. However, the metabolic processes and pharmacokinetic characteristics of DH in rats have not been studied. This study aims to identify its metabolites, as well as develop and validate a rapid and efficient bioanalytical method for quantifying DH in rat plasma over a wide range of concentrations. Its metabolites were characterized in silico, in vitro, and in vivo. A series of 16 metabolites were identified, of which 12 were phase I metabolites and 4 were phase II metabolites. A low probability of DH binding to DNA, protein, and glutathione is predicted by the in silico model. The main metabolic processes of DH were demethylation, dehydrogenation, glucuronidation, and sulfation. Concentration–time profiles were generated by analyzing the plasma, and the outcomes were analyzed via non-compartmental analysis to identify the pharmacokinetic parameters. Among the detected parameters were the volume of distribution, estimated at 126,728.09 ± 56,867.09 mL/kg, clearance at 30,148.65 ± 15,354.27 mL/h/kg, and absolute oral bioavailability at 16.11%. The plasma distribution volume of DH was substantially higher than the overall plasma volume of rats, which suggests that DH has a specific tissue distribution in rats. This study suggests that DH is appropriately bioavailable and excreted via a variety of routes and has low toxicity. Full article

The antibiotic resistance crisis has seriously jeopardized public health and human safety. As one of the ways of horizontal transfer, transformation enables bacteria to acquire exogenous genes naturally. Bisphenol compounds are now widely used in plastics, food, and beverage packaging, and have become a new environmental pollutant. However, their potential relationship with the spread of antibiotic resistance genes (ARGs) in the environment remains largely unexplored. In this study, we aimed to assess whether the ubiquitous bisphenol S (BPS) could promote the transformation of plasmid-borne ARGs. Using plasmid pUC19 carrying the ampicillin resistance gene as an extracellular ARG and model microorganism E. coli DH5α as the recipient, we established a transformation system. Transformation assays revealed that environmentally relevant concentrations of BPS (0.1–10 μg/mL) markedly enhanced the transformation frequency of plasmid-borne ARGs into E. coli DH5α up to 2.02-fold. Fluorescent probes and transcript-level analyses suggest that BPS stimulated increased reactive oxygen species (ROS) production, activated the SOS response, induced membrane damage, and increased membrane fluidity, which weakened the barrier for plasmid transfer, allowing foreign DNA to be more easily absorbed. Moreover, BPS stimulates ATP supply by activating the tricarboxylic acid (TCA) cycle, which promotes flagellar motility and expands the search for foreign DNA. Overall, these findings provide important insight into the role of bisphenol compounds in facilitating the horizontal spread of ARGs and emphasize the need to monitor the residues of these environmental contaminants. Full article

In order to increase nutrient input and alleviate the poor growth of blueberry (Vaccinium corymbosum L.) in neutral soil with strong nitrification, the application of nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) as an enhanced efficiency fertilizer is a strategy to reduce nitrogen (N) loss and improve N supply. However, few studies have systematically investigated the effect of DMPP application on blueberry and its soil condition in detail so far. In this study, a pot experiment was conducted to elucidate the effect of DMPP at four gradient levels including 0.5% (w/w applied-N) DMPP (DL), 1% DMPP (DM), 2% DMPP (DH), and no DMPP (CK) on the dynamics of soil mineral N (NH₄⁺-N and NO₃⁻-N), soil chemical properties, as well as the agronomic characteristics and physiological indexes of blueberry plants in the neutral soil–blueberry system. The addition of DMPP significantly increased the retention of soil ammonium nitrogen and the content of total mineral nitrogen. qPCR analysis showed that DMPP inhibited the ammoxidation process mainly by reducing the abundance of the ammonia-oxidizing bacteria (AOB) amoA gene rather than the ammonia-oxidizing archaea (AOA) amoA gene. No significant inhibitory effect of DMPP was observed for the nitrite dehydrogenase gene nxrA and nitrite reductase gene nirS. Soil NH₄⁺-N and available phosphorus content were both enhanced with the DMPP application rates both in bulk and rhizosphere soil. Applying 1% DMPP to the neutral soil for blueberry was sufficient to safely inhibit soil nitrification, not only increasing ammonium nitrogen content by 10.42% and 26.79%, but also enhancing available phosphorus content by 9.19% and 22.41% compared with CK in bulk and rhizosphere soil, respectively. Moreover, 1% DMPP addition increased the nitrogen and phosphorus concentration of blueberry leaves by 12.17% and 26.42%, respectively, compared with CK. The total branch length and the dry weight of blueberry plant were also increased by 16.8% and 33.1%, respectively. These results provide valuable agronomic information for the application of DMPP in blueberry cultivation. Fertilization applied with 1% DMPP has great economic potential to improve both nitrogen and phosphorus absorption of blueberry so as to promote the vegetative growth of blueberry. Full article

Persistent malodor affects many people worldwide and is usually associated with poor dental hygiene. This pilot trial aimed to determine whether proper dental hygiene (DH) and a probiotic dietary supplement support oral health in volunteers with persistent malodor. Volunteers (n = 35) were randomly assigned to the probiotic or placebo cohort. The probiotic cohort (n = 20) brushed and flossed their teeth twice daily and used probiotics for 30 days; the placebo cohort (n = 15) followed the same hygiene practices and used the placebo. The intervention phase was followed by a 30-day follow-up period. Measured outcomes were malodor and tongue-coating scores, probiotic DNA levels, salivary cytokines, and salivary pH. DH and probiotics significantly decreased malodor (~50% during intervention) and tongue coating scores (~45% during intervention). These changes remained through the course of the trial. The probiotic DNA levels increased in the probiotic cohort and dropped in the placebo cohort after the intervention started. The malodor moderately correlated with the tongue coating P. acidilactici level. The addition of probiotics increased IL-10 levels during the intervention and decreased IL-8, TNF-α, and IL-6 by the end of the study. People with malodor may benefit from using DH and probiotics. Additional trials are needed to definitively establish the benefits of probiotic dietary supplements. Full article

A method for measuring multi-joint finger trajectories is proposed using MediaPipe. In this method, a high-speed camera is used to record finger movements. Subsequently, the recorded finger movement data are input into MediaPipe, where the system automatically extracts the coordinate data of the key points in the finger movements. From this, we obtain data pertaining to the trajectory of the finger movements. In order to verify the accuracy and effectiveness of this experimental method, we compared it with the DH method and the Artificial keypoint alignment method in terms of metrics such as MAPE (Mean Absolute Percentage Error), maximum distance error, and the time taken to process 500 images. The results demonstrated that our method can detect multiple finger joints in a natural, efficient, and accurate manner. Then, we measured posture for three selected hand movements. We determined the position coordinates of the joints and calculated the angular acceleration of the joint rotation. We observed that the angular acceleration can fluctuate significantly over a very short period of time (less than 100 ms), in some cases increasing to more than ten times the initial acceleration. This finding underscores the complexity of finger joint movements. This study can provide support and reference for the design of finger rehabilitation robots and dexterous hands. Full article

Introduction: Stress-induced hyperglycemia (SIH) and malnutrition are common in trauma patients and are linked to worse outcomes. This study examined the influence of nutritional status, determined by the Geriatric Nutritional Risk Index (GNRI), on the incidence of SIH in trauma patients. Methods: A retrospective analysis was conducted on adult trauma patients admitted to a Level I trauma center from 1 January 2009 to December 31, 2021. Patients were categorized into four groups: SIH, diabetic hyperglycemia (DH), diabetic normoglycemia (DN), and non-diabetic normoglycemia (NDN). Nutritional status was assessed using GNRI: high risk (GNRI < 82), moderate risk (82 ≤ GNRI < 92), low risk (92 ≤ GNRI ≤ 98), and no risk (GNRI > 98). Incidence of SIH and outcomes were analyzed across GNRI groups. Results: SIH was associated with higher mortality across all GNRI groups compared to NDN, with the highest rate (45.7%) in the high-risk group. Mortality decreased as GNRI increased in all glucose groups. NDN patients had the lowest mortality rates across GNRI groups. There was no correlation between GNRI and SIH incidence (p = 0.259). Conclusion: SIH significantly influenced mortality across all nutritional status groups, with the highest impact in malnourished patients. Although malnutrition did not affect SIH incidence, both SIH and poor nutritional status independently contributed to worse trauma outcomes. Targeted management of hyperglycemia and nutritional deficiencies is crucial for improving survival. Full article

In vitro embryonic technology is crucial for improving farm animal reproduction but is hampered by the poor quality of oocytes and insufficient development potential. This study investigated the relationships among changes in the gut microbiota and metabolism, serum features, and the follicular fluid metabolome atlas. Correlation network maps were constructed to reveal how the metabolites affect follicular development by regulating gene expression in granulosa cells. The superovulation synchronization results showed that the number of follicle diameters from 4 to 8 mm, qualified oocyte number, cleavage, and blastocyst rates were improved in the dairy heifers (DH) compared with the non-lactating multiparous dairy cows (NDC) groups. The gut microbiota was decreased in Rikenellaceae_RC9_gut_group, Alistipes, and Bifidobacterium, but increased in Firmicutes, Cyanobacteria, Fibrobacterota, Desulfobacterota, and Verrucomicrobiota in the NDC group, which was highly associated with phospholipid-related metabolites of gut microbiota and serum. Metabolomic profiling of the gut microbiota, serum, and follicular fluid further demonstrated that the co-metabolites were phosphocholine and linoleic acid. Moreover, the expression of genes related to arachidonic acid metabolism in granulosa cells was significantly correlated with phosphocholine and linoleic acid. The results in granulosa cells showed that the levels of PLCB1 and COX2, participating in arachidonic acid metabolism, were increased in the DH group, which improved the concentrations of PGD₂ and PGF_2α in the follicular fluid. Finally, the expression levels of apoptosis-related proteins, cytokines, and steroidogenesis-related genes in granulosa cells and the concentrations of steroid hormones in follicular fluid were determinants of follicular development. According to our results, gut microbiota-related phosphocholine and linoleic acid participate in arachidonic acid metabolism in granulosa cells through the gut–follicle axis, which regulates follicular development. These findings hold promise for enhancing follicular development and optimizing oocyte quality in subfertile dairy cows. Full article

Artificial neural networks (ANNs) can be used for accurate heat load forecasting in district heating systems (DHSs). This paper presents an application of a shallow ANN with two hidden layers in the case of a local DHS. The developed model was used to write a simple application in Python 3.10 that can be used in the operation of a district heating plant to carry out a preliminary analysis of heat demand, taking into account the ambient temperature on a given day. The model was trained using the real data from the period 2019–2022. The training was sufficient for the number of 150 epochs. The prediction effectiveness indicator was proposed. In the considered case, the effectiveness of the trained network was 85% and was better in comparison to five different regression models. The developed tool was based on an open-source programming environment and proved its ability to predict heating load. Full article

Wheat (Triticum aestivum L.) is a crucial cereal crop, contributing around 20% of global caloric intake. However, challenges such as diminishing arable land, water shortages, and climate change threaten wheat production, making yield enhancement crucial for global food security. The heading date (HD) is a critical factor influencing wheat’s growth cycle, harvest timing, climate adaptability, and yield. Understanding the genetic determinants of HD is essential for developing high-yield and stable wheat varieties. This study used a doubled haploid (DH) population from a cross between Jinmai 47 and Jinmai 84. QTL analysis of HD was performed under three phosphorus (P) treatments (low, medium, and normal) across six environments, using Wheat15K high-density SNP technology. The study identified 39 QTLs for HD, distributed across ten chromosomes, accounting for 2.39% to 29.52% of the phenotypic variance. Notably, five stable and major QTLs (Qhd.saw-3A.7, Qhd.saw-3A.8, Qhd.saw-3A.9, Qhd.saw-4A.4, and Qhd.saw-4D.3) were consistently detected across varying P conditions. The additive effects of these major QTLs showed that favorable alleles significantly delayed HD. There was a clear trend of increasing HD delay as the number of favorable alleles increased. Among them, Qhd.saw-3A.8, Qhd.saw-3A.9, and Qhd.saw-4D.3 were identified as novel QTLs with no prior reports of HD QTLs/genes in their respective intervals. Candidate gene analysis highlighted seven highly expressed genes related to Ca²⁺ transport, hormone signaling, glycosylation, and zinc finger proteins, likely involved in HD regulation. This research elucidates the genetic basis of wheat HD under P stress, providing critical insights for breeding high-yield, stable wheat varieties suited to low-P environments. Full article