Search Results (44,271)

The irregular joint network unique to columnar joints separates the rock mass into several irregular polygonal prisms. Similar physical model specimens of columnar jointed rock mass (CJRM) were fabricated using a rock-like material. The effect of the irregularity of the joint network was considered in the horizontal plane, and the effect of the dip angle of the joint network was considered in the vertical plane. The strength and deformation moduli of the specimen were investigated using uniaxial compression tests. A total of four failure modes of regular columnar jointed rock mass (RCJRM) and irregular columnar jointed rock mass (ICJRM) were identified through the tests. The peak stress of the irregular columnar jointed rock mass specimen is reduced by 56.65%. The strength and deformation moduli of RCJRM were greater than those of ICJRM, while the anisotropic characteristics of ICJRM were stronger. The failure mode of CJRM was determined by the dip angle. With the increase in the dip angle, the strength and deformation moduli of irregular columnar jointed rock mass are a symmetrical “V” type distribution, 45° corresponds to the minimum strength, and 30° obtains the minimum deformation modulus. With the increase in the irregularity coefficient, the strength and deformation moduli of CJRM decreased first and then increased gradually. When the irregularity coefficient is 0.1, the linear deformation modulus reaches the minimum value. When the irregularity coefficient is 0.7, the median deformation modulus reaches the minimum value. The fitting function proposed in the form of the cosine function managed to predict the strength value of CJRM and showed the strength of the anisotropic characteristics caused by the change in the dip angle. Compared with the existing physical model test results, it is determined that the strength of the specimen is positively correlated with the addition amount of rock-like material and the loading rate, and negatively correlated with the water consumption. Full article

The deep learning steel plastic constitutive model training method was studied based on the recurrent neural network (RNN) model to improve the allocative efficiency of the deep learning steel plastic constitutive model and promote its application in practical engineering. Two linear hardening constitutive datasets of steel were constructed using the Gaussian stochastic process. The RNN, long short-term memory (LSTM), and gated recurrent unit (GRU) were used as models for training. The effects of the data pre-processing method, neural network structure, and training method on the model training were analyzed. The prediction ability of the model for different scale series and the corresponding data demand were evaluated. The results show that LSTM and the GRU are more suitable for stress–strain prediction. The marginal effect of the stacked neural network depth and number gradually decreases, and the hysteresis curve can be accurately predicted by a two-layer RNN. The optimal structure of the two models is A50-100 and B150-150. The prediction accuracy of the models increased with the decrease in batch size and the increase in training batch, and the training time also increased significantly. The decay learning rate method could balance the prediction accuracy and training time, and the optimal initial learning rate, batch size, and training batch were 0.001, 60, and 100, respectively. The deep learning plastic constitutive model based on the optimal parameters can accurately predict the hysteresis curve of steel, and the prediction abilities of the GRU are 6.13, 6.7, and 3.3 times those of LSTM in short, medium, and long sequences, respectively. Full article

The interaction of the SARS-CoV-2 spike protein with membrane-bound angiotensin-converting enzyme-2 (ACE-2) receptors in epithelial cells facilitates viral entry into human cells. Despite this, ACE-2 exerts significant protective effects against coronaviruses by neutralizing viruses in circulation and mitigating inflammation. While SARS-CoV-2 reduces ACE-2 expression, vitamin D increases it, counteracting the virus’s harmful effects. Vitamin D’s beneficial actions are mediated through complex molecular mechanisms involving innate and adaptive immune systems. Meanwhile, vitamin D status [25(OH)D concentration] is inversely correlated with severity, complications, and mortality rates from COVID-19. This study explores mechanisms through which vitamin D inhibits SARS-CoV-2 replication, including the suppression of transcription enzymes, reduced inflammation and oxidative stress, and increased expression of neutralizing antibodies and antimicrobial peptides. Both hypovitaminosis D and SARS-CoV-2 elevate renin levels, the rate-limiting step in the renin-angiotensin-aldosterone system (RAS); it increases ACE-1 but reduces ACE-2 expression. This imbalance leads to elevated levels of the pro-inflammatory, pro-coagulatory, and vasoconstricting peptide angiotensin-II (Ang-II), leading to widespread inflammation. It also causes increased membrane permeability, allowing fluid and viruses to infiltrate soft tissues, lungs, and the vascular system. In contrast, sufficient vitamin D levels suppress renin expression, reducing RAS activity, lowering ACE-1, and increasing ACE-2 levels. ACE-2 cleaves Ang-II to generate Ang_(1–7), a vasodilatory, anti-inflammatory, and anti-thrombotic peptide that mitigates oxidative stress and counteracts the harmful effects of SARS-CoV-2. Excess ACE-2 molecules spill into the bloodstream as soluble receptors, neutralizing and facilitating the destruction of the virus. These combined mechanisms reduce viral replication, load, and spread. Hence, vitamin D facilitates rapid recovery and minimizes transmission to others. Overall, vitamin D enhances the immune response and counteracts the pathological effects of SARS-CoV-2. Additionally, data suggests that widely used anti-hypertensive agents—angiotensin receptor blockers and ACE inhibitors—may lessen the adverse impacts of SARS-CoV-2, although they are less potent than vitamin D. Full article

Prolonged use of atypical antipsychotics (AAPs) is commonly associated with increased cardiovascular disease risk. While weight gain and related health issues are generally considered the primary contributors to this risk, direct interference with mitochondrial bioenergetics, particularly in the liver where these drugs are metabolized, is emerging as an additional contributing factor. Here, we compared the effects of two AAPs with disparate metabolic profiles on the response of Fao hepatoma cells to oxidative stress: olanzapine (OLA), which is obesogenic, and aripiprazole (ARI), which is not. Results showed that cells treated with ARI exhibited resistance to H₂O₂-induced oxidative stress, while OLA treatment had the opposite effect. Despite enhanced survival, ARI-treated cells exhibited higher apoptotic rates than OLA-treated cells when exposed to H₂O₂. Gene expression analysis of pro- and anti-apoptotic factors revealed that ARI-treated cells had a generally blunted response to H₂O₂, contrasting with a heightened response in OLA-treated cells. This was further supported by the reduced activation of MAPKs and STAT3 in ARI-treated cells in response to H₂O₂, whereas OLA pre-treatment enhanced their activation. The loss of stress response in ARI-treated cells was consistent with the observed increase in the mitochondrial production of O₂ ^-, a known desensitizing factor. The physiological relevance of O₂⁻ in ARI-treated cells was demonstrated by the increase in mitophagy flux, likely related to mitochondrial damage. Notably, OLA treatment protected proteasome activity in Fao cells exposed to H₂O₂, possibly due to the better preservation of stress signaling and mitochondrial function. In conclusion, this study highlights the underlying changes in cell physiology and mitochondrial function by AAPs. ARI de-sensitizes Fao cells to stress signaling, while OLA has the opposite effect. These findings contribute to our understanding of the metabolic risks associated with prolonged AAP use and may inform future therapeutic strategies. Full article

Introduction: Obesity is one of the major healthcare challenges. It affects one in eight people around the world and leads to several comorbidities, including type 2 diabetes, hyperlipidemia, and arterial hypertension. GLP-1 analogs have become major players in the therapy of obesity, leading to significant weight loss in patients. However, benefits resulting from their usage seem to be greater than simple appetite reduction and glucose-lowering potential. Recent data show better cardiovascular outcomes, which are connected with the improvements in the course of atherosclerosis. Macrophages are crucial cells in the forming and progression of atherosclerotic lesions. Previously, it was shown that in vitro treatment with GLP-1 analogs can affect macrophage phenotype, but there is a paucity of in vivo data. Objective: To evaluate the influence of in vivo treatment with liraglutide on basic phenotypic and functional markers of macrophages. Methods: Basic phenotypic features were assessed (including inducible nitric oxide synthase, arginase 1 and mannose receptors), proinflammatory cytokine (IL-1β, TNFα) release, and oxidative stress markers (reactive oxygen species, malondialdehyde) in macrophages obtained prior and after 3-month therapy with liraglutide in patients with obesity. Results: Three-month treatment with subcutaneous liraglutide resulted in the alteration of macrophage phenotype toward alternative activation (M2) with accompanying reduction in the TNFα release and diminished oxidative stress markers. Conclusions: Our results show that macrophages in patients treated with GLP-1 can alter their phenotype and function. Those findings may at least partly explain the pleiotropic beneficial cardiovascular effects seen in subjects treated with GLP-1 analogs. Full article

The shear connector of a steel composite bridge is designed by predicting fatigue life using the fatigue strength curves (S-N curve) based on push-out test results. The fatigue strength curves of the current design codes present only a linear relationship between the stress range and fatigue life on a log scale based on push-out experiment results. However, an alternative to the current empirical formula is necessary for the fatigue design of shear connections involving many detailed variations or high strength steel materials. This study collected and reanalyzed data from push-out fatigue tests to determine the factors influencing fatigue life and propose a machine learning-based fatigue life prediction model. The proposed machine learning model demonstrated an improvement in predictive performance of approximately 2 to 8 times compared to the existing design codes when evaluated against experimental data. Feature importance analysis based on the proposed model revealed that the stress range most significantly influenced fatigue life prediction. Model validation results indicated that the proposed model provided reliable predictions with accuracy and generalization performance. Moreover, it effectively accounted for uncertainty by incorporating features previously overlooked in existing design codes. Plans for fine-tuning pretrained models were also discussed. Full article

Hemobiologic reactions associated with the hemoincompatibility of extracorporeal circuit material are an undesirable and inevitable consequence of all blood-contacting medical devices, typically considered only from a clinical perspective. In hemodialysis (HD), the blood of patients undergoes repetitive (at least thrice weekly for 4 h and lifelong) exposure to different polymeric materials that activate plasmatic pathways and blood cells. There is a general agreement that hemoincompatibility reactions, although unavoidable during extracorporeal therapies, are unphysiological contributors to non-hemodynamic dialysis-induced systemic stress and need to be curtailed. Strategies to lessen the periodic and direct effects of blood interacting with artificial surfaces to stimulate numerous biological pathways have focused mainly on the development of ‘more passive’ materials to decrease intradialytic morbidity. The indirect implications of this phenomenon, such as its impact on the overall delivery of care, have not been considered in detail. In this article, we explore, for the first time, the potential clinical and economic consequences of hemoincompatibility from a value-based healthcare (VBHC) perspective. As the fundamental tenet of VBHC is achieving the best clinical outcomes at the lowest cost, we examine the equation from the individual perspectives of the three key stakeholders of the dialysis care delivery processes: the patient, the provider, and the payer. For the patient, sub-optimal therapy caused by hemoincompatibility results in poor quality of life and various dialysis-associated conditions involving cost-impacting adjustments to lifestyles. For the provider, the decrease in income is attributed to factors such as an increase in workload and use of resources, dissatisfaction of the patient from the services provided, loss of reimbursement and direct revenue, or an increase in doctor–nurse turnover due to the complexity of managing care (nephrology encounters a chronic workforce shortage). The payer and healthcare system incur additional costs, e.g., increased hospitalization rates, including intensive care unit admissions, and increased medications and diagnostics to counteract adverse events and complications. Thus, hemoincompatibility reactions may be relevant from a socioeconomic perspective and may need to be addressed beyond just its clinical relevance to streamline the delivery of HD in terms of payability, future sustainability, and societal repercussions. Strategies to mitigate the economic impact and address the cost-effectiveness of the hemoincompatibility of extracorporeal kidney replacement therapy are proposed to conclude this comprehensive approach. Full article

Background and Objectives: Hypertension increases the risk of developing atherosclerosis and arterial stiffness, with secondarily enhanced wall stress pressure that damages the artery wall. The coexistence of atherosclerosis and hypertension leads to artery stenosis and microvascular angiopathies, during which the intravascular mechanical hemolysis of red blood cells (RBCs) occurs, leading to increased platelet activation, dysfunction of the endothelium and smooth muscle cells due to a decrease in nitric oxide, and the direct harmful effects of hemoglobin and iron released from the red blood cells. This study analyzed the impact of hypertension and physical exercise on the risk of hemolysis in the left coronary artery. Methods: To analyze many different cases and consider the decrease in flow through narrowed arteries, a flow model was adopted that considered hydraulic resistance in the distal section, which depended on the conditions of hypertension and exercise. The commercial ANSYS Fluent 2023R2 software supplemented with user-defined functions was used for the simulation. CFD simulations were performed and compared with the FSI simulation results. Results: The differences obtained between the FSI and CFD simulations were negligible, which allowed the continuation of analyses based only on CFD simulations. The drops in pressure and the risk of hemolysis increased dramatically with increased flow associated with increased exercise. A relationship was observed between the increase in blood pressure and hypertension, but in this case, the increase in blood pressure dropped, and the risk of hemolysis was not so substantial. However, by far, the case of increased physical activity with hypertension had the highest risk of hemolysis, which is associated with an increased risk of clot formation that can block distal arteries and lead to myocardial hypoxia. Conclusions: The influence of hypertension and increased physical exercise on the increased risk of hemolysis has been demonstrated. Full article

In the central region of Chile, the Mega-Drought together with the demographic increase near the coast threatens groundwater availability and the hydrogeological functioning of coastal wetlands. To understand the hydric relationship between an aquifer and a wetland in a semi-arid coastal region of Central Chile (Valparaíso, Chile), as well as its geoenvironmental effects, four data collection campaigns were conducted in the wetland–estuary hydric system and surroundings, between 2021 and 2022, including physical, hydrochemical, and isotopic analyses in groundwater (n = 16 sites) and surface water (n = 8 sites). The results generated a conceptual model that indicates a hydraulic connection between the wetland and the aquifer, where the water use in one affects the availability in the other. With an average precipitation of 400 mm per year, the main recharge for both systems is rainwater. Three specific sources of pollution were identified from anthropic discharges that affect the water quality of the wetland and the estuary (flow from sanitary landfill, agricultural and livestock industry, and septic tank discharges in populated areas), exacerbated by the infiltration of seawater laterally and superficially through sandy sediments and the estuary, increasing salinity and electrical conductivity in the coastal zone (i.e., 3694 µS/cm). The Del Sauce subbasin faces strong hydric stress triggered by the poor conservation state of the riparian–coastal wetland and groundwater in the same area. This study provides a detailed understanding of hydrological interactions and serves as a model for understanding the possible effects on similar ecosystems, highlighting the need for integrated and appropriate environmental management. Full article

Chagas disease is a prevalent health problem in Latin America which has received insufficient attention worldwide. Current treatments for this disease, benznidazole and nifurtimox, have limited efficacy and may cause side effects. A recent study proposed investigating a wide range of nitroindazole and indazolone derivatives as feasible treatments. Therefore, it is proposed that adding a nitro group at the 5-position of the indazole and indazolone structure could enhance trypanocidal activity by inducing oxidative stress through activation of the nitro group by NTRs (nitroreductases). The study results indicate that the nitro group advances free radical production, as confirmed by several analyses. Compound 5a (5-nitro-2-picolyl-indazolin-3-one) shows the most favorable trypanocidal activity (1.1 ± 0.3 µM in epimastigotes and 5.4 ± 1.0 µM in trypomastigotes), with a selectivity index superior to nifurtimox. Analysis of the mechanism of action indicated that the nitro group at the 5-position of the indazole ring induces the generation of reactive oxygen species (ROS), which causes apoptosis in the parasites. Computational docking studies reveal how the compounds interact with critical residues of the NTR and FMNH₂ (flavin mononucleotide reduced) in the binding site, which is also present in active ligands. The lipophilicity of the studied series was shown to influence their activity, and the nitro group was found to play a crucial role in generating free radicals. Further investigations are needed of derivatives with comparable lipophilic characteristics and the location of the nitro group in different positions of the base structure. Full article

Childhood maltreatment has been demonstrated to impact brain development. However, whether childhood maltreatment can influence the effects of recent stress on brain networks remains unclear. This study aimed to investigate whether childhood maltreatment moderates the longitudinal relationship between recent life stress and within- and between-network connectivity in key brain networks, including the anterior salience (ASN), central executive (CEN), default mode (DMN), and emotional regulation network (ERN). A cohort of 172 individuals from the Neuroscience in Psychiatry Network (NSPN) underwent MRI scans at two specific time points and undertook evaluations of childhood maltreatment and recent life stress. The results showed that childhood abuse moderated the association of recent life stress with the within-network connectivity of ASN and ERN but not DMN and CEN. Furthermore, recent life stress significantly interacted with childhood abuse to be associated with the between-network connectivity of ASN-DMN, ASN-CEN, ASN-ERN, DMN-ERN and CEN-ERN. Overall, among youth exposed to higher degrees of childhood abuse, greater recent life stress was longitudinally associated with increased network connectivity. Understanding these interactions can provide valuable insights for developing prevention strategies and interventions aimed at mitigating the lasting impact of childhood maltreatment on brain development and overall well-being. Full article

Under extended-phase-shift (ESP) control, the current stress of the dual active bridge converter (DAB) is relatively high, which reduces the efficiency of the converter. To solve this problem, a particle swarm optimization (PSO) algorithm based on minimizing the current stress is proposed in this paper. The optimal phase-shift ratio of the DAB converter with ESP control is obtained by using the algorithm’s optimization characteristic. This approach ensures that the converter achieves minimal current stress, thereby enhancing the steady-state performance of the DAB converter. Moreover, in terms of dynamic performance, traditional PI control has poor dynamic response ability when there are sudden changes in load and input voltage. To solve this problem, the voltage dynamic matrix control (DMC) algorithm is introduced to combine with the PSO algorithm to minimize the current stress of the DAB converter under EPS control while enhancing the dynamic response capability of the DAB converter. A simulation model was constructed for comparative validation on MATLAB/Simulink 2019, demonstrating the correctness and effectiveness of the improved control method. Full article

Our previous study showed that magnetic field pretreatment promoted germination and phenolic enrichment in quinoa. In this study, we further investigated the effects of NaCl stress on the growth and phenolic synthesis of germinated quinoa after magnetic field pretreatment (MGQ). The results showed that NaCl stress inhibited the growth of MGQ, reduced the moisture content and weight of a single plant, but increased the fresh/dry weight. The higher the NaCl concentration, the more obvious the inhibition effect. In addition, NaCl stress inhibited the hydrolysis of MGQ starch, protein, and fat but increased the ash content. Moreover, lower concentrations (50 and 100 mM) of NaCl stress increased the content of MGQ flavonoids and other phenolic compounds. This was due to the fact that NaCl stress further increased the enzyme activities of PAL, C4H, 4CL, CHS, CHI, and CHR and up-regulated the gene expression of the above enzymes. NaCl stress at 50 and 100 mM increased the DPPH and ABTS scavenging capacity of MGQ and increased the activities of antioxidant enzymes, including SOD, POD, CAT, APX, and GSH-Px, further enhancing the antioxidant system. Furthermore, principal component analysis showed that NaCl stress at 100 mM had the greatest combined effect on MGQ. Taken together, NaCl stress inhibited the growth of MGQ, but appropriate concentrations of NaCl stress, especially 100 mM, helped to further increase the phenolic content of MGQ and enhance its antioxidant system. Full article

This study explores the effects of trees on the acoustic and thermal environment in addition to people’s responses to trees in different contexts. Through field measurements conducted during the summer of 2023 at the campus of the Southwest University of Science and Technology in Mianyang, residents’ neutral points were locally found to be 52.2 dBA (acoustic) and 23.8 °C (thermal). Further, at their maximum, the trees were able to reduce heat stress by 4 °C (indicated by the physiologically equivalent temperature—PET) and the noise level by 10 dBA (indicated by the A-weighted sound pressure—LAeq); this was achieved by trees with a crown diameter of 20 m. Subjective acoustic and thermal responses varied depending on the context. Acoustically, their neutral LAeq values toward the sounds of traffic, teaching, sports, and daily life were 46.9, 52.5, 51.0, and 52.7 dBA, respectively. Thermally, pedestrians’ neutral PET values were 24.2, 26.1, 22.3, and 25.1 °C, respectively, under the same conditions. These phenomena might be a consequence of the effects of sound frequencies. Future urban forestry research should focus on planting for environmental quality improvement. Full article

The objective of this study is to assess the influence of genetic polymorphisms in DGAT1, LEP, and SCD1 on the oxidative stress biomarkers and bioactive protein levels in Hereford bulls. A total of sixty-eight bulls were analyzed at 22 months of age to assess growth metrics and carcass quality, with a focus on polymorphisms in these genes. The key markers of oxidative stress, including malondialdehyde (MDA), and the activities of antioxidant enzymes such as glutathione reductase (GluRed), glutathione peroxidase (GPx), and superoxide dismutase (SOD) were measured, alongside bioactive compounds like taurine, carnosine, and anserine. The results show that the TT genotype of DGAT1 is linked to significantly higher MDA levels, reflecting increased lipid peroxidation, but is also associated with higher GluRed and GPx activities and elevated levels of taurine, carnosine, and anserine, suggesting an adaptive response to oxidative stress. The LEP gene analysis revealed that the CC genotype had the highest MDA levels but also exhibited increased GPx and SOD activities, with the CT genotype showing the highest SOD activity and the TT genotype the highest total antioxidant status (TAS). The SCD1 AA genotype displayed the highest activities of GluRed, GPx, and SOD, indicating a more effective antioxidant defence, while the VA genotype had the highest MDA levels and the VV genotype showed lower MDA levels, suggesting protective effects against oxidative damage. These findings highlight genotype specific variations in the oxidative stress markers and bioactive compound levels, providing insights into the genetic regulation of oxidative stress and antioxidant defences, which could inform breeding strategies for improving oxidative stress resistance in livestock and managing related conditions. Full article