Elucidating the pathogenic mechanism underlying plasticizer-induced chronic kidney disease via integrated network toxicology and machine learning.

Intervertebral disc degeneration (IVDD) is a leading cause of low back pain, yet clinically, there remains no effective therapeutic approach to reverse its progression, imposing a substantial socioeconomic burden. While multiple factors contribute to IVDD pathogenesis, cellular senescence has emerged as a critical risk factor associated with both the incidence and progression of IVDD. Ageing and other damage factors drive nucleus pulposus cells (NPCs) towards a senescent phenotype characterized by increased secretion of proinflammatory factors, resulting in NPC dysfunction and tissue degeneration, which are hallmarks of IVDD. In this study, we demonstrated that PRMT2 deficiency disrupted arginine methylation‒ubiquitination crosstalk, driving NPC inflammatory senescence and accelerating IVDD progression. Mechanistically, PRMT2 loss reduced FBXO7 methylation at Arg 504, promoting the FBXO7-MED12 interaction to facilitate MED12 ubiquitination and subsequent proteasomal degradation. MED12 deficiency induced pathological R-loop accumulation, which activated the cytosolic DNA-sensing cGAS-STING axis, triggering inflammatory response cascades. Notably, engineered extracellular vesicles (EVs) delivering MED12-overexpressing plasmids effectively inhibited NP cell senescence and attenuated IVDD progression. Together, our findings establish that dysregulated methylation‒ubiquitination crosstalk critically drives IVDD progression and reveal MED12 as a promising therapeutic target for ameliorating the impact of IVDD.

Semen cryopreservation is vital for fertility preservation in men with oligoasthenoteratozoospermia (OAT). While cryopreservation increases sperm DNA fragmentation (SDF), patient-specific risk factors in severe OAT remain poorly defined. We aimed to quantify the change in DNA fragmentation index (DFI) and identify clinical predictors of susceptibility. This retrospective cohort study enrolled 340 men with severe OAT (sperm count < 5 million/mL, total motility < 42%, progressive motility < 30%, morphology < 4%). DFI was assessed in fresh and post-thaw samples using the TUNEL assay. Correlations and multivariate regression analyses evaluated relationships between DFI change and age, body mass index (BMI), sperm parameters, and smoking status. The mean DFI increased significantly from 22.0% (IQR 15.0-29.0%) in fresh semen to 36.0% (IQR 23.0-54.0%) postcryopreservation (p < 0.001). The median absolute increase (ΔDFI) was 9.5% (IQR 6.0-25.0%). Univariate analysis identified significant correlations between the ΔDFI and higher BMI (ρ = 0.544, p < 0.001), lower sperm count (ρ = -0.638, p < 0.001), and poorer sperm morphology (ρ = -0.669, p < 0.001). In the final multivariate linear regression model, higher BMI and poorer sperm morphology remained the only significant independent predictors of a greater increase in DFI after cryopreservation (both p < 0.001). This model explained 93.7% of the variance in the ΔDFI (Adjusted R² = 0.937, p < 0.001). Age and sperm count were not independent predictors in the final model. Smoking status and varicocele grade were not significantly associated with the ΔDFI. Cryopreservation significantly exacerbates sperm DNA damage in severe OAT, but this effect is not uniform. Higher BMI and poorer sperm morphology are independent risk factors for greater damage, identifying a vulnerable patient subgroup. These men may benefit from personalized counseling and optimized cryopreservation protocols to mitigate DNA damage and improve future assisted reproductive technology outcomes.

Wearable-device geometry and tissue mechanical variability determine sacral soft-tissue loading and pressure injury risk.

Rising warnings of a potential sixth mass extinction and ecosystem degradation, fueled by climate change and human activities, highlight the need for an accurate measurement of human impacts on biodiversity loss to support effective policymaking. This study incorporates the extinction rate metric with the life-cycle impact assessment (LCIA) model to develop a set of policy-relevant, closed-loop spatiotemporal damage factors (DFs). Here, biodiversity damage is expressed in E/MSY (expected extinctions per million species years), representing extinction rate-based impacts and intrinsic biodiversity value. This approach enabled quantification of the biodiversity extinction rate due to future land use changes. The total net extinction rate was estimated at 161.9 E/MSY, and the global weighted average DF was estimated at 1.73 × 10-05 E/MSY/km2 as a species richness- and area-weighted summary of spatially heterogeneous damage. The grid-scaled DF results were provided at a global resolution of 0.25 arc-degrees. DFs indicated marginal extinctions from land use changes within each grid cell, providing a means to customize the disaggregated-scale DF for various LCA inventories. These results improve the interpretability of location-based biodiversity assessments, making them more relevant to policy decisions.

Obesity and hypertension are major risk factors for cardiovascular target organ damage in childhood, including increased left ventricular mass index (LVMI) and left ventricular hypertrophy (LVH). Blood pressure variability (BPV) has been suggested as a potential contributor to cardiovascular damage; however, its role in pediatric obesity remains unclear. This study was aimed at evaluating short-term BPV and pulse wave analysis (PWA) parameters in children and adolescents with obesity and their associations with LVMI and LVH. This retrospective cross-sectional study included 42 children and adolescents with obesity evaluated between October 2023 and August 2025, and 42 age- and sex-matched healthy children and adolescents (8-18years). All participants underwent 24-h ambulatory blood pressure monitoring with simultaneous PWA and echocardiographic assessment of LVMI. Short-term BPV was assessed using standard deviation (SD), coefficient of variation (CV), and average real variability (ARV). LVH was defined as LVMI above the 95th percentile for age and height. Correlation analyses and multivariable logistic regression analysis were performed. Participants with obesity had higher ambulatory blood pressure levels, BPV indices, pulse wave velocity and central blood pressure values than healthy controls (p < 0.05). LVH prevalence was higher in the obese group (40% vs. 9%; OR = 6.29, 95% CI: 1.90-20.9). Short-term BPV parameters were not independently associated with LVH and showed no significant correlations with LVMI or the LVMI ratio. Despite increased BPV and arterial stiffness in children and adolescents with obesity, short-term BPV was not independently associated with LVMI or LVH. Further prospective studies are warranted to clarify the clinical relevance of BPV in pediatric obesity.

Based on multidimensional data analysis, potential biomarkers for ulcerative colitis were screened, and the effects of curcumin chitosan microspheres on the expression of key targets in ulcerative colitis and their role in alleviating inflammation were observed. Potential biomarkers related to UC progression were identified through differential expression analysis (using the limma package, with |log2FC| > 1 and corrected P < 0.05), weighted gene coexpression network analysis, and three machine learning algorithms (LASSO, random forest, SVM-RFE) on the basis of the datasets GSE107499 and GSE87473 in the GEO database. The core genes selected through this process were externally validated via the independent dataset GSE47908. A UC mouse model was constructed using 6-8-week-old C57BL/6 mice, and CCM was applied to the UC mice. Colonic tissues were collected for pathological examination and determination of inflammatory factor levels. Changes in the protein expression of the core genes were detected via immunohistochemistry. After rigorous screening and external validation, four core genes were finally identified: FCN3, FGR, HSD11B1 and PIM2. CCM treatment improved pathological damage and inflammatory factor levels in the colon tissue of UC mice, and the protein expression levels of FCN3, FGR, HSD11B1 and PIM2 in the colon tissue were inhibited. Four potential targets of UC, namely, FCN3, FGR, HSD11B1, and PIM2, were identified. CCM may improve the degree of the UC inflammatory response by downregulating the expression of key genes.

This study evaluates airport pavement performance under heavy multi-wheel aircraft using a hybrid Mechanistic–Empirical (M–E) and 3D Finite Element (FE) approach. The framework combines Federal Aviation Administration Rigid and Flexible Iterative Elastic Layered Design (FAARFIELD) with detailed 3D FE modeling to assess stress, strain, fatigue, and rutting. A flexible runway and rigid concrete apron were analyzed under wide-body aircraft at maximum landing weight. M–E results indicated a fatigue damage factor of 0.60 and a rutting of about 5 mm over a 50-year period, showing rutting as the main distress for flexible pavement. FE simulations captured localized stress beneath wheels and predicted an instantaneous vertical displacement of 3.55 mm, consistent with mechanistic results. The agreement between the two methods confirms structural adequacy while highlighting proximity to rutting limits. This hybrid approach improves long-term performance predictions and supports resilient, sustainable airport infrastructure aligned with Sustainable Development Goals.

Peptic ulcer disease is a common gastrointestinal disorder caused by an imbalance between damaging factors and mucosal protection. Alcohol induces gastric injury through oxidative stress, inflammation, and apoptosis, while phenytoin may have potential preventive effects in ulcer. This study aimed to evaluate the gastroprotective effects of phenytoin against ethanol-induced gastric ulcers in rats, focusing on oxidative stress, inflammatory, and apoptotic biomarkers, and to elucidate the underlying molecular mechanisms. Thirty-two male Wistar rats were randomly divided into four groups: control, ethanol-induced gastric ulcer (ETH), phenytoin-treated (ETH + Phen), and omeprazole-treated (ETH + Ome). Gastric ulcers were induced by oral administration of absolute ethanol. Ulcer area, gastric content volume, oxidative stress markers (TAC, MDA, GSH, SOD, CAT), inflammatory mediators (NF-κB, TNF-α, IL-1β, iNOS, COX-2), and apoptotic markers (Bax, Bcl-2, Caspase-3) were measured using biochemical assays, real time PCR, and ELISA. Ethanol administration significantly increased ulcer area, gastric content volume, MDA levels, NF-κB activation, pro-inflammatory cytokines, and pro-apoptotic markers, while reducing TAC, GSH, and antioxidant enzyme activities. Preventive phenytoin treatment significantly attenuated these effects, reducing ulcer area, restoring antioxidant balance, suppressing NF-κB-mediated inflammation, and modulating apoptotic signaling. Both phenytoin and omeprazole improved these parameters compared with the ethanol group; however, no direct statistical comparison between the two treatments was performed. Phenytoin exhibits significant gastroprotective effects against ethanol-induced gastric injury, which may be associated with modulation of oxidative stress, inflammatory pathways, and apoptosis.

A mathematical model for the drift and damage of drifting fish eggs incorporating multi-source damage factors

Prognostic value of dipping status in untreated adult hypertensives from the Algerian population

Mechanism of endoplasmic reticulum stress: Insights for potential therapeutic benefits in burns.

Widespread exposure to per- and polyfluoroalkyl substances (PFAS) is a growing public health concern, but its link to muscle damage remains largely unexplored. As PFAS exposure is associated with liver dysfunction, which is an established risk factor for muscle damage, we examined their associations and potential mediating pathways. A total of 1261 participants were recruited from Guangdong province, China, from November 2018 to August 2019 and examined for muscle mass, strength, serum PFAS levels, and biomarkers of liver function. The key results demonstrated significant positive associations between serum PFAS exposure and sarcopenia risk. Specifically, a per ln ng/mL increase in linear perfluorooctane sulfonate (PFOS), branch PFOS, and perfluorooctanoic acid (PFOA) was associated with adjusted odds ratios of 2.32 (95% CI: 1.77 to 3.00), 2.18 (95% CI: 1.67 to 2.90) and 3.01 (95% CI: 1.96 to 4.70), respectively. Analysis of PFAS mixtures via the BKMR model revealed a linear dose-response relationship of sarcopenia, with PFOS and PFOA being the primary contributor. Importantly, mediation analyses showed that liver function biomarkers served as significant mediators of the PFAS-sarcopenia association. Notably, liver synthesis function markers (albumin and globin) mediated a substantial proportion of the association, ranging from 3.48% to 82.42%, whereas liver injury markers (aspartate aminotransferase and gamma-glutamyl transferase) accounted for only 1.54% to 15.44%. This study underscores the need to be aware of the increased risk of muscle damage associated with PFAS exposure, which may primarily operate through liver function abnormalities.

MicroRNAs(miRNAs) have been shown to suppress the onset and progression of heart disease and have recently been widely proposed as biomarkers. However, few literatures have been reported on whether they protect against Anderson-Fabry-induced myocardial damage. The aim was to explore whether miR-19a-3p could be used as a biomarker for the diagnosis and risk assessment of Anderson-Fabry disease (AFD), distinguishing AFD from healthy controls and myocardial damage caused by AFD. 60 AFD patients and an equal number of healthy controls were recruited to analyze miR-19a-3p expression. ROC analysis evaluated their diagnostic ability, and statistical analysis demonstrated the association of clinical indicators of cardiac damage with miR-19a-3p. 53.3% of AFD patients exhibited cardiac damage, with notable structural changes in cardiac characteristics. MiR-19a-3p expression level was downregulated in AFD and AFD cardiomyopathy patients and showed high diagnostic accuracy for identifying both AFD and associated cardiac injury. It negatively correlated with severity of cardiac injury. Multivariate analysis identified miR-19a-3p as a significant independent protective factor in cardiac damage in AFD. The study identified downregulated miR-19a-3p as a potent diagnostic biomarker for AFD and its associated cardiomyopathy. MiR-19a-3p was established as an independent protective factor in cardiac damage. Thus, it was proposed as a promising candidate biomarker for AFD cardiomyopathy.

Rock masses in short-term freeze–thaw zones tend to fail under long-term loading. Therefore, investigating the creep damage characteristics of rocks under short-term freeze–thaw cycles is of great significance for the stability evaluation of rock engineering. In this study, white sandstone was used as the research material. Multi-gradient short-term freeze–thaw cycle tests and graded loading creep acoustic emission (AE) tests were performed to investigate the creep behavior and AE response characteristics of sandstone after short-term freeze–thaw action, and a creep damage constitutive model was established. The results show the following: (1) The mass loss rate, P-wave velocity reduction rate, and porosity growth rate of sandstone increase with increasing freeze–thaw cycles and duration. (2) The instantaneous axial strain of specimens increases with the stress level under different freeze–thaw durations and cycle numbers. (3) The cumulative AE event rate decreases significantly with increasing freeze–thaw cycles and duration. (4) Based on the seven-element viscoelastic model, a creep damage constitutive model was developed by introducing the freeze–thaw damage factor (D), with an average goodness-of-fit of 0.964. The findings can provide a theoretical reference for the long-term stability assessment and disaster early warning of geotechnical engineering in short-term freeze–thaw regions.

Schisandra chinensis (Turcz.) Baill. (Schisandraceae) is a medicinal plant widely distributed in East Asia and has long been used in traditional herbal medicine. Phytochemical studies have identified lignans as the major bioactive constituents of S. chinensis, among which Schisandrin B (Sch B) is one of the most abundant and pharmacologically active compounds. Previous studies have demonstrated that Sch B exhibits a variety of biological activities, including antioxidant, anti-inflammatory, hepatoprotective, and cytoprotective effects. As a natural lignan compound derived from S. chinensis, Sch B has attracted increasing attention for its potential protective effects against environmental and inflammatory insults. This study aimed to investigate the protective effects of Sch B against PM2.5-induced inflammatory injury in THP-1 cells and to elucidate the underlying molecular mechanisms. An in vitro PM2.5-induced THP-1 cell injury model was established by stimulating THP-1 cells with PM2.5. Subsequently, Sch B was applied to the model, and inflammation-related indicators and pathways were detected using methods such as ELISA, PCR, and Western Blot (WB). The results showed that Sch B significantly inhibited interleukin-1β (IL-1β) secretion and attenuated PM2.5-induced pyroptosis in THP-1 cells. Mechanistically, Sch B alleviated cell membrane damage and inflammatory factor release by suppressing Caspase-1 activation and inhibiting the cleavage of gasdermin D (GSDMD) into its active N-terminal fragment (N-GSDMD). Furthermore, Sch B treatment was associated with the up-regulation of ALG-2, ALIX, and TSG101, suggesting the potential involvement of ESCRT-III-associated membrane repair mechanisms. In conclusion, Sch B, a natural lignan compound derived from S. chinensis, exhibits protective effects against PM2.5-induced THP-1 cell pyroptosis by reducing cell membrane damage and inflammatory cytokine release. These effects are associated with the inhibition of Caspase-1 activity and GSDMD cleavage, as well as the activation of ESCRT-III-associated membrane repair responses. Collectively, these findings highlight the potential of Sch B as a natural cytoprotective compound against particulate matter-induced inflammatory injury.

The Numerical Manifold Method (NMM) introduces two independent cover systems-mathematical and physical-allowing discontinuities associated with crack propagation to be represented in a natural manner. To clarify the instability pattern and crack evolution of stratified rock slopes under top loading, this study implements a quadrilateral NMM framework incorporating the LT criterion, formulated from the Mohr-Coulomb strength theory, together with a damage factor. The LT criterion is used to determine the onset and propagation of cracks, while the damage factor serves to distinguish crack types. The proposed framework is first examined through a Brazilian splitting test, which confirms its capability to resolve crack development in a transparent and physically consistent way. It is then applied to systematically investigate the failure pattern and crack propagation characteristics of stratified slopes containing cracks of different inclinations or randomly distributed bedding cracks under overload conditions. The results show that, as crack inclination increases, the failure pattern of top-loaded stratified slopes shifts from shallow bedding-parallel shear failure to deep sliding-tensile composite failure. For slopes with randomly distributed bedding cracks, progressive failure follows a sequence of dispersed crack initiation, coalescence, penetration, and subsequent layered sliding-splitting. The proposed method captures the complex discontinuous failure process with high fidelity, demonstrating its effectiveness for stability analysis of stratified slopes with inherent cracks. The findings provide a theoretical basis for hazard assessment and protective design of top-loaded stratified rock slopes.

Ferroptosis induced by iron overload has been recognized as a critical factor in germ cell damage and subsequent male infertility. However, current ferroptosis inhibitors are often constrained by systemic side effects and limited targeting. Herein, we developed graphitic carbon nitride (g-C3N4) nanosheets as a multisite iron chelation strategy to inhibit iron overload-induced ferroptosis and prevent male reproductive dysfunction. Characterized by excellent stability and intrinsic fluorescence, the g-C3N4 nanosheets enable specific iron ion (Fe3+ and Fe2+) sequestration, exhibiting iron-responsive fluorescence quenching with remarkable selectivity and sensitivity. Both in vitro and in vivo studies confirmed that iron overload induces significant germ cell damage, whereas g-C3N4 nanosheets treatment targeted ferroptosis via the Nrf2 pathway, thereby preserving male reproductive function. Moreover, g-C3N4 exhibited excellent biosafety, with minimal cytotoxicity in vitro and no adverse effects in vivo. These findings highlight the potential of g-C3N4 nanosheets as a promising therapeutic platform for the treatment of ferroptosis-related diseases.

The TFAM-OGG1 axis mediates T-2 toxin-induced chondrocyte mitochondrial dysfunction and cartilage degeneration.

Despite the increasing prevalence of cosmetic-related adverse reactions, their potential prognoses and associated risk factors have received limited attention within the medical community. A retrospective analysis was conducted on 7794 cases of cosmetics-related adverse reactions reported in Wuhan, China, from 2017 to 2023. Data were collected from multiple sources, including medical institutions, cosmetic manufacturers, distributors, individual consumers and regulatory agencies. Demographic characteristics, clinical diagnoses, symptom profiles and allergy histories were systematically analysed using descriptive statistics. Cases were stratified by recovery outcome into complete versus incomplete groups to identify prognostic factors. Comparative analyses were performed using χ2 tests, with statistically significant variables (p < 0.05) further evaluated through multivariate logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical analyses were performed using SPSS version 25.0, with a significance level set at p < 0.05. Among the 7794 patients, the majority (76.56%) achieved complete recovery, while a substantial proportion (23.44%) experienced persistent or permanent symptoms, such as post-inflammatory hyperpigmentation (PIH), atrophic scarring and other forms of skin damage. Statistical analysis identified age and a history of allergies as significant risk factors for long-term skin damage. Patients under 20 years of age were 2.06 times more likely to suffer persistent or permanent symptoms compared to those over 50 years (p = 0.000). Additionally, individuals with a history of food allergy were 3.16 times more prone to long-term skin damage (p < 0.05). A history of drug allergy also significantly increased the risk, with an OR of 1.887 (95% CI: 1.34, 2.66; p = 0.000). This study identified younger age (< 20 years) and a history of food or drug allergies as significant risk factors for long-term symptoms following cosmetic adverse reactions. These insights assist dermatologists in recognising high-risk individuals and guiding tailored preventive strategies. Integrating these indicators into clinical evaluation and patient counselling may enhance early intervention, ultimately reducing the likelihood of persistent or irreversible cutaneous sequelae. Overall, the findings highlight the importance of individualised risk assessment and proactive management in ensuring cosmetic safety and optimising dermatological and public health outcomes.