Search Results (6,205)

Follicle-stimulating hormone receptor (FSHR) is expressed on the plasma membrane of granulosa cells in the ovarian follicles. FSHR is involved in the development and maturation of Graafian follicles, along with granulosa proliferation and estrogen synthesis. There are two well-characterized non-synonymous single-nucleotide gene polymorphisms in the exon 10 of the human FSHR gene, namely rs6165 (c.919G>A, Ala307Thr) and rs6166 (c.2039A>G, Ser680Asn). Recent research clarifies the association of rs6165/rs6166 with susceptibility to infertility-associated ovarian diseases, ranging from polycystic ovarian syndrome, premature ovarian insufficiency, endometriosis, to ovarian cancer, along with response/resistance to ovulation induction/ovarian stimulation with clomiphene citrate, letrozole, metformin, FSH preparations, and adjunctive growth hormone in infertility treatment. This narrative review aims to update the knowledge on the relationship among rs6165/rs6166, infertility etiology, and differential responses to oral ovulation induction agents, FSH preparations, and adjunctive growth hormone. The re6165/rs6166 genotype-guided choice of individualized ovulation stimulation preparations has great potential to reduce unexpected poor or high ovarian responses in ovulation induction and ovarian stimulation and improve clinical outcomes in reproductive medicine. Current evidence is insufficient, and further studies are warranted to ascertain its potential for clinical implementation. Full article

Muscle regeneration following injury reveals a striking paradox: the same phenomenon, fiber branching, can serve as both a beneficial adaptation in healthy muscle and a pathological hallmark in disease. In healthy muscle, branched fibers emerge as an adaptive response to extreme mechanical loading, redistributing stress, enhancing hypertrophy, and protecting against injury. Conversely, in conditions such as Duchenne Muscular Dystrophy, excessive and complex branching contributes to mechanical weakness, increased susceptibility to damage, and progressive functional decline. This review explores the dichotomy of fiber branching in muscle physiology, synthesizing current research on its molecular and cellular mechanisms. By understanding the paradoxical nature of fiber branching, we aim to uncover new perspectives for therapeutic strategies that balance its adaptive and pathological roles to improve outcomes for muscle diseases. Full article

The use of large-aperture scanning mirrors for high-resolution and wide-swath imaging represents a major trend in Earth observation technology. However, to improve dynamic response performance, scanning mirror assemblies are highly lightweighted, resulting in reduced overall stiffness. This makes the mirror surface susceptible to thermal and inertial loads during operation, leading to degraded surface accuracy and poor imaging quality. Moreover, dynamic scanning mirror has the multi-disciplinary coupling effects and non-circular structural characteristics. It poses significant challenges for surface figure analysis. To address these issues, this paper proposes a surface analysis method for high-dynamic scanning mirrors under multi-physics coupling in non-circular domains. First, a finite element model of the mirror assembly is established based on the minimum aperture and angular velocity parameters. Through finite element analysis, the surface response of the scanning mirror assembly under thermal loads, dynamic inertial loads, and their coupled effects is quantitatively investigated. Subsequently, an analytical approach, which combines rigid-body displacement separation and Gram–Schmidt orthogonalization, is developed to construct non-circular Zernike polynomials, enabling high-precision fitting and reconstruction of the mirror’s dynamic surface distortions. Numerical experiments validate the accuracy of the model. Results show that for a scanning mirror with an aperture of 466 mm × 250 mm under the coupled condition of a 5 °C temperature rise and 50 N·mm torque, the surface figure achieves RMS < 2 nm and PV < 22 nm, with a fitting accuracy achieves 10⁻⁶. These results verify the accuracy and reliability of the proposed method. The surface analysis approach presented in this study provides theoretical guidance and a design framework for subsequent image quality evaluation and assurance. Full article

S. suis is a prominent zoonotic pathogen responsible for diseases such as arthritis in piglets, swine septicemia, and meningitis. The emergence of multi-drug resistance (MDR) underscores the urgent need for the development of novel antibacterial strategies. In this context, a systematic evaluation of the antibacterial potential of the bacteriophage lytic enzyme Ply900 was conducted in this study, along with an analysis of its domain functions and an in vivo study of its therapeutic dynamics. Ply900 exhibits potent in vitro lytic activity against multiple bacteria, including Streptococcus suis, Streptococcus agalactiae, and Staphylococcus aureus. Notably, it possesses broad biochemical stability, with tolerance to diverse environmental conditions. In a mouse model of S. suis serotype 2 SC19 infection, both the direct Ply900 treatment group and the triple therapy group achieved effective eradication of S. suis, with markedly improved survival rates. The remaining bacteria remained susceptible to Ply900, with no evidence of induced resistance development. Mechanistic analysis revealed that the SH3B domain of Ply900 enhances targeted cleavage efficiency by binding synergistically to peptidoglycan with the CHAP domain, with CYS-34, HIS-59, and ASP-28 serving as key amino acid sites for Ply900’s cleavage activity. Collectively, these findings lay the foundation for the potential dual applications of the lysin Ply900, both in the clinical treatment of S. suis infections and in the prevention and control of these pathogenic bacteria in livestock farming. Full article

Climate variability plays a crucial role in shaping drinking water quality, yet the quantitative links between meteorological factors and microbiological contamination remain underexplored in temperate continental climates. A secondary data analysis was conducted on 15,394 microbiological water quality test results collected between 2015 and 2024, including heterotrophic plate counts (22 °C and 37 °C), coliform bacteria, and Escherichia coli, and their associations with local meteorological conditions across groundwater wells and piped distribution networks were examined. A clear distinction emerged: groundwater wells showed higher vulnerability to primary microbial contamination (coliforms and E. coli), whereas distribution networks exhibited higher odds of heterotrophic plate count exceedances, indicating greater susceptibility to post-treatment microbial regrowth. In groundwater wells, temperature showed strong positive associations with all microbial indicators (p < 0.001), with pronounced summer peaks in coliforms and E. coli, while precipitation triggered short-term contamination spikes characterized by a 2-day lag. In contrast, piped networks exhibited weaker and more delayed meteorological responses. These results highlight the need for a shift from climate-responsive to climate-pre-emptive water quality monitoring by incorporating meteorological forecasts, especially for non-chlorinated groundwater sources. Full article

Standard epidemiological models often treat human behavior as static, failing to capture the dynamic feedback loops that shape epidemic waves. To address this, we developed a compartmental model of COVID-19 that couples the disease dynamics with two co-evolving behavioral games governed by imitation dynamics: an altruistic self-isolation game for infected individuals and a self-interested vaccination game for susceptible individuals. Our simulations reveal a fundamental behavioral paradox: strong adherence to self-isolation, while effective at reducing peak infections, diminishes the perceived risk of disease, thereby undermining the incentive to vaccinate. This dynamic highlights a critical trade-off between managing acute crises through non-pharmaceutical interventions and achieving long-term population immunity. We conclude that vaccination has a powerful stabilizing effect that can prevent the recurrent waves often driven by behavioral responses to non-pharmaceutical interventions. Public health policy must therefore navigate the tension between encouraging short-term mitigation behaviors and communicating the long-term benefits of vaccination to ensure lasting population resilience. Full article

Sarcoidosis is an immune-mediated granulomatous disease whose etiology has remained unresolved despite more than a century of investigation. Accumulating microbiological and immunopathological evidence now implicates Cutibacterium acnes—a ubiquitous indigenous commensal—as the most consistent antigenic trigger. Its frequent detection within sarcoid granulomas by quantitative PCR, in situ hybridization, and species-specific immunohistochemistry suggests latent intracellular persistence and the potential for endogenous reactivation. To explain how a noncontagious commensal can drive granulomatous inflammation, this review proposes the concept of Endogenous Hypersensitivity Infection (EHI). EHI describes a host-centered process in which reactivation of latent intracellular microbes leads to the breakdown of immune tolerance and provokes Th1-dominant hypersensitivity responses in genetically and immunologically susceptible individuals. This framework bridges the traditional divide between infection and autoimmunity, reframing sarcoidosis as a disorder of disrupted host–commensal homeostasis rather than a classical infectious or autoimmune disease. By integrating microbiological, immunological, and pathological evidence, this review synthesizes the mechanistic basis of EHI and outlines how tolerance failure to C. acnes can account for the paradoxical clinical behavior of sarcoidosis. The EHI paradigm further provides a unifying conceptual lens through which related chronic inflammatory disorders—including Crohn’s disease, chronic rhinosinusitis, and atopic dermatitis—may be reinterpreted. Full article

The greater amberjack (Seriola dumerili) is an economically important marine species that is prone to bacterial infections, resulting in high mortality rates and substantial economic losses. In this study, a virulent bacterial strain, Vh-2, was isolated from diseased greater amberjack and identified as Vibrio harveyi. Experimental infections caused high mortality and severe splenic damage characterized by tissue necrosis, abnormal pigment deposition, cellular disintegration, and extensive immune cell infiltration. A virulence gene analysis revealed that Vh-2 harbored multiple virulence-associated genes such as toxR, toxS, vhpA, vhpB, vhhA, vhhB, luxR, and pap6. Antibiotic susceptibility testing demonstrated ampicillin resistance but sensitivity to ceftriaxone, florfenicol, and meropenem. Transcriptomic profiling of infected spleens identified 396 differentially expressed genes (DEGs) compared to the control group, of which 293 were upregulated and 103 were downregulated. A functional enrichment analysis indicated that these genes were primarily involved in cell cycle regulation, DNA repair, metabolic processes, and immune-related pathways. These findings enhance our understanding of V. harveyi pathogenesis and immune responses of S. dumerili and provide new insights into the prevention and control of V. harveyi infections in marine fish. Full article

This paper presents research on an online preload detecting method for power transformer windings that is highly sensitive, survivable and repeatable. Traditional frequency response analysis methods exhibit limitations in sensitivity, accuracy, and interference resistance, making it difficult to detect small loosening. Although the FBG offer superior performance, quartz optical fibers exhibit limited deformation capacity and are susceptible to damage from short circuit impacts. To identify FBG placement locations with minimal impact exposure, this study compared FBG sensors at different installation positions through 42 short circuit impacts. Results confirmed that the FBG positioned at the top of pressure board experienced the least impact damage. Subsequently, a transformer equipped with this online preload detecting system underwent 12 short circuit impact tests. Simulation results and hoisting cover findings aligned with the FBG online detecting data. This study proposes an experimentally validated online preload detecting method, providing a reliable and reproducible technical pathway for transformer condition assessment. Full article

The aim of this study was to investigate the effects of three lipopolysaccharides (LPS), obtained from Hafnia alvei PCM 1200, Proteus penneri 12, and Proteus vulgaris 9/57, on the fluidity of liposomal lipid membranes. The experiments were performed on liposomes composed of egg yolk lecithin (EYL) in the liquid-crystalline phase and synthetic lecithin (DPPC) in the gel phase. The experimental results were compared with data obtained from a computational model of the membrane surface layer. Membrane fluidity was assessed using EPR spectroscopy with the spin probes TEMPO (surface layer; changes in the F parameter) and 16-DOXYL (hydrophobic core; changes in the τ parameter). In EYL liposomes, all LPS samples induced a reduction in surface-layer fluidity (decrease in the F/F₀ ratio). In contrast, effects on the hydrophobic core (τ/τ₀) were observed only at low dopant concentrations (<0.2%), above which membrane fluidity plateaued. In DPPC membranes, the response was more complex: local minima in F/F₀ and maxima in τ/τ₀ were detected, indicating transient alterations in membrane stiffening and plasticization that depended on the specific LPS applied. Computational simulations of the membrane surface further confirmed the greater susceptibility of low-mobility systems (corresponding to the gel phase) to dopant-induced perturbations. In the model, the best agreement with the EPR data was obtained when an effective dopant charge of q = 3 was assumed. Full article

The increasing use of Technology-Critical Elements (TCEs) in modern technology has led to widespread environmental release, raising questions about their biological effects, as emerging evidence suggests significant toxicity. We investigated the effects of three technology-critical elements, Indium oxide (In₂O₃), Lanthanum nitrate hexahydrate (La(NO₃)₃·6H₂O) and Cerium(III) nitrate hexahydrate (Ce(NO₃)₃·6H₂O), on human dermal fibroblasts (BJ) and hepatocarcinoma cells (HepG2), assessing their uptake, impact on viability, and induced cellular stress responses, quantified by markers of inflammation, oxidative stress, and membrane damage. Our results show a strong differential susceptibility: normal BJ fibroblasts proved vulnerable, whereas HepG2 cells were highly resistant. This divergence occurred despite substantial and comparable accumulation of all three TCEs in both cell lines, indicating that toxicity is uncoupled from the magnitude of the uptake. Mechanistically, the differential toxicity correlated strongly with opposing antioxidant responses. Additionally, low concentrations of cerium (III) nitrate (12.5–50 µg/mL) uniquely stimulated the proliferation of HepG2 cells (up to 129% of control). While these findings identify multiple mechanistic hazards regarding the potential of low-level technology-critical element exposure, they must be interpreted cautiously and warrant further investigation in more complex biological models. Full article

Background/Objectives: Sex-specific differences in the mechanisms of acute liver injury remain poorly understood. CDK5 regulatory subunit-associated protein 3 (CDK5RAP3) is crucial for liver development and endoplasmic reticulum (ER) homeostasis. This study aimed to investigate sex-dependent changes in CDK5RAP3 expression in a carbon tetrachloride (CCl₄)-induced acute liver injury model and to explore the mechanisms underlying differential susceptibility between males and females. Methods: Acute liver injury was induced in male and female mice by CCl₄ administration. Liver injury was evaluated by serum biochemical parameters and histopathological analysis. CDK5RAP3 expression, inflammatory cytokines, and ER stress-related apoptotic markers were assessed. Hepatocyte apoptosis was examined by TUNEL staining. In addition, CDK5RAP3 was conditionally deleted in mouse embryonic fibroblasts (MEFs) using 4-hydroxytamoxifen to assess its direct role in regulating inflammatory and apoptotic responses in vitro. Results: CCl₄ exposure caused liver injury in both sexes, with male mice showing more severe biochemical and histological damage. CDK5RAP3 expression was significantly reduced after CCl₄ treatment, particularly in males. Inflammatory mediators and ER stress-associated apoptotic markers were upregulated, accompanied by increased hepatocyte apoptosis. A similar enhancement of inflammatory and apoptotic signaling was observed in CDK5RAP3-deficient MEFs. Conclusions: Downregulation of CDK5RAP3 is associated with ER stress, inflammation, and apoptosis, contributing to increased susceptibility of male mice to acute liver injury. These findings provide insight into sex-specific mechanisms of hepatic injury and highlight CDK5RAP3 as a potential therapeutic target. Full article

Against the backdrop of intensifying global climate change and expanding human encroachment into mountainous regions, landslides have increased markedly in both frequency and destructiveness, emerging as a key risk to socio-ecological security and development in mountain areas. Rigorous assessment and forward-looking prediction of landslide disaster vulnerability (LDV) are essential for targeted disaster risk reduction and regional sustainability. However, existing studies largely center on landslide susceptibility or risk, often overlooking the dynamic evolution of adaptive capacity within affected systems and its nonlinear responses across temporal and spatial scales, thereby obscuring the complex mechanisms underpinning LDV. To address this gap, we examine Yunnan Province, a landslide-prone region of China where intensified extreme rainfall and the expansion of human activities in recent years have exacerbated landslide risk. Drawing on the vulnerability scoping diagram (VSD), we construct an exposure–sensitivity–adaptive capacity assessment framework to characterize the spatiotemporal distribution of LDV during 2000–2020. We further develop a multi-model, multi-scale integrated prediction framework, benchmarking the predictive performance of four machine learning algorithms—backpropagation neural network (BPNN), support vector machine (SVM), random forest (RF), and XGBoost—across sample sizes ranging from 2500 to 360,000 to identify the optimal model–scale combination. From 2000 to 2020, LDV in Yunnan declined overall, exhibiting a spatial pattern of “higher in the northwest and lower in the southeast.” High-LDV areas decreased markedly, and sustained enhancement of adaptive capacity was the primary driver of the decline. At approximately the 90,000-cell grid scale, XGBoost performed best, robustly reproducing the observed spatiotemporal evolution and projecting continued declines in LDV during 2030–2050, albeit with decelerating improvement; low-LDV zones show phased fluctuations of “expansion followed by contraction”, whereas high-LDV zones continue to contract northwestward. The proposed multi-model, multi-scale fusion framework enhances the accuracy and robustness of LDV prediction, provides a scientific basis for precise disaster risk reduction strategies and resource optimization in Yunnan, and offers a quantitative reference for resilience building and policy design in analogous regions worldwide. Full article

Seasonal biomass-burning haze in Northern Thailand produces sharp fluctuations in ambient fine particulate matter (PM), posing heightened health risks, particularly for individuals with diabetes mellitus (DM). To identify PM-responsive biomarkers and assess whether metabolic status modifies these responses, we first performed small RNA sequencing in a discovery cohort using plasma samples collected during low- and high-PM periods. Thirteen circulating microRNAs (miRNAs) were differentially expressed, including reduced miR-542-3p and elevated miR-29a-3p, novelmiR-203, and novelmiR-754, with predicted targets enriched in immune and endoplasmic-reticulum stress pathways. These four miRNAs were quantified by RT-qPCR in a longitudinal cohort of adults with (n = 28) and without DM (n = 29) sampled at three PM-defined timepoints across one full haze cycle. In non-DM individuals, miR-542-3p decreased at peak exposure while miR-29a-3p and novelmiR-203 increased, with values returning toward baseline at re-exposure. DM participants showed altered baseline levels and attenuated or reversed seasonal changes. Plasma IL-8 rose markedly at peak PM in both groups, mirroring exosome concentration increases measured by NTA, indicating a transient systemic inflammatory response. In an independent clinical cohort, only miR-542-3p differed significantly between lung-cancer patients and healthy controls. These findings indicate that PM exposure reconfigures circulating miRNA, exosomal, and cytokine profiles, and that DM modifies these responses, highlighting miR-542-3p and miR-29a-3p as environmentally responsive and disease-relevant biomarker candidates. Full article

Cholangiocarcinoma (CCA) is a highly aggressive cancer of the biliary tract, distinguished by significant intratumoral heterogeneity (ITH), which contributes to therapy resistance and unfavorable clinical outcomes. Traditional genome profiling has revealed recurring driver changes in CCA; yet, genomic data alone fails to elucidate functional pathway activation, adaptive signaling, and the diverse treatment responses reported among tumor locations and disease subtypes. This review analyses the use of integrated sequencing technologies, proteogenomics, and phosphoproteomics to systematically characterize intratumoral heterogeneity in cholangiocarcinoma and convert molecular diversity into therapeutically applicable discoveries. We present evidence that the combination of genomic sequencing and mass spectrometry–based proteomics facilitates the direct correlation of genetic mutations with protein expression, post-translational modifications, and signaling system activity. Phosphoproteomic profiling specifically offers functional insights into kinase-driven networks that dictate tumor aggressiveness, therapeutic susceptibility, and adaptive resistance mechanisms, which cannot be anticipated only from DNA-level analysis. We propose that integrating proteogenomic and phosphoproteomic analyses into diagnostic and therapeutic assessments can enhance molecular classification, reveal subtype- and region-specific therapeutic dependencies, and guide rational combination treatment strategies, based on recent extensive proteogenomic studies and functional proteomic investigations in CCA. Pathway-level analysis of intratumoral heterogeneity provides a framework for selecting targeted medicines, predicting resistance, and informing personalized treatment strategies in CCA. The combination of sequencing, proteogenomics, and phosphoproteomics is essential for advancing precision oncology in cholangiocarcinoma. The implementation of this multi-layered analytical approach may better patient classification, refine therapy choices, and eventually improve clinical outcomes for individuals with this particular heterogeneous cancer. Full article