Search Results (158,167)

Metallothionein (MT) is a multifunctional metal-binding protein with broad applications in medicine, healthcare, and food industries, but its large-scale use is limited by inefficient industrial synthesis. To address this and obtain optimal fermentation parameters for large-scale MT production, this study used the recombinant marine-derived MT-producing Pichia pastoris strain SMD1168-MT. We first optimized the strain’s growth and induced fermentation conditions, then constructed a Back Propagation (BP) neural network model for in-depth parameter optimization and accurate MT expression prediction. Results showed the optimal growth conditions for SMD1168-MT were: 30 °C, initial pH 8.0, shaking speed 220 r/min, and 4% inoculum size. The BP model exhibited high accuracy (training set: R² = 0.8430, MAE = 0.0129, RMSE = 0.0175; validation set: R² = 0.8337, MAE = 0.0144, RMSE = 0.0174). Combined with Particle Swarm Optimization (PSO), the optimal fermentation conditions were: 7.7% methanol, initial OD₆₀₀ 8.2, 240 r/min, 50 h induction, and 125 μmol/L Zn²⁺. Validation confirmed MT expression reached 0.2141 mg/mL (2.93-fold). This study demonstrates that the BP neural network effectively optimizes recombinant P. pastoris-based marine-derived MT fermentation, improving yield and providing a basis for industrial scale-up. Full article

Life expectancy (LE) varies widely across Organization of Islamic Cooperation (OIC) countries, reflecting differences in economic, social, environmental, and health-system conditions. This review aimed to synthesize quantitative evidence on determinants of LE at birth in OIC member countries. The study was conducted in accordance with the PRISMA guidelines, and a systematic search of electronic databases was performed up to September 2025. After screening 5312 records and assessing full texts, studies were appraised using the Joanna Briggs Institute checklists, with an inclusion threshold of ≥80%. A total of 54 studies, mainly ecological, time-series, and panel analyses using national-level data, were included. Higher gross domestic product per capita, education, employment, and health expenditure were consistently associated with longer LE. In contrast, poverty, income inequality, air pollution, and carbon dioxide emissions were associated with shorter LE. Clear differences were observed across World Bank income groups, with LE being lowest in low-income OIC countries and highest in high-income Gulf Cooperation Council states, where gains were driven more by health-system resources than by income growth. Improving LE in OIC countries requires integrated economic, social, environmental, and health-system policies. Full article

Corporate carbon reduction is essential for sustainable development, yet little is known about whether equity linkages within supply chains facilitate firms’ low-carbon transition. Using data on Chinese A-share listed firms from 2008 to 2022, this study examines the effect of supply chain shareholding, defined as equity ownership by suppliers and customers in a focal firm, on corporate carbon emission intensity. We find that supply chain shareholding significantly reduces corporate carbon emission intensity, and this result remains robust after a series of robustness and endogeneity tests. Mechanism analyses show that supply chain shareholding lowers carbon emission intensity by strengthening corporate green governance, promoting green innovation, and facilitating cleaner production. Further analyses indicate that this effect is more pronounced under stricter air quality requirements, in regions with stronger environmental regulation, and among heavily polluting industries. These findings highlight the role of supply chain governance in corporate carbon reduction and suggest that equity linkages within supply chains can support firms’ low-carbon transition. Full article

Enteroviruses represent important human pathogens, posing a substantial disease burden, particularly in children under 5 years of age. Enteroviruses are the primary causative agents of hand-foot-and-mouth disease (HFMD) and are strongly associated with acute flaccid myelitis (AFM), with severe cases potentially resulting in significant neurological complications. Inactivated vaccines against EV-A71 based on the C4 genotype are currently available. However, there are no licensed direct antiviral agents for severe cases. By focusing on viral proteins and host factors, researchers have made great strides in the creation of antiviral medications that target enteroviruses. However, several viral candidates failed to progress in clinical development due to limited efficacy or side effects. This review discusses key findings in enterovirus antiviral research, analyzes the advantages and limitations of each drug target, and highlights knowledge gaps that need to be addressed to advance further development in this field. Full article

Virtual reality (VR) is increasingly used as an interactive instructional medium in engineering education, yet evidence on practical implementation and student-reported experience remains limited. This study examined students’ perceived experience and usability across VR and traditional instruction within a crossover design in a UV-C water disinfection lesson. Using a mixed 2 × 2 crossover design, 52 undergraduate engineering students completed both a VR lesson (Meta Quest 3; Unreal Engine 5.4) and a content-aligned traditional session delivered with slides and a physical UV disinfection stand. After each session, participants reported perceived flow (short Flow Index) and engagement (adapted User Engagement Scale); the System Usability Scale (SUS) was completed after the VR session only. A brief knowledge quiz and open-ended feedback were also collected and used descriptively. Students reported higher perceived flow and engagement in the VR condition than in the traditional condition, and VR usability was generally rated acceptable-to-excellent, with higher SUS scores observed in the VR-first sequence than in the traditional-first sequence. Qualitative feedback emphasized clarity and interactivity, and most participants expressed a preference for a blended approach. Overall, the results support the practical feasibility and positive user acceptance of the VR lesson in this instructional context. The findings also suggest that perceived usability may be associated with instructional sequence, although this pattern should be interpreted cautiously within the perception-based scope of the study. Full article

Background/Objectives: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) necessitates innovative strategies to overcome conventional resistance mechanisms. This study investigated the potential of the natural flavonolignan silibinin (SIL) as an antivirulence agent against S. aureus, with a particular emphasis on its putative multi-target antibacterial activity and its capacity to potentiate the effects of ciprofloxacin (CIP). Methods: The antibacterial and antivirulence properties of SIL were assessed using both in vitro and in silico approaches. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) were determined, and its synergistic interaction with CIP was evaluated using checkerboard assays. Inhibition of biofilm formation, as well as disruption of established biofilms, was assessed using an MTT-based viability assay. Staphyloxanthin (STX) inhibition was examined through pigment extraction and spectrophotometric quantification of pathway intermediates. Molecular docking studies were conducted to predict the binding affinities of the compounds to key bacterial targets, while safety was evaluated through haemolytic and cytotoxicity assays. Results: SIL exhibited weak to moderate direct antibacterial activity (MICs of 256–512 µg/mL), which is characteristic of many natural product scaffolds. Notably, SIL potentiated the activity of CIP, reducing its MIC by up to fourfold against selected resistant strains of S. aureus. SIL significantly inhibited biofilm formation and disrupted established mature biofilms in a strain-dependent manner. In vitro metabolic profiling and in silico analyses provided mechanistic insights into the effects of SIL on STX biosynthesis. Precursor accumulation data suggest inhibition at the diapophytoene desaturase (CrtN) catalytic step, representing a potential mechanism not previously reported for flavonolignans. Molecular docking studies further predicted favourable binding affinities for CrtM and other key targets. Importantly, SIL exhibited no haemolytic activity and low cytotoxicity in macrophages at synergistic concentrations. Conclusions: This study provides evidence that SIL functions as a dual-action agent, potentiating ciprofloxacin efficacy while reducing STX production and inhibiting biofilm formation, thereby impairing key virulence mechanisms of S. aureus. These findings, together with its favourable safety profile, provide a strong rationale for the development of silibinin-based topical adjuvants to combat drug-resistant Staphylococcus infections in humans. Full article

Background/Objectives: Periodontitis represents a significant global health burden, yet preventive health literacy remains critically low among emerging adults—a developmental stage where lifelong health behaviors crystallize. This study evaluated the effectiveness of the GUM (an acronym of Gum Understanding Mission) game, an interactive gamified digital tool incorporating AI-informed or manual feedback, for improving periodontitis literacy among tenth-semester Software Engineering students at the University of Guayaquil. Methods: In a controlled pre-test/post-test experiment, 50 participants were randomly assigned to either the GUM game intervention or a traditional lecture. Both groups completed identical knowledge assessments immediately before and after their respective 50-min instructional sessions. The GUM game featured adaptive questioning, immediate elaborated feedback, and comprehensive performance analytics, while the control group received instructor-led didactic instruction with a subsequent question-and-answer session. Results: The GUM group improved from a baseline of 21% to 94% correct responses, while the lecture group increased from 22% to 67% ($p<0.001$). Error reduction was 74% in the GUM group versus 45% in the control group. However, the study’s scope is currently limited to a single, digitally literate cohort, and knowledge retention over time was not assessed. Conclusions: These findings suggest that a self-directed, feedback-driven serious game can substantially outperform traditional methods in fostering periodontitis literacy within this population. Further research is needed across diverse populations with extended follow-up periods to assess knowledge retention and generalizability. Full article

Background/Objective: In recent years, epidemiological and clinical evidence has suggested an association between the use of second-generation antipsychotics (SGAs) and hyperglycemic complications: notably, diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS). However, the role of first-generation antipsychotics (FGAs) remains less well understood. To conduct a systematic review of evidence established in case reports (CRs) on adverse drug reactions, specifically DKA and HHS, associated with the use of both FGAs and SGAs in order to identify patterns that may inform clinical awareness and future research. Methods: Pertinent bibliographic databases (MEDLINE, EMBASE, PsycINFO and the Cochrane Central Register of Controlled Trials (CENTRAL)) were searched using index phrases and keywords up until 17 October 2025. Eligible CRs discussed exposure to at least one US FDA-approved antipsychotic drug (APD) and assessed either DKA or HHS. Results: A total of 151 CRs were included in the systematic review (DKA, n = 121; HHS, n = 28; both conditions, n = 2). Patients aged 30 to 39 years accounted for the highest number of emergencies (n = 49, 32.5%), which occurred mostly in males (n = 108, 71.5%). The most common mental health diagnosis was schizophrenia (n = 77, 51%), followed by bipolar disorder (n = 26, 17.2%). Olanzapine was associated with the highest number of DKA cases (n = 53, 43.1%), followed by clozapine (n = 24, 19.5%). The average blood glucose at presentation was 842.8 mg/dL for DKA patients and 1252.8 mg/dL for HHS patients. The average hemoglobin A1c levels (HbA1c) were 11.5% and 12%, respectively, for these two conditions. Of the 12 reported fatalities, treatment with olanzapine was noted in four DKA cases and in one HHS case. Conclusion: This analysis provides additional evidence of an association between the use of atypical APDs and DKA or HHS. Clinicians should continue to monitor metabolic risk factors for these conditions, as well as educating patients about the prevention of acute diabetic complications. Full article

Objective: This study aimed to evaluate the health-related quality of life (HRQoL) of informal caregivers providing primary care to elderly chronically ill patients receiving home health care services in Türkiye and to identify patient and caregiver characteristics independently associated with HRQoL. Methods: This cross-sectional study included 499 patient–caregiver dyads enrolled in home health care services at a training and research hospital in İzmir, Türkiye. Data were collected through face-to-face interviews using a sociodemographic questionnaire, the Palliative Performance Scale (PPS), and the Short Form 36 (SF-36). One-sample t-tests compared SF-36 scores with Turkish normative values. Multivariate linear regression identified independent predictors of the Physical Component Summary (PCS) and Mental Component Summary (MCS) scores. Results: Caregivers scored significantly lower than population norms across all SF-36 subdimensions (p < 0.001), with the largest impairments in Role Physical (mean difference: −53.0) and Role Emotional (−42.9). In multivariate analyses, independent predictors of poorer physical health (PCS) were severe patient functional dependence (PPS ≤ 30: β = −0.260, p < 0.001), older caregiver age (≥65 years: β = −0.089, p = 0.044), unemployment (β = −0.118, p = 0.014), additional care recipients (β = −0.095, p = 0.026), and caregiver’s own chronic illness (β = −0.169, p < 0.001). Poorer mental health (MCS) was independently associated with caregiver’s own chronic illness (β = −0.138, p = 0.002), receipt of caregiving payment (β = −0.137, p = 0.004), and university-level education (β = −0.108, p = 0.040), whereas the presence of a support person was protective (β = 0.096, p = 0.038). Conclusions: Informal caregivers of home health care-dependent elderly patients experience significantly reduced quality of life across all health domains compared with the general population. The independent determinants of caregiver health are multidimensional, encompassing patient-related factors, socioeconomic characteristics, and psychosocial resources. These findings underscore the urgent need for health systems to implement tailored interventions that address the distinct physical and mental health needs of caregivers, with particular attention to those who are elderly, chronically ill, socioeconomically disadvantaged, or highly educated. Full article

High-geothermal tunnels are subjected to complex thermo–hydro–mechanical (THM) coupling effects, where the interaction of temperature, seepage, and stress significantly influences the stability of surrounding rock. To address the limitations of conventional models assuming uniform initial temperature, a THM-coupled numerical model incorporating an in situ temperature gradient is established based on the Sangzhuling Tunnel. The concept of the thermal influence zone is quantitatively defined by an equivalent-radius method, and its spatiotemporal evolution is systematically investigated. In addition, the distinct roles of temperature and pore water pressure in controlling deformation and plastic-zone evolution are comparatively clarified. The results show that the thermal influence zone expands nonlinearly with increasing initial rock temperature and gradually stabilizes over time. Temperature and pore water pressure both promote the development of the plastic zone, which predominantly propagates along directions approximately 45° to the horizontal. Under the geological and boundary conditions considered in this study, temperature plays a dominant role by inducing thermal stress and degrading mechanical properties, leading to significant expansion of the plastic zone and increased vault deformation. In contrast, pore water pressure mainly reduces effective stress, thereby influencing deformation distribution, especially at the tunnel invert. Overall, THM coupling significantly amplifies surrounding rock failure compared with single-field conditions. The findings provide quantitative insights into the evolution of the thermal influence zone and its coupled control on deformation and plasticity, offering a theoretical basis for support design and stability control in high-geothermal tunnels. Full article

The Tibetan Plateau (TP) atmospheric heat source crucially modulates East Asian summer monsoon precipitation, yet its synergy with upstream oceanic signals remains elusive. Using observations (1971–2020) and CMIP6 simulations, we investigate mechanisms coupling the summer TP heating and precipitation over the Middle and Lower Yangtze River (MLYR). SVD analysis reveals a robust positive coupling between them. Mechanistically, TP heating triggers a quasi-stationary Rossby wave train, inducing a “saddle-like” circulation that drives intense MLYR moisture convergence (contributing >90% to precipitation changes). Crucially, we re-examine the upstream oceanic precursor to propose a “dual-pathway superposition” framework. Contrary to the assumed linear causal chain, four-quadrant analysis reveals the spring Indian Ocean Basin Warming (IOBW) and summer TP heating are largely independent drivers (R = 0.24). While IOBW thermodynamically excites an Anomalous Anticyclone supplying abundant MLYR moisture, it lacks robust control over TP heating, which is dominated by internal atmospheric dynamics. However, our findings reveal a critical non-linear synergy: extreme MLYR rainfall strictly requires the coincidental phase overlap of these independent pathways (strong dynamic lifting coupled with oceanic moisture). CMIP6 simulations corroborate this independence, further emphasizing that extreme MLYR rainfall results from phase superposition rather than a single causal chain. Full article

Purpose: The primary aim of the present study was to examine the extent to which participation in organized youth basketball training contributes to physical activity across intensity zones during training sessions in relation to biological maturation status. Methods: Participants were classified into three maturity groups based on predicted age at peak height velocity (PHV): −2.5 to −1.5, −1.5 to −0.5, and ≥−0.5 to 0.83 years from PHV. Data from two training sessions per participant were averaged to obtain representative individual values. One-way analyses of variance (ANOVAs) were used to examine differences in anthropometric, physical performance, and field performance variables between PHV groups. Physical activity patterns were analyzed using two-way mixed-design ANOVAs with PHV stage as the between-subject factor and intensity zone (MET- and HRR-based) as the within-subject factor. Results: Across all maturity groups, approximately 10–17% of total training time was spent in light-intensity activity, while the majority of time was accumulated in moderate-to-vigorous intensity zones (approximately 35–50%, depending on the classification method). Significant maturity-related differences were observed in anthropometric variables and physical performance measures, with more mature players demonstrating superior sprint performance, jumping ability, and grip strength. Field performance indicators also differed between PHV groups, with more mature athletes exhibiting higher external and internal training loads. In contrast, no significant interactions or main effects of PHV stage were observed for physical activity intensity distribution. Conclusions: Organized basketball training contributes substantially to moderate-to-vigorous physical activity accumulated during training sessions. However, these findings reflect training-specific activity and should not be interpreted as representing total daily physical activity. No differences in activity intensity distribution were observed between maturation groups, although this finding should be interpreted with caution, given methodological limitations. These results highlight the need to consider biological maturation when designing youth training programs. Full article