This study examined whether the national availability and composition of mental health professionals, primarily non-psychiatrist providers, are associated with the population prevalence of depression, controlling for economic and demographic factors. A cross-sectional ecological analysis used data from 131 countries, sourcing workforce statistics from the WHO Mental Health Atlas 2020 and depression prevalence from GBD 2019. Ordinary Least Squares (OLS) regression models, adjusted for log Gross Domestic Product (GDP) per capita and urbanisation, assessed total workforce density, disaggregated provider densities (psychiatrists vs. psychologists) and the psychiatrist share of the workforce. Heteroskedasticity-consistent standard errors were applied. Adjusted analysis showed a significant inverse association between overall workforce density and prevalence (β = -.031, p < .001) suggesting that higher workforce density correlates with lower depression prevalence. Psychologist density showed a stronger inverse association (β = -.038, p = .001) than psychiatrist density (β = -.024, p = .048) suggesting that greater availability of psychologists is more strongly correlated with lower depression prevalence. Critically, a higher proportion of psychiatrists was independently associated with increased depression prevalence (β = 1.89 percentage points, p = .032). Analysis of regional variation indicated that the inverse association between psychologist availability and depression prevalence was globally observed, with the steepest marginal effects noted in lower-income settings. Mental health workforce expansion is correlated with reduced depression, notably when systems include non-psychiatrist providers. These findings indicate that broadening service delivery capacity beyond psychiatric care could potentially improve the effectiveness of national mental health systems, pending further investigation.

Depression remains a major global health burden, and conventional antidepressants, although effective, are limited by side effects and withdrawal symptoms. To map umbrella-level evidence on single-agent nutraceutical and herbal interventions for clinically diagnosed depression in adults. This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews and Joanna Briggs Institute guidance. PubMed, PsycINFO, Scopus, and Cochrane Library were searched (2015-2025) for umbrella reviews assessing oral nutraceuticals or herbal medicines for depression. Nine umbrella reviews met inclusion criteria, covering omega-3 fatty acids, vitamin D, probiotics, saffron, St John's wort, zinc, and folate. Umbrella reviews generally reported potential antidepressant benefits and acceptable safety profiles for several interventions, although trial overlap and heterogeneity limited certainty. Evidence indicates promising but inconsistent efficacy across several nutraceutical and herbal agents. Standardized reporting, consideration of baseline nutrient status, and economic evaluation are needed to clarify their role in depression care.

Diabesity, the coexistence of type 2 diabetes mellitus (T2DM) and obesity, represents one of the major global health challenges. This review aims to synthesize current evidence on personalized medical nutrition therapy (MNT) and structured physical exercise as cornerstones of diabesity management, with a particular focus on very-low-energy ketogenic therapy (VLEKT). Conventional pharmacotherapies improve glycemic control and promote weight reduction but often fail to fully address the multifactorial pathophysiology of diabesity. MNT has demonstrated significant efficacy in improving glycemic regulation, reducing weight, and modulating cardiometabolic risk factors. Among dietary strategies, the Mediterranean diet provides sustainable benefits, while more intensive interventions such as low-energy diets and ketogenic diets can induce rapid and clinically meaningful improvements, with emerging evidence supporting favorable effects on gut microbiota and inflammation. Complementary lifestyle interventions, particularly structured exercise programs combining aerobic and resistance training, further enhance metabolic outcomes and may contribute to T2DM remission in selected patients. Integration of MNT with incretin-based therapies holds promise for optimizing efficacy while preserving nutritional adequacy and functional health. Effective management of diabesity requires a multidisciplinary, precision-based approach. Personalized MNT and structured exercise represent foundational strategies, while pharmacological therapies provide valuable adjuncts. Among available options, VLEKT stands out for its ability to target key mechanisms of diabesity, including insulin resistance, adiposity, and chronic inflammation. Future diabesity care will rely on integrating nutrition, physical exercise, and pharmacotherapy within individualized frameworks to achieve sustained metabolic control and improved quality of life.

Dengue fever, a viral disease caused by the dengue virus, is transmitted via the bite of Aedes aegypti mosquito. Dengue is an endemic disease in more than a hundred countries. It is a global public health concern with 390 million infections occurring every year. An estimated 500,000 of these cases develop into severe dengue, resulting in approximately 25,000 deaths annually. The failure of chemical insecticides to combat and control mosquitoes, due to widespread resistance, creates an urgent need to search for effective natural alternatives. Chrozophora oblongifolia is an herbal and medicinal plant that has many pharmacological activities. In this study, we evaluated the efficacy of methanolic and acetone leaf extracts of C. oblongifolia plant against 3rd instar larvae and adults of Ae. aegypti mosquito using five concentrations ranging from 125-1000 mg/L. Mortality rates for the larval, pupal, and adult stages resulting from the larval treatment were recorded. Methanolic and acetone extracts exhibited lethal toxic effects on larvae, pupae, and adults. Both extracts showed complete larval mortality by 100% at the highest concentration of 1000 mg/L. The methanolic extract showed greater efficacy with LC50 of 339.87 mg/L compared to the acetone extract, which had LC50 of 372 mg/L. Due to the increasing number of multi-drug-resistant microbial strains, there is a need to find natural products to overcome this problem. In addition to its larvicidal properties, C. oblongifolia was assessed for antimicrobial activity. The methanol leaf extract displayed antimicrobial efficacy against Staphylococcus aureus, Escherichia coli, and Candida albicans. The minimum inhibitory concentration (MIC) was 5000 µg/mL for S. aureus and E. coli, while for C. albicans was 10000 µg/mL. Our Gas Chromatographic-Mass Spectroscopy (GC-MS) analysis of the methanolic extract revealed more than twenty phytochemical constituents, including nine major compounds. The major identified compounds exhibited potential larvicidal and antimicrobial activities. Based on this current study, it is suggested that C. oblongifolia plant could be used as a safe natural insecticide for controlling and combating the dengue vector Ae. aegypti mosquito and as an effective natural antimicrobial agent.

Background Childhood obesity is a growing global public health issue, with increasing prevalence worldwide, including in China. The rise in obesity-related pediatric conditions requiring surgical intervention underscores the need to address this challenge in pediatric surgical care. However, research on this topic is limited. This study aimed to assess pediatric surgical nurses’ knowledge, attitudes, behaviors, and factors influencing their behavioral intentions. Methods This is a dual-center, cross-sectional study. Nurses in direct clinical care roles at two medical institutions in China were randomly selected and completed a questionnaire assessing their knowledge, attitudes, and behavioral intentions. Factors associated with their attitudes, and behavioral intentions were investigated. Results A total of 178 nurses participated in the study. Most demonstrated an acceptable level of obesity-related health knowledge and generally positive attitudes toward pediatric patients with obesity. However, gaps in professional preparedness and persistent weight bias were identified. Behavioral intentions were positively correlated with nurses’ BMI ( r = 0.16, p = 0.04) and positive attitudes ( r = 0.20, p = 0.01), and negatively correlated with perceived weight bias ( r = −0.39, p &amp;lt; 0.01) and negative attitudes toward treating pediatric patients with obesity ( r = −0.45, p &amp;lt; 0.01). Behavioral intentions were not correlated with obesity-related knowledge or other participant characteristics. Conclusion Nurses’ attitudes and personal factors, rather than knowledge alone, are more correlated with caregiving behavioral intentions toward pediatric patients with obesity. Addressing biases and enhancing professional preparedness through targeted education are crucial for improving care in pediatric surgical settings in China.

Utilizing treatment strategies based on collateral sensitivity (CS) represents a promising approach to suppressing antibiotic resistance. Although the mechanism of CS between numerous drugs has been researched, the mechanism of CS between tigecycline and colistin remains unclear. Therefore, the purpose of our research is to investigate the possible mechanism by which tigecycline affects colistin CS in the Enterobacter cloacae complex. Tigecycline induction significantly reduced the minimum inhibitory concentration of carbapenem-resistant Enterobacter cloacae complex (CRECC) to colistin, and sequencing revealed a single-base deletion at the RamR binding site. Complementation experiments demonstrated that deletion of the RamR binding site increased the resistance of CRECC417 to colistin and tigecycline by 2-fold and 4-fold, respectively. Transcriptomic comparison analysis of strains before and after CRECC417 induction revealed a total of 1,977 genes with significant differences in expression. Genes associated with carbohydrate, amino acid, and inorganic ion metabolism were the most highly enriched. Furthermore, the observed increase in colistin susceptibility in CRECC417R can be attributed to the inhibition of quorum sensing and biofilm formation pathways, as well as increased expression levels of genes associated with lipopolysaccharide biosynthesis and modification.IMPORTANCEDue to the overuse of antibiotics, antimicrobial resistance (AMR) has become a serious threat to global public health. Dosage regimens based on bacterial CS can reduce antibiotic use without reducing efficacy, thereby reducing antibiotic-related toxicity risks, expanding the scope of antibiotic application, and limiting the development of antibiotic resistance. In this study, we analyzed the drug resistance mutations and global transcriptional changes in CRECC after tigecycline induction through genomics and transcriptomics. Our study showed that tigecycline exposure significantly inhibited quorum sensing pathways and biofilm formation. There were significant changes in the transcriptional levels of genes related to cell membrane lipopolysaccharide synthesis and modification, but no mutations were found in genes related to colistin resistance. These findings provide valuable insights for further investigation into the CS between tigecycline and colistin.

Introduction Anaemia remains a major global public health concern, disproportionately affecting young women of reproductive age. University students represent a nutritionally vulnerable group; however, males are often underrepresented in anaemia surveillance. This study aimed to estimate the prevalence of anaemia among university students in the UAE and to identify gender-specific determinants. Methods A cross-sectional study was conducted among students aged 18–35 years at a large university in the UAE. Sociodemographic data were collected via questionnaire. Haemoglobin concentration was measured using the HemoCue Hb 201 + system. Anthropometric measures and body composition were assessed, and dietary intake was evaluated using a 24-h recall. Results The median age was 20.0 years (IQR: 19.0–22.0) and median BMI was 23.7 kg/m 2 (IQR: 20.7–27.6). Compared with males, females were more likely to be underweight and less likely to be obese, exhibited lower fat-free, muscle, and bone mass, higher fat mass percentage, and lower dietary intakes. Overall anaemia prevalence was 49.10% (95%CI 45.30–52.90), with significantly higher rates among females (60.70, 95%CI 56.20–65.20) than males (24.60, 95%CI 18.80–30.40). No determinants were identified among females. In males, anaemia was inversely associated with height, fat-free mass, muscle mass, bone mass, and dietary iron and zinc intakes; height emerged as the strongest independent predictor. Conclusion Anaemia is highly prevalent among UAE university students. These findings highlight the importance of including male students in screening and prevention strategies and adopting gender-specific approaches to anaemia control.

Multiple outbreaks of Ebola virus in West Africa have posed significant threats to global public health owing to its high pathogenicity and fatality rates. Current treatments for Ebola Virus Disease are limited, underscoring the imperative for novel antiviral therapies. VP30, a critical RNA synthesis factor, interacts with nucleoprotein (NP) to facilitate Ebola viral genome transcription and replication. Notably, the host ubiquitin-ligase retinoblastoma-binding protein 6 (RBBP6) binds to VP30 at the same interface as NP, thereby inhibiting VP30-NP interactions and indicating that targeting this interface could advance antiviral drug development. In this study, we engineered six peptide mutants through amino acid substitutions at key VP30 binding sites. These mutants were fused to DNA-binding protein from starved cells 4 (DPS4) to assemble nanoparticles, enabling surface display of the peptides. Antiviral effects were evaluated using minigenome and transcription and replication-competent virus-like particles (trVLPs) systems. Among the variants, RPL1 and NPL3 peptides exhibited relatively strong apparent affinities with the VP30 and potent antiviral activity by disrupting Ebola viral genome transcription and replication. To elucidate the binding details between the peptides and VP30, we determined crystal structures of complexes between RPL1 or NPL3 peptides and VP30 via X-ray crystallography. Concurrently, molecular dynamics (MD) simulations revealed the dynamic binding processes of these peptides to VP30. Structural analyses confirmed that the peptides bind to the VP30/NP interface and compete with NP. Our findings demonstrate that DPS4-fusion peptides effectively deliver peptides into cells as nanoparticles and inhibit VP30-NP interactions, presenting a novel antiviral strategy for Ebola virus.

Antimicrobial resistance (AMR) constitutes one of the most severe and pressing threats to global public health, food security, and environmental integrity. This review synthesizes current evidence across interconnected One Health domains—humans, animals, food, and the environment—to delineate the scope, mechanisms, and drivers of AMR transmission. Our analysis reveals three principal findings. First, the scope of AMR is alarmingly extensive, with antibiotic-resistant bacteria (ARB) and genes (ARGs) now pervasive across all four ecological compartments, transcending traditional clinical boundaries. Second, this widespread distribution is critically facilitated by horizontal gene transfer mechanisms, particularly via mobile genetic elements such as plasmids, which enable ARGs to disseminate rapidly between diverse bacterial populations across different ecosystems. Third, we identify multiple interconnected drivers that actively promote this cross-ecosystem spread, encompassing both evolutionary and transmission drivers. By characterizing these critical transmission pathways and underlying drivers, this review provides an integrated framework to identify critical transmission risks and inform integrated strategies for mitigating antimicrobial resistance across One Health domains.

The unabating rise of antimicrobial resistance makes the development of novel and effective antibiotics an urgent global health need. Progress toward assuaging this need is, however, limited by low levels of investment and patently low financial incentives. Eliminating inefficiencies in antibiotic development is therefore important to ensure effective deployment of limited resources. Metal interference in high-throughput assays, mechanism of action studies, and the eventual pharmacokinetics of antibiotics in development is an overlooked confounder in this process. In this Viewpoint, we, focusing on antibiotics, briefly provide a compartment-based approach to anticipating various possibilities for such interference and recommend toolkits for identification.

Mycobacterium abscessus infections represent a growing global health concern due to their severe pathology and difficulty of treatment, largely driven by their intrinsic antimicrobial resistance. While phage therapy has emerged as a promising alternative approach, studies have predominantly focused on glycopeptidolipids (GPL)-deficient M. abscessus rough variants instead of the GPL-producing smooth variants predominant in Asia. Here, we aim to develop phage cocktails targeting both smooth and rough morphotypes. In the process, we found that phage treatment of smooth variants can select for rough morphotype switching from smooth-to-rough variants in vitro and in vivo, resulting in phage resistance associated with mutations within the GPL biosynthetic locus. We validated our findings in vitro and in vivo, suggesting a two-layered phage combination that surpasses single-phage treatments and potentially improves clinical phage cocktail strategies. This work underlines the need to better understand mechanisms of phage resistance in phage therapy and associated potential adverse effects and solutions. Phage resistance in M. abscessus through morphotype switching is clinically significant, as it may complicate treatment outcomes but could be averted with proper phage combinations.

Introduction: Antimicrobial resistance is a notable threat to global health. In an institution-specific report generated through National Surgical Quality-Improvement Pediatric Program (NSQIP-P) for our institution, our orthopaedic surgery department was a high outlier for postoperative antibiotic prophylaxis duration of &gt;24 hours. We describe an initiative to reduce the incidence of postoperative duration of antibiotics of &gt;24 hours for pediatric patients undergoing orthopaedic surgery. Methods: An interdisciplinary team was formed to identify and monitor interventions for improvement. Patients undergoing orthopaedic surgeries and receiving postoperative intravenous antibiotics were included. First-stage interventions included verbal education for front-line staff to ensure that postoperative antibiotic prescribing did not exceed two doses. Second-stage interventions included a modification that changed the default postoperative antibiotic dose from three to two doses for the three most used orthopaedic admission order sets in the electronic medical record. Patient-level, electronic health record data elements were extracted and presented through a created electronic dashboard to track near-real-time metrics. Surgical site infections were tracked through NSQIP-P database as a balancing measure. Results: A total of 2,546 surgical cases met study criteria: 1,680 and 866 cases in the pre- and post-intervention cohorts, respectively. Cefazolin was the primary postoperative antibiotic prescribed in 95.4% of cases. In the preintervention cohort, &lt;24 hours of postoperative antibiotics was 36.7% compared with 84.7% (48.0% improvement) in the post–second stage intervention cohort. A sampling of postintervention cases demonstrated no notable increase in surgical site infection events compared with matched period sampling of preintervention cases. Conclusion: NSQIP-P can be leveraged to improve antibiotic stewardship in pediatric orthopaedic surgical cases. Multidisciplinary collaboration, front-line staff education coupled with electronic medical record order set modification, and near-real-time data tracking for provider feedback resulted in a 48.0% improvement of patients receiving &lt;24 hours of perioperative antibiotics. Level of Evidence: III

Sepsis remains a leading global health challenge, characterized by high mortality and a persistent lack of disease-modifying therapies. Despite decades of investment, therapeutic progress has been constrained by reductionist strategies that target isolated pathogenic components. This perspective argues that these failures reflect a fundamental mischaracterization of sepsis—not as a disorder of discrete pathways, but as the collapse of complex biological systems in which normally coordinated processes become desynchronized. We identify the intermediate filament protein vimentin as a determinant of system fate governing the transition from adaptive host defense to pathological breakdown. Acting as a context-dependent network integrator and signal amplifier, vimentin coordinates antagonistic cellular programs by integrating biochemical and biophysical cues across immune, vascular, and metabolic systems. Under physiological stress, this coordination enables the orderly activation and resolution of inflammatory and suppressive responses required for pathogen control and restoration of homeostasis. In sepsis, persistent or excessive insults drive vimentin-mediated overactivation, uncoupling these programs and propagating systems-level instability that culminates in organ dysfunction. By integrating mechanistic, preclinical, and emerging clinical evidence, this perspective proposes vimentin modulation as a clinically translatable, systems-oriented strategy aimed at realigning host response networks to address the dynamic, opposing pathologies of sepsis that have eluded current therapies.

Antimicrobial resistance is a major global health threat, creating an urgent need for effective non-antibiotic antimicrobial strategies. In this study, CS–AgNPs were synthesized by electron-beam radiolysis, providing a clean, dose-controllable route that avoids additional chemical reducing agents. The effects of irradiation dose and chitosan concentration on nanoparticle formation, physicochemical properties, and antibacterial activity were systematically evaluated. Spectroscopic and structural analyses confirmed the formation of highly crystalline, face-centered cubic silver nanoparticles uniformly dispersed within the chitosan matrix, with Ag–polymer coordination involving –NH2 and –OH functional groups. Under the optimal conditions (8 kGy, 0.06 mmol AgNO3, and 0.05% w/v chitosan), ultrasmall, well-dispersed CS–AgNPs were obtained, with an average size of 5.30 ± 2.01 nm and high phase purity. Antibacterial evaluation demonstrated potent, concentration-dependent activity against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli, with low minimum inhibitory and minimum bactericidal concentrations (MIC/MBC = 1.96 µg/mL). These findings define a clear structure–property–activity relationship and support a synergistic antibacterial effect between nanosilver and chitosan, while maintaining favorable in vitro cytocompatibility and hemocompatibility within the effective concentration range. Overall, electron-beam radiolysis represents a promising scalable platform for producing broad-spectrum antimicrobial nanomaterials with potential utility in addressing antimicrobial resistance.

Background/Objectives: Dementia remains one of the major global health challenges of the modern era. Researchers worldwide continue to seek effective therapeutic strategies to combat this neurodegenerative condition. Silymarin is a natural compound with strong neuroprotective and antioxidant properties that holds great potential for dementia management; however, its poor aqueous solubility and limited ability to cross the blood–brain barrier (BBB) have restricted its clinical application. This study focused on the formulation and evaluation of a heparin–pullulan silymarin liposomal (HPSL) nano-gel to enhance the neuroprotective efficacy of silymarin, with potential for improved brain targeting effects. Methods: The HPSL nano-gel was synthesized using the thin-film hydration technique and optimized based on entrapment efficiency, particle size distribution, zeta potential, and in vitro release kinetics. The neuroprotective efficacy of the HPSL nano-gel was evaluated in mice using behavioral evaluations, biochemical quantification of oxidative stress markers, evaluation of cholinergic enzyme activity and detailed histopathological examination of brain tissues. Results: Morphological characterization using scanning electron microscopy (SEM) confirmed a uniform nano-scale structure. The optimized formulation (HPSL-3) exhibited a particle size of 406.07 ± 19.33 nm, zeta potential of −23.72 ± 7.64 mV and an entrapment efficiency of 73.53 ± 12.05%, indicating good colloidal stability and efficient drug loading. The in vitro release profile followed non-Fickian diffusion kinetics, suggesting sustained drug release behavior. Behavioral studies in scopolamine-induced amnesic mice (elevated plus maze, hole board, and light/dark paradigms) demonstrated significant (p ≤ 0.001) improvements in learning and memory retention. Biochemical analyses showed increased levels of ChAT, SOD, CAT, and GSH, along with decreased AChE and MDA levels, supporting the neuroprotective potential of the formulation. Histopathological evaluation revealed marked attenuation of neuronal degeneration, inflammation, and edema (HAI = 4) compared to the scopolamine-treated group (HAI = 11). Conclusions: Overall, the HPSL-2 formulation effectively enhanced silymarin delivery across the BBB, demonstrating potent antioxidant, neuroprotective, and cholinergic modulatory effects. These findings suggest that HPSL-2 represents a promising nano-carrier system for the management of dementia and other oxidative-stress-related neurological disorders.

Mosquitoes are the main vectors of arboviruses, which infect millions of people every year. These viruses depend on host factors, such as the proprotein convertase furin, for replication. While the interactions between arboviruses and furin have been widely studied in mammals, little is known about furin homologs and their role in virus replication in mosquitoes. We performed a comparative analysis of the sequences and predicted structures of human and other dipteran furin with their mosquito homologs. We used RT-qPCR to determine the mRNA expression of the identified furin genes. We synthesized the FITC-labeled furin inhibitor MI-1190 to analyze the uptake in C6/36 cells, larvae, and female mosquitoes. Then, we tested the toxicity of peptidomimetic furin inhibitors (MI-1148, MI-1554, and MI-1851) in vitro through cellular ATP quantification and in vivo by adding the inhibitor to the breeding water of larvae and microinjection of females. Finally, we evaluated their antiviral efficiency by quantifying the relative fluorescence generated by the viral reporter expression in cell culture and female mosquitoes. We identified two furin encoding genes (FLP1 and two FLP2 transcripts) and confirmed their mRNA expression in all developmental stages of Aedes albopictus and two of its cell lines. The inhibitor MI-1190 was successfully taken up in C6/36 cells, as well as by early larval stages and adult female mosquitoes. The three selected inhibitors significantly curtailed the spread of Semliki Forest virus in cell culture, thereby demonstrating their antiviral efficacy in mosquito cells. However, the antiviral effect observed in vitro did not translate in vivo, where the effect of furin inhibitor MI-1851 showed only a minor impact. Identifying and characterizing host factors from mosquitoes as antiviral targets is a complementary step towards developing new strategies to combat arbovirus transmission and address the ongoing global health challenge.

Nephrolithiasis is a major global health challenge, with oxidative stress and mitochondrial dysfunction emerging as key drivers of renal injury and stone formation. l-ergothioneine (l-Erg), a naturally occurring antioxidant transported by OCTN1, has shown promising effects in cystinuria models, preventing stone formation. Despite evidence supporting an indirect mechanism of action, key mechanistic aspects have yet to be fully clarified. This study aimed to evaluate whether l-Erg can prevent stone progression in cystinuria and in other types of lithiasis, such as calcium oxalate nephrolithiasis, and to further elucidate its mechanistic basis. Using mouse models, l-Erg significantly reduced cystine stone growth and renal inflammation, and its combination with d-penicillamine enhanced stone dissolution and mitigated drug-related toxicity. In calcium oxalate nephrolithiasis, l-Erg decreased crystal deposition, preserved renal architecture, normalized glutathione levels, and restored mitochondrial respiration. Transcriptomic analysis revealed downregulation of immune pathways and activation of cell cycle genes, suggesting attenuation of inflammation and promotion of tubular repair. This study is the first to demonstrate that l-Erg exerts renoprotective effects through combined antioxidant and mitochondrial mechanisms in two major forms of nephrolithiasis and introduces a dual therapeutic approach combining an antioxidant with a cystine-solubilizing agent. By targeting oxidative stress and mitochondrial dysfunction, l-Erg represents a promising therapeutic strategy for nephrolithiasis, either alone or as an adjunct to current treatments. Antioxid. Redox Signal. 00, 000-000.

Purpose This research aims to examine how leadership behaviors shape collective behavioral responses during crises while accounting for the influence of national culture and perceived corruption. Drawing on signaling theory, the authors investigate how charismatic and humane-oriented leadership operated within different cultural and institutional contexts to influence community mobility during the pre-vaccine phase of the COVID-19 pandemic. Design/methodology/approach Using cross-national data from 59 countries, the authors use partial least squares structural equation modeling (PLS-SEM) to assess relationships among national culture dimensions, leadership styles, leadership effectiveness and community mobility. To interpret heterogeneous and counterintuitive effects, the authors conduct post hoc importance–performance map analysis (IPMA) and finite mixture PLS. Findings Leadership – particularly humane-oriented leadership – plays a central mediating role in shaping collective quarantine behavior. IPMA results indicate that charismatic leadership demonstrates high performance but comparatively lower importance, suggesting that its behavioral influence diminishes without relational grounding. IPMA results further reveal that national culture exerts differentiated effects depending on the construct examined within the model: specifically, while cultural dimensions have limited direct influence on community mobility, several other dimensions constrain leadership effectiveness. Moreover, masculinity supports leadership effectiveness but is less conducive to collective behavioral restraints. Research limitations/implications This study advances leadership and cross-cultural research by integrating signaling theory with PLS-SEM to explore how leadership styles and cultural dimensions influence crisis behavior. It offers a quantitative framework for future studies on leadership effectiveness in high-uncertainty, global contexts. Practical implications Effective crisis management depends on leadership communication, trust-building and cultural alignment. Policymakers should consider cultural boundary conditions when designing public health interventions. Social implications Trustworthy and culturally aware leadership helps reduce public anxiety and fosters solidarity during crises. Effective leadership communication can combat misinformation, encourage compliance with health measures and ultimately protect vulnerable populations. Building social trust through leadership is essential for resilience in future global health emergencies. Originality/value This research offers a novel signaling theory perspective on crisis leadership by combining cross-national quantitative analysis with advanced PLS-based techniques to explain how leadership shapes collective behavior during the COVID-19 pandemic.

Male infertility is a major yet understudied global health concern. This study aims to analyze the temporal trends in the global and regional burden of male infertility from 1990 to 2021, explore influencing factors, assess the relationship with sociodemographic development, analyze health inequalities, and forecast future trends. Using epidemiological data on male infertility from the Global Burden of Disease Study database for 1990-2021, we calculated prevalence, disability-adjusted life years (DALYs), and other indicators. Joinpoint regression, age-period-cohort analysis, and decomposition analysis were used to examine temporal trends and influencing factors. Data envelopment analysis was used to assess the relationship between male infertility and the sociodemographic index (SDI). The slope index of inequality (SII) and concentration index were used to analyze health inequalities. Autoregressive integrated moving average (ARIMA) and Bayesian age-period-cohort (BAPC) models were used to forecast prevalence from 2022 to 2036. The global crude prevalence rate of male infertility was 1389.1 per 100,000 population in 2021, and the age-standardized prevalence rate was 1354.8 per 100,000 population. Eastern Europe had the highest prevalence, while Australasia had the lowest prevalence. Overall, prevalence showed a decreasing-then-increasing trend from 1990 to 2021, with the fastest growth occurring from 2010 to 2014. The trend of DALY changes is basically consistent with the incidence rate, with a rapid increase after 2010. The risk of infertility increased with age up to approximately 37.5 years and subsequently declined, with an overall downward trend observed after 1994. Population growth was the main driver of increasing prevalence. The increase in DALY rates is also mainly driven by population growth, contributing up to 68.06% globally, and the impact of population aging in high-SDI regions on DALY rates initially shows a significant negative effect. As SDI increased, the DALY rate generally decreased, but there was room for improvement in some countries. The inequality between high and low-SDI regions increased. Prevalence was predicted to rise in the future. The global burden of male infertility is increasing overall, with lower prevalence in high-SDI regions and higher DALYs in low-SDI regions. Attention should be paid to rapidly growing populations, improving reproductive health services, and equitable access. Screening and interventions for high-risk populations should be strengthened to curb the rising prevalence trend.

Gastric cancer (GC) remains a major global health burden, and increasing evidence suggests that ferroptosis plays an important role in regulating tumor cell survival. Phosphatidylserine decarboxylase (PISD) is a key mitochondrial enzyme responsible for phosphatidylethanolamine (PE) synthesis; however, its molecular function in GC remains poorly understood. In this study, we suggest that downregulation of PISD is associated with enhanced ferroptosis in GC cells by disrupting mitochondrial PE homeostasis and impairing mitochondrial function. Mechanistically, PISD depletion reduces PE levels, is accompanied by a reduction in signal transducer and activator of transcription 3 (STAT3) phosphorylation, and decreases GPX4 expression, leading to enhanced lipid peroxidation, iron accumulation, and redox imbalance. Pharmacological inhibition of ferroptosis using Ferrostatin-1 (Fer-1), activation of STAT3 by ML115, or supplementation with lysophosphatidylethanolamine (LPE) partially rescues PISD knockdown-induced ferroptosis. In vivo, PISD downregulation is significantly accompanied by a reduction in tumor growth in GC xenograft models. Collectively, our findings reveal a previously unrecognized role of PISD in linking mitochondrial phospholipid metabolism to STAT3/GPX4-dependent ferroptosis, providing mechanistic insights into the regulation of ferroptosis in gastric cancer.