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A study on the differences in recovery effects of different types of nutritional supplements on competitive performance of esports athletes under mental fatigue.

BACKGROUND: To compare the effects of different nutritional supplements on the recovery of core competitive performance abilities in esports athletes following mental fatigue and to observe changes in the autonomic nervous system during recovery after nutritional supplementation by monitoring heart rate variability (HRV). METHODS: A randomized crossover within-subject controlled experimental design was adopted, including nutritional supplement type (caffeine, nitrate, Ginkgo biloba extract, catechins, placebo)&#x2009;&#xd7;&#x2009;mental fatigue state (initial, fatigued, post-supplementation). Twenty high-level first-person shooter (FPS) esports athletes were recruited. Mental fatigue was induced using a Stroop task. After ingesting the different supplements and resting for 60&#x2009;minutes, the participants completed assessments of shooting accuracy, shooting stability, spatial localization, and multitasking ability using the KovaaK's simulation trainer. HRV indices were also recorded to evaluate changes in autonomic regulation. RESULTS: For shooting accuracy, compared with the placebo condition, all four supplements significantly improved shooting accuracy scores following mental fatigue (all p&#x2009;<&#x2009;0.05); however, no significant differences were observed among the effects of the different supplements. For shooting stability, caffeine, nitrate, and catechins produced significant recovery effects on shooting stability (all p&#x2009; <&#x2009;0.05); however, no significant differences were observed among the effects of these three supplements. For spatial localization and multitasking ability, the improvements in these two abilities in the post-supplementation state may have resulted from natural recovery, and none of the four nutritional supplements demonstrated a significant recovery effect. The HRV results showed that indices including RMSSD and SDNN changed under some supplement conditions. CONCLUSIONS: Mental fatigue significantly reduced the competitive performance of esports athletes. Four types of nutritional supplements all promoted the recovery of shooting accuracy, while caffeine, nitrate, and catechins promoted the recovery of shooting stability. However, no additional recovery advantages of the nutritional supplements over placebo were identified for spatial localization or multitasking ability. Changes in HRV may reflect changes in autonomic regulation during recovery, but further research is still warranted.

Humans

Effects of faba bean-based crisping culture on phenotypic characteristics, muscle quality, and serum metabolome in Nile tilapia: Screening biomarkers to assess the degree of crisping.

Feeding Nile tilapia (Oreochromis niloticus) a faba bean-based crisping diet enhances muscle hardness (crispness) and overall flesh quality. However, the underlying mechanisms and reliable biomarkers remain insufficiently defined. This study integrated phenotypic traits, muscle texture, collagen content, serum antioxidant enzyme activities (SOD, CAT, and GSH-Px), MDA levels, and serum metabolomics to understand the determinants of muscle crisping. Fish were assigned to a crisping diet or a control group for 90&#xa0;days. Individuals in the crisping group were implanted with passive integrated transponder (PIT) tags to enable correlation analyses among phenotypic traits (body weight/length/frame changes), serum indicators (NAM, FAD, and GSH-Px) and muscle hardness. Compared with controls, the crisping diet significantly increased muscle hardness, gumminess, and chewiness, accompanied by elevated collagen content. Antioxidant profiles were altered, with higher activities of serum SOD and CAT, together with elevated MDA levels and reduced GSH-Px activity (P&#xa0;<&#xa0;0.05). Metabolomic analysis identified 830 differential metabolites (682 upregulated and 148 downregulated), predominantly comprising carboxylic acids and derivatives, glycerophospholipids, and benzene derivatives. Enrichment analysis indicated significant involvement in general metabolic pathways, ATP-binding cassette (ABC) transporters, amino acid biosynthesis, and glycine, serine, and threonine metabolism (P&#xa0;<&#xa0;0.05). Notably, acetylpyruvate was upregulated in glutathione metabolism, nicotinate and nicotinamide metabolism, and galactose metabolism; pantothenic acid was upregulated in glycine, serine, and threonine metabolism; whereas &#x3b4;-tocotrienol was downregulated. Correlation analysis revealed weak negative associations between muscle hardness and phenotypic traits (body weight/length/frame changes D5-7, D5-10, D7-8) (P&#xa0;<&#xa0;0.05). In contrast, serum NAM and FAD were weakly positively correlated with muscle hardness, whereas GSH-Px showed a weak negative correlation (P&#xa0;<&#xa0;0.05). Collectively, these findings suggest that body weight, body length, frame measurements (D5-7, D5-10, and D7-8), and serum NAM, FAD, and GSH-Px are associated with the degree of muscle crispness in Nile tilapia fed a faba bean-based crisping diet and may serve as candidate biomarkers under these culture conditions.

Animals

Transcranial Photobiomodulation Variables Assessment Battery: Development and Validation.

Transcranial photobiomodulation (tPBM) response variability is partly driven by biophysical characteristics such as skin tone and hair properties that attenuate photon penetration, and by lifestyle factors including sleep quality, alcohol use, and nicotine consumption that disrupt the mitochondrial and vascular pathways on which tPBM acts. To date, no validated self-report tool exists to capture these moderators systematically. To address this gap, the tPBM Variables Assessment Battery was developed and psychometrically evaluated. It integrates adapted versions of established measures (Brief Pittsburgh Sleep Quality Index, E-cigarette Dependence Scale, Hair Scale Assessment PRO, Monk Skin Tone Scale, and Heaviness of Smoking Index), validated wellbeing evaluators (Ryff's Psychological Wellbeing), and custom measures (Hairstyle Classification, Hair Color Classification). Face and content validity met recommended expert thresholds, internal consistency was acceptable across adapted subscales, and criterion validity analyses confirmed meaningful associations between the lifestyle components and PROMIS-10 global health outcomes. The battery is low-burden, digitally deployable, and psychometrically defensible, offering a practical tool for characterizing the variables most likely to moderate tPBM response in home-use studies.

Humans

Alarms and alarm management with automated versus conventional ventilation in neurocritical care patients.

INTRODUCTION: False or clinically irrelevant alarms are a major driver of ICU alarm fatigue and nursing workload. Ventilator alarms make up a large share, and although automated ventilation modes can reduce manual adjustments, their effect on alarm burden is still unclear. This issue can be particularly relevant in neurocritical care patients, where precise ventilator and alarm management is imperative for patient safety. OBJECTIVES: This explorative post hoc analysis of a randomized clinical trial compared alarm frequency and management between automated ventilation and conventional ventilation in neurocritical care patients. METHODS: Ventilator alarms and manual ventilator changes were captured continuously from the ventilator for up to 24&#xa0;h per patient. The primary endpoint was a composite of workload-relevant alarms; with alarm management interventions at the ventilator as a key secondary outcome. Additional endpoints included redundant alarms, alarm duration and ventilator management. RESULTS: 13 patients received automated ventilation and 24 received conventional ventilation. No difference was observed in workload-relevant alarm frequency between automated and conventional ventilation (3.28 [2.87 to 4.30] vs 3.73 [1.66 to 7.33] alarms per hour; P&#xa0;=&#xa0;0.81), while alarm management interventions at the ventilator were lower with automated ventilation (0.14 [0.10 to 0.15] vs 0.21 [0.17 to 0.31] interventions per hour; P&#xa0;=&#xa0;0.01). Other alarm frequencies, duration of alarms and ventilator management were similar. CONCLUSIONS: In this exploratory post hoc analysis of a randomized clinical trial in neurocritical care patients during the early phase of mechanical ventilation, automated ventilation did not reduce the frequency of total or workload-relevant alarms, nor their duration, but was associated with fewer alarm management interventions compared to conventional ventilation. IMPLICATIONS FOR CLINICAL PRACTICE: Automated ventilation may not reduce alarm frequency in neurocritical care patients, but the observed reduction in alarm-related bedside interventions suggests a potential benefit for nursing workload.

Humans

CanDo (Canadian Donor Milk) randomised controlled trial: pasteurised human donor milk supplementation in the well-baby unit - protocol.

INTRODUCTION: Mother's milk is the gold standard for feeding newborns. Despite lactation support while in hospital, supplementation rates remain high in Canadian well-baby units at 35-50%. When supplementation is needed, the choice between formula milk and pasteurised human donor milk (donor milk) remains uncertain with a lack of clinical trials to inform this practice. This study aims to compare the effect of supplementing mother's milk with donor milk versus formula in infants at higher risk for supplementation (infants of diabetic mothers, infants born small for gestational age or with a birth weight less than 2.5&#x2009;kg and late preterm infants born between 350/7 and 366/7 weeks gestation). METHODS AND ANALYSIS: This is an ongoing, open-label, single-centre, randomised controlled trial conducted at Mount Sinai Hospital, Toronto, Canada. A total of 112 infants (56 per group) will be randomised to receive donor milk or infant formula as a supplement to mother's milk during their initial hospital stay, when supplementation is deemed necessary by the family and/or healthcare team. The primary outcome is exclusive human milk feeding at 4 months of age. Secondary outcomes include any or exclusive human milk feeding at 1, 2 and 3 months; infant growth and health indicators and breastfeeding self-efficacy. Exploratory outcomes encompass infant temperament; parental mental health (assessed using the State-Trait Anxiety Inventory and Edinburgh Postnatal Depression Scale); milk cortisol concentrations; and informal milk sharing comparing donor milk and formula supplementation. Follow-up includes monthly telephone assessments and a virtual or in-person visit at 4 months post partum. Data will be analysed using intention-to-treat principles. ETHICS AND DISSEMINATION: The CanDo trial has received ethics approval from the Mount Sinai Hospital Research Ethics Board and the University of Toronto. Results will be disseminated through peer-reviewed journals, conference presentations and stakeholder engagement with hospital and public health decision-makers. Findings will address a critical evidence gap regarding the use of donor milk supplementation in well-baby units and may inform future clinical practice and policy in newborn feeding. TRIAL REGISTRATION NUMBER: NCT06315127.

Humans

Single nucleus multiomics reveals an early inflammatory response to high-fat diet in mouse islets.

In periods of sustained hyper-nutrition, pancreatic &#x3b2;-cells undergo functional compensation through transcriptional upregulation of gene programs driving insulin secretion. This adaptation is essential for maintaining systemic glucose homeostasis and metabolic health. Using single nuclei multiomics, we have mapped the early transcriptional adaptive mechanisms in murine islets of Langerhans exposed to high-fat diet (HFD) for 1 and 3 wk. We show that &#x3b2;-cells exhibit the largest transcriptional response to HFD, characterized by early activation of pro-inflammatory eRegulons and down-regulation of &#x3b2;-cell identity genes, particularly in a distinct subset of &#x3b2;-cells. These observations extend to humans, where the prevalence of an &#x3b2;-cells with a high inflammatory signature is increased in diabetes. Collectively, these observations point to cellular crosstalk through pro-inflammatory signaling as a central and early driver of &#x3b2;-cell dysfunction that limits the compensatory capacity of &#x3b2;-cells, which is closely linked to the development of diabetes.

Animals

Maternal Intake of Vitamins A, C, D, and E During Pregnancy and Risk of Type 1 Diabetes in the Child: The Norwegian Mother, Father, and Child Cohort Study.

BACKGROUND: Dietary vitamins play a role in antioxidant defense and immunoregulation. However, prospective studies exploring the association between vitamin intakes during pregnancy and the child's risk of type 1 diabetes are limited. OBJECTIVES: This population-based prospective cohort study aimed to investigate the association between maternal intake of vitamins A, C, D, and E during pregnancy and risk of type 1 diabetes in children. METHODS: We included 85,244 children born between 2002 and 2009 in the Norwegian Mother and Child Cohort Study, with follow-up until 31 December, 2021. Maternal intake of vitamins from food and dietary supplements from conception to the 22nd week of pregnancy was assessed with a validated food frequency questionnaire. Cox proportional hazards regression was used to estimate hazard ratios (HRs), adjusting for background factors. RESULTS: During follow-up, 529 (0.6%) children were diagnosed with type 1 diabetes at a mean age of 9.4 y (standard deviation: 4.1 y) No associations were observed between maternal pregnancy intake of vitamin A [HR: 0.993; 95% confidence interval (CI): 0.983, 1.003/100 &#x3bc;g], vitamin C (HR: 1.000; 95% CI: 0.993, 1.007/10 mg), vitamin D (HR: 0.991; 95% CI: 0.978, 1.003/1 &#x3bc;g), or vitamin E (HR: 0.999; 95% CI: 0.996, 1.004/10 mg) and risk of type 1 diabetes in the child when adjusted for potential confounders. The results were similar when intakes were assessed separately from food and dietary supplements and after restriction to children with human leukocyte antigen DQ2 and/or DQ8 risk haplotypes. CONCLUSIONS: This prospective cohort study does not support the hypothesis that higher maternal intake of vitamins A, C, D, and E during pregnancy would decrease risk of type 1 diabetes in the child. Corroborated with previous evidence, our findings support a general pattern of null associations.

Humans

Application of 13C MRS demonstrates carbohydrate feeding spares muscle but not liver glycogen utilization during high-intensity interval exercise.

We examined liver and muscle glycogen utilization during high-intensity interval cycling, and the impact of carbohydrate (CHO) feeding, using noninvasive 13C magnetic resonance spectroscopy (MRS). Following 24 h of standardized dietary intake, nine male cyclists completed 8 &#xd7; 5-min intervals (1-min recovery), ingesting either placebo (PLA), 60 g maltodextrin (CHO), or 60 g maltodextrin plus caffeine, taurine, l-theanine, l-citrulline, and citicoline (CHO+) in a randomized crossover design. 13C MRS and 1H imaging were performed pre- and postexercise to determine liver and muscle glycogen and liver volume, respectively. Liver glycogen utilization was not significantly different between trials (P = 0.101) despite lower postexercise plasma glucagon concentrations in CHO and CHO+ (P = 0.001). In contrast, muscle glycogen utilization was significantly lower (&#x223c;40%) with CHO feeding compared with PLA (P = 0.006), yet this sparing effect was not evident with CHO+ (P = 0.073) in accordance with a higher mean power output during the late intervals (+2.8%, P = 0.046). Plasma glucose was comparable between trials (P = 0.175), whereas plasma lactate was higher in CHO+ versus CHO (P = 0.003), alongside lower blood bicarbonate (P = 0.005), base excess (P < 0.001), and total CO2 (P = 0.004). These findings demonstrate preferential use of skeletal muscle glycogen during high-intensity interval training (HIIT), which is attenuated under conditions of CHO feeding. This sparing effect is, however, not evident with the coingestion of a caffeine-containing multi-ingredient blend, potentially due to an increased capacity to sustain higher power outputs resulting in greater glycogen utilization.NEW & NOTEWORTHY Using 13C MRS, we provide data demonstrating preferential use of skeletal muscle glycogen during HIIT. Furthermore, data show muscle glycogen utilization is attenuated with CHO feeding, yet sparing is not evident when coingesting a caffeine-containing formulation, potentially reflecting increased capacity to perform more total work rather than a direct metabolic effect of caffeine. In contrast, liver glycogen utilization was not significantly different with CHO feeding despite a modest reduction of &#x223c;5 g versus placebo.

Male

ORBIT: Oncogenic Representation Learning via Bi-Prototype Contrastive Learning in Hyperbolic Space for cancer driver gene identification.

Accurate identification of cancer driver genes is crucial for precision oncology but remains challenging due to the complexity of integrating heterogeneous data and modeling dynamic biological systems. To address these limitations, we propose ORBIT (Oncogenic Representation Learning via Bi-Prototype Contrastive Learning in Hyperbolic Space). Our framework synergistically fuses multi-omics profiles with functional network data using a context-adaptive graph reweighting mechanism to capture cancer-specific dynamics. The model employs a bi-prototype contrastive learning strategy within hyperbolic space, which aligns gene representations around distinct driver and non-driver semantic anchors while preserving the intrinsic hierarchy of biological networks. Comprehensive evaluations demonstrate that ORBIT achieves highly competitive stability in pan-cancer analysis while consistently outperforming state-of-the-art methods in cancer-specific predictions. Furthermore, functional enrichment analysis confirms that the model effectively segregates core cancer pathways, and drug sensitivity profiling validates the clinical relevance of the identified drivers. By integrating hyperbolic geometry with context-adaptive learning, ORBIT offers a robust and interpretable paradigm for precision medicine. The source codes and datasets are publicly accessible at https://github.com/spcho-dev/ORBIT.

Humans

From population to individual: advocating personalised digital tools for heat-health early warning in a changing climate.

Escalating heat extremes under climate change are imposing substantial health burdens, with 2023 and 2024 consecutively breaking global temperature records. Mounting evidence suggests that heatwaves elevate the risks of hospitalisation and mortality across multiple disease categories, including ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and acute kidney injury. Nonetheless, most existing heat-health warning systems remain primarily reliant on population-level predictions, and considering individual differences and disease-specific considerations when defining warning levels would benefit the effectiveness of early prevention for high-risk groups. In this Viewpoint, which is based on the framework of precision public health-delivering the right intervention to the right population at the right time-we propose a framework for personalised digital heat-health early warning tools comprising three dimensions: individualised, risk-stratified prediction models that generate tiered early warnings; personalised health prompts coupled with theory-informed behavioural interventions; and adaptive, equity-oriented alert delivery mechanisms tailored to diverse populations. Such tools have the potential to bridge precision disease prevention and climate adaptation, thereby helping to mitigate heat exposure risks and disease burdens, particularly among high-risk populations. Future implementation research will be essential to address substantial challenges related to feasibility, validation, and equity.

Journal Article

Complete Revascularization Guided by Functional Coronary Angiography in STEMI.

BACKGROUND: Complete coronary-artery revascularization is recommended in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease, but the preferred strategy for identifying nonculprit lesions that warrant treatment remains uncertain. METHODS: In this international, randomized trial, we assigned patients with STEMI and multivessel disease in whom the culprit lesion had been successfully treated to undergo complete coronary-artery revascularization guided by functional coronary angiography (physiology-guided group) or by conventional angiography (angiography-guided group). The primary outcome was a composite of death from any cause, myocardial infarction, cerebrovascular accident (stroke or transient ischemic attack), or ischemia-driven revascularization, assessed in a time-to-event analysis. The primary safety outcome was a composite of contrast-associated acute kidney injury or major bleeding. RESULTS: A total of 1823 patients underwent randomization; 913 were assigned to the physiology-guided group and 910 assigned to the angiography-guided group. The median age of the patients was 66 years (interquartile range, 58 to 76), and 24% were women. At a median follow-up of 17.9 months, a primary-outcome event had occurred in 81 patients (8.9%) in the physiology-guided group and in 125 patients (13.7%) in the angiography-guided group (hazard ratio, 0.62; 95% confidence interval [CI], 0.47 to 0.83; P<0.001). A primary-safety-outcome event occurred in 42 patients (4.6%) in the physiology-guided group and in 65 patients (7.1%) in the angiography-guided group (hazard ratio, 0.63; 95% CI, 0.43 to 0.93; P&#x2009;=&#x2009;0.02). CONCLUSIONS: In patients with STEMI and multivessel coronary artery disease, a strategy of complete coronary-artery revascularization guided by functional coronary angiography resulted in a lower risk of a primary-outcome event (death, myocardial infarction, cerebrovascular accident, or ischemia-driven revascularization) than a strategy guided by conventional angiography. (Funded by the Italian Health Ministry and others; AIR-STEMI ClinicalTrials.gov number, NCT05818475.).

Aged

Using Organoids to Unlock the Potential of Human Torpor for Spaceflight.

PURPOSE OF REVIEW: This paper reviews the current understanding of the potential for humans to enter a state of torpor/hibernation, and discusses the possibility of inducing torpor in astronauts for long-duration space travel, including some of the physiological, technological, and ethical considerations associated with its implementation. By exploring means to induce torpor in various human organoid systems, we hope such research can provides insights to comprehensive solutions to overcome some of the major hurdles that limit the potential for human to enter a state of torpor during long-duration deep-space missions, and contribute to the ongoing efforts to make such missions more feasible and safer for astronauts. RECENT FINDINGS: On future deep space missions such as NASA's planned missions to the Moon, Mars, and near-Earth asteroids, astronauts will be continuously exposed to environments that are radically different from those on Earth, each presenting multiple logistical and physiological challenges. Beyond the well-documented physiological effects of microgravity, space travelers will encounter a complex radiation environment that may contribute to significant short- and long-term adverse effects on human physiology and increase the risk of cancer and other diseases. Besides these physical challenges, life support systems must also be designed to mitigate psychological impacts of long-term isolation and confinement - all of which collectively pose formidable engineering problems. Hibernation/torpor is a state of prolonged inactivity and metabolic depression used by a wide variety of mammals to survive periods of cold temperatures and food scarcity, including some primates and perhaps even an extinct early line of hominins that lived nearly half a million years ago. Since modern humans share common ancestry with these hominins and hibernating primates, it is likely the human genome encodes the necessary genetic information to hibernate, or at least enter the similar, more transient state of torpor. The reduced body activity, lowered metabolism, and decreased energy requirements that characterize torpor suggest that developing means of inducing such a state in astronauts could address these challenges, including providing a degree of radioprotection. SUMMARY: This review explores the potential application of human torpor as a countermeasure to address the many challenges posed by long-duration spaceflight beyond low-Earth orbit (LEO), discusses various natural hibernating model systems for studying means of inducing a torpor-like state in humans, and highlights the vast potential of using human organoids to test and validate mechanisms that govern induction and maintenance of torpor to identify the means to one day safely induce this state in astronauts to provide additional protection from the myriad stressors of spaceflight.

Astronaut Health

Increasing gut short-chain fatty acids protects intestinal barrier function but does not spare muscle glycogen or impact aerobic performance.

Animal studies suggest gut microbiota-derived short-chain fatty acids (SCFA) provide an intestinal barrier-protecting, glycogen-sparing energy source that increases aerobic endurance performance, but confirmation in humans is needed. This study aimed to determine whether increasing colonic SCFA availability impacts intestinal barrier function, substrate metabolism, muscle glycogen and aerobic performance in healthy adults. Using a randomized, double-blind, crossover design 12 active men (age 18-30&#xa0;years;40.0&#xa0;&#xb1;&#xa0;7.1&#xa0;mL/kg/min) performed prescribed exercise and consumed a provided diet supplemented with acetylated and butyrylated high-amylose maize starch engineered to deliver SCFA to the colon (HAMS-A/B) or low-amylose maize starch (LAMS) for 7 days, separated by a 2 week washout. Indirect calorimetry, stable isotopes and blood, muscle and urine biomarkers were measured on intervention day 8 while participants completed 90&#xa0;min of steady-state cycle ergometry (ExSS; 60 &#xb1; 5%) followed by a 5&#xa0;km treadmill time trial. HAMS-A/B, relative to LAMS, increased faecal and serum SCFA. Multiple markers of intestinal barrier damage and permeability were lower, and the respiratory exchange ratio during ExSS was higher (0.02 [95% confidence interval (CI): 0.01, 0.03], Ptreatment&#xa0;<&#xa0;0.001) following HAMS-A/B versus LAMS. However no between-treatment difference in glucose turnover, muscle glycogen depletion (14&#xa0;&#xb5;mol/kg/g dry wt. [95% CI: -116, 143], Pinteractio n&#xa0;=&#xa0;0.613) or TT performance (5&#xa0;s [95%CI: -44, 54], Ptreatment&#xa0;=&#xa0;0.816) was observed. Increasing colonic and circulating SCFA modestly altered substrate oxidation and preserved intestinal barrier function during endurance exercise. However effects were not sufficient to spare muscle glycogen or increase aerobic endurance performance, leaving the practical relevance unclear and underscoring challenges inherent in translating promising preclinical findings to humans. KEY POINTS: Animal studies suggest gut microbiota-derived short-chain fatty acids (SCFA) provide an intestinal barrier-protecting, glycogen-sparing energy source that increases aerobic endurance performance, but confirmation in humans is lacking. A gut microbiota-targeted dietary supplementation strategy was used to deliver SCFA to the colon and successfully increased colonic and systemic SCFA concentrations in healthy, physically active adults before and during an endurance exercise bout and aerobic performance test. Increasing colonic and systemic SCFA availability preserved intestinal barrier function but did not impact glucose turnover, alter protein expression in muscle or spare muscle glycogen during endurance exercise. Increasing colonic and systemic SCFA availability did not impact aerobic endurance performance.

Humans

Direct and spillover hospitalisation patterns during climate hazards across regions of different health-system resilience levels in China: a nationwide retrospective analysis.

BACKGROUND: Health-system resilience serves as a key contributor in mitigating adverse health impacts during climate hazards. However, quantitative insights into resilience-associated health-care utilisation patterns and targeted adaptation policies remain scarce. We aimed to capture the spatiotemporal health impacts in disaster-exposed counties and their neighbouring counties in China during storms, floods, tropical cyclones, and blizzards or winter storms; understand the association between health-system resilience metrics and hazard-attributable hospitalisations; and develop evidence-based adaptation policies towards climate extremes. METHODS: In this retrospective, observational analysis of county-level aggregated hospitalisation data, we used a propensity score matching-difference-in-differences framework to assess the spatiotemporal changes of nine types of disease-specific hospitalisations in both disaster-exposed and neighbouring regions during storms, floods, tropical cyclones, and blizzards in China. We quantified the relative importance and health gains of health-system metrics during such hazards through random forest approach with interpretable partial dependence plots to derive evidence-based adaptation recommendations. FINDINGS: We included hospitalisation data from Jan 1, 2016 to Dec 31, 2023. In this period, 3241 county-hazard event combinations and 41&#x2009;747&#x2009;482 hospitalisations were recorded across 955 Chinese counties. The disaster-exposed regions experienced an initial decline in hospitalisation rates, followed by admission surges after disasters. For example, infectious disease admissions decreased by 11&#xb7;92% (95% CI -10&#xb7;53 to -13&#xb7;31) during the flood-active period but increased by 7&#xb7;68% (6&#xb7;46-8&#xb7;91) after 1-2 weeks of floods. Neighbouring zones were also affected through spillover effects, with infectious disease admissions increasing by 3&#xb7;18% (1&#xb7;76-4&#xb7;61) after 1-2 weeks of the floods. Cardiovascular disease, injuries, infectious, respiratory, and mental disorders were more sensitive across all regions. Particularly for disaster-exposed counties, cardiovascular hospitalisations increased by 14&#xb7;31% (7&#xb7;34-21&#xb7;29) during the tropical cyclone-active period. Notably, compared with low-resilience counties, high-resilience counties were associated with 19&#xb7;48-30&#xb7;03% smaller hazard-related relative changes in hospitalisation rates during the hazard-active period and 27&#xb7;07-31&#xb7;08% smaller hazard-related relative changes in hospitalisation rates in post-hazard periods. For instance, during the storm-active period, the increase in respiratory hospitalisations was 7&#xb7;21% (0&#xb7;67-13&#xb7;75) in high-resilience counties versus 12&#xb7;13% (5&#xb7;20-19&#xb7;05) in low-resilience counties. Health workforce (relative importance 14&#xb7;58% during the hazard-active period and 13&#xb7;80% during the post-hazard period) and service delivery (14&#xb7;10% during the hazard-active period and 14&#xb7;17% during the post-hazard period) were identified as key contributors of health-system resilience. Empirical synergistic effects were observed when combining interventions during the post-hazard period, with the combined effect of service delivery (individual contribution 8%) and workforce (individual contribution 4%) exceeding the sum of their individual contributions (16% reduction in cumulative excess admissions) by 33%. INTERPRETATION: Climate hazards are associated with substantial changes in hospitalisation rates in both disaster-exposed and neighbouring regions. Health-system resilience is essential in addressing disaster-health challenges. Targeted adaptation interventions should be context-appropriate and threshold-aware, thereby maximising the public health benefits relative to resilience-oriented investments in health systems. FUNDING: Gates Foundation and the National Natural Science Foundation of China.

Journal Article

Cognitive behavioural therapy-based interventions on stress outcomes in pregnant women: A systematic review and meta-analysis.

BACKGROUND: Stress symptoms were the most common psychological problem in pregnancy. Cognitive behavioural therapy-based interventions are effective for antenatal depression and anxiety symptoms; but there are fewer studies for stress symptoms. OBJECTIVE: The review aims to (1) examine the effectiveness of cognitive behavioural therapy-based interventions in reducing stress outcomes (pregnancy-specific stress symptoms, generic symptoms, and objective stress) in pregnant women, and (2) identify significant moderators affecting the effectiveness of the intervention. DESIGN: Systematic review, meta-analysis, and meta-regression analysis of randomised controlled trials. METHODS: We conducted a three-step search (12 databases, 4 clinical registries, and citation searches) in English and Chinese up to July 24, 2025, by two independent reviewers. Meta-analysis, subgroup, and meta-regression analyses were performed using the R software. Quality assessment and certainty of the evidence were assessed with the Cochrane risk-of-bias tool version 2 and Grading of Recommendations, Assessment, Development, and Evaluation criteria. Publication bias was assessed using funnel plots and Egger's test. RESULTS: We included 20 randomised controlled trials involving a total of 6966 pregnant women from nine countries. Random-effects meta-analyses found that interventions significantly alleviated pregnancy-specific stress symptoms (Hedges' g&#xa0;=&#xa0;-0.84, 95% Confidence Interval, CI -1.42, -0.26, p&#xa0;<&#xa0;.01, I2&#xa0;=&#xa0;92.3%), reduced generic stress symptoms (g&#xa0;=&#xa0;-0.64, 95% CI -1.09, -0.20, p&#xa0;<&#xa0;.01, I2&#xa0;=&#xa0;87.4%) with median and large effect sizes at post-intervention. No effect was found in lowering cortisol levels (g&#xa0;=&#xa0;-0.99, 95% CI -2.58, -0.60, p&#xa0;=&#xa0;.12, I2&#xa0;=&#xa0;84%) at post-intervention. Subgroup and meta-regression analyses indicated that region, age of participants, use of intention-to-treat, missing data management analyses, frequency, modalities, and approaches of interventions, use of different comparators, and attrition rate were significant factors affecting the effectiveness of interventions. Subgroup analyses suggested that the intensity of intervention should be more than once per week using a blended mode among Asian populations. Multivariate meta-regression analyses indicated that both younger age (&#x3b2;&#xa0;=&#xa0;0.13, p&#xa0;=&#xa0;.02) and a lower attrition rate (&#x3b2;&#xa0;=&#xa0;0.03, p&#xa0;=&#xa0;.03) significantly improved the effectiveness of interventions. The overall certainty of the evidence was rated as either very low or low. CONCLUSIONS: Cognitive behavioural therapy-based interventions can supplement antenatal care to alleviate pregnancy-specific stress symptoms and generic stress symptoms, particularly in young Asian women. However, the evidence has some uncertainties. These findings should be interpreted with caution due to substantial heterogeneity. Well-designed trials on a large-scale with long-term follow-ups were needed. REGISTRATION: PROSPERO registration ID: CRD420251115913.

Humans

Light regulates capsaicinoid biosynthesis via the CaHY5-CaBBX2-CaACS8 module in pepper.

Capsaicinoids are a class of unique alkaloids that confer the pungent taste to pepper fruits. However, it remains largely unknown how light regulates the biosynthesis of capsaicinoids. We conducted a metabolic analysis on light- and dark-adapted pepper fruits. The results showed that dark-adapted pepper fruits had lower capsaicinoid contents and correspondingly downregulated transcription of capsaicinoid biosynthetic genes (CBGs), indicating that light plays a crucial role in capsaicinoid biosynthesis. Furthermore, silencing of CaHY5, a pivotal transcription factor gene in the light signaling pathway, decreased the content of capsaicinoid and suppressed the expression of CBGs, whereas transient overexpression of CaHY5 generated exactly opposite results. CaHY5 can bind to the G-box motif in the promoters of CaBBX2 and CaACS8, thereby enhancing their transcriptional levels. The activated CaBBX2 then binds to the T/G-box in the CaACS8 promoter to stimulate its expression. CaBBX2 or CaACS8 silencing led to decreased levels of capsaicinoids, while their transient overexpression produced increased capsaicinoid contents. Collectively, our results indicated that the light-activated CaHY5-CaBBX2-CaACS8 regulatory module plays a pivotal role in capsaicinoid biosynthesis. These findings provide new insights into the influence of light on capsaicinoid biosynthesis and potential targets for activation of this biosynthetic pathway in pepper.

Capsicum

Acetazolamide to prevent ventilatory drive withdrawal in REM sleep apnoea: a randomised controlled trial.

BACKGROUND: Obstructive sleep apnoea (OSA) pathogenesis during rapid-eye movement (REM) sleep has been linked to dips in ventilatory drive and downstream genioglossus hypotonia. The carbonic anhydrase inhibitor acetazolamide is known to increase ventilatory drive and improve OSA severity. Therefore, we tested the effect of acetazolamide on REM-predominant OSA severity (apnoea hypopnoea index (AHI) and hypoxic burden, co-primary outcomes) and underlying physiological mechanisms (ventilatory drive, ventilation and pharyngeal muscle activity). METHODS: 11 participants with REM-predominant OSA per baseline polysomnography (REM AHI/non-REM AHI&#x2265;2) were allocated to receiving acetazolamide 500&#x2009;mg for three nights (first night at half dose) or placebo according to a randomised, crossover, double-blind design. Detailed physiological polysomnography with recording of diaphragm and genioglossus electromyography was conducted after each intervention, with a 1-week washout in between. RESULTS: As hypothesised, acetazolamide reduced AHI by 35.5% (95% CI 23.1% to 46.3%) and hypoxic burden by 35.9% (95% CI 21.1% to 48.4%) vs placebo (p<0.001), meeting the primary endpoint. Mechanistic analysis in REM revealed that, unexpectedly, acetazolamide did not mitigate dips in ventilatory drive versus placebo (first decile (+0.1 (-1.0 to 1.3) L/min, p=0.8). Rather, acetazolamide reduced collapsibility (increased ventilation at eupneic drive: +1.4 (1.2 to 1.8) L/min) and raised muscle responsiveness (ventilation vs drive slope: +32 (25 to 41) %ventilation/drive, p<0.001; genioglossus versus drive slope: +0.33 (0.13 to 0.54) %max/(L/min), p=0.001). CONCLUSIONS: Acetazolamide modestly improved REM OSA, with meaningful improvements in upper airway physiology, but failed to mitigate the dips in ventilatory drive responsible for REM OSA. TRIAL REGISTRATION NUMBER: NCT05589792.

Humans