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Although recent stressful life events (SLEs) have been implicated as a risk factor for schizophrenia, prospective evidence and the underlying immunometabolic mechanisms remain unclear. This study investigated the association between recent SLEs and schizophrenia risk and explored the potential mediating role of immunometabolic markers.
Methods
Data were drawn from the UK Biobank prospective cohort. Cox proportional hazards models, linear mixed-effects models, and mediation analyses were applied.
Results
We included 493,294 participants (mean [SD] age, 56.55 [8.09] years; 45.56% male) free of schizophrenia at baseline, among whom 492 schizophrenia cases were identified over a median follow-up of 13.91 years. Exposure to any recent SLEs was associated with a 49% higher risk of schizophrenia, with evidence of a dose–response relationship (e.g. highest SLE score group: HR, 7.15, 95% CI: 5.74–9.11). Among individual SLE types, ‘serious illness, injury, or assault to yourself’ and ‘financial difficulties’ showed the strongest associations with schizophrenia risk. Recent SLEs were associated with alterations in multiple immunometabolic markers, several of which were also significantly associated with schizophrenia risk. Mediation analyses indicated that specific immunometabolic markers (e.g. C-reactive protein and degree of unsaturation) partially mediated the association between recent SLEs and subsequent schizophrenia risk, with proportion mediated estimates of 9.0% and 11.7%, respectively.
Conclusions
In this cohort of predominantly middle-aged and older adults, recent SLEs were associated with increased subsequent schizophrenia risk. Immunometabolic pathways may partially underlie this association, supporting further investigation of integrated psychosocial and biological approaches to schizophrenia risk stratification.
This study presents an experimental investigation into the influence of a step on the detachment characteristics of a supersonic Coanda jet. A parametric analysis was conducted by systematically varying the Coanda surface radius, jet outlet height and step height. Flow morphology was captured using high-speed schlieren and shadowgraph visualisation, while the critical nozzle pressure ratio ($\textit{NPR}$) for jet detachment was precisely measured with pressure transducers. For the baseline configuration without a step, the detachment $\textit{NPR}$ (denoted $\textit{NPR}$d) was predicted by a macroscopic mechanical model balancing centrifugal force and the radial pressure gradient, confirming a power-law relationship with the geometric ratio. The introduction of a step revealed a novel ‘step stall’ phenomenon: while increasing the step height initially enhances attachment and raises $\textit{NPR}$d by simplifying wave structures and suppressing separation bubbles, a further increase beyond a critical optimal value causes a sharp drop in performance. This optimal step height, which maximises the detachment $\textit{NPR}$, is shown to have a linear relationship with the normalised Coanda radius. The phenomenon is explained by the ineffective wall–jet interaction when an excessive step height prevents the jet’s core from being effectively ‘grabbed’ by the curved surface. These findings provide critical insights and practical design guidelines for optimising the Coanda effect in advanced flow control applications.
Methanol- and ethylene glycol-grafted kaolinite were prepared via a stepwise intercalation–grafting strategy using dimethyl sulfoxide-intercalated kaolinite as an intermediate, with the aim of elucidating the structural differences between the two grafted products and clarifying the role of interlayer water. The products were systematically characterized by X-ray diffraction (XRD), Fourier-transform infrared (FTIR) spectroscopy, solid-state magic-angle spinning nuclear magnetic resonance (MAS NMR), elemental analysis (CHNS) and thermogravimetry–differential scanning calorimetry (TG–DSC). Compared with methoxy-modified kaolinite, the ethylene glycol-grafted kaolinite exhibited enhanced structural ordering, greater organic loading and improved thermal stability. The covalently grafted ethylene glycol molecules adopt a trans configuration in the interlayers of kaolinite, accompanied by a minute fraction of non-bonded ethylene glycol molecules and some amount of interlayer water molecules. Although the confined water in both systems originated from condensation reaction, it probably played opposite roles: it facilitated the ethylene glycol grafting while hindering that for methanol.
The Endangered Great Bustard Otis tarda dybowskii utilises the agricultural landscapes of Cangzhou, North China Plain, for its overwintering period. However, their daytime habitat utilisation and diurnal behavioural rhythms remained undocumented. Employing 205 presence records collected over three winters (2019–2022) and 1,254 minutes of continuous video footage in 2022, our study reveals that birds used low-stature crop cover: 56.6% of locations were in winter wheat fields and 38.1% in maize stubble, while fallow land accounted for only 5.4%. From continuous focal-group video sampling, foraging (44.7%) and resting (standing 30.4%, lying 8.7%) dominated the daytime activity budget. Behaviour varied significantly among five two-hour blocks (07:30–17:30): resting peaked at 07:30–09:30, and foraging remained active in the evening (15:30–17:30), when flocks generally entered a large-scale and rapid foraging state. Based on these patterns, we propose a practical management approach that prioritises maintaining low-stature winter croplands and implementing seasonal, low-conflict disturbance reduction around repeatedly used fields, with emergency-only supplementary feeding during extreme snow/ice events. Embedding such measures into local agri-environment policy may help secure key overwintering habitat for Great Bustards and other farmland-dependent migratory birds.
Virtual reality (VR) is a transformative technology for studying language processing and learning. It offers realistic and naturalistic environments while maintaining experimental control, supporting the exploration of social and sensorimotor cues that have often been overlooked in traditional psycholinguistic research. It can also be integrated with behavioral and neurocognitive measures to examine how learning processes influence learning outcomes. These VR characteristics have brought new opportunities and contributed to the expansion of theoretical frameworks on language processing and learning. Through reviewing recent empirical findings, we establish VR as a novel methodology for investigating how embodied and social experiences shape language processing and learning. We emphasize that realizing this potential fully requires real-time multimodal tracking of learning processes, systematic examination of individual differences and development of richer virtual environments and VR-suitable assessment tasks. This review provides methodological insights for future VR research on the neurocognitive bases of language processing and learning.
We numerically investigate the propulsion of a two-dimensional compliant membrane executing prescribed harmonic heave in the near wake of a stationary circular cylinder at Reynolds number $\textit{Re}=3000$. Using a partitioned high-fidelity fluid–structure interaction solver with nonlinear iterative force correction, we map the coupled response over $A^* \in [0.05,0.5]$ and $f^* \in [0.1,0.6]$, where $A^*$ is dimensionless flapping amplitude and $f^*$ is dimensionless flapping frequency. The parameter sweep reveals a sharp transition in the force maps from weakly forced, wake-following behaviour to a high-performance regime in which cycle-averaged lift and lift-to-drag increase abruptly. This transition coincides with intermittent exposure of the membrane to higher-momentum fluid and a pronounced amplification of deformation. A frequency-resolved analysis, combined with a body-frame Fourier mode decomposition of the flow, identifies four distinct flapping states, namely a wake-dominated state, two flapping-dominated states associated with lift reduction and lift gain and a two-way lock-in state. In the latter, vortex shedding locks onto the imposed actuation, while the first fluid-loaded structural mode approaches the actuation frequency, producing selective amplification of low-order deformation. The resulting curvature-induced camber intensifies leading-edge suction and increases the cross-membrane pressure difference, establishing feedback that reorganises upstream shedding. Motivated by these mechanisms, we derive scaling relations for the cycle-averaged lift, drag and power that separate quasi-steady motion, added-mass effects, curvature-induced contributions, wake-momentum deficit and transverse shear. For the present reference compliance, the scaling clarifies how flexibility is detrimental when the membrane remains fully immersed within the wake core, yet beneficial when intermittent wake exposure permits passive camber amplification to offset momentum deficit with limited drag penalty. These results provide a mechanistic framework for the present reference-compliance configuration and identify how wake exposure, imposed heaving and membrane response combine to produce two-way lock-in.
Vortex-induced vibration forever (VIVF) is classically associated with a single elastically mounted cylinder, for which oscillations persist at infinite reduced velocity when the mass ratio ($m^*$) falls below a critical value ($m_{cr}^*$). The existence and characteristics of such permanent vibration under unsteady wake conditions remain unclear. This study investigates the vibration response of an extreme-light cylinder placed in the wake of an upstream fixed cylinder without restoring forces, with particular emphasis on the existence and variation of a critical mass ratio $m_{cr}^*$ with the spacing ratio ($L/D$). The Reynolds number is set to 60, the mass ratio $m^*$ ranges from 0.2 to 14 and the spacing ratio $L/D$ ranges from 1.1 to 6.0. Three vibration regimes are identified in the $(L/D,\, m^*)$ parameter space: non-vibration (NV), limited-range vibration (LRV) and infinite-range vibration (IRV). A critical mass ratio $m_{cr}^*$ emerges at the LRV–NV boundary, where the vibration amplitude continuously diminishes to zero as $m^*$ approaches $m_{cr}^*$, in contrast to the abrupt transition observed in single-cylinder VIVF; this extinction coincides with the disappearance of the second-order flow mode. Furthermore, $m_{cr}^*$ is governed by the spacing ratio relative to the vortex formation length $L_{\!f}/D$ of a stationary cylinder: when $L/D \lt L_{\!f}/D$, $m_{cr}^*$ increases with $L/D$, whereas for $L/D \gt L_{\!f}/D$, it decreases with further increase in $L/D$. In contrast, within the IRV regime the flow maintains persistent co-shedding behaviour and no critical mass ratio is observed within the investigated $m^*$ range, indicating that wake interference reshapes the stability boundary of the system.
Social isolation and loneliness are recognised as important risk factors for various health outcomes. However, their impact on functional bowel disorders (FBDs) remains underexplored.
Aims
To explore the associations of social isolation and loneliness with the risk of FBDs in a large prospective cohort.
Method
We included 396 009 participants from UK Biobank who were free of cancer and FBDs at baseline. Social isolation and loneliness were assessed using validated self-reported questionnaires. Incident FBDs were ascertained during follow-up. Cox proportional hazards models were used to estimate hazard ratios and 95% CIs. Mediation, subgroup and sensitivity analyses were conducted.
Results
Over a mean follow-up of 15.2 years, 31 877 incident FBDs cases were recorded. Compared with the least isolated, the most isolated had a higher risk of FBDs (hazard ratio 1.15, 95% CI 1.11–1.20). Loneliness was also associated with higher risk (hazard ratio 1.28, 95% CI 1.21–1.35). The highest risk was observed among participants who were most isolated and lonely (hazard ratio 1.46, 95% CI 1.33–1.60). Depression, anxiety and low physical activity partially mediated the associations between social isolation/loneliness and FBDs. The association between social isolation and FBDs risk appeared stronger among male, overweight and unemployed individuals, whereas middle-aged adults were more susceptible to loneliness-related risk.
Conclusions
Social isolation and loneliness were associated with a higher risk of FBDs, particularly when co-occurring. These findings underscore the potential relevance of social disconnection to FBDs and suggest that it may represent a target for future preventive strategies.
Exhumation-induced stress triggers natural hydraulic fracturing, governing fluid overpressure limits in deeply buried strata. In the Sichuan Basin (South China), the geomechanical response of Lower Cambrian shale to multi-phase differential exhumation remains poorly quantified. We integrated apatite and zircon thermochronology, vitrinite reflectance, residual stratal thickness, and Skempton’s poroelastic model to reconstruct the exhumation and pore pressure history of the Qiongzhusi Formation. Results reveal a four-stage, northwestward-migrating exhumation since the Cretaceous, featuring severe uplift (3000–4000 m) along basin margins and the Weiyuan anticline, versus moderate uplift (2000–2500 m) in the Ziyang intra-basin area. This differential exhumation halted thermal evolution, establishing a spatial thermal maturity distribution (VR = 3.2%–4.0%) and a lower boundary at ∼5500 m, below which graphitization degrades rock properties. Crucially, differential exhumation magnitude and varying initial pore pressures at maximum burial (∼7000 m) governed stress trajectories during uplift. Driven by higher initial pressure, the moderately exhumed Ziyang area reached the natural fracturing threshold at 4100 m, significantly deeper than the heavily exhumed Weiyuan area (3250 m). These critical failure depths mechanistically define the upper limits for overpressure preservation, demonstrating that differential exhumation and poroelastic relaxation fundamentally control the vertical boundaries of overpressured shale compartments.
Coarctation of the aorta is a congenital cardiovascular disease with focal aortic luminal narrowing, and paediatric patients face a high postoperative restenosis risk. This study aimed to develop and validate an interpretable machine learning model for early predicting restenosis after paediatric coarctation of the aorta direct repair using preoperative and intraoperative data.
Methods:
A total of 117 patients (2016–2024) were retrospectively enrolled, divided into restenosis (21 cases, 17.9%) and non-restenosis (96 cases, 82.1%) groups (restenosis was defined as a peak systolic pressure gradient >20 mmHg measured by echocardiography). Recursive feature elimination with cross-validation screened key variables; six machine learning models were built with 5-fold randomised search cross-validation tuning, using the area under the curve as the primary metric. SHapley Additive exPlanation analysed feature contributions.
Results:
The multilayer perceptron model performed best (mean area under the curve = 0.8333, 95% CI: 0.7111–0.9555, accuracy = 0.8376) with balanced precision-recall. SHapley Additive exPlanation identified low body surface area as the top risk factor. Resection and extended end-to-end anastomosis/end-to-side anastomosis were preferred surgically, while resection with end-to-end anastomosis should be avoided; end-to-side anastomosis reduced restenosis risk in patients with aortic arch hypoplasia.
Conclusion:
Machine learning models enable personalised, high-accuracy restenosis prediction. SHapley Additive exPlanation-facilitated risk factor identification optimises treatment strategies. Future prospective studies are needed to validate the models and develop clinical tools.
The carbon isotopic compositions (δ13C and Δ14C) of dissolved inorganic carbon (DIC) in water samples are influenced by various storage conditions, but the extent and mechanisms of these changes remain unclear. In this study, we systematically evaluated the effects of storage temperature, pretreatment (filtration and addition of mercuric chloride, HgCl2), and container material (glass vs. plastic) on δ13CDIC and Δ14CDIC. The δ13CDIC values in samples preserved with HgCl2 exhibited the smallest variation (δ13CDICmax−δ13CDICmin ranging from 0.7‰ to 1.0‰), followed by those stored under refrigeration (∼4°C; variations of 1.3‰ to 1.4‰). These storage conditions also effectively constrained variations in Δ14CDIC over storage periods of up to 60 days in polyethylene terephthalate (PET) bottles. In contrast, comparisons with glass bottles, combined with analysis of PET-derived compounds and associated enzymatic activity, indicated that the degradation of PET-derived compounds provided a plausible explanation for the observed radiocarbon depletion. For long-term storage (>110 days), isotopic fractionation was primarily governed by exchange between DIC and atmospheric CO2, attributable to the permeability of PET bottles. This study provides a quantitative, mechanism-based assessment of storage-induced effects on δ13CDIC and Δ14CDIC, offering practical guidance for minimizing storage-induced uncertainty in carbon isotopic studies.
Environmental constitutionalism refers to the growing constitutional recognition of the environment. Given the diverse designs of constitutional environmental provisions across the world, environmental constitutionalism is construed broadly to reflect both rights and non-rights provisions related to environmental protection. The constitutional entrenchment of environmental rights is the most common expression of environmental constitutionalism. Yet, such a purely rights-based approach ignores the distinctive constitutional design formulated as non-rights directive principles. Central to this debate is the perceived appropriateness, or inappropriateness, of treatment by courts of directive principles as if they are judicially enforceable rights. By exploring the limitations of this twofold division of environmental constitutionalism into conventional rights and directive principles, this article argues that such an approach positions the enforcement of environmental constitutionalism into the binaries of courts versus legislatures. However, environmental constitutionalism should be repositioned towards a collaborative model, the achievement of which requires interactive dynamics among the legislature, the executive, and the judiciary. Through a relational perception of separation of powers, this article offers an innovative understanding of environmental constitutionalism by integrating environmental governance with the values of constitutional collaboration, within which shared responsibility for enforcement is placed among the separated powers.
Passive exoskeletons offer several advantages, including lightweight design, simple structure, and inherent energy efficiency. Most existing passive exoskeletons rely on clutch mechanisms to control spring-based energy storage and release, typically focusing only on recovering biomechanical energy during the stance phase of gait. In this study, we propose and analyze a lightweight passive ankle exoskeleton capable of harvesting and releasing energy during both the stance and swing phases of walking. The device aims to enhance gait assistance while maintaining structural simplicity and minimizing weight. By integrating the optimal stiffness ratio between the stance and swing phases, derived from musculoskeletal model simulations, with previously established optimal stance-phase stiffness parameters, we determined a suitable stiffness coefficient for the swing-phase spring. To validate the design, we conducted comparative experiments on participants walking with exoskeletons configured with different stiffness coefficients. Spatiotemporal parameters, metabolic energy cost, and muscle activation patterns were analyzed to evaluate performance. The results demonstrate that the proposed exoskeleton effectively reduces Soleus muscle activation while increasing tibialis anterior activity, leading to a 6.84% reduction in walking energy cost compared to a nonassistive condition. Furthermore, energy recovery during the swing phase alone contributes an additional 1.67% reduction in energy expenditure, improving overall walking efficiency. The proposed design also eliminates complex clutch components, significantly simplifying manufacturing and reducing costs, thereby enhancing the applicability of passive exoskeletons in daily mobility and rehabilitation scenarios.
Schizophrenia is a chronic psychiatric disorder associated with significantly elevated mortality. While antipsychotics are the cornerstone of treatment, their long-term effects on survival remain uncertain, particularly in non-Western populations. We aimed to assess the real-world association between antipsychotic treatment patterns and all-cause mortality among adults with schizophrenia in China.
Methods
This population-based cohort study included 435,816 adults from the Community Schizophrenia Registry System of Guangdong Province, China. Patients were classified into four groups: antipsychotic monotherapy, polytherapy, non-antipsychotic treatment and non-drug treatment. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) for mortality.
Results
Over a median follow-up of 7.2 years, 73,527 deaths (16.9%) occurred. Antipsychotic polytherapy (57.6%) was the most common regimen, followed by monotherapy (27.6%). Compared with the non-drug group, mortality risks were significantly lower for polytherapy (aHR: 0.18; 95% CI: 0.18–0.19), monotherapy (aHR: 0.24; 95% CI: 0.24–0.25) and non-antipsychotic treatment (aHR: 0.22; 95% CI: 0.21–0.23). Both first- and second-generation antipsychotics showed comparable mortality benefits. While most polytherapy regimens performed similarly to or better than monotherapy, combinations like risperidone–sulpiride were associated with higher mortality. Subgroup analyses showed stronger benefits in women, younger individuals, rural residents and those with less severe illness.
Conclusions
Antipsychotic treatment is associated with significantly reduced mortality among patients with schizophrenia in China, with effects varying by patient characteristics and drug regimen.
Obesity is a well-established risk factor for major depressive disorder (MDD), yet the risk is not uniform, highlighting the need for precise risk stratification. This study aimed to develop a metabolomics-based prediction model to identify high-risk metabolic phenotypes among obese participants and to elucidate the causal metabolic pathways involved.
Methods
Forty-one-thousand-four-hundred-fifty-nine obese participants were followed for a median of 14.4 years. We integrated multiple machine learning (ML) algorithms to develop predictive models for 3-, 5-, and 9-year MDD risk, with a temporal validation within the same biobank. Furthermore, we investigated the potential causal relationships within the obesity-metabolite-MDD using mediation Mendelian randomization (MR).
Results
During follow-up, 3,642 incident MDD cases were documented. The optimized LightGBM model demonstrated superior predictive performance, achieving AUCs of 0.844 (95% CI: 0.773–0.914), 0.824 (95% CI: 0.771–0.875), and 0.834 (95% CI: 0.796–0.871) for 3-, 5-, and 9-year intervals, respectively, significantly outperforming existing clinical models. Temporal validation confirmed the model’s robustness (AUCs: 0.738–0.776). MR analysis confirmed that key metabolites causally mediate the pathway from obesity to MDD (mediation proportions: −11.5% and −35.3%, all PME < 0.05).
Conclusions
These findings challenge the notion of a uniform obesity–MDD association, demonstrating that metabolomic signatures can effectively stratify MDD risk. We present a validated ML framework for the early identification of high-risk individuals with obesity, offering a precision medicine approach to guide targeted metabolic and psychiatric interventions.