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Effects of apple phenolics on the human metabolome: modulation of key metabolic pathways.

Apples are widely recognized for their potential health benefits, partly attributed to their phenolic compounds. However, their impact on human metabolism remains incompletely understood. This study investigated metabolic effects of apple-derived phenolic compounds using untargeted metabolomics approach across multiple biofluids. In a crossover intervention study, 30 healthy men consumed a phenolic-rich apple juice or a placebo for two weeks. Blood, urine and saliva samples were collected before and after each intervention and analyzed by direct infusion ultra-high resolution mass spectrometry. Consumption of apple phenolic compounds resulted in significant alterations of the human metabolome, including increased levels of phenolic-derived degradation products and microbial-associated metabolites across all biofluids. Pathway enrichment analysis revealed pronounced effects on phenylalanine and tyrosine metabolism, as well as linoleic and arachidonic acid metabolism, Overall, these findings demonstrate that apple phenolic compounds induce measurable, microbiota-associated and systemic metabolic changes, providing new insights into their metabolic fate and biological relevance.

Humans

Development of a cell-based nanoluciferase reporter system for high-throughput screening of HBV cccDNA inhibitors.

Hepatitis B virus (HBV) persistence is sustained by the viral covalently closed circular DNA (cccDNA) minichromosome, which remains a major barrier to curative antiviral therapies. The lack of reliable quantitative cccDNA detection methods and surrogate markers has hindered efforts to target cccDNA in antiviral high-throughput screening (HTS). Here, we established a novel inducible cccDNA-dependent nanoluciferase (NLuc) reporter cell line, designated HepBLE12, by inserting an in-frame 11-amino acid split-NLuc HiBiT tag into the precore (pC) coding region of an HBV transgene. The resulting 1.3-kDa HiBiT tag on pC serves as the detection module of the split NLuc system, generating quantitative luminescence upon high-affinity complementation with the cognate 18-kDa LgBiT subunit in cell lysates. Notably, the HiBiT assay enables direct detection of intracellular HiBiT-pC protein rather than secreted HBeAg, providing a reporter signal more closely linked to cccDNA activity. HepBLE12&#x202f;cells exhibited inducible and robust viral DNA replication, and the cccDNA-dependent HiBiT signal was validated under diverse experimental conditions that modulate cccDNA formation or transcription. We further miniaturized the assay to a 384-well format and optimized key parameters following standard HTS assay development practices. The assay was successfully automated and demonstrated excellent performance in a multi-day variability study and a pilot screen, with signal-to-background (S/B)&#x202f;&#x2248;&#x202f;9, coefficient of variance (CV)&#x202f;<&#x202f;10%, and average Z-factor value of 0.74, exceeding canonical HTS quality benchmarks. Together, the HepBLE12 cell-based HTS platform provides a robust and practical tool for identifying inhibitors targeting HBV cccDNA.

Hepatitis B virus

Unconfined compressive strength prediction for the ordinary Portland cement-steel slag-silica fume ternary system based on response surface methodology.

This research was undertaken to address environmental concerns associated with industrial solid waste and to reduce cement consumption in geotechnical engineering. It specifically investigates the feasibility of using steel slag (SS) and silica fume (SF) as partial substitutes for ordinary Portland cement (OPC) in soil stabilization. The effects of SS, SF, OPC, and initial moisture content on the unconfined compressive strength (UCS) of stabilized soil were investigated through single-factor experiments and response surface methodology (RSM). The results show that SS and SF can synergistically enhance the strength of stabilized soil, although their interaction effect was not statistically significant within the investigated ranges. Compared with soil stabilized solely with OPC, the addition of 18 % SS and 10 % SF reduced OPC consumption by 3 % without compromising strength. Microstructural and compositional analyses further revealed that SS mainly supplied calcium- and silica-bearing components, while SF provided highly reactive silica and micro-filling effects, jointly promoting hydration reactions and improving the compactness of the stabilized soil matrix. As a result, more hydration products were formed in the OPC/SS/SF-stabilized soil than in the OPC-stabilized soil, which contributed to pore filling and strength enhancement. This study provides useful guidance for the sustainable utilization of industrial solid waste and the low-carbon development of soil stabilization materials.

Construction Materials

Unraveling the Clinical Spectrum of DNASE1L3 Deficiency: Insights from Case Series and Systematic Literature Review.

BACKGROUND: DNASE1L3 deficiency is a rare monogenic cause of lupus and lupus-like autoimmunity resulting from impaired extracellular DNA clearance and sustained immune activation. Although most reported patients present with early-onset systemic lupus erythematosus (SLE), emerging evidence suggests broader phenotypic variability, including vasculitic and overlap manifestations. Whether these presentations represent distinct clinical entities or a continuum of DNASE1L3-associated immune dysregulation remains unclear. We aimed to define the clinical spectrum of DNASE1L3 deficiency and examine the relationship between recurrent pathogenic variants and disease severity. METHODS: We conducted a combined pediatric case series and systematic literature review. Four children with genetically confirmed biallelic DNASE1L3 variants followed at a tertiary pediatric rheumatology centre were retrospectively analysed for clinical, immunological, genetic, treatment, and outcome data. In parallel, a systematic search of PubMed/MEDLINE, Scopus, and Web of Science identified previously reported patients with confirmed biallelic pathogenic or likely pathogenic DNASE1L3 variants and extractable patient-level clinical data. To facilitate cross-case comparison, we applied an exploratory three-tier descriptive framework reflecting increasing disease severity: vasculitic or organ-limited disease (G1), systemic lupus or overlap phenotypes without irreversible organ damage (G2), and severe systemic organ-damaging disease (G3). The assigned grades were descriptive rather than permanent categories, as some patients may meet the criteria for a higher grade if broader systemic manifestations or irreversible organ damage develop during follow-up. FINDINGS: Fifteen reports provided extractable patient-level data, corresponding to 45 unique previously reported patients after accounting for known or probable overlapping reports. Combined with four patients from our centre, the analysis included 49 genetically confirmed individuals. SLE-dominant disease was the most frequent phenotype (27 [60%] of 45), followed by hypocomplementaemic urticarial vasculitis/HUVS-dominant disease (10 [22.2%]) and overlap phenotypes (8 [17.8%]). Renal involvement was reported in 30 (66.7%) of 45 patients, and disease onset occurred by age 3&#xa0;years in 20 (44.4%). Persistent hypocomplementemia affecting C3 and C4 was frequently reported across the spectrum. Recurrent DNASE1L3 variants were observed across multiple phenotypic and severity grades. Variants such as p.Asn191Ser and p.Thr97Ilefs*2 occurred in patients spanning organ-limited vasculitic disease, lupus overlap phenotypes, and severe multisystem lupus with major organ involvement. CONCLUSION: DNASE1L3 deficiency was associated with a broad clinical spectrum of immune-mediated disease rather than a single clinicopathological entity. The occurrence of identical pathogenic variants across distinct phenotypic and severity states argues against a simple genotype-phenotype model and suggests that additional modifiers influence disease expression.

Humans

A system-level metastable model of cancer evolution: integrating replication stress, cell cycle deregulation and chromosomal instability.

INTRODUCTION: Cancer cell proliferation occurs within the context of persistent genomic instability. In this review, we propose the RS-CCD-CIN axis as a systems-level framework in which replication stress (RS), cell cycle deregulation (CCD) and chromosomal instability (CIN) form an interdependent triad that shapes tumour evolution. This axis represents a constrained metastable state in which genomic instability is tolerated and buffered. The objective of this review is to synthesize the current understanding of how the RS-CCD-CIN axis contributes to tumour heterogeneity, adaptability and therapy response. DISCUSSION: Evidence indicates that RS, CCD and CIN operate as a dynamic, interconnected network rather than as independent processes. Replication stress induces DNA damage and mutagenesis, while partial checkpoint disruption permits cells with unresolved lesions to proliferate. Chromosomal instability generates both structural and numerical alterations, contributing to intratumoural heterogeneity. Together, these processes facilitate adaptation to environmental and therapeutic pressures. Extrachromosomal DNA, micronuclei formation and cytosolic DNA signalling, including the cGAS-STING pathway, connect genomic instability to adaptive responses and immune modulation. Single-cell and spatial profiling reveal temporal and spatial variability in RS, CCD and CIN states, highlighting the limitations of static biomarkers. Therapeutically, targeting individual components often yields limited durability, whereas approaches that simultaneously perturb multiple aspects of the RS-CCD-CIN axis may improve clinical outcomes. CONCLUSIONS: This review highlights the RS-CCD-CIN axis as a fragile and metastable architecture that supports cancer evolution, while also being susceptible to collapse. A deeper understanding of this interconnected framework may inform the development of therapeutic strategies and enhance the management of resistance.

Humans

Perioperative care for patients with opioid exposure and opioid use disorder: screening and treatment strategies.

PURPOSE OF REVIEW: The prevalence of opioid tolerance, dependence, and use disorder is increasing among patients presenting for surgical care, yet perioperative management strategies for these patients remain inconsistent. This review examines the impact of preoperative opioid exposure on surgical outcomes, the scope of untreated opioid use disorder (OUD) among surgical patients, and advances in clinical and systems-level approaches to perioperative care. RECENT FINDINGS: Preoperative opioid exposure independently predicts worse surgical outcomes, including higher opioid consumption, readmissions, complications, and mortality, in a dose-dependent manner. Perioperative opioid exposure predicts persistent opioid use after surgery, with the duration of exposure a stronger predictor of subsequent OUD than daily dose. Data-driven prescribing guidelines and structured opioid tapering reduce overprescribing without compromising pain control. Among surgical patients with diagnosed OUD, approximately two-thirds do not receive medications for opioid use disorder (MOUD), though treatment engagement and maintenance substantially improve outcomes. Evidence now clearly supports perioperative buprenorphine continuation over interruption. SUMMARY: Effective perioperative management of opioid-complex surgical patients requires systematic screening, evidence-based prescribing, MOUD continuation, and institutional infrastructure. The primary barrier is shifting from evidence generation to implementation.

Humans

Impact of Integrated Continuous Team Midwifery Care on Breastfeeding Success within the Iranian Health System: A Randomized Controlled Trial.

INTRODUCTION: Supporting women during the perinatal period helps build confidence, strengthens early bonding between mother and baby, and encourages successful breastfeeding. Continuous midwifery care models are one of the ways that support women in this periods. OBJECTIVE: This study aimed to evaluate the effect of integrated continuous team midwifery care (ICTMC) in enhancing breastfeeding success in the Iranian health system. METHODS: In this randomized controlled trial, 200 low-risk primiparous women with a gestational age of less than 12 weeks were recruited from public health centers. Participants were randomly assigned to either the intervention group, which received continuous midwifery care throughout pregnancy, childbirth, and postnatal follow-up, or the control group, which received routine care. The primary outcomes were early skin-to-skin contact and breastfeeding success at the time of discharge and at 4-6 weeks postpartum. Data were analyzed using Stata, employing descriptive statistics, Chi-square, independent t-test, Phi/Cramer's V, and Cohen's d. The p < 0.05 is significant. Data were analyzed with SPSS 26. RESULTS: ICTMC groups were significantly more likely to initiate skin-to-skin contactearly skin-to-skin contact immediately after birth (92% vs. 74%, p < 0.001) and achieve successful breastfeeding at the discharge time (88% vs. 70%, p = 0.002) compared to the control group. At 6 weeks postpartum, breastfeeding success remained higher in the intervention group (82% vs. 65%, p = 0.004). CONCLUSION: Women with ICTMC, effectively support skin-to-skin contactearly mother-infant bonding and enhance breastfeeding success among low-risk primiparous women. Integrating this model into routine maternal care may improve perinatal outcomes.

Humans

Urban stormwater infrastructure as a microplastic superhighway: a critical review of transport dynamics, modelling, and mitigation across pavements and drainage networks.

This review examines the transport, fate, modelling, and mitigation of Microplastics (MPs) in urban stormwater infrastructure, with emphasis on pavements, runoff pathways, micro-drainage, and macro-drainage systems. Following a systematic review approach, more than 1000 records were screened and approximately 50 core studies were retained when they addressed urban stormwater or drainage-related MP transport with adequate methodological reporting; marine-only studies and biological-effect studies without direct relevance to transport processes were excluded. The evidence shows that stormwater systems function not merely as passive conduits but as dynamic reactive transport systems with temporary storage, where particle mobilisation, sedimentation, resuspension, and temporary retention regulate MP export. Road surfaces, especially high-traffic areas, are major reservoirs of tyre wear, road-marking, atmospheric, and litter-derived particles that are rapidly mobilised during rainfall. Conventional grab sampling may underestimate MP loads, which in some cases exceed treated wastewater effluent loads by up to six-fold. Drainage structures such as manholes can immobilise up to 17.3% of near-neutrally buoyant particles, while biofouling and aggregation may shift buoyant polymers from wash-load to bedload. Mitigation systems, including permeable pavements, bioretention, wetlands, and technical inserts, can achieve high removal of coarse MPs, but performance declines for fine particles below 100&#xa0;&#xb5;m. The review highlights the need for standardised flow-proportional sampling, physically informed modelling, and treatment-train strategies targeting both surface sources and in-network storage.

Microplastics

Modelling peak microbial pollution events caused by combined sewer overflows in a source-to-sea system.

Predicting peak microbial pollution events in downstream coastal bathing waters caused by combined sewer overflows (CSOs) is essential for protecting public health. In urban areas, wastewater effluents, CSOs, and surface runoff can contribute to elevated microorganism loads to downstream waters. These pressures are likely to be intensified by growing population density and more frequent heavy rainfalls due to climate change. This study developed a process-based model to simulate Escherichia coli (E. coli) emissions, transport, and fate from the initial sources to coastal beaches. A three-year retrospective simulation (2017-2019) shows that E. coli concentrations in CSO discharges varied widely across the catchment (4.6 - 7.3 (log10&#xa0;CFU 100&#xa0;ml-1)). 99th percentile E. coli concentrations (4.0 (log10&#xa0;CFU 100&#xa0;ml-1)) at the inland water outlet were dominated by local CSO emissions, whereas 90th percentile E. coli concentrations (3.6 (log10&#xa0;CFU 100&#xa0;ml-1)) reflected cumulative upstream contributions from both CSO and effluent emissions. With the simulation accuracy of 89%, the model reliably reproduced the E. coli dynamics on the downstream beach and showed strong performance in representing peak concentrations based on Complementary Cumulative Distribution Function (CCDF) analysis. The process-based model enables quantitative tracking of source contributions and identification of pollution hotspots, providing support for mitigation measures. The study lays down a source-to-sea modelling framework for representing pollution transport across the aquatic continuum and provides a transferable tool for microbial pollution forecasting and climate adaptation planning.

Climate projection

Dual signal-enhanced immunochromatographic test strip based on Au@PtNPs: From sensitive detection of thiamethoxam to multiplex pesticide screening in vegetables.

Immunochromatographic test strip (ICTS) is a rapid analytical technique widely used in environmental and food detection owing to its merits of simple operation and short analysis time. Herein, three-dimensional nanoflower-structured gold&#x2011;platinum nanoparticles (Au@PtNPs) were synthesized via a seed-growth method. Compared with conventional gold nanoparticles (AuNPs), Au@PtNPs exhibited stronger signal intensity, excellent catalytic performance, and efficient antibody binding efficiency. Colorimetric Au@PtNPs-ICTS and catalytic colorimetric Au@PtNPs-ICTS were developed for the sensitive detection of thiamethoxam (THI) in vegetables. The limits of detection (LODs) for colorimetric Au@PtNPs-ICTS and catalytic colorimetric Au@PtNPs-ICTS quantitative analysis were 0.18&#xa0;ng/mL and 0.093&#xa0;ng/mL, respectively, representing approximately 3-fold and 6-fold improvement compared to AuNPs-ICTS (0.56&#xa0;ng/mL). Furthermore, highly sensitive detection of multiple pesticide residues (chlorpyrifos, acetamiprid, and imidacloprid) was achieved by replacing the corresponding target antigens and antibodies, which further verified the universality of this immunochromatographic strategy.

Thiamethoxam

CNNM2 in schizophrenia: multilevel evidence of genetic susceptibility, magnesium homeostasis, neurodevelopment and cognitive dysfunction.

Schizophrenia (SCZ) is a common psychiatric disorder with a complex, genetically and environmentally influenced etiology, but the specific pathogenesis remains unclear. In recent years, the SCZ susceptibility gene CNNM2 (encoding cyclin M2) located at the 10q24.32-33 locus has received widespread attention. The well-validated SCZ risk interval 10q24.32-33 harbors two independent risk variants: rs11191580 in NT5C2 (significantly associated with CNNM2 mRNA and protein levels) and rs7914558 in CNNM2. Results from functional genomic analyses indicate that lower CNNM2 expression is significantly associated with SCZ. Imaging genetics studies have demonstrated that carriers of risk alleles of CNNM2 SNPs exhibit alterations in brain structure. Animal model studies have revealed that Cnnm2 downregulation in mice leads to impairments in sensorimotor gating and cognitive function. As an Mg2+ transporter, CNNM2 primarily maintains systemic Mg2+ homeostasis. According to clinical studies, a proportion of patients with SCZ exhibit reduced Mg2+ concentrations in plasma and cerebrospinal fluid. CNNM2 dysfunction may contribute to the pathology of SCZ by disrupting Mg2+ homeostasis, thereby affecting neurodevelopment and synaptic plasticity. A systematic consolidation of current evidence supporting the involvement of CNNM2 in SCZ pathogenesis provides a direction for further investigation of the pathological mechanisms underlying this disease, and for identification of novel targets for clinical intervention..

Schizophrenia

Comparison of the predictive performance of systemic immune-inflammation index and neutrophil-to-lymphocyte ratio for three-month poor functional outcome in ischemic stroke: a systematic review and meta-analysis.

INTRODUCTION: Ischemic stroke (IS) is a leading cause of global mortality and disability. Early and accurate prognosis is crucial for patient management. The neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) are emerging inflammatory biomarkers; however, their relative predictive value for three-month poor functional outcome (modified Rankin Scale [mRS]&#x2009;>&#x2009;2) remains uncertain. METHODS: We systematically searched PubMed, Embase, Web of Science, and the Cochrane Library up to 20 July 2025, adhering to PRISMA guidelines. Observational studies reporting the association of SII or NLR with three-month poor outcome were included. Study quality was evaluated using the Newcastle-Ottawa Scale. Area under the curve (AUC), odds ratios (OR), and standardized mean differences (SMD) were pooled using random-effects models in Stata 16.0. RESULTS: Twenty-one studies involving 7520 IS patients were analysed. NLR demonstrated marginally superior discriminative ability compared to SII (AUC 0.71, 95% CI: 0.67-0.76 vs. 0.68, 95% CI: 0.64-0.71), though this difference was not statistically significant. Elevated NLR was significantly associated with poor outcome (OR = 1.26, 95% CI: 1.17-1.37, p&#x2009;<&#x2009;.001), whereas SII was not (OR = 1.00, 95% CI: 1.00-1.00, p&#x2009;=&#x2009;.384). Both markers showed moderate effect sizes (SMD: NLR = 0.69, SII = 0.72; p&#x2009;<&#x2009;.001). NLR performed better in non-intervention and Chinese subgroups, while SII exhibited consistent AUC values across treatment and ethnic subgroups. CONCLUSION: NLR and SII are accessible prognostic markers in IS. NLR demonstrates superior accuracy and a significant association with poor outcome, while SII shows greater stability across patient subgroups. Both may assist in risk stratification, in resource-limited settings.

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

Closed-loop vasopressor systems for hemodynamic control in perioperative and critical care settings: a systematic review and meta-analysis.

Maintaining mean arterial pressure (MAP) within a predefined target is central to haemodynamic management in surgical and critically ill adults receiving vasopressors. Closed-loop vasopressor (CLV) systems automate titration to optimise blood pressure control, but their clinical effectiveness remains uncertain. We performed a systematic review and meta-analysis comparing CLV with manual titration. This PRISMA 2020-compliant review was prospectively registered in PROSPERO (CRD420250655697). MEDLINE, Embase, Scopus, Web of Science, CENTRAL, and the Cochrane Library were searched (January 2000-June 2025). Randomised controlled trials enrolling adults receiving vasopressors in perioperative or intensive care settings were included. Primary outcomes were time within the MAP target range and time spent in hypotension or hypertension. Risk of bias was assessed using RoB 2.0 and certainty of evidence using GRADE. Random- or fixed-effects models were selected according to heterogeneity. Six randomized controlled trials (215 patients) were included in the systematic review, whereas five perioperative trials contributed to the meta-analysis of haemodynamic control outcomes, and one ICU-based study was summarized narratively because it did not report comparable MAP control endpoints. CLV increased time within the MAP target range (mean difference [MD] 33.94%, 95% CI 20.41-47.46; I2&#x2009;=&#x2009;77%) and reduced time in hypotension (MD&#x2009;-&#x2009;18.24%, 95% CI&#x2009;-&#x2009;28.95 to&#x2009;-&#x2009;7.53; I2&#x2009;=&#x2009;73%). There was no significant difference in time in hypertension, cumulative norepinephrine dose, or major/minor adverse events. ICU length of stay was not pooled because of clinical and methodological heterogeneity. Certainty of evidence ranged from low to high (moderate for haemodynamic control outcomes). CLV systems improved haemodynamic control, primarily in perioperative settings,&#xa0;but heterogeneity and small samples limit confidence in effect size and generalisability.&#xa0;Evidence in critically ill populations remains limited, and larger trials are needed to determine whether improvements in these physiological surrogate endpoints translate into meaningful patient-centred outcomes.

Humans

The Impact of Baseline Negative Emotions on Postoperative Quality of Life in Adolescent Idiopathic Scoliosis Patients: A 2-Year Follow-Up Study.

OBJECTIVE: Adolescent idiopathic scoliosis (AIS) is a three-dimensional spinal deformity that develops during puberty without a clear etiology. Beyond physical manifestations, AIS severely impacts adolescents' psychological and social well-being, leading to anxiety, depression, and low self-esteem. While advancements in surgical techniques have enhanced objective outcomes, existing studies on AIS have primarily focused on objective indices, with limited attention to the long-term impact of preoperative negative emotions on patient-reported subjective quality of life. METHODS: This was a retrospective cohort study. A total of 112 eligible AIS patients who underwent posterior spinal correction surgery between April and August 2023 were enrolled. Inclusion criteria included confirmed AIS, completion of 2-year follow-up, and informed consent; exclusion criteria included missing imaging/questionnaire data, comorbid psychiatric/neurological diseases, or prior spinal surgery. Patients were grouped using the Hospital Anxiety and Depression Scale (HADS) administered on admission. Quality of life was assessed preoperatively and 2&#x2009;years postoperatively using the Scoliosis Research Society-22 (SRS-22, evaluating self-image, mental health, pain, function, treatment satisfaction) and Short Form 36 Health Survey (SF-36, assessing 8 physical and mental health dimensions). Statistical analysis was performed via SPSS, using independent t-tests, paired t-tests, Mann-Whitney U test, and chi-square test. p&#x2009;<&#x2009;0.05 was considered significant. RESULTS: There were no significant differences in baseline characteristics (age, gender, BMI, surgical parameters, scoliosis type, preoperative/postoperative Cobb angles) between the two groups (all p&#x2009;>&#x2009;0.05). Preoperatively, SRS-22 and SF-36 scores showed no inter-group differences (all p&#x2009;>&#x2009;0.05). Postoperatively, the Negative Emotion Group had significantly lower scores in SRS-22 mental health (3.9&#x2009;&#xb1;&#x2009;0.3 vs. 4.5&#x2009;&#xb1;&#x2009;0.2) and treatment satisfaction (4.0&#x2009;&#xb1;&#x2009;0.3 vs. 4.6&#x2009;&#xb1;&#x2009;0.7), as well as SF-36 general health (68.6&#x2009;&#xb1;&#x2009;6.4 vs. 79.7&#x2009;&#xb1;&#x2009;13.3), role-emotional (61.3&#x2009;&#xb1;&#x2009;9.3 vs. 70.8&#x2009;&#xb1;&#x2009;9.7), and mental health (61.8&#x2009;&#xb1;&#x2009;14.3 vs. 68.9&#x2009;&#xb1;&#x2009;10.7) (all p&#x2009;<&#x2009;0.05); no inter-group differences were observed in physical function-related dimensions. Both groups showed significant improvements in physical function-related dimensions postoperatively. The Non-Negative Emotion Group also exhibited significant improvements in SRS-22 self-image/pain and SF-36 bodily pain (all p&#x2009;<&#x2009;0.05), while the Negative Emotion Group showed no significant improvements in these dimensions. CONCLUSIONS: Preoperative anxiety and depression do not affect the recovery of physical function in AIS patients after spinal correction surgery but significantly impede improvements in subjective quality of life dimensions, including mental health and treatment satisfaction. These findings highlight the need to integrate psychological assessment and targeted interventions into the perioperative management of AIS. Such a patient-centered approach will help optimize both physical and psychological outcomes, ultimately achieving comprehensive rehabilitation for AIS adolescents.

Humans

Risk of stroke in SLE: a systematic review and meta-analysis.

UNLABELLED: The association between SLE and composite stroke, ischaemic stroke and haemorrhagic stroke remains incompletely understood. This meta-analysis aims to assess the risk of stroke in patients with SLE. METHODS: Data sources included PubMed, Embase, the Cochrane Library and reference lists of included studies. This meta-analysis included cohort studies evaluating whether stroke risk is associated with SLE. The risk of bias was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). Risk ratios (RRs) with 95% CIs were pooled using a random-effects model, and publication bias was assessed with funnel plots and Egger's test. RESULTS: A total of 25 cohort studies involving 5&#x2009;220&#x2009;837 individuals were included in this meta-analysis, which were published between 2001 and 2026. The pooled analysis demonstrated a significantly increased risk of stroke in patients with SLE (RR of 2.60, 95%&#x2009;CI 2.21 to 3.05, I&#xb2;=97.9%, p<0.001). The risk of composite stroke (RR of 2.83, 95%&#x2009;CI 2.25 to 3.57, I&#xb2;=98.0%, p<0.001), ischaemic stroke (RR of 2.34, 95%&#x2009;CI 1.75 to 3.12, I&#xb2;=97.6%, p<0.001) and haemorrhagic stroke (RR of 2.66, 95%&#x2009;CI 1.57 to 4.49, I&#xb2;=96.2%, p<0.001) was also increased in SLE. Despite the large heterogeneity, the sensitivity analysis indicated that the results were robust, and there was little evidence of publication bias. CONCLUSION: The risk of composite stroke, ischaemic stroke and haemorrhagic stroke is increased in SLE. PROSPERO REGISTRATION NUMBER: CRD420261294082.

Humans

Probiotic-derived extracellular vesicles as food-based nanocarriers: Mechanisms, functional applications, and future perspectives in food systems.

Probiotic-derived extracellular vesicles (PDEVs) are a promising type of postbiotic nanoparticle derived by fermentation of probiotics, and have gained growing interest as a potential application in food science and nutrition. These are lipid bilayer vesicles of nanoscale, which are naturally released by probiotic cells and contain a wide variety of bioactive molecules, such as proteins, nucleic acids, and metabolites. Moreover, PDEVs are highly stable, biocompatible, and can be easily engineered to have surfaces with high functionality, which makes them good candidates in functional engineering. In contrast to traditional live probiotics, PDEVs overcome the difficulties of preserving microbial viability during processing and storage, thus providing superior safety, stability, and predictable biological performance. This is a systematic review of the various functions of PDEVs in food systems. We conclude on the processes through which PDEVs control intestinal barrier integrity, alter gut microbiota composition, and alter host immune responses, and their potential to enhance gut health when added to functional foods. In addition to their health-promoting effects, PDEVs have shown significant potential as natural antimicrobial agents to preserve food and as effective nanocarriers of hydrophobic bioactive compounds, including fucoxanthin, to improve their stability, bioavailability, and targeted delivery. Moreover, PDEVs can be used as new regulators of microbial fermentation. However, it should be noted that a lot of the evidence that is available is still preliminary and the effectiveness of these applications in real food-processing and storage conditions has not been fully proven. Although they have potential, there are a number of challenges that still hinder the widespread use of PDEVs in the food industry. These involve the creation of scalable and cost-effective production processes, batch-to-batch consistency, vesicle stability in a variety of food matrices, and regulatory and safety considerations. Other emerging engineering approaches, such as surface functionalization and cargo loading, are also discussed in this review and could further increase the specificity, functionality, and application versatility of PDEVs in food systems. Moving forward, the incorporation of PDEVs into the next generation functional foods, novel food preservation methods, and customized nutrition plans should be prioritized in future studies. Further developments in these fields can make PDEVs useful platforms at the interface of food microbiology, nanotechnology, and human health.

Probiotics

Experiences and perceptions of lay bystanders responding to out-of-hospital cardiac arrest: A qualitative systematic review.

BACKGROUND: To synthesize the experiences and perceptions of lay bystanders before, during, and after responding to out-of-hospital cardiac arrests. METHODS: Seven English and Chinese databases were searched from their inception to July 31, 2026, supplemented with citation tracking. Two reviewers independently selected studies, appraised methodological quality using the Joanna Briggs Institute (JBI) critical appraisal checklist for qualitative research, and extracted the findings and supporting illustrations. Unequivocal and credible findings were synthesized using JBI meta-aggregation, and confidence was assessed using confidence in the evidence from reviews of qualitative research. RESULTS: Eight studies involving 209 participants were included. Thirty-three findings were grouped into 12 categories and 4 were synthesized findings concerning the motivators and inhibitors of response, recognition and appraisal of out-of-hospital cardiac arrest, conditions facilitating or impeding cardiopulmonary resuscitation and automated external defibrillator use, and post-event psychological responses and adjustment. Confidence in the evidence from reviews of qualitative research was moderate for the 1st 3 synthesized findings, and low for the 4th. CONCLUSION: Bystander response is a continuum that extends from event recognition and action to post-event adjustment. Out-of-hospital cardiac arrest systems should provide realistic preparations, clear on-scene support, proportionate information, and psychological support after an event.

Humans