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Relationships Between Risky Substance Use and Irritable Bowel Syndrome (IBS) Severity, Mental Health, and Smoking-Related Processes in Adults with IBS Who Smoke.

Objective: Irritable Bowel Syndrome (IBS) is a debilitating chronic pain condition that presents a major and growing public health burden. Combustible cigarette smoking plays a role in the maintenance of IBS, and the co-occurrence of these conditions warrants greater focus. Moreover, given that smoking co-occurs with other substance use behaviors, the impact of these comorbid behaviors on physical and mental health-related outcomes among individuals with IBS who smoke is warranted. The goal of the present cross-sectional study was to assess relationships of risky alcohol, cannabis, and opioid use with IBS severity, anxiety and depression, and smoking-related processes among adults with IBS who smoke. Methods: In total, 263 adults who met Rome IV criteria for IBS and who smoked combustible cigarettes were included in the study. Hierarchical regression analyses were conducted to examine the influence of risky substance uses on IBS symptom severity, IBS-related quality of life, anxiety, depression, perceived barriers for smoking cessation, and cigarette dependence. Results: Results indicated that opioid use was statistically related to all criterion variables, whereas alcohol use was specifically associated with depression and anxiety. Cannabis use showed a statistically significant association only with anxiety symptoms. Conclusions: The present investigation is among the first to explore the role of risky substance use in terms of a wide array of IBS, mental health, and smoking processes among adults with IBS who smoke. The findings suggest that substance use should be a focal point of screening and intervention for the IBS population to optimize outcomes beyond the reach of medical therapies.

Irritable bowel syndrome

Multi-omics analysis reveals stage-associated differences in gut immunity and microbiota between juvenile and adult common carp (Cyprinus carpio).

In vertebrates, the development of intestinal immunity is closely associated with dynamic changes in the gut microbiota. However, stage-associated differences in intestinal immunity and gut microbial communities remain poorly characterized in teleost fish. In this study, transcriptomic analysis combined with 16S rRNA gene sequencing was employed to characterize intestinal immunity and gut microbial communities in juvenile and adult common carp (Cyprinus carpio). Transcriptomic profiling revealed marked developmental differences in intestinal immune function. Juvenile carp exhibited a predominantly innate immune phenotype, characterized by elevated expression of pro-inflammatory cytokines, antimicrobial peptides, and lysozyme-related genes. This immune profile was accompanied by enhanced mucosal barrier function and a relatively pro-inflammatory intestinal environment. In contrast, adult carp displayed increased expression of genes associated with adaptive immunity, suggesting that adult common carp exhibit relatively stronger adaptive immune characteristics than juvenile fish. Gut microbiota analysis demonstrated significant stage-dependent differences in microbial diversity and community composition. Juvenile fish were enriched with bacterial taxa potentially associated with innate immune activation, whereas adult fish harbored distinct microbial communities linked to intestinal homeostasis and barrier maintenance. Furthermore, correlation analyses identified significant associations between specific microbial taxa and innate immune-related gene expression, suggesting a close association between gut microbiota composition and intestinal immune characteristics in juvenile and adult common carp. Collectively, these findings reveal stage-associated differences in intestinal immunity and gut microbial communities between juvenile and adult common carp, thereby providing insights into intestinal immune characteristics at different developmental stages in teleost fish.

Animals

Active Site Assembly by SMG5 as a Mechanism for SMG6 Endonuclease Licencing in Nonsense-mediated mRNA Decay.

Nonsense-mediated mRNA decay (NMD) is a conserved eukaryotic surveillance pathway that eliminates transcripts containing premature termination codons (PTCs). Substantial progress has been made in defining the transcript features that mark aberrant translation termination for NMD activation, yet key mechanistic steps remain incompletely understood - including how recruitment of the central NMD factor UPF1 is coupled to the downstream effector phase in which targeted mRNAs are nucleolytically degraded. In metazoans, NMD employs an endonucleolytic route mediated by SMG6, a PIN-domain nuclease, alongside SMG5 and SMG7, which act downstream of PTC recognition. SMG5 has recently been proposed to licence SMG6 activity, yet the molecular basis of this licencing has remained elusive. Here, we combine AlphaFold structural predictions with biochemical assays to investigate interactions among human SMG5, SMG6, and SMG7. Structural models predict a high-confidence interface between SMG5 and SMG6 PIN domains that forms a composite active site: a conserved SMG5 aspartate (D893) complements the SMG6 acidic triad to reinstate the canonical tetrad required for PIN-domain catalysis. In vitro, SMG6 alone exhibits weak endonucleolytic activity, which is enhanced ∼10-fold by the SMG5 PIN domain. Mutational analyses confirm that conserved residues from both proteins are essential for this composite configuration. Our findings reveal that the SMG5 PIN domain, previously considered catalytically inert, plays a critical role in activating SMG6 by completing its active site. This work provides mechanistic insight into the SMG5-dependent licencing step and uncovers a composite PIN nuclease architecture at the heart of the metazoan NMD effector phase.

Nonsense Mediated mRNA Decay

Ultrasound protocols used to detect vascular gas emboli in divers: a systematic review.

INTRODUCTION: Venous gas emboli (VGE) detected via ultrasound can be used as a surrogate marker for decompression stress. While Doppler ultrasound is the historical gold standard, two-dimensional (2D) ultrasonography offers advantages for on-site monitoring, including a wider field of view and reduced dependence on noise-free environments. This systematic review evaluates 2D ultrasonography protocols used in decompression research since the 2015 International Meeting on Ultrasound for Diving Research, identifying methodological similarities, differences, and adherence to consensus recommendations. METHODS: A search of PubMed and Scopus identified studies using 2D ultrasound to detect VGE in divers. Inclusion criteria were: (1) use of 2D ultrasound, (2) detection of VGE or monitoring of decompression stress, (3) inclusion of a diver cohort, and (4) publication after 2015. Data extraction focused on VGE scoring systems, ultrasound hardware, measurement protocols, and operator experience. Risk of bias was assessed using ROBINS-I-V2, and compliance with the 2015 consensus recommendations was evaluated. RESULTS: Twenty studies were included. The Eftedal-Brubakk scale was most commonly used (n = 15), with cardiac ultrasound as the primary imaging modality; one study assessed a peripheral vessel. Common shortcomings included post-dive measurements lasting less than two hours, underreporting of operator experience and hardware specifications, limited individual-level data, and inappropriate use of parametric statistics for ordinal bubble grade data. No study fully complied with all consensus recommendations. CONCLUSIONS: This review demonstrates that, although two-dimensional ultrasound is widely used for post-dive VGE assessment, methodological heterogeneity with multiple shortcomings remain. Furthermore, nearly all studies restricted imaging to the heart, thus leaving peripheral vessel assessment largely unexplored.

Embolism, Air

The future of pediatric vesicoureteral reflux management.

BACKGROUND AND OBJECTIVE: Vesicoureteral reflux (VUR) is a common condition in pediatric urology, yet important uncertainties persist regarding risk stratification, imaging strategies, and prevention of long-term renal damage. Emerging technologies may help address these challenges. This review provides a forward-looking overview of recent advances in artificial intelligence (AI) and immunomodulation that may influence future management of pediatric VUR. METHODS: A forward-looking literature review was performed using the PubMed database (January 2000-March 2025), focusing on studies addressing AI, immunomodulation, or vaccination in the context of VUR and urinary tract infections. Criteria of inclusion were the relevance to pediatric VUR, the novelty of the proposed concept, the potential clinical implications and, for the AI literature, the existence of a clinical evaluation of the algorithm on a dataset from patients. KEY FINDINGS AND LIMITATIONS: AI-based models show promising performance in supporting clinical decision-making, including prediction of the need for voiding cystourethrography, automated grading of VUR, estimation of recurrent urinary tract infection risk and prediction of chemoprophylaxis. These tools may facilitate more individualized diagnostic and therapeutic strategies, although current evidence is largely retrospective and requires prospective validation. Immunization and immunomodulatory approaches aim to reduce infection burden and modulate inflammatory pathways associated with renal scarring. While early experimental and adult clinical data are encouraging, pediatric-specific evidence remains limited, and clinical applicability in children with VUR is not yet established. CONCLUSION: Artificial intelligence and immunologically targeted strategies represent complementary, emerging approaches that may contribute to more personalized management of pediatric VUR. At present, both should be regarded as exploratory tools whose clinical impact will depend on further validation and appropriately designed pediatric studies.

Humans

Can host genetics transform the sustainable control of tropical theileriosis? Insights from the Tick-Theileria interface.

Tropical theileriosis, caused by the tick-transmitted apicomplexan parasite Theileria annulata, remains a major constraint on cattle production across North Africa, the Mediterranean basin, the Middle East and South Asia. Current control depends on acaricides, the theilericidal drug buparvaquone and live attenuated schizont vaccines, but acaricide resistance, buparvaquone-resistance mutations and the logistical demands of vaccination are eroding the sustainability of these tools. Host genetics offers a complementary and durable alternative. Indigenous Bos indicus breeds are consistently more resistant to ticks and tolerate T. annulata infection better than exotic Bos taurus cattle, and this advantage has a measurable heritable component. Unlike previous reviews, which treat tick resistance, T. annulata immunobiology and livestock genomic selection as separate subjects, we integrate all three and assess host genetics specifically against the failure modes of current control. We review the tick, parasite and host interface, the evidence for natural resistance, and the genetic and immunological mechanisms involved, including signal-regulatory protein, bovine major histocompatibility complex class II and inflammatory pathway genes. We then assess whether genomic selection, multi-omics, machine learning and gene editing can translate these mechanisms into resistant cattle, and we weigh the biological, economic and infrastructural barriers to implementation. The evidence indicates that host genetics will not replace existing control but could reduce reliance on acaricides and chemotherapy. That contribution remains prospective rather than demonstrated: no resistance marker for T. annulata has yet been validated, prediction accuracies are moderate and transfer poorly between breeds, and no endemic production system has implemented selection for resistance.

Animals

Ecological Restoration of the Soil-Like Function in the Bauxite Residue: Natural Microbiomes Mediated Molecular Transformation of Dissolved Organic Matter.

Soilization of bauxite residues offers a scalable route for long-term carbon management and ecological restoration. However, the microbial processes that transform exogenous organic inputs into stable soil-like carbon pools remain poorly resolved. Here, we combined cross-ecosystem meta-analysis, machine-learning prediction, native synthetic community (SynCom) construction, 13C-labeled straw microcosms, field validation, Fourier transform ion cyclotron resonance mass spectrometry, and genome-resolved metagenomics to unravel microbiome-mediated carbon transformation at the dissolved organic matter (DOM) molecular scale. Our meta-analysis revealed that alkaline industrial wastes retained soil-like DOM signatures but were enriched in microbial humic- and protein-like components, indicating active yet incomplete carbon processing. Guided by these patterns, native SynCom inoculation increased 13C incorporation into total organic carbon (TOC) and dissolved organic carbon (DOC), enlarged biodegradable and adsorbable DOC fractions, and shifted DOM from recalcitrant aromatic pools toward oxygenated carbohydrate-, tannin-, and phenolic-like molecular classes. Genome-resolved analyses linked this transformation to complementary polymer degradation and nutrient-cycling functions across fungal and bacterial guilds, including enriched carbohydrate-active enzymes in straw-carbon-utilizing metagenome-assembled genomes. Null model and thermodynamic analyses further showed that microbial communities were constrained by homogeneous selection, whereas DOM molecules were diversified through variable selection and redox-dependent transformation. Field-scale validation confirmed that SynCom promoted TOC and DOC accumulation and humic-like, high-density DOM fractions under alkaline conditions. Together, these findings establish a mechanistic framework in which functional microbiomes couple plant carbon depolymerization, DOM molecular diversification, and mineral-interactive carbon stabilization, providing a microbiome-guided strategy for carbon sequestration and soilization in the bauxite residue.

Soil

Rotavirus vaccine effectiveness against rotavirus and acute gastroenteritis mortality: an analysis of pooled case-control studies from the MNSSTER-V dataset.

BACKGROUND: Rotavirus accounts for an estimated 25% of diarrhoea deaths in children under 5 years globally, and more than 140 countries have included rotavirus vaccines in their routine national infant vaccination programmes. We aimed to calculate rotavirus vaccine effectiveness against rotavirus-positive and all-cause acute gastroenteritis deaths. METHODS: The Multi-National Subpopulations Study to Evaluate Rotavirus Vaccines (MNSSTER-V) dataset combines child-level data from test-negative case-control studies of rotavirus vaccine effectiveness that enrolled children under 5 years of age seeking care for acute gastroenteritis at hospitals or emergency departments in 24 countries between July 1, 2007, and Aug 24, 2023. Children were included in this study if they were: younger than 5 years, met the acute gastroenteritis case definition (had at least three episodes of diarrhoea in a 24-h period, had non-bloody and non-chronic diarrhoea, and were enrolled within 7 days of diarrhoea onset), met vaccine card quality metrics, had vaccine delivery dates if the child was reported to have received a rotavirus vaccine, and had a reported outcome of death or discharge. In-hospital acute gastroenteritis deaths were characterised, and rotavirus vaccine effectiveness against all-cause and rotavirus-positive acute gastroenteritis mortality was calculated using an unconditional logistic regression model with adjustment for national under-5 mortality strata and child's age. Vaccine effectiveness analyses against all-cause and rotavirus-positive acute gastroenteritis mortality were restricted to children aged at least 3 months who received any routine vaccines from countries reporting at least one acute gastroenteritis death. FINDINGS: From the MNSSTER-V dataset, we included 27 252 children younger than 5 years enrolled from 22 countries; outcomes of patients were not available for two countries. At least one in-hospital acute gastroenteritis death was reported from 16 countries including 21 522 children; in total, 183 all-cause acute gastroenteritis deaths and 25 rotavirus-positive deaths were reported. Among children aged at least 3 months who had received any routine vaccines, receiving at least one dose of a rotavirus vaccine had an adjusted vaccine effectiveness of 75·8% (95% CI 28·4 to 91·8; n=13 630) against rotavirus-positive acute gastroenteritis mortality and 20·8% (-47·0 to 57·3; n=20 005) against all-cause acute gastroenteritis mortality. INTERPRETATION: Rotavirus vaccines are effective in preventing rotavirus-positive acute gastroenteritis mortality. Continued efforts to improve vaccine delivery could help to reduce acute gastroenteritis mortality due to rotavirus worldwide. FUNDING: None.

Humans

Safety and Tolerability of Oral Islatravir Once Monthly as Pre-exposure Prophylaxis in Cisgender Men and Transgender Women Who Have an Elevated Likelihood of HIV-1 Exposure: Results From the IMPOWER-24 Randomized Phase 3 Study.

BACKGROUND: Islatravir once monthly (qm), a nucleoside reverse transcriptase translocation inhibitor with a long half-life, was evaluated for safety and tolerability in cisgender men and transgender women who have sex with men and are at increased likelihood of HIV-1 (HIV) exposure. METHODS: IMPOWER-24 (NCT04652700) was a double-blind, Phase 3 study. Participants were randomized 2:1 to islatravir 60 mg oral qm or emtricitabine (FTC; 200 mg) coformulated with either tenofovir disoproxil (245 mg) or tenofovir alafenamide (TAF; 25 mg) once daily (qd). After &#x223c;9 months, blinded islatravir was discontinued due to lymphocyte reductions; participants were offered open-label comparator for 20 months. RESULTS: In total, 494 participants were enrolled (328 islatravir; 166 comparator): 91.5% were cisgender men, 41.7% were White, and median age was 27 years. Mean blinded dosing duration was 4.7 months (islatravir) versus 4.3 months (comparator). Overall, 211 participants (64.3%) in the islatravir group and 128 (77.1%) in the comparator group had &#x2265;1 adverse event (AE). Most AEs were mild or moderate, with 1 AE leading to product discontinuation (islatravir; gastroesophageal reflux). Serious AEs occurred in <2%; none were related to study product. Change in total lymphocytes in the islatravir group at Month 3 was -7.4%; a trend toward recovery was observed after islatravir was stopped. Mean total lymphocytes remained within normal range. No HIV infections occurred in either group during the double-blind phase. CONCLUSIONS: Islatravir qm was generally well tolerated; decreases in total lymphocytes were observed with islatravir. Original primary efficacy objectives were not assessed due to early study stoppage.

Humans

Copper-Containing Surface Engineering for Soft-Tissue Biomedical Devices: Structure-Function Relationships and Ion Release-Driven Biological Performance, A Systematic Review.

Copper and copper-based materials have gained increasing attention for the functional modification of implantable medical devices intended for prolonged soft-tissue contact, including vascular stents, catheters, and intrauterine devices. Owing to their broad-spectrum antimicrobial activity, redox reactivity, and involvement in angiogenesis and cellular signaling, copper-based systems offer significant potential for multifunctional surface engineering. However, achieving a balance between antibacterial efficacy, corrosion behavior, controlled ion release, and cytocompatibility remains a critical challenge. This PRISMA-compliant systematic review analyzes copper-containing materials and surface modification strategies for soft-tissue biomedical applications. A structured search of Scopus, Web of Science, and PubMed (2015-2025) identified 65 eligible studies. The review encompasses bulk copper-containing alloys, electrochemical and chemical surface modification techniques, physical vapor deposition approaches, and advanced hybrid systems integrating copper with polymers, hydrogels, or metal-phenolic networks. Across the reviewed literature, antibacterial performance was strongly dependent on copper concentration, microstructural distribution, and spatiotemporal ion release profiles. Moderate, well-controlled copper incorporation frequently improved antibacterial efficacy while maintaining acceptable hemocompatibility and cytocompatibility, particularly in vascular and blood-contacting devices. In contrast, excessive copper loading often accelerated corrosion and induced adverse cellular responses. Emerging multifunctional architectures demonstrated improved regulation of biological interactions, enabling simultaneous antibacterial, antithrombotic, and proendothelial effects. Overall, copper-based surface technologies represent a versatile platform for soft-tissue implant modification. Future translational progress will require precise control of copper release kinetics and comprehensive long-term in vivo validation to ensure safety and sustained therapeutic performance. From the authors' perspective, the most promising future direction involves multifunctional copper-based hybrid coatings capable of dynamically regulating ion release, host tissue integration, and antibacterial performance simultaneously. Strategies integrating hierarchical architectures, stimulus-responsive release systems, and clinically scalable fabrication methods are expected to play a key role in translating copper-containing surfaces from experimental concepts toward commercially viable soft-tissue biomedical devices.

Copper

Mineral-driven molecular signatures of energy metabolism underpin sperm motility in buffalo.

The success of spermatogenesis depends on the interplay of various biomolecules that ultimately determine sperm quality. In this study, RNA-seq analysis of frozen-thawed buffalo sperm (n&#x202f;=&#x202f;8) revealed the presence of 263 mineral-associated genes (>1 FPKM) in high (n&#x202f;=&#x202f;4) and 181 in low motile (n&#x202f;=&#x202f;4) sperm groups. Among these, 177 mineral-associated genes were commonly expressed between them, and the majority were upregulated (>1 fold), LOC102391588 (ncRNA; 37-fold), ZNF699 (26.5-fold), MYZAP (13-fold), etc., in the high motile group. The expression of selected mineral-associated genes was validated. The top enriched functions in commonly expressed genes were regulation of transcription by RNA polymerase II (FDR: 4.7&#x202f;&#xd7; 10&#x207b;2; ZNF331, ZNF692, ZNF180, etc.), followed by spermatogenesis (FDR: 2.9&#x202f;&#xd7; 10&#x207b;2; CALR3, ADAM18, ADAM29, etc.), proton transmembrane transport (FDR: 4.0&#x202f;&#xd7; 10&#x207b;2; ATP6V0E1, ATP1A4, ATP6V1B2, etc.) and flagellated sperm motility (FDR: 2.3&#x202f;&#xd7; 10&#x207b;1; CATSPERD, EFCAB6, CABS1, etc.). Additionally, the chromatin remodeling pathway (FDR: 3&#x202f;&#xd7; 10&#x207b;2; PTP4A1, PPM1A, DUSP1, etc.) emerged as the most significant and may suggest that these minerals influence genome packaging and sperm functionality. Mineral-associated genes were predominantly associated with zinc (49%), followed by calcium (20%), phosphorus (10%), iron (5%), sodium (2%), potassium (2%), copper (1%) and other trace elements (11%). Although the current study uses frozen-thawed sperm, the findings indicate that mineral-associated genes are crucial for promoting membrane stability, energy production, motility and chromatin integrity, which may contribute to the superior fertilizing ability of sperm.

Animals

Diversity and population connectivity of members of the family Eunicidae inhabiting deep-water corals in the North Atlantic.

Eunicid polychaetes are often found in association with Cold Water Corals (CWCs), even establishing symbiotic relationships, such as those described between Desmophyllum pertusum and Eunice norvegica. While genetic connectivity of CWCs across the North Atlantic has been widely studied, little is known about their associated fauna in this regard. Here, we present a study combining a focused analysis of the genetic and genomic connectivity of E. norvegica with a regional assessment of the distribution and evolutionary relationships of three CWC-associated eunicid species from the Cantabrian Sea and the North of the United Kingdom (190-1,230&#xa0;m depth). An integrative approach using genetic (16S, COI and 18S), morphological and ecological data allowed the identification of the eunicids studied, with new records of Eunice cf. nicidioformis and Leodice cf. antarctica in the Cantabrian Sea, as well as previously undocumented associations with CWC species. In addition, RADseq data contributed to the delimitation of the closely related species E. norvegica and Eunice philocorallia. Moreover, the genetic connectivity of E. norvegica was studied trough a RADseq (1,067 neutral SNPs) approach. Our results indicate a single panmictic population across approximately 2,000&#xa0;km, suggesting that oceanographic currents facilitate passive dispersal of E. norvegica lecithotrophic larvae, aided by coral host stepping-stones. The connectivity patterns observed for E. norvegica mirror those of D. pertusum, on which the worm is ecologically dependent. Our study highlights the importance of using integrated genetic, morphological and ecological data to characterise and delineate understudied CWC-associated species and improve our understanding of their dispersal capabilities and genetic connectivity to inform future conservation recommendations.

Animals

Phase 3 Trial of Oral Infigratinib in Children with Achondroplasia.

BACKGROUND: Achondroplasia is a genetic skeletal condition caused by FGFR3 pathogenic variants. Infigratinib, an oral FGFR1-3 tyrosine kinase inhibitor, down-regulates key pathways in the pathogenesis of achondroplasia. METHODS: In this phase 3, multicenter, double-blind, placebo-controlled trial, we randomly assigned children with achondroplasia (3 to 17 years of age) in a 2:1 ratio to receive infigratinib (at a dose of 0.25 mg per kilogram of body weight) or placebo once daily for 52 weeks. The primary end point was the change from baseline in the annualized height velocity in the infigratinib group as compared with the placebo group at week 52. Key secondary end points were the change from baseline in the height z score and in the upper-to-lower body segment ratio at week 52. The primary analysis evaluated the treatment effect at week 52 in the full analysis population, with missing data handled with a prespecified imputation approach. RESULTS: In all, 114 patients underwent randomization: 75 patients to receive infigratinib (with 1 withdrawal before treatment) and 39 patients to receive placebo. The difference between infigratinib and placebo in the least-squares mean change from baseline to week 52 was 1.74 cm per year (95% confidence interval [CI], 1.31 to 2.17; P<0.001) for the annualized height velocity, 0.32 (96% CI, 0.23 to 0.41; P<0.001) for the height z score, and -0.02 (96% CI, -0.06 to 0.01) for the upper-to-lower body segment ratio. Adverse events occurred in 71 of 74 patients (96%) in the infigratinib group and in 37 of 39 patients (95%) in the placebo group; serious adverse events occurred in 4 of 74 patients (5%) and 1 of 39 patients (3%), respectively. No serious adverse events or adverse events leading to treatment discontinuation were considered by the investigator to be related to infigratinib or placebo. CONCLUSIONS: In children with achondroplasia, treatment with once-daily oral infigratinib for 52 weeks resulted in a significantly greater increase from baseline in the annualized height velocity than placebo. (Funded by BridgeBio Pharma; PROPEL 3 ClinicalTrials.gov number, NCT06164951; EudraCT number, 2023-506130-67.).

Adolescent

The effect of tDCS on emotion-related risk-taking behavior and delay discounting in adults with ADHD.

INTRODUCTION: Adults with Attention Deficit Hyperactivity Disorder (ADHD) often engage in risky behaviors due to impaired decision-making processes. This study aims to investigate the effects of transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (dlPFC) and ventromedial prefrontal cortex (vmPFC) on emotion-related risk-taking behavior and delay discounting in adults with ADHD. METHODS: Thirty adults with ADHD underwent three tDCS conditions, administered in a randomized order with at least one week between sessions: (1) left dlPFC anode/right vmPFC cathode, (2) left dlPFC cathode/right vmPFC anode, and (3) sham stimulation. In each session, participants completed the Delay Discounting Task (DDT) and the Modified Balloon Analogue Risk Task (mBART) under three emotional conditions (neutral, positive, and negative) which were induced using emotionally congruent photographs and sounds. Galvanic skin responses (GSR) were also recorded. In the DDT, both area under the curve (AUC) values and log-transformed discounting rates (log k) were calculated for small, medium, and large reward magnitudes (RM). Exploratory electric field modeling was also performed to characterize current distribution. RESULTS: The findings demonstrated task-specific effects of tDCS on decision-making. Although no overall tDCS effect was observed on DDT performance, significant tDCS&#x202f;&#xd7;&#x202f;RM interactions emerged, particularly for smaller rewards. In contrast, exploratory analyses suggested that tDCS affected all mBART scores. Emotional condition did not influence consistently behavioral performance in either task, whereas both emotional stimulation and tDCS significantly affected GSR responses. However, exploratory electric field modeling indicated a broad prefrontal current distribution extending beyond the intended cortical targets. CONCLUSIONS: These findings suggest preliminary evidence that prefrontal tDCS can influence risk-related decision-making and autonomic responses in adults with ADHD. However, its effects on delay discounting appear to be context-dependent and limited to specific RMs. Future studies combining neuroimaging with individualized electric field modeling are needed to clarify the neural mechanisms underlying the observed effects of tDCS and to optimize stimulation protocols in adults with ADHD.

Humans

Integrated phytochemical and bioactivity profiling of Xanthium strumarium fruits from Korea and China: Implications for origin-specific quality specification.

BACKGROUND: Geographic origin influences the phytochemical composition and biological activities of medicinal plant resources. Xanthium strumarium L. (XS) fruit is widely used in East Asian traditional medicine. However, current pharmacopeial standards primarily recognize Chinese-derived material, despite the availability and traditional use of XS in Korea. To address this gap and support origin-informed quality specification, we compared fruits from Korea (XS-K) and China (XS-C) using chloroplast genome sequencing, targeted phytochemical profiling (high-performance liquid chromatography (HPLC) for selected phenolics and gas chromatography-flame ionization detection (GC-FID) for fatty acids and phytosterols, and multivariate chemometric analysis. RESULTS: Chloroplast genome analysis revealed high overall similarity but localized divergence around the rpoC2 locus and a greater mutation burden in XS-C, supporting origin-associated genomic differentiation. Phytochemical profiling revealed distinct origin-dependent metabolic signatures. XS-K showed higher levels of phytosterols, chlorogenic acid, 4,5-dicaffeoylquinic acid (4,5-DCQ), and xanthatin was detected only in XS-K, whereas XS-C exhibited greater abundance of total fatty acids, particularly oleic acid. Unsupervised clustering and log2 fold-change ranking confirmed clear compositional separation, and variable importance in projection (VIP) analysis identified chlorogenic acid, &#x3b2;-sitosterol, oleic acid, 4,5-DCQ, and xanthatin as major discriminators between origins. Bioactivity assays demonstrated that XS-K exerted stronger antioxidant effects in ABTS, DPPH and FRAP assays, stronger skin-related enzyme inhibition, and greater antibacterial activity against Staphylococcus aureus, consistent with its enriched phenolic and sterol profile. CONCLUSION: Together, chloroplast sequence variation, targeted metabolite quantification, and screening bioassays consistently distinguished XS-K from XS-C. These findings support the use of candidate markers for the origin-based authentication and quality control of XS fruit-derived ingredients. &#xa9; 2026 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Fruit

Orthoplastic management of open calcaneal fractures: A systematic review of flap selection and complications.

BACKGROUND: Open calcaneal fractures are rare, high-energy injuries involving extensive soft-tissue loss and comminuted bone disruption. Successful management depends on coordinated orthoplastic reconstruction to achieve stable fixation and durable coverage. Multiple flap types have been described, yet comparative outcomes remain poorly defined. METHODS: A systematic review was performed in accordance with PRISMA guidelines (PROSPERO: CRD420251138394). MEDLINE, Embase, Cochrane CENTRAL, and Scopus were searched from January 2000 to July 2025. Studies reporting flap-based reconstruction for open calcaneal fractures in adults were included. Extracted data included flap type, fixation method, follow-up duration, and complications such as infection, necrosis, vascular crises, flap loss, and amputation. RESULTS: Thirteen studies comprising 88 major flap reconstructions were analysed. Overall flap survival was 97.7%, with two failures (both muscle/myocutaneous). Fasciocutaneous flaps showed the lowest complication rates (8.3%) with no reported cases of infection, while muscle/myocutaneous flaps demonstrated cases of infection (20%) and accounted for both flap failures and the only reported amputation. Chimeric flaps were increasingly used in recent series (n&#x202f;=&#x202f;32), achieving reliable survival but higher vascular compromise (6.3%). Osteocutaneous flaps were rare (n&#x202f;=&#x202f;4) and primarily used for defects with bone loss, showing infection in 50% of cases. Meta-analysis was not possible due to heterogeneity and small sample sizes. CONCLUSIONS: Fasciocutaneous flaps provide reliable, low-complication coverage for clean wounds, while muscle flaps remain valuable for contamination or complex cases with extensive tissue loss. Chimeric, and osteocutaneous flaps show promise, but larger, standardised studies are needed to clarify their roles in hindfoot reconstruction.

Humans

Lipid metabolism is a key central, systemic and gut microbial feature of the decline in rat hippocampal function during middle age.

Middle age is emerging as a turning point in brain ageing, prognostic of future cognitive health and amenable to intervention. Metabolic and proteomic differences during this period are not yet fully understood and may potentially influence functions of the hippocampus, a brain area that regulates memory and anxiety. While the gut microbiota is implicated in brain ageing, the relationship between the gut microbiota, the metabolic state, and hippocampal proteome in middle age has not been investigated. We hypothesise that peripheral metabolic or protein features are associated with hippocampal vulnerability in middle age. Therefore, young adult and middle-aged rats were assessed for behavioural, proteomic, metabolic, and gut microbiota differences. Proteomic profiling of the hippocampus revealed differential expression of proteins indicative of altered synaptic signalling. Concurrently, adult hippocampal neurogenesis was decreased in middle age. Hippocampal microglia exhibited a lipid rich, inflammatory phenotype in middle age which correlated with poorer memory performance. CSF and serum proteomic and metabolomic analyses identified dysregulated lipid-related pathways potentially contributing to hippocampal vulnerability in middle age. Furthermore, 16S rRNA sequencing revealed reduced abundance of bacteria involved in lipid metabolism regulation. However, faecal microbiota transfer from young to middle aged rats was not sufficient to robustly improve hippocampus-dependent spatial memory. Together, these findings highlight dysfunctional lipid metabolism as a key feature of middle age that may contribute to decline in hippocampal function. Given that the scope for intervention is limited during older age, targeting biomarkers involved in metabolic and lipid homeostasis may be pivotal for the development of pharmacological or lifestyle-based interventions during middle age which could ultimately delay future cognitive ageing.

Animals

Development and Validation of a Predictive Model for Identification of Cognitive Impairment Risk in Older Adults with Subjective Cognitive Decline&#xff1a;A Longitudinal Study.

BACKGROUND: Subjective cognitive decline (SCD) is a transitional state between objective cognitive impairment and cognitively intact mental status, providing a critical window for implementing preventive interventions to delay objective cognitive decline. AIMS: We aimed to develop a predictive model for SCD progression in older adults with mild cognitive impairment (MCI). This model will facilitate the identification of risk factors and establishment of targeted interventions for community-based SCD management. METHODS: Data from the China Health and Retirement Longitudinal Study (CHARLS) was utilized in this study, extracting 18 indicators. Potential predictors selected through univariate Cox regression and LASSO regression analyses were sequentially incorporated into a multivariable Cox regression model. A nomogram was constructed to establish a predictive model. Model validation encompassed Area Under Curve (AUC) metrics for discriminative capacity, complemented by quantitative assessments using calibration curve analysis for precision verification and decision curve analysis (DCA) for clinical utility evaluation. RESULTS: A total of 1099 older adults with SCD were included in the final analysis, of whom 114 (10.3%) developed MCI. Multivariable Cox regression identified residence, marital status, educational level, social participation, gait speed, and baseline cognitive function. The model demonstrated time-dependent AUC values of 0.885, 0.830, 0.839, and 0.836 in the training set when evaluating discriminative capacity at 2-, 4-, 7-, and 9-year, respectively. The predictive model showed excellent predictive ability according to AUC, calibration curve, and DCA. CONCLUSIONS: A predictive model was created to estimate the risk of developing MCI in older individuals with SCD, offering clinician-actionable intervention benchmarks for preventive care.

Humans