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Transforming Curcuma longa leaf waste into cellulose scaffolds.

The constant dearth of transplantable tissues and organs in India required the development of substitute biomaterials for tissue engineering. Plant-based decellularized scaffolds have become attractive options because of their abundance, ethical acceptability, architectural diversity, and lower risks of zoonotic transmission. Curcuma longa leaves were investigated in this study as a possible source of cellulose-based scaffolding for use in biomedical applications. After cuticle removal, an immersion decellularization technique utilizing sodium dodecyl sulphate (SDS) and triton-X-100 was developed to successfully remove cellular and nuclear material while maintaining leaf parenchyma architecture. Histology, DAPI staining, scanning electron microscopy, and a notable decrease in leftover DNA content all demonstrated efficient decellularization. When contrasted with native leaves, the resultant decellularized C. longa leaf scaffolds showed significant increase in porosity, water vapor transmission rate and swelling percent, and significantly lower contact angle with an optimum surface roughness promoting cell adhesion. Mechanical test manifest higher tensile strength with decreased stiffness. Fourier transform infrared spectra of leaf scaffold reveals persistence of different components except cuticle but the intensity of different peaks was decreased. The leaf scaffolds showed superior hemocompatibility and excellent compatibility with Madin-Darby canine kidney cells (MDCK) which is demonstrated by cell attachment and proliferation. MTT assay of seeded scaffold showed significantly higher metabolically active cell. In vivo subcutaneous implantation of decellularized scaffolds showed host tissue incorporation, accumulation of collagen, and neovascularization. C. longa leaf scaffolds can be utilized as cost effective and sustainable biomaterials for soft tissue engineering and regenerative medicine.

Curcuma

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 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 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

Genome mining of alkaliphilic cyanobacterial consortia: identification of biosynthetic gene clusters in Sodalinema and associated heterotrophs.

Alkaline soda lakes are high-pH environments that host specialized microbial communities with potential for biotechnology and natural product discovery. We characterized three Sodalinema-dominated cyanobacterial consortia enriched from Canadian soda lakes over 510 days. Using hybrid metagenomic sequencing and metatranscriptomics across pH, alkalinity, and temperature gradients, we reconstructed high-quality metagenome-assembled genomes and assessed functional activity. All consortia converged toward cyanobacteria dominance and exhibited temperature optima between 21°C and 30°C. Phylogenetic analysis placed Sodalinema genomes within a distinct clade affiliated with Candidatus Sodalinema alkaliphilum. Genomic analysis indicated complete biosynthetic pathways for vitamin B5, vitamin B7, and the molybdenum cofactor, but incomplete pathways for vitamins B1, B9, and B12, consistent with patterns observed in Sodalinema yuhuli. Metatranscriptomic profiles showed increased expression of genes involved in phycocyanin and carotenoid biosynthesis at pH 10.2 relative to pH 8.5. Biosynthetic gene cluster analysis revealed that most secondary metabolic potential resided in heterotrophic community members. Roseinatronobacter encoded pathways for N-acyl homoserine lactones, osmoprotectants, betalactones, and prodigiosin, while Alkalimonas, Wenzhouxiangella, and members of the Kiloniellales encoded clusters for lanthipeptides, cyclodipeptides, hydrogen cyanide, and pyrroloquinoline quinone. These findings indicate functional partitioning within the consortia and highlight the contribution of heterotrophs to secondary metabolism.IMPORTANCEAlkaline soda lakes contain microbial communities adapted to high pH that remain underexplored for biotechnology. This study focuses on Sodalinema, a filamentous cyanobacterium that dominates enriched consortia from Canadian soda lakes, and its associated heterotrophic partners. We show that while Sodalinema drives primary productivity, heterotrophic bacteria encode most of the pathways for antimicrobial and signaling compounds. These interactions may support community stability and defense against competing microorganisms. By linking genomic potential with gene expression, this work identifies alkaline cyanobacterial consortia as a source of bioactive compounds and provides a framework for exploring extremophilic microbial communities for natural product discovery.

Sodalinema

Diverse structures of mcr-10-bearing plasmids and high colistin resistance in Enterobacter cloacae complex clinical isolates from South Korea.

BACKGROUND: The emergence of mcr-mediated colistin resistance in Enterobacter cloacae complex (ECC) poses a significant threat to antimicrobial therapy. Among mcr variants, mcr-10 has been identified in various environments, but its genetic diversity, structural context, and functional role in colistin resistance remain unclear. METHODS: We investigated 183 ECC isolates and identified 60 colistin-resistant strains through minimum inhibitory concentration (MIC) testing. The presence of mcr-10 was screened using reference genomes from NCBI, and whole plasmid sequencing was conducted on mcr-10-positive isolates. The genetic environment of mcr-10 was analyzed via synteny and structural annotation. RESULTS: Whole-plasmid sequencing of eight mcr-10-positive ECC isolates identified three replicon types among the mcr-10-harboring plasmids: IncFIB (n=3), IncFII (n=3), and IncFII/IncFIB (n=2). Although all plasmids shared the xerC-mcr-10 cassette, they lacked a conserved backbone and showed diverse genetic contexts with variable insertion sequences near mcr-10, indicating marked structural heterogeneity. No additional antimicrobial resistance genes were detected on these plasmids. When introduced into E. coli DH5α, the plasmids increased colistin MICs only modestly, whereas representative plasmids transferred into colistin-susceptible E. roggenkampii and E. kobei conferred high-level resistance comparable to that of the parental mcr-10-positive isolates. Consistently, qRT-PCR showed higher mcr-10 expression in ECC transformants than in E. coli under colistin exposure, supporting a hostdependent effect on mcr-10-mediated colistin resistance. CONCLUSION: These findings highlight the diversity of mcr-10-carrying plasmids and suggest that mcr-10-mediated colistin resistance is shaped by the host genetic background. Further studies are needed to clarify the mechanisms underlying mcr-10 expression.

Colistin

Proteomic insights into the immunomodulatory effects of Ca/Sr co-doped sol-gel coatings for titanium implants.

Ionic functionalization of biomaterial coatings has emerged as a powerful strategy to regulate early host responses at the implant interface. However, how combined Ca/Sr incorporation governs the adsorbed proteome and downstream immune signaling remains poorly understood. This study analyses, employing in vitro tests and proteomics, the effect of adding Sr and Ca to Si-based coatings designed to bioactivate Ti implants. Hybrid Si-based coatings were synthesized by the sol-gel route with a fixed Ca content (0.5 wt%) and increasing Sr contents (0.5, 1.0, 1.5 wt%), and their physicochemical properties, ion release kinetics, and hydrolytic stability were characterized. The coatings remained highly crosslinked despite Ca/Sr incorporation, whereas the highest Sr content increased hydrolytic degradation to around 70% after 56 days. Proteomic analysis identified 183 adsorbed proteins, of which 56 were differentially adsorbed on Ca/Sr-coatings, mainly associated with immune and coagulation pathways. In vitro, RAW 264.7 showed increased gene expression of TNF-α and TGF-β; with an enhanced TNF-α secretion by the addition of Ca and Sr. In parallel, MC3T3-E1 indicated that Ca/Sr-coatings were not cytotoxic and did not impair cell proliferation. However, ALP activity was reduced in the co-doped groups, indicating that the immunomodulatory effects induced by Ca/Sr incorporation were not accompanied by enhanced early osteogenic differentiation. The Ca/Sr combination induced alterations in the adsorption of immune-related proteins, which correlated with the in vitro findings. The deeper insight into how Ca/Sr mixtures modulate protein adsorption on biomaterial surfaces may be key to understanding the immunomodulatory capacity of these bioactive cations.

Animals

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

Long-term consequences of childhood sexual abuse: An umbrella review of diagnostic meta-analyses.

BACKGROUND: Childhood sexual abuse (CSA) is a public health issue with an estimated worldwide prevalence of 12.7%, potentially leading to a host of lifelong and significant mental, physical, and behavioral health. The aim of this study was to comprehensively map the long-term consequences of childhood sexual abuse on physical, psychiatric, and behavioral health outcomes. METHODS: An umbrella review of meta-analyses of observational studies, registered on PROSPERO, was conducted to examine the diverse repercussions of childhood sexual abuse on adult health. Three bibliographic databases (PsycINFO, PubMed and Scopus) were searched from the inception of the respective databases to November 1st, 2022. Thirty-eight meta-analyses representing about 20 million individuals were analyzed, revealing a range of long-lasting consequences associated with CSA. RESULTS: Among physical pathologies, cervical cancer and functional neurological syndromes emerged as the most prominent, exhibiting significantly elevated odds ratios (ORs) of 4.18 IC95% and 3.30 IC95%, respectively. Sleep disorders and borderline personality disorders were the most prevalent mental health disorders associated with CSA, with respective ORs of 16.17 IC95% and 5.96 IC95%. Early sexual initiation (OR=3.59 IC95%, sexual assault (OR=3.36 IC95%, and prostitution (OR=3.24 IC95%) emerged as the most common behavioral consequences. Notably, no significant differences in the consequences of CSA were observed between men and women, except for reproductive health outcomes. DISCUSSION: When faced with certain pathologies, clinicians should consider and discuss sexual abuse with their patients. The consequences of abuse have a multifactorial origin, which is a weakness, as are the problems of defining abuse. The strength of our study is that it lists the consequences published in high-quality studies. CONCLUSION: This umbrella review provides compelling evidence of the profound and far-reaching impact of childhood sexual abuse on a broad spectrum of physical, mental, and behavioral health issues.

Humans

The effect of metformin on the pharmacokinetics of rifampicin, isoniazid, and pyrazinamide in adults with tuberculosis.

Metformin is under investigation as adjunctive host-directed therapy for tuberculosis (TB), which might interact with first-line TB treatment. We used population pharmacokinetic modeling to assess whether metformin alters first-line TB-drug pharmacokinetics in HIV/TB-coinfected adults without diabetes. Rifampicin, isoniazid, and pyrazinamide pharmacokinetics were investigated in participants from a randomized clinical trial of adjunctive metformin (500 mg twice daily to week 12) in adults starting HIV-associated TB treatment. Antiretroviral therapy (ART)-na&#xef;ve participants initiated dolutegravir-based ART within 8 weeks. Intensive and semi-intensive sampling was conducted at week 5; concentration-time data were analyzed using non-linear mixed-effects modeling. Data from 78 individuals (43 receiving metformin, median weight 60.8 kg, 62.8% male, 79.5% on ART) were analyzed. Rifampicin and pyrazinamide were described by one-compartment models with linear elimination; typical clearances were 15.8 L/h (95% CI: 13.5-18.7) and 3.88 L/h (95% CI: 3.54-4.08), respectively. Isoniazid followed a two-compartment model with a mixture model for acetylator status; clearance was 10.5 L/h (95% CI: 9.44-11.9) in slow acetylators and 28.8 L/h (95% CI: 25.6-31.0) in fast/intermediate acetylators. Metformin reduced isoniazid bioavailability by 15.6% (95% CI: 4.45-26.4%, P < 0.009) and rifampicin bioavailability by 24.0% (95% CI: 7.83-36.3%, P < 0.007), decreasing the area under the curve from 0 to 24 h from 18.2 to 15.6 mg&#xb7;h/L and from 35.9 to 27.1 mg&#xb7;h/L, respectively. No significant effect on pyrazinamide was detected. We found that non-diabetic patients on metformin had lower isoniazid and rifampicin bioavailability. Lowered rifampicin exposure might be clinically relevant; simulations suggest that this could be offset by a single 150 mg rifampicin dose.CLINICAL TRIALSThis study is registered with ClinicalTrials.gov as NCT04930744.

Humans

Associations of clinical and laboratory parameters with pediatric urolithiasis composition: A retrospective, single-center study.

OBJECTIVE: To investigate demographic, clinical, and laboratory factors associated with distinct stone compositions in children. METHODS: This retrospective study included 237 children aged <14 years who underwent stone composition analysis between July 2008 and November 2023. Demographic, clinical, and laboratory data were collected, and propensity score matching (PSM) was used to control for confounding factors. RESULTS: The urate component (uric acid anhydrous, ammonium acid urate, and sodium urate) was most prevalent in infants, males, and non-Han children, whereas the calcium oxalate component predominated in older children. Analysis of coexisting components revealed urate is the most common partner to calcium oxalate (67.6%), and vice versa (82.8%). Struvite most frequently coexisted with carbonate apatite (60%), while carbonate apatite most often coexisted with calcium oxalate (54%). After PSM, the urate component was independently associated with host metabolic dysregulation, including lower high-density lipoprotein (&#x3b2; = -0.175, 95% CI: -0.279 to -0.071, p = 0.001) and with coagulation dysfunction, as evidenced by a prolonged prothrombin time (&#x3b2; = 0.595, 95% CI: 0.125 to 1.064, p = 0.014). Additionally, preoperative urinary tract infection (UTI) and congenital urinary tract anomalies were independently associated with both carbonate apatite and struvite components, with directionally consistent but quantitatively unstable signals in the struvite cohort, whereas the calcium oxalate component exhibited an inverse association with UTI (OR = 0.156, 95% CI: 0.030 to 0.819, p = 0.028). Furthermore, the carbonate apatite component was also independently associated with an elevated systemic immune-inflammation index (&#x3b2; = 416.53, 95% CI: 60.05 to 773.01, p = 0.024) and systemic inflammation response index (&#x3b2; = 1.286, 95% CI: 0.086 to 2.487, p = 0.038). CONCLUSION: Urate component was prevalent in infants, males, and non-Han children, whereas calcium oxalate predominated in older children. After adjusting for confounders, urate composition was associated with metabolic abnormalities, the carbonate apatite component was linked to infection and anatomical malformations, and a similar directional pattern was observed in the struvite cohort.

Humans

Functions of tandem-repeat galectins and domain coordination governs galectin-4 activity in grass carp (Ctenopharyngodon idella).

Galectins are &#x3b2;-galactoside-binding lectins that play essential roles in innate immunity. Among them, tandem-repeat galectins (TrGals), typically composed of two distinct carbohydrate-recognition domains (CRDs) connected by a linker peptide, are well established as key regulators of pathogen recognition and host defense in mammals. However, their structural diversity and immunological functions in teleost fish remain poorly understood. In this study, five TrGals (Gal-4, Gal-8a, Gal-8b, Gal-9, and Gal-9like) were identified in grass carp. Sequence and structural analysis revealed that Gal-8a/b, Gal-9, and Gal-9like possess the canonical two-CRD architecture, whereas Gal-4 uniquely contains four highly similar tandem-repeat domains. All five TrGals were broadly expressed across examined tissues, with predominant expression in the liver. Upon Aeromonas hydrophila infection, Gal-4, Gal-8a, Gal-8b, and Gal-9 were rapidly up-regulated at early time points (3-6&#x202f;h). To elucidate the functional significance of CRD number, recombinant full-length CiGal-4 (CiGal4-full) and three truncated variants containing one, two, or three CRDs (CiGal4-1CRD, CiGal4-2CRD, and CiGal4-3CRD) were generated and systematically characterized. All recombinant proteins contained the conserved &#x3b2;-sheet structure typical of galectin CRDs. Functional assays revealed that CiGal4-full displayed the strongest growth-inhibitory activity against all tested bacteria, whereas CiGal4-1CRD showed the weakest effect. Notably, CiGal4-2CRD exhibited the most potent bactericidal activity, surpassing the full-length protein, while CiGal4-3CRD showed no further enhancement. CiGal4-full and CiGal4-2CRD showed superior carbohydrate-binding activities compared with the other variants. Collectively, these results reveal that CRD copy number alone does not linearly determine galectin function. Instead, domain organization and conformational coordination are critical for optimizing antimicrobial activity. This study provides new insights into the structure-function relationships and evolutionary diversification of galectins in teleosts and highlights their potential as novel antimicrobial and immunomodulatory agents in aquaculture.

Animals

Characterization and application potential of two newly isolated phages targeting the prevalent multidrug resistant Salmonella serovars in China.

The escalating global threat of multidrug resistant (MDR) Salmonella, a foodborne pathogen with animal-derived foods serving as the primary transmission vehicle, underscores the urgent need for effective lytic phages for biocontrol. From 142 environmental and farm samples in Shandong Province, we isolated 103 phages active against MDR S. Enteritidis and S. Typhimurium, which were the most prevalent Salmonella serovars in China. Two Siphoviridae phages vB-SenS-S1 and vB-SenS-SEC2 were selected for further study. With optimal multiplicities of infection (MOIs) of 10-2 (vB-SenS-S1) and 10-5 (vB-SenS-SEC2), both phages exhibited a 20&#xa0;min latent period, yielding burst sizes of 52 and 37 PFU/cell, respectively. They also demonstrated stability across a range of temperatures (50-60&#xa0;&#xb0;C), pH levels (5-11), and after 1&#xa0;h of UV exposure. Genomic analysis identified vB-SenS-S1 (43,002&#xa0;bp, 47.04% GC) and vB-SenS-SEC2 (42,948&#xa0;bp, 47.65% GC) as novel double-stranded DNA phages. Functional annotation confirmed the presence of genes essential for structural assembly, host lysis, and DNA replication/metabolism, and also verified the absence of resistance, virulence, and lysogeny-associated genes. Both phages vB-SenS-S1 and vB-SenS-SEC2 exhibited synergy with colistin and tetracycline. The synergy with colistin was particularly potent, leading to complete bacterial eradication in vitro. The in vivo therapeutic efficacy was further validated in both Galleria mellonella larvae and murine models of MDR Salmonella infection. Combination therapy with vB-SenS-SEC2 and colistin not only dramatically increased survival but also achieved a significant reduction in bacterial burden across multiple visceral organs of infected mice. Moreover, vB-SenS-S1 (108 PFU/mL) completely inhibited MDR Salmonella on chicken meat at 4&#xa0;&#xb0;C and -20&#xa0;&#xb0;C when initial contamination was &#x2264;103&#xa0;CFU/mL. This study not only expands the diversity of Salmonella phages but also highlights their potential as biocontrol agents in both clinical veterinary use and food decontamination, thereby enhancing food quality and safety at both the meat production source and the terminal product.

Animals

Fracture-related infection following open forefoot fractures caused by dropped objects.

INTRODUCTION: This study evaluated the rate of fracture-related infection (FRI) of open forefoot fractures caused by dropped objects, and examined associations of treatment characteristics, including intravenous and oral antibiotics and operative debridement, with FRI. METHODS: Patients aged 18-80 years who sustained an open metatarsal or phalanx fracture caused by a dropped object between January 2021 and June 2024 were retrospectively identified from two Level 1 trauma centers. The primary outcome was FRI, determined based on the FRI consensus criteria. FRI rates were compared between those who underwent irrigation and debridement (I&D) at bedside versus in the operating room, and between those who received oral versus intravenous (IV) antibiotics. Patient characteristics were also analyzed to determine host factors associated with FRI. RESULTS: A total of 86 patients (median age 41 years [IQR: 29-56], 58% male) were included. Eighty-five patients (99%) received antibiotics, 31 (36%) of whom received intravenous antibiotics. Sixty-six patients (77%) received an I&D at presentation, 57 (66%) at bedside and 9 (10%) in the operating room. Thirteen patients (15%, 95% CI: 8.3%-24%) developed FRI. No significant difference in FRI rate was found between patients who underwent I&D at bedside versus in the operating room (12% versus 11%, p&#x202f;>&#x202f;0.99). Among patients who did not undergo I&D in the operating room, no significant difference in FRI rate was found between patients who received oral versus IV antibiotics (17% versus 13%, p&#x202f;=&#x202f;0.74). Insulin-dependent diabetes was associated with an increased risk of FRI (60% versus 12%, p&#x202f;=&#x202f;0.02). CONCLUSIONS: In this cohort, one in seven patients developed FRI. No statistically significant differences in FRI rates were observed by I&D setting (bedside versus operative) or antibiotic route (oral versus IV), including in a subgroup analysis excluding patients treated with operating room I&D. These findings are limited by sample size and potential treatment selection bias and should not be interpreted as evidence of equivalence. Management should be individualized based on clinical judgement, resource availability, and patient factors. These findings can help guide the management protocols for "dropped objects" open forefoot fractures presenting to urgent care and the emergency department. LEVEL OF EVIDENCE: Therapeutic Level III.

Humans

Insights into the fate and dynamics of antibiotic resistance in multidrug-resistant Bacillus cereus during in vitro simulated gastrointestinal digestion.

Bacillus cereus, an important pathogen responsible for causing foodborne diseases worldwide, releases pore-forming enterotoxins, which target host epithelial cells, leading to osmotic lysis and ultimately manifesting as diarrheal syndrome. Moreover, some B. cereus strains carry antimicrobial resistance genes that confer multidrug resistance against a spectrum of antibiotics. Characterizing the survival traits of multidrug-resistant (MDR) B. cereus strains in the intestinal microenvironment is essential for developing targeted strategies to effectively manage diarrheal foodborne diseases caused by this pathogen. This study used whole-genome sequencing (WGS) to evaluate the pre- and post-digestion toxigenic potential, antimicrobial resistance profiles, and genetic diversity of MDR B. cereus strains isolated from food samples in Guangdong Province, China. The four B. cereus isolates investigated in this study exhibited a genetic diversity, as determined by multilocus sequence typing analysis of WGS data. All four isolates produced the diarrheal toxins Hbl, Nhe, and CytK to varying levels, indicative of their potential to cause outbreaks of foodborne diseases. Each of the four isolates exhibited resistance to more than three classes of antibiotics, fulfilling the criterion for multidrug resistance. At an initial concentration of 9 log colony-forming units (CFU)/mL, the intestinal concentration of these four isolates crossed the threshold required to induce widespread diarrhea in the general population. Under rice slurry protection, all tested isolates maintained intestinal concentration beyond the threshold when the initial concentration was increased to &#x2265;8 log CFU/mL. Moreover, the upregulations of genes associated with acid tolerance, bile tolerance and stress response were observed in the surviving MDR B. cereus isolates. Digestion markedly altered the antibiotic resistance profiles of the MDR B. cereus isolates. In the absence of a food matrix, the MDR isolates lost their resistance to imipenem, meropenem, amoxicillin-clavulanic acid, and trimethoprim-sulfamethoxazole post-digestion and was influenced by the initial concentration of the strains. In the presence of food matrix rice slurry, the effects of digestion on the antibiotic resistance of MDR B. cereus isolates can be mitigated, enabling them to maintain their antibiotic resistance to the greatest extent. Most remarkably, after digestion, the isolates Bce055 and Bce166 exhibited newly emergent resistance to cefotetan and trimethoprim-sulfamethoxazole, respectively. Our findings clarify the fate of MDR B. cereus isolates in the gastrointestinal tract and inform the development of prevention and control strategies for foodborne diseases caused by this pathogen.

Drug Resistance, Multiple, Bacterial

Community-tailored One Health educational intervention to enhance knowledge and practices for zoonotic disease prevention in rural Thailand: A protocol for a prospective cluster randomised controlled Trial in Chanthaburi, Thailand (Saan Suk trial).

BACKGROUND: Zoonotic infectious disease risk arises at human-animal-environment interfaces where pathogen spillover can occur. Rural communities living in biodiverse settings may experience frequent contact with wildlife and shared environments through livelihoods, food practices, and economic activities. Reducing spillover risk and strengthening pandemic prevention requires both structural and individual-level change. Community-based interventions that promote awareness, risk perception, self-efficacy, pro-environmental behaviour, and safe coexistence with wildlife may support prevention by shifting behavioural determinants of zoonotic disease risk. The Saan Suk intervention was co-developed with rural communities in Thailand using a Human-Centred Design approach and is grounded in the Health Belief Model and One Health principles. The intervention is intended to be feasible, acceptable, and deliverable through Thailand's established Village Health Volunteer (VHV) system. METHODS: This protocol describes a parallel-arm, cluster-randomised controlled superiority trial that will be conducted during July - October 2026, in Chanthaburi Province, Thailand. 24 villages will be equally randomised to the Saan Suk intervention or the current practice (control). In intervention villages, trained VHVs will deliver, once a week over four weeks, a multimodal One Health educational intervention designed to improve knowledge of zoonotic spillover, promote protective behaviours, reduce risky wildlife-related contacts, and support respectful coexistence with wildlife. Trained outcome assessment teams will conduct structured interviews with 42 adult participants per village, yielding a total sample size of 1,008 participants. The sample size was calculated for the primary outcome, accounting for clustering, with 90% power to detect a medium effect size (6 points on the 0-100 knowledge scale) at a significance level of 0.05, accounting for a design effect with an ICC of 0.028. The primary outcome is knowledge of zoonotic spillover, transmission pathways, risk factors, protective and risky behaviours, and safe coexistence with wildlife. Secondary outcomes include attitudes, self-efficacy, preventive and risky behaviours, and reported contacts with major local reservoir hosts. A structured questionnaire was developed, expert-reviewed, and piloted for the outcome assessment. Outcomes will be analysed using mixed-effects regression models with random effects for village and adjustment for relevant pre-specified confounders. Primary analyses will follow the intention-to-treat principle. DISCUSSION: This trial will evaluate whether a co-designed, VHV-delivered One Health educational programme can improve knowledge of zoonotic disease prevention and behavioural determinants in rural communities living in close contact with wildlife and shared ecosystems. If effective and feasible, Saan Suk could inform integration into routine VHV training and community-based zoonotic disease and pandemic prevention strategies. TRIAL REGISTRATION: The Saan Suk trial is registered with the German Clinical Trials Register (DRKS). Registration ID: DRKS00038582; date of registration: 11 May 2026.

Zoonoses

Wedge tarsectomy using patient specific instrumentation for complex multiplanar foot deformity Reconstruction: A prospective case series.

BACKGROUND: Bony correction in complex cavovarus deformities is often multiplanar. We examine our results following wedge tarsectomy (WT) using patient-specific instrumentation (PSI). METHODS: This single-centre, prospective case series evaluated noncorrectable cavovarus feet undergoing PSI-guided WT. Accuracy of PSI guides/plans, operative duration, and adjunctive procedures were recorded. Weightbearing CT (WBCT) measurements and PROM scores were recorded preoperatively and postoperatively, with 1 year follow-up. Data was then statistically analysed. RESULTS: Eleven patients were included. Planned correction was achieved (two required minor intraoperative adjustments to the initial osteotomy and nine required adjunctive procedures). Mean operative time was 135&#x202f;min. Postoperative improvements were significant radiologically and in MOxFW walking distance. All fused by 3 months, with no significant complications. CONCLUSION: PSI-guided wedge tarsectomy safely achieves predictable multiplanar corrections. Our unit's experience has been excellent, with improvement in patients' walking, particularly with larger deformity corrections. LEVEL OF EVIDENCE: Level IV, prospective case series.

Humans

Specific Instruments for Caregiving Competence Among Family Caregivers of Cancer Patients: A COSMIN Systematic Review of Psychometric Properties.

OBJECTIVE: To evaluate and summarize the psychometric properties of specific instruments for caregiving competence among family caregivers of cancer patients. METHODS: Systematically searched eight databases for studies published up to November 2025. The methodological quality and psychometric properties of the instruments were evaluated using COSMIN 2.0. Evidence grades were rated using the modified GRADE system (four grades: "High," "Moderate," "Low," and "Very Low"), and recommendations were formulated (Category A: recommended, Category B: potential with further validation, and Category C: not recommended). RESULTS: Seven studies were included, comprising three specific instruments: the Care Competency Scale for Family Caregivers in Home Palliative Care (CCSHPC) (n = 1), the Caregiver Caregiving Self-Efficacy Scale-Oral Cancer (CSES-OC) (n = 1), and the Caring Ability of Family Caregivers of Patients with Cancer Scale (CAFCPCS) (n = 5). Both the CCSHPC and CAFCPCS received Category B recommendations, demonstrating "adequate" content validity with evidence grades rated "very low" and "low," respectively. The CAFCPCS also shows good structural validity ("moderate") and internal consistency ("low") in some cultural contexts. The CSES-OC is a Category C recommendation, with high-quality evidence indicating "inadequate" criterion validity. CONCLUSION: Few specific instruments exist, and most did not strictly follow COSMIN guidelines. The CAFCPCS is provisionally recommended based on relative evidence superiority rather than complete psychometric validation. Further cross-cultural and localized instrument development is warranted. IMPLICATIONS FOR NURSING PRACTICE: Use well-validated specific instruments to identify strengths and weaknesses in the caregiving competencies of family caregivers of cancer patients, enabling them to deliver high-quality home-based cancer care.

Female

Structural and tissue-specific organisation of endocrine Fgf19 and Fgf21 signalling in rainbow trout.

Endocrine fibroblast growth factors (FGF19 subfamily) play a key role in regulating metabolic homeostasis in vertebrates. However, their functional diversification in salmonids remains poorly understood. In this study, we conducted an integrative characterisation of Fgf19 and Fgf21 signalling in rainbow trout (Oncorhynchus mykiss) by combining phylogenetic, structural and expression analyses. Phylogenetic analyses revealed the conservation of single fgf19 and fgf21 genes, despite the extensive expansion of receptors post-Ss4R (salmonid-specific fourth-round whole genome duplication). Structural modelling and molecular dynamics simulations demonstrated the stable interactions of both ligands to multiple Fgfr isoforms, with receptor-specific energetic profiles and conserved core interaction residues. Tissue expression profiling revealed clear differences from mammalian models, such as predominant hepatic fgf19 expression and the absence of hepatic fgf21 under basal conditions. In addition, there were complex and tissue-dependent distributions of fgfr and klotho transcripts. These findings support a receptor-driven diversification model of endocrine Fgf signalling in salmonids, suggesting enhanced endocrine plasticity associated with the retention of receptors following post-genomic duplication. Taken together, our findings provide new insights into the structural and regulatory organisation of endocrine Fgf signalling, as well as its potential role in metabolic regulation in rainbow trout.

Animals

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