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Tissue-derived extracellular matrix hydrogels instruct epigenetic adaptation in metastatic colonization.

The extracellular matrix (ECM) plays a central role in regulating tumor progression and metastatic colonization by providing biochemical and mechanical signals that shape cancer cell fate. However, most organoid culture systems rely on basement membrane extracts that fail to reproduce the tissue-specific extracellular environments encountered during metastasis. Here, we develop tissue-derived decellularized matrix hydrogels to reconstruct organ-specific microenvironments and investigate epigenetic adaptation to ECM cues during metastatic colonization. Patient-derived colorectal cancer organoids cultured in colon-derived matrices exhibited enhanced maintenance of stem-like phenotypes and colon-specific chromatin accessibility landscapes compared with cultures grown in basement membrane extracts, demonstrating improved physiological relevance for primary tumor modeling. When exposed to matrices derived from secondary organs, the organoids showed distinct growth phenotypes accompanied by rapid, tissue-dependent chromatin accessibility remodeling, indicating that ECM composition alone can reshape regulatory programs governing metastatic adaptation. Notably, liver-derived matrices selectively activated hepatocyte nuclear factor 4 alpha (HNF4A)-associated transcriptional networks and created a context-specific dependence on c-MET signaling for survival. Functional perturbation of HNF4A or c-MET signaling confirmed that both are required for organoid formation specifically within the liver matrix environment. Together, these findings establish tissue-derived matrix hydrogels as instructive bioactive materials that actively regulate cancer cell epigenetic states and reveal microenvironment-specific therapeutic vulnerabilities during early metastatic colonization.

Journal Article

BIOCARD framework: integrating fecal bile acids, lipids, and metabolites to assess response to a cardiovascular health intervention.

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality, particularly in under-resourced populations. Although nutritional interventions are important for CVD prevention, their outcomes are commonly evaluated using conventional clinical and behavioral indicators, which may not fully capture early molecular responses. In this study, we developed the BIOCARD framework, an exploratory fecal multi-omics platform integrating bile acids, lipids, and metabolites to evaluate intervention outcomes related to cardiovascular health. Fecal samples were collected from caregiver-child participants enrolled in a 10-week randomized controlled trial comparing a multicomponent garden-based intervention (SHA) with an education-only control group (MSP). Fecal polar metabolites, lipids, and bile acids were analyzed by UHPLC-HRMS-based approaches and integrated with conventional health indicators. Traditional clinical indicators in the present study showed limited sensitivity for detecting intervention-related differences. In contrast, fecal multi-omics analyzes revealed intervention-associated differences in metabolites, lipids, and bile acids, with children showing more apparent molecular variation than parents. Network analysis further revealed associations between selected molecular features and cardiovascular-related indicators, including blood pressure, body fat, skin carotenoids, and Healthy Eating Index scores. Together, these findings suggest that the BIOCARD framework may serve as an exploratory molecular approach to complement traditional outcome measures and improve the evaluation of nutritional interventions for cardiovascular health.

Humans

Mendelian randomisation for rheumatology: beyond hype-what it's good for, what it can't do, and how to read it critically.

Mendelian randomisation (MR) has become abundant in the literature, with variation in quality and frequent overinterpretation of causality. This creates a problem for clinical readers, reviewers, and editors: some MR studies can sharpen causal thinking, prioritise drug targets, and challenge misleading observational claims, whereas others are little more than automated exposure-outcome scans with causal claims disproportionate to the evidence. MR can strengthen causal inference when randomised trials are impractical and conventional observational studies are vulnerable to confounding, reverse causation, or selection bias. In rheumatology, credible MR can contribute to questions about disease aetiology, modifiable risk factors, therapeutic target validation, adverse-effect anticipation, and phenotype validation. However, its interpretation depends on whether the exposure is plausibly instrumentable, whether the genetic instruments are biologically defensible, whether assumptions are interrogated in ways appropriate to the design, and whether findings are triangulated with clinical, observational, experimental, and mechanistic evidence. Instead of recapitulating all methodological issues of MR, this review aims to help rheumatologists distinguish robust MR from weak or overinterpreted analyses quickly. We provide an accessible framework for reading and triaging MR studies in rheumatology. Papers that use poorly justified instruments, treat medication use as drug-target evidence, interpret genetic liability as diagnosis, rely on mechanical sensitivity analyses, ignore prior evidence or ask no clinically meaningful question can often be passed over by readers. The goal is not to discourage MR in rheumatology, but to raise the standard; useful MR should clarify causal reasoning rather than simply generate another statistically significant association.

Journal Article

A mechanism-guided framework for prioritizing membrane-interaction anti-Vibrio peptides from peptidomics data.

A mechanism-guided framework for prioritizing membrane-interaction antimicrobial peptide candidates from proteomics-derived peptide mixtures is presented. The framework integrates conservative machine-learning-based antimicrobial peptide (AMP) screening with a literature-derived membrane-interaction plausibility (MAP) assessment and a data-driven membrane-interaction ranking function (AIPx), followed by structural visualization for interpretability. MAP encodes physicochemical characteristics commonly associated with peptide-membrane interaction and provides a graded plausibility assessment. Building upon this physicochemically interpretable framework, AIPx ranks peptides using feature weights calibrated from experimentally characterized anti-Vibrio peptides, where minimum inhibitory concentration (MIC) values are used as a coarse-grained ranking reference rather than a direct prediction target. In a peptidomics-based peptide fractionation study targeting Vibrio spp., AIPx exhibited a consistent relationship with experimentally observed antibacterial activity. Distributional analysis revealed that peptide fractions exhibiting high anti-Vibrio activity are characterized by enrichment of high-ranking peptides rather than by AMP abundance alone. By structuring AMP identification and prioritization as sequential stages, the MAP + AIPx framework enables interpretable and experimentally actionable candidate selection by reducing biologically implausible candidates. The framework facilitates species-oriented prioritization of AMP candidates, addressing a key challenge in antimicrobial peptide discovery where activity may depend on target-specific membrane characteristics. Moreover, the approach is extensible through species-specific calibration and supports interpretable, mechanism-informed prioritization in antimicrobial peptide discovery.

Proteomics

Age- and sex-adjusted genomic differences between Korean and Beat AML cohorts.

Genomic profiling plays a central role in risk stratification and therapeutic decision-making in acute myeloid leukemia (AML), yet the clinical implications of population-specific genomic architectures remain incompletely defined. We conducted a prospective, multicenter study of 603 adults with newly diagnosed AML in Korea, integrating targeted sequencing of 83 recurrently mutated genes with comprehensive clinical annotation across treatment intensities, including allogeneic hematopoietic stem cell transplantation (allo-HSCT). For contextual comparison, genomic profiles were evaluated against the Beat AML cohort. The overall genomic landscape was broadly conserved, supporting shared core disease biology across populations. However, RUNX1::RUNX1T1, CEBPA, GATA2, KIT, and DDX41 mutations were more frequent in the Korean cohort, whereas FLT3 and NPM1 mutations were less common. These differences translated into a distinct distribution of European LeukemiaNet (ELN) 2022 risk categories, with implications for therapeutic stratification. Notably, most DDX41 alterations were germline (3.2%), highlighting the need for systematic germline evaluation with implications for genetic counseling and donor selection. Although unadjusted overall survival appeared longer in the Korean cohort, this difference was not significant after adjustment for key clinical variables. These findings indicate that population-specific genomic distributions reshape the clinical application of risk stratification and support population-aware precision medicine strategies in AML.

Journal Article

A genome-wide coverage-based pipeline for the identification of host-derived candidate DNA biomarkers from cell-free blood.

We have created a new data-analysis pipeline for the discovery of host-specific candidate DNA biomarkers derived from sequencing data of cell-free blood. Unlike approaches that rely on specific molecular or genetic signatures, our method leverages the coverage distribution of cell-free DNA sequences mapped to a reference genome, applying statistical analyses to identify informative short genomic regions for biomarker discovery. The pipeline is applicable to diverse diseases and can be used to analyze cell-free DNA sequences from plasma or serum to identify candidate biomarkers that are characteristic of disease states in mammals. Core functionalities were developed in Java and integrated with open-source software tools for the preprocessing of raw sequencing data, complemented by Python scripts for the machine-learning analysis and statistical validation. The pipeline is designed for HPC use and users can access the pipeline through a Galaxy workflow, which offers a user-friendly web interface for input selection prior to execution and analysis progress monitoring. Performance tests, carried out using duplicate sets of COVID-19 samples and controls, showed linear scalability of execution time with an increasing dataset size, as well as a substantial reduction in execution time through parallelized computation, whereby each HPC node is used to process the data of one chromosome. Further statistical tests confirmed the quality of the pipeline's results by showing that the set of identified candidate biomarkers remained stable across varying dataset sizes.

Biomarkers

Synaptic vesicle glycoprotein 2A PET imaging in parkinsonian α-synucleinopathies: a systematic review.

Synaptic dysfunction is increasingly recognized as an early and biologically relevant component of α-synucleinopathies. However, conventional imaging biomarkers mainly assess dopaminergic dysfunction, glucose metabolism, or structural damage rather than presynaptic density itself. Synaptic vesicle glycoprotein 2A (SV2A) PET enables in vivo assessment of presynaptic terminal integrity and may provide complementary information in Parkinson's disease (PD), Parkinson's disease dementia/dementia with Lewy bodies (PDD/DLB), and multiple system atrophy (MSA). This systematic review synthesized the available evidence on SV2A-targeted PET in parkinsonian α-synucleinopathies, focusing on regional imaging patterns, clinical associations, longitudinal findings, and methodological determinants of interpretation. Seventeen reports were included. In PD, the most recurrent finding was reduced SV2A binding in the substantia nigra, although additional involvement of brainstem, caudate, striatal, thalamic, raphe, or cortical regions was reported in selected cohorts. In PDD/DLB, abnormalities appeared broader and more cortical, with evidence of association between cortical SV2A binding and cognitive performance. In MSA, one study suggested a distinct infratentorial and cerebellar pattern with potential relevance for phenotypic stratification. SV2A PET is a promising research biomarker for biological characterization of synucleinopathies. However, the field remains limited by small cohorts, methodological heterogeneity, variable quantification strategies, limited longitudinal evidence, and potential cohort overlap. Multicentre validation and harmonized protocols are required before clinical translation.

Humans

Real-World Efficacy and Safety of Standard-of-Care Chimeric Antigen Receptor T-Cell (CART) and Bispecific T-Cell Engager (TCE) Therapies in Relapsed/Refractory Multiple Myeloma (RRMM).

We aimed to evaluate the real-world (RW) efficacy and safety of standard-of-care CART versus TCE therapies in relapsed/refractory myeloma (RRMM), to assess utilization, outcomes, and tolerability of these therapies in a RW oncology in the US. Data were derived from the US-based, electronic health record-derived deidentified Flatiron Health Research Database, 2021-2024. A total of 419 patients (CART n = 220; TCE n = 199) with a confirmed diagnosis of myeloma who received CART or TCE as a standard-of-care treatment after at least 2 prior lines of therapy were included. Patients in the CART cohort were younger, had better ECOG PS, and a higher receipt of a prior autologous stem cell transplant versus bispecific TCE cohort. In CART versus TCE cohort, the overall response rates (ORR) were 83.3% versus 66.3%, median duration of response 7.9 months versus 4.3 months, progression free survival (PFS) 13.6 months versus 10.5 months, and overall survival (OS) of 29.8 months versus 21.9 months, respectively. A higher percentage of hematologic toxicity, infections, and cytokine release syndrome (CRS) were noted in the CART versus TCE cohort. This study provides insights on the RW effectiveness of CART versus TCE in the treatment of RRMM; highlights the differences in patient selection, clinical responses, treatment duration, and toxicity profiles.

CART

Tracking GAD-specific T-cell expansions in Type 1 diabetes by intradermal GAD-Alum challenge.

Identifying and monitoring autoreactive T cells that drive beta cell destruction remains a major obstacle to developing effective immunotherapies for type 1 diabetes (T1D). These cells are extremely rare in peripheral blood and cannot be accessed directly from the pancreas. We used intradermal injection of Glutamic Acid Decarboxylase (GAD)-Alum to recruit GAD-specific T cells to accessible sites in the skin and skin-draining lymph nodes (LNs), sampled by skin suction blisters and ultrasound-guided LN aspiration. Peripheral blood samples obtained before GAD injection were restimulated with GAD in vitro to detect reactive CD4+ T cells. Single-cell RNA sequencing (scRNAseq) followed by re-expression of selected T cell receptors (TCRs) confirmed antigen specificity. Up to 70% of T cells at the skin injection site were clonally-expanded and 4 of 14 (28%) re-expressed TCRs were GAD-reactive. In LNs 1 of 14 (4%) clonally-expanded TCRs was GAD-reactive, representing ~0.08% of all T-cells. GAD-reactive cells across compartments displayed Th1 and Th17-associated transcription signatures. These results demonstrate the intradermal autoantigen challenge and scRNAseq, enable direct identification and molecular profiling of autoreactive T cells in vivo. This minimally invasive approach provides a powerful platform for tracking antigen-specific T cells to monitor disease activity and evaluate immune interventions in T1D.

Autoimmunity

Pathway incompatibility between NF-κB and RAS signaling constrains oncogenicity in B-cell leukemia.

Oncogenic pathways do not always cooperate; in some contexts, their co-activation is antagonistic and suppresses tumorigenesis, a phenomenon we termed pathway incompatibility. However, the mechanisms underlying this antagonism and the role of receptor context in shaping these interactions remain unclear. During normal B-cell development, precursor B-cell receptor (pre-BCR) signaling supports survival and proliferation of early B-cell precursors before transition to expression of the mature B-cell receptor (BCR). B-cell acute lymphoblastic leukemia (B-ALL), the most common childhood cancer, is characterized by developmental arrest prior to BCR expression, and approximately 35% of cases harbor activating RAS-ERK mutations that mimic pre-BCR-dependent survival signaling. NF-κB plays context-dependent roles in B-cell malignancies, but whether it influences the compatibility between oncogenic RAS signaling and BCR expression remains poorly understood. Activation of canonical NF-κB induced apoptotic depletion of RAS-driven B-ALL cells. Mechanistically, NF-κB suppressed pre-BCR-dependent survival signaling while promoting expression of BCR components. Consistent with this shift, oncogenic RAS signaling was poorly tolerated in BCR-positive cells unless BCR expression was disrupted. Pharmacologic activation of NF-κB reduced ERK signaling and selectively impaired viability of RAS-driven B-ALL cells, with enhanced effects in combination with ERK inhibition. Together, these findings show that canonical NF-κB signaling promotes BCR expression, which constrains oncogenic RAS activity, and establish pathway incompatibility as a mechanism through which receptor context can limit oncogenic potential.

Cancer biology

Biliary Cirrhosis in Myhre Syndrome: The First Case Report of Liver Transplantation and a Review of Reported Hepatic Findings.

Myhre syndrome is a rare autosomal-dominant disorder caused by gain-of-function pathogenic variants in SMAD4 and is now recognized as a progressive multisystem fibrotic disease. Although transforming growth factor-β (TGF-β) signaling plays a central role in hepatic fibrogenesis, hepatobiliary involvement in Myhre syndrome has not been systematically evaluated. We report the first case of Myhre syndrome complicated by rapidly progressive biliary cirrhosis requiring liver transplantation in a 15-year-old male with a confirmed SMAD4 p.Ile500Val variant. Following an infectious episode, the patient developed severe cholestasis with imaging and histopathologic findings consistent with fibro-obliterative cholangiopathy, ultimately necessitating living donor liver transplantation. A systematic review of 55 published reports comprising 217 patients with Myhre syndrome revealed that hepatic evaluation was rarely performed and that previously reported liver abnormalities were mild and secondary, most commonly related to right heart dysfunction or metabolic disease, with no prior cases of progressive biliary fibrosis. This case suggests that dysregulated SMAD4-TGF-β signaling may predispose selected organs to fibro-obliterative injury and that infection-driven inflammation may act as a critical trigger for hepatic fibrosis in Myhre syndrome, expanding the recognized spectrum of organ involvement in this disorder.

Humans

Metatranscriptomic analysis of viral sequences associated with Culex nigripalpus at an Alabama aquaculture site.

Mosquitoes associated with aquaculture habitats can harbor diverse viruses, yet the viromes of many locally abundant species remain poorly characterized. At an aquaculture-associated site in Auburn, Alabama, we surveyed mosquito populations and found Culex nigripalpus to be the dominant species collected. To characterize viruses associated with this mosquito, we performed RNA-seq on pooled female Cx. nigripalpus and compared complementary bioinformatic workflows for viral detection and genome recovery. One workflow removed host-associated reads by mapping to the closest available mosquito reference genome prior to assembly, whereas a second workflow used fully de novo assembly and viral database annotation. Additional protein-level filtering, cross-workflow comparison, and comparison of Trinity and rnaSPAdes assemblies were used to prioritize well-supported viral candidates. Across the original analyses, 16 submitted accessions corresponding to 12 collapsed virus/name groups were recovered, including Merida virus, Hubei mosquito virus 5, Zhejiang mosquito virus, Hubei virga-like virus 3, Rinkaby virus, Elemess virus, Qingnian mosquito virus, Serbia narna-like virus 2, XiangYun narna-levi-like virus 8, Ecclesville picorna-like virus, and baculovirus-like fragments. Several candidates were supported across multiple workflows, while others were recovered only under specific analytical conditions, indicating that candidate recovery was influenced by assembly and filtering choices. Selected viral contigs were independently supported by RT-PCR amplification. Overall, these results provide a first characterization of viral sequences associated with Cx. nigripalpus from an Alabama aquaculture-associated site and show that comparison across assembly and filtering strategies helped prioritize the most consistently supported viral candidates.

Animals

A User-Friendly Protocol for Microinjection into Teleost Embryos to Study Gene Function.

Zebrafish (Danio rerio) and medaka (Oryzias latipes) are popular teleost models used in developmental biology and functional genomics. To achieve high-quality and reproducible microinjections, it is essential to have robust protocols for breeding, egg collection, and the precise delivery of genetic material. In this protocol, we present a comprehensive and optimized methodology for setting up breeding tanks under controlled photoperiod conditions to maximize egg yield while minimizing contamination. We provide detailed procedures for sex identification, pair selection, the use of grated breeding inserts, and methods to increase egg collection efficiency. We outline procedures for making injection gel beds, pulling needles, and calibration using one-microliter microcapillaries to achieve consistent nanoliter-scale injections. Our protocol outlines settings for the pico-liter injector that are optimized to deliver a precise amount per pulse with minimal variability. Finally, we demonstrate the application of these methods for gene knockdown using morpholino antisense oligonucleotides, gene knockout using CRISPR-Cas9, and gain-of-function mRNA overexpression experiments. Phenotypic assessments conducted at various developmental stages to evaluate gene-specific effects reveal consistent phenotypic outcomes between the morpholino and CRISPR-Cas9 approaches. This easy and comprehensive protocol enables efficient, precise, and scalable genetic manipulation of zebrafish and medaka embryos, thereby supporting advanced functional studies in developmental biology and disease modeling. To our knowledge, this is the first unified protocol for both zebrafish and medaka microinjection systems achieving 97.7% phenotype penetrance in CRISPR-Cas9 knockouts with precision together with a triple validation approach that confirms gene function across multiple techniques.

Animals

Re-evaluating pediatric laryngoscope blade size recommendations: Comparable intubation performance across blade sizes in pediatric manikin models.

BACKGROUND: Pediatric airway management traditionally emphasizes strict adherence to age-based laryngoscope blade size recommendations, despite limited empirical validation. OBJECTIVES: To evaluate whether intubation performance varies across a range of blade sizes, and whether a Macintosh 2 blade performs comparably across multiple pediatric age groups in a simulation setting. METHODS: We conducted a randomized crossover simulation study using three pediatric airway manikins (neonate, infant, and child age groups). Emergency medicine residents and faculty physicians performed intubations using multiple laryngoscope blade types and sizes, including standard and nonstandard options. Primary outcomes were intubation time and first-attempt success. Secondary outcomes included complications and operator-rated ease of glottic view and tube passage. Between-blade differences were estimated with 95% confidence intervals. RESULTS: Across manikin sizes and blade types, intubation times were short and first-attempt success rates exceeded 98% in most conditions. Performance remained consistent even with blade sizes outside conventional age-based recommendations. Between-blade differences in intubation time were small, and complication rates were low across conditions. The Macintosh 2 blade performed comparably across all manikin sizes, with similar intubation times, high success rates, and favorable ease ratings. CONCLUSIONS: Intubation performance in pediatric manikin models was similar across a wide range of blade sizes. These hypothesis-generating findings warrant prospective clinical evaluation of simplified blade selection strategies for pediatric intubation.

Manikins

Genome-wide identification and expression profiling of CSP and OBP genes in Stictocephala bisonia reveals candidate genes potentially associated with insecticide response.

Stictocephala bisonia is an important invasive agricultural pest. Due to the frequent application of insecticides in its habitat, this species is under intense selection pressure. Chemosensory proteins (CSPs) and odorant-binding proteins (OBPs) are known to play key roles in insecticide resistance, but their specific functions in S. bisonia remain unclear. In this study, we identified a total of 22 SbisCSPs and 16 SbisOBPs based on the S. bisonia genome. To screen for candidate genes potentially linked to insecticide resistance, we adopted a multi-criteria screening strategy that integrated phylogenetic analysis, molecular docking with three insecticides, and tissue-specific expression profiling. Phylogenetic analysis identified several SbisCSPs and SbisOBPs clustering with genes known to be involved in insecticide resistance, serving as an initial evolutionary filter. Molecular docking results indicated that λ-Cyhalothrin exhibited the strong predicted binding affinity with most of SbisCSPs and SbisOBPs. Subsequent qPCR validation of seven prioritized candidates revealed distinct expression patterns: SbisCSP22 was highly expressed in adults and demonstrated strong binding affinity to all three insecticides tested, suggesting a potential role in mediating multi-insecticide response. Conversely, SbisCSP17 was significantly upregulated in larvae, clustered with genes known to mediate imidacloprid resistance, and exhibited strong binding affinity to imidacloprid. Given its larval-specific expression and the soil-dwelling behavior of larvae, we hypothesize that SbisCSP17 is a key candidate gene for larvae coping with soil-treated insecticides.

Animals

Genome-wide analysis of the plant-specific PLATZ gene family in Taraxacum kok-saghyz and its roles in response to drought and salt tolerance.

Abiotic stress severely limits plant growth and productivity. Taraxacum kok-saghyz Rodin (TKS), known for its environmental resilience, represents a valuable resource for identifying stress-tolerant genes to improve stress-adaptive crops. Plant AT-rich protein and zinc-binding protein (PLATZ) transcription factors serve as core regulators of plant growth, developmental processes, and adaptive responses to various stress conditions; however, they remain uncharacterized in TKS. Here, we identified 10 TksPLATZ genes through a whole-genome analysis. Phylogenetically, these genes were grouped into five distinct evolutionary branches. Promoter sequence analysis revealed multiple types of cis-acting regulatory elements that are connected with hormonal signal responses and environmental stress adaptation. Integrated analysis of transcriptome datasets and RT-qPCR validation demonstrated that TksPLATZ genes display tissue-specific expression profiles and show distinct responsive patterns to drought and salt stress treatments. Among them, TksPLATZ1, TksPLATZ2 and TksPLATZ7 were markedly induced under both stressors and were selected for further functional study. We demonstrated that TksPLATZ1, TksPLATZ2 and TksPLATZ7 localize to the cell nucleus and act as transcriptional activators and repressors, respectively. Phenotypic data from overexpression experiments in plants confirm that heterologous expression of TksPLATZ1, TksPLATZ2, and TksPLATZ7 enhances the tolerance of Arabidopsis to salt and osmotic stress. These findings provide valuable genetic resources for improving plant tolerance to environmental stresses.

Salt Tolerance

Comparative analyses of olfactory receptor repertoires in Schizothorax fish based on the chromosome-level genomes: Implications for regulatory roles of dietary differentiation and ploidy variation.

The olfactory receptor (OR) genes constitute the molecular basis of fish olfaction, mediating survival behaviors and environmental adaptation while coevolving with habitat-driven evolution. Schizothorax, a cyprinid genus endemic to the Qinghai-Tibetan Plateau, exhibits remarkable dietary divergence and ploidy variation in response to plateau environmental changes, which presumably facilitates the adaptive evolution of OR genes. However, the evolutionary patterns of OR genes associated with trophic divergence and ploidy variation in this genus remain unclear. In this study, three species were selected: the herbivorous diploid S. macropogon, the carnivorous diploid S. lantsangensis, and the herbivorous tetraploid S. curvilabiatus. S. macropogon possessed 142 OR genes (92.25% functional), primarily located on chromosomes 14 and 24, with the fewest sequence clusters. Such compact gene repertoire and highly overlapping chromosomal clusters indicated specialization for a herbivorous olfactory niche. S. lantsangensis contained 127 OR genes (93.70% functional), concentrated on chromosomes 4 and 5, with fewer sequence clusters and a scattered distribution, reflecting evolution of OR genes under carnivorous feeding habits. The herbivorous tetraploid S. curvilabiatus exhibited striking features: 316 OR genes (94.30% functional), the most subfamilies, unique ε and κ OR subfamilies, and species-specific motifs. These characteristics revealed that ploidy, rather than herbivory, dominated OR gene evolution. In conclusion, dietary differentiation and ploidy variation together drove olfactory adaptive evolution in Schizothorax, providing new insights into vertebrate OR gene ecological adaptation.

Animals

Hybrid robotic transversus abdominis release (hrTAR) for complex ventral hernias: a systematic review and preliminary synthesis.

Hybrid robotic transversus abdominis release (hrTAR) combines robotic posterior component separation with a planned limited open phase. Evidence supporting this strategy is sparse. Following PRISMA 2020, we searched PubMed, Embase, Scopus, and the Cochrane Library and registered the protocol in PROSPERO (CRD420261303285). Eligible studies reported hrTAR outcomes for ventral or incisional hernia repair. Findings were synthesized narratively; no pooled effect estimates were calculated. Three reports contained 85 hrTAR cohort entries. Because two reports came from the same institution and overlap could not be excluded, this total should not be interpreted as a unique-patient count. Surgical-site outcomes were heterogeneous: two reports used SSO endpoints (4% and 5%), whereas another reported surgical-site events in 25% of patients, including seroma and wound infection. Mean length of stay ranged from 1.8 to 3.7 days; the sample-size-weighted mean across studies reporting means was 2.9 days. One propensity-matched comparison reported shorter hospitalization and lower 30-day SSO with hrTAR than open TAR. No perioperative deaths or recurrences were reported during limited follow-up. hrTAR appears feasible in selected patients, but available evidence is exploratory. Standardized prospective multicenter studies with non-overlapping cohorts and longer follow-up are needed before comparative effectiveness, economic value, or wider adoption can be supported.

Humans