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PubMed2026

Unveiling the power of TIIC: A prognostic tool for esophageal adenocarcinoma.

BACKGROUND: Esophageal adenocarcinoma (EAC) remains a lethal malignancy with limited prognostic tools for guiding immunotherapy. Tumor-infiltrating immune cells (TIICs) play a critical role in EAC prognosis and treatment response. METHODS: We integrated single-cell RNA sequencing and bulk transcriptome data from TCGA and GEO databases. TIIC-specific RNAs were identified via tissue specificity index calculation combined with machine learning feature selection. Twenty machine learning algorithms were benchmarked to construct an optimal TIIC signature score (TIIC-Score) based on the comprehensive C-index. Immunotherapy response, genomic mutation, and copy number variation were analyzed. Summary-data-based Mendelian randomization (SMR) and two-sample Mendelian randomization (MR) were performed to explore genetic associations. Core prognostic TIIC-related genes were functionally validated in esophageal cancer cell lines through loss-of-function assays. RESULTS: The TIIC-Score demonstrated robust prognostic value for 1-, 2-, and 3-year overall survival across multiple cohorts, outperforming 22 published models. High TIIC-Score was associated with poor survival and increased chromosomal instability. Mutation profiling revealed high frequencies of TP53 (78.2%), TTN (48.7%), and SYNE1 (30.8%). MR analysis identified a significant association between gastro-oesophageal reflux and EAC risk at SNP rs8130507. Functionally, CCNI was upregulated in esophageal cancer cells, and its knockdown suppressed malignant phenotypes while promoting apoptosis, supporting its pro-tumorigenic role. CONCLUSION: The TIIC-Score provides a novel prognostic framework for EAC that effectively stratifies patient risk and may help identify individuals most likely to benefit from immunotherapy.

Esophageal adenocarcinoma↗

PubMed2026

Analyzing salinity tolerance in grass carp (Ctenopharyngodon idella): Insights from genome-wide association study and genomic selection.

Grass carp (Ctenopharyngodon idella) is one of the most widely cultured freshwater fish species globally. However, the expansion of its farming scale faces severe limitation owing to freshwater scarcity; therefore, the development of strains with greater salinity tolerance is key for expanding production using brackish water resources. To investigate the genetic basis of salinity tolerance in grass carp, a genome-wide association study (GWAS) was conducted using 200 individuals representing extreme phenotypes, namely salinity-tolerant and salinity-sensitive groups. In total, 17 single nucleotide polymorphisms (SNPs) related to salinity tolerance were detected, which were distributed across 11 chromosomes. Through gene annotation, 38 candidate genes were obtained from these loci. Enrichment analysis revealed these candidate genes are primarily implicated in key biological processes, including osmotic regulation, energy metabolism, and stress responses. Analyses of different SNP densities revealed that the 5 K SNP density panel can balance prediction accuracy and computational efficiency. The BayesA model achieved the highest prediction accuracy under the GWAS_Evenly selection strategy, with substantial reductions in mean absolute error and mean square error. This study reveals the genetic mechanisms of salinity tolerance in grass carp, which might be optimized through genomic selection, and provides insights for selectively breeding new varieties with greater salinity tolerance.

Animals↗

PubMed2026

Tigecycline-resistant Staphylococcus in waiting pens of a pig slaughterhouse: genomic insights into a food safety alert.

BACKGROUND: The waiting pens of slaughterhouses represent a critical control point in the 'farm-to-fork' continuum, yet their role in the emergence and dissemination of antimicrobial resistance remains understudied. This study investigated tigecycline-resistant Staphylococcus (TRS) in these high-risk zones to assess their prevalence, resistance mechanisms, and transmission dynamics. METHODS: 400 samples were collected from the waiting pens of a pig slaughterhouse in Guangzhou, China. Antimicrobial susceptibility testing, whole-genome sequencing, phylogenetic analysis, and molecular cloning were employed to characterize resistance mechanisms and transmission patterns. RESULTS: 78 TRS strains were isolated and classified into three species, including S. borealis, S. ureilyticus, and S. pasteuri. These isolates exhibited multidrug-resistant phenotypes and carried new mutations in rpsJ and tet(M), which were functionally confirmed to reduce tigecycline susceptibility. Phylogenetic evidence demonstrated clonal transmission between pig farms and the slaughterhouse. The tet(M) gene was located within Staphylococcal cassette chromosome mec elements mediated by IS257, while tet(L) was carried by plasmids formed through IS256/IS257-mediated recombination. CONCLUSIONS: Waiting pens serve as crucial reservoirs for the amplification and dissemination of antimicrobial resistance. Our findings underscore the urgent need for enhanced biosecurity measures, improved waste management, and routine molecular surveillance in these high-risk zones to mitigate the spread of resistance along the food production chain.

Animals↗

PubMed2026

Genome-wide characterization of the TGF-β superfamily identifies bmp15, gdf9, and gsdf as sex-biased candidate regulators of gonadal differentiation in the synchronous hermaphrodite Plectropomus leopardus.

The transforming growth factor-β (TGF-β) superfamily plays conserved roles in vertebrate reproduction and gonadal sex differentiation. However, its genomic repertoire and sex-biased expression patterns remain unclear in the leopard coral grouper (Plectropomus leopardus), a species with synchronous hermaphroditism. Here, we performed a genome-wide identification of the TGF-β superfamily, identifying 42 genes from the chromosome-level genome. Phylogenetic and synteny analyses indicated that segmental duplication under purifying selection contributed to family expansion. Expression profiling across multiple tissues and four gonadal developmental stages (undifferentiated, 120 dph; early differentiated, 15 months; mature testis, 3 years; mature ovary, 3 years) identified eight gonad-enriched genes, among which bmp15 and gdf9 exhibited pronounced female-biased expression, with transcripts localized exclusively to the oocyte cytoplasm, particularly in stage II-III oocytes. In contrast, gsdf showed male-biased expression and was localized in spermatogenic cells of the testis. These reciprocal expression patterns indicate that bmp15/gdf9 and gsdf are candidate factors associated with gonadal sex differentiation. Our study provides the first comprehensive characterization of the TGF-β superfamily in P. leopardus and highlights bmp15, gdf9, and gsdf as candidate sex-differentiation factors in this hermaphroditic species.

Animals↗

PubMed2026

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↗

PubMed2026

Genome-guided stage- and tissue-resolved transcriptome analysis of Serrodes campana identifies sex-biased antennal expression and candidate chemosensory-related genes.

Serrodes campana is an erebid moth of ecological and forestry relevance; its larvae are mainly associated with the soapberry tree, Sapindus mukorossi, whereas adults exhibit fruit-piercing behavior. However, stage- and tissue-resolved transcriptomic resources for this species remain limited. Here, using a chromosome-level reference genome, we performed a genome-guided transcriptome analysis of S. campana based on 12 RNA-seq libraries representing major developmental stages and key adult tissues. Global transcriptomic analyses revealed pronounced transcriptional differentiation across developmental stages and tissue types. Tissue-enriched gene sets and functional enrichment analyses identified distinct molecular signatures associated with developmental, sensory, and pheromone-associated tissues. Comparative analysis of female and male antennae further revealed sex-biased expression of several candidate chemosensory-related genes. Among 153 curated chemosensory-related candidate genes, most odorant receptor genes showed strong antennal enrichment, whereas other major chemosensory gene families displayed broader but still tissue-preferential expression patterns. In addition, an exploratory comparison of female terminal abdominal gland tissue and male terminal abdominal coremata revealed divergent expression profiles and highlighted candidate genes potentially associated with pheromone-related physiology, reproduction, and tissue-specific signaling. Together, this study provides the first genome-guided stage- and tissue-resolved transcriptomic resource for S. campana and offers a useful foundation for future studies of chemosensory detection, sex-biased gene expression, and pheromone-associated biology in this species.

Animals↗

PubMed2026

Reference genome of the Californian trapdoor spider Aptostichus stephencolberti Bond 2008 (Araneae: Mygalomorphae: Euctenizidae).

We present a reference genome assembly for the trapdoor spider Aptostichus stephencolberti. This species, described in 2008, is endemic to the highly fragmented coastal dune habitats of Northern California from Monterey to the San Francisco Bay Area. Trapdoor spiders are ideal taxa for landscape scale genomic studies owing to their extreme site fidelity and limited dispersal capabilities; these same characteristics make them prone to extinction. Genomic studies of species like A. stephencolberti can reveal novel areas of endemism and high conservation value that may not be evident in species with wider ranges and greater dispersal capabilities. As part of the California Conservation Genomics Project, we constructed the A. stephencolberti reference genome from high quality long-read sequences, scaffolded with proximity ligation Omni-C data. The primary assembly comprises 551 scaffolds spanning 3.63 Gbp, a scaffold N50 of 62.2 Mbp and BUSCO completeness of 95.6%. We estimate 52 chromosomes yet find no (TTAGG)n telomer repeats. Expanding the telomeric repeat search finds an ancestral loss of the repeat from all spiders. Automated annotation using the NCBI refseq pipeline and RNAseq data from whole adults finds 14,067 genes with a BUSCO annotation completeness of 95.56%. Repeat annotation identified 77% of the genome to be interspersed repeats. This resource, the first for family Euctenizidae will facilitate future study and resulting conservation actions of A. stephencolberti and other Aptostichus sp. populations associated with the rapidly changing California coastal dune ecosystem.

Aptostichus stephencolberti↗

PubMed2026

Safety, tolerability, and efficacy of alixorexton, a selective orexin 2 receptor agonist for narcolepsy type 1 (Vibrance-1): a randomised, double-blind, placebo-controlled, phase 2 trial.

BACKGROUND: The clinical potential of orexin 2 receptor (OX2R) agonism for improving measures of wakefulness and cataplexy in patients with narcolepsy type 1 has been described in a phase 2 study. Here, we aimed to evaluate the safety, tolerability, and efficacy of alixorexton, another oral OX2R agonist, in narcolepsy type 1. METHODS: In this randomised, double-blind, placebo-controlled, phase 2 trial, adult participants (aged 18-70 years) with narcolepsy type 1 were recruited from 46 hospitals and private research centres across the USA, Europe, and Australia. Participants were centrally randomly assigned (1:1:1:1) in blocks of four via an interactive response technology system stratified by region and baseline weekly cataplexy rate (WCR) to receive 4 mg, 6 mg, or 8 mg tablets of alixorexton or placebo once daily for 6 weeks, followed by an optional 7-week open-label extension. Participants had narcolepsy type 1, diagnosed per the International Classification of Sleep Disorders, Third Edition, and confirmed by overnight polysomnography and the Multiple Sleep Latency Test or cerebrospinal hypocretin-1 concentrations. The sponsor, assessors, investigators, and participants were masked during the randomised double-blind treatment period. Efficacy and safety assessments were conducted in participants who received at least one dose of study drug. The primary endpoint was change from baseline to week 6 in mean sleep latency (MSL) on the Maintenance of Wakefulness Test (MWT). Safety endpoints included treatment-emergent adverse events. This trial was registered with ClinicalTrials.gov (NCT06358950) and is completed. FINDINGS: Between May 24, 2024, and May 5, 2025, 153 individuals were screened and 92 participants were randomly assigned to receive alixorexton 4 mg (n=23), 6 mg (n=22), 8 mg (n=24), or placebo (n=23). Mean age was 33·5 years (SD 12·1), 57 (62%) were women, and 35 (38%) were men. At week 6, the observed MSL on the MWT was 2·3 min (SD 2·7) for placebo, 24·0 min (8·7) for alixorexton 4 mg, 25·9 min (9·4) for 6 mg, and 28·2 min (11·4) for 8 mg. Alixorexton improved MSL on the MWT, with a least-squares mean placebo-corrected change from baseline of 22·2 min (95% CI 17·2-27·2) for alixorexton 4 mg, 24·1 min (19·0-29·1) for 6 mg, and 26·0 min (21·0-31·0) for 8 mg (adjusted p=0·0099 for 4 mg, adjusted p<0·0001 for 6 mg and 8 mg). Treatment-emergent adverse events occurring in at least 5% of participants given alixorexton and more frequently than those given placebo up to week 6 were pollakiuria (38 [55%]), insomnia (19 [28%]), salivary hypersecretion (17 [25%]), micturition urgency (ten [14%]), blurred vision (ten [14%]), and hyperhidrosis (five [7%]). INTERPRETATION: In this phase 2 trial, once-daily oral alixorexton provided clinically meaningful improvements at 6 weeks for participants with narcolepsy type 1, including in wakefulness, excessive daytime sleepiness, and cataplexy. The treatment was generally well tolerated, with adverse events consistent with the known on-target effects of OX2R agonists. Together, these findings support the further phase 3 evaluation of alixorexton as a potential therapeutic option for people with narcolepsy type 1. FUNDING: Alkermes.

Humans↗

PubMed2026

Systematic modular engineering of genome-integrated Escherichia coli MG1655 for high-level 2'-fucosyllactose production.

2'-Fucosyllactose (2'-FL), the most abundant human milk oligosaccharide (HMO), has attracted considerable interest for its prebiotic and immunomodulatory functions, with broad applications in infant nutrition. In this study, we report the development of a high-yield, genome-integrated 2'-FL-producing strain based on Escherichia coli MG1655 through systematic modular optimization. Starting from a single-copy BKHT strain (MGC06), we first optimized the copy number of the α-1,2-fucosyltransferase (α-1,2-FT) gene BKHT. Subsequently, the GDP-L-fucose supply was enhanced through coordinated genomic integration of the gene clusters cpsG-cpsB and gmd-fcl, while the multidrug efflux transporter gene mdfA was integrated to improve product export and strain robustness. BKHT copy number was then re-evaluated in the optimized background, with four copies yielding the highest production. The final engineered strain, harboring all genetic modifications stably integrated into the chromosome, produced 17.18 g/L 2'-FL in shake-flask culture. In fed-batch fermentation using a 5-L bioreactor, this strain achieved a titer of 154.12 g/L after 60 h, with a productivity of 2.57 g/L/h. Notably, throughout the entire fermentation process, no antibiotics or inducers were supplemented, underscoring the genetic stability and regulatory compliance of this plasmid-free system. To our knowledge, this represents the highest 2'-FL titer reported to date, positioning our engineered strain as a promising candidate for commercial 2'-FL production.

Escherichia coli↗

PubMed2026

Genome-wide identification of the HSP70 superfamily in tropical sea cucumber Stichopus monotuberculatus and their expression analysis under low-salinity stress.

Heat shock proteins (HSPs) are a group of evolutionarily conserved molecular chaperones that serve as indispensable core regulators in preserving cellular homeostasis and orchestrating organismal stress responses. The tropical sea cucumber Stichopus monotuberculatus, a high-value aquaculture species, is sensitive to fluctuations in environmental salinity-a challenge that has emerged as a critical bottleneck limiting its large-scale commercial cultivation. However, no systematic investigation has been conducted to characterize the HSP70 superfamily in S. monotuberculatus and elucidate its functional roles in salinity adaptation. In the present study, we performed a comprehensive genome-wide scan and identified 19 HSP70 superfamily genes in the S. monotuberculatus genome, with the HSP70IV subfamily showing remarkable gene expansion, containing 8 distinct copies. Phylogenetic analysis, conserved motif identification, and gene structure characterization demonstrated high evolutionary conservation within each HSP subfamily. These genes were unevenly distributed across the chromosomes of S. monotuberculatus, and prediction of cis-acting elements revealed that their upstream regulatory regions were enriched with numerous functional elements associated with stress response and immune regulation. Salinity stress experiments revealed that under severe low-salinity conditions (18‰), the expression levels of SmHSPA14L and multiple HSP70IV subfamily members were significantly elevated, while SmHYOU1D was significantly downregulated; in contrast, only subtle changes were detected in the expression of most HSP70 genes under moderate low-salinity stress (24‰). These findings strongly suggest that HSP70 genes, particularly the expanded HSP70IV subfamily, may act as key modulators in the low-salinity stress response. This work provides valuable insight into the molecular mechanisms underlying salinity adaptation in tropical sea cucumbers.

Animals↗

PubMed2026

Surgical management of esophageal atresia with tracheoesophageal fistula in extremely low birth weight neonates: A systematic review.

BACKGROUND: Surgical management of esophageal atresia/tracheoesophageal fistula (EA/TEF) in extremely low birth weight (ELBW) neonates remains challenging and controversial. This study systematically reviews surgical strategies and outcomes in this population. METHODS: Following PRISMA guidelines, Cochrane, Embase, MEDLINE, Scopus, and Web of Science (2004-2024) were searched in February 2025 for studies on surgical management of ELBW neonates with EA/TEF (PROSPERO CRD42025636228). Fatal chromosomal abnormalities were excluded. Demographics, comorbidities, surgical techniques, and complications were analyzed descriptively. Risk of bias was assessed. RESULTS: Eleven publications (five case reports and six case series) comprising 30 patients (Gross type B/C = 1/29) met the eligibility criteria. Mean gestational age was 28.1 (23-34) weeks, and mean birth weight was 760.4 (422-995) g. Twelve primary repairs (PR) and 18 delayed primary repairs (DPR) were performed, including staged repair (n = 11), lower esophageal banding (n = 4), and other techniques (n = 3). Postoperatively, four anastomotic leaks were managed conservatively, six strictures and one recurrent TEF required endoscopic intervention, three fundoplications and two aortopexies were reported (follow-up: 1-198 months, n = 19). Overall mortality was 30% (PR: 8.3%; DPR: 44.4%). Mortality was 60% among neonates with major congenital heart defects (CHD) and 40% among those with VACTERL association. EA/TEF-related complications contributed to 33.3% of deaths. CONCLUSIONS: Mortality in this cohort remains high, particularly with major CHD, and is largely unrelated to EA/TEF-specific complications. In selected cases, PR appears feasible as an alternative to DPR, although conclusions are limited by the small sample size and heterogeneous studies.

Humans↗

PubMed2026

Genome-wide characterisation of the myosin light chain gene family in Chinese perch (Siniperca chuatsi) and its expression patterns in muscle fibre types and injury response.

The Class II myosin light chain (myl) genes in Chinese perch (Siniperca chuatsi) have not yet been systematically characterised, and relationships with muscle fibre specification, development, and injury-associated remodelling remain unclear. In this study, fast and slow muscle fibres were initially distinguished using myofibrillar ATPase histochemistry. Subsequently, genome-wide mining identified 16 Class II myl genes, comprising eight essential and eight regulatory light-chain subunits. Their conserved-domain features, chromosomal distribution, phylogenetic relationships and expression profiles were analysed. Transcriptomic profiling showed that summed myl transcript abundance was higher in fast muscle than in slow muscle, accounting for 67.2% of the pooled myl transcript pool across the two muscle types (paired t-test, raw P = 0.036). mylpfa, myl1 and mylz3 were the major fast-muscle-associated genes, whereas myl10, myl2b and myl13 were preferentially expressed in slow muscle at the transcript level. These patterns support these genes as candidate fibre-type-associated expression markers. Developmental profiling identified stage-associated myl expression patterns, including a possible expression shift between mylpfb and mylpfa. In the descriptive injury-repair time course (d0-d7), FPKM profiles indicated that fast-muscle-associated genes (mylpfa, mylz3 and myl1) were lower at d1 and recovered by d3, whereas several slow-muscle-associated genes showed biphasic transcript-level increases. The slow-muscle-associated RLC gene mylpfb showed a delayed expression peak at d7. Notably, the embryonic isoform myl6l showed a modest increase from approximately 2 FPKM at d0 to 4-5 FPKM after injury, suggesting a possible injury-associated expression pattern that requires further validation. Together, these findings provide a genome-wide description of the Chinese perch myl gene family and identify candidate fibre-type-associated genes and descriptive injury-associated isoform expression patterns.

Animals↗

PubMed2026

Molecular evaluation of residual disease following neoadjuvant chemotherapy in triple-negative breast cancer CALGB 40603 (Alliance).

BACKGROUNDDespite therapeutic advances in early-stage triple-negative breast cancer (TNBC), residual disease (RD) following neoadjuvant therapy remains a key predictor of a worse prognosis and obstacle to improving patient outcomes.METHODSTo better characterize RD and identify survival-associated features, we performed comprehensive transcriptomic profiling of 340 pretreatment stage II/III TNBCs and 70 matched posttreatment RD samples from the randomized CALGB 40603 (Alliance) phase II clinical trial. To explore preclinical treatment strategies for RD, patient-derived xenograft (PDX) mouse models mimicking RD were treated with antibody-drug conjugates (ADCs).RESULTSOur study shows prognostic genomic features measured pretreatment may differ from prognostic features measured posttreatment from RD specimens. Patients with a genomic PAM50 subtype of basal-like in RD specimens had a poor survival outcome, and their matching pretreatment tumors were characterized by elevated chromosomal amplifications of oncogenic drivers and significantly reduced B and T cell expression features. Paired analyses of basal-like RD and matched pretreatment tumors revealed further lymphocyte depletion in RD, along with lower expression of MHC class I and interferon signaling, indicating an immune-cold RD microenvironment. Treatment of a basal-like and conventional chemotherapy-resistant PDX model, resembling basal-like RD, with sacituzumab govitecan or trastuzumab deruxtecan produced a marked antitumor response.CONCLUSIONRD biology differs from pretreatment tumors, with basal-like subtype RD following neoadjuvant chemotherapy being immune cold and associated with poor survival. Preclinical modeling suggests this high-risk group may benefit from adjuvant ADC therapy.TRIAL REGISTRATIONClinicalTrials.gov NCT00861705.FUNDINGNIH NCI U10CA180821 (Alliance for Clinical Trials in Oncology), NCI U24CA176171 (Alliance for Clinical Trials in Oncology), NCI UG1CA233373 (Alliance for Clinical Trials in Oncology), NCI Breast SPORE program P50-CA058223; Susan G. Komen SAC-160074; Breast Cancer Research Foundation BCRF-23-127; NIH NCI R01-CA229409; UNC LCCC Triple Negative Breast Cancer Center.

Humans↗

PubMed2026

Genetic mutations driving ciprofloxacin resistance in laboratory-evolved Salmonella Typhimurium.

Ciprofloxacin resistance in Salmonella Typhimurium is a significant public health concern, and the mechanisms by which the resistance evolves are poorly defined. Here, by serial passaging under antibiotic selection, we isolated ciprofloxacin-resistant S. Typhimurium mutants and subjected them to whole-genome sequencing to reveal the major mutations associated with resistance. The Low CipR mutant acquired four chromosomal mutations in ramR, icdA, lipB, and gyrA, and the High CipR mutant gained additional mutations in gyrB, yaiC, and corA. Functional characterization determined that mutations in ramR resulted in efflux pump upregulation, while disruptions in the TCA cycle caused by mutations in icdA and lipB led to metabolic alterations. These changes indirectly enhanced resistance by increasing the expression of the global regulator MarA and reducing OmpF-dependent membrane permeability. Despite the observation of the G105A substitution in GyrA, enzymatic assays confirmed the failure to support resistance to ciprofloxacin, possibly because the structural alteration remained minimal. GyrB488-489dup was associated with maintained supercoiling under ciprofloxacin and enhanced fluoroquinolone resistance, suggesting a major role in resistance evolution. Other mutations in yaiC impaired biofilm and, in corA, intracellular accumulation of magnesium, possibly stabilizing the bacterial cell envelope under antibiotic pressure. The findings provide novel explanations for the multifaceted mechanisms leading to ciprofloxacin resistance in Salmonella and suggest targets to combat antimicrobial resistance.IMPORTANCEAntibiotic resistance in Salmonella Typhimurium is an increasing public health concern, yet the genetic changes that allow bacteria to become resistant are not fully understood. In this study, we evolved ciprofloxacin-resistant Salmonella in the laboratory and identified the mutations that arise during resistance development. We found that resistance does not result from a single change but from multiple adaptations affecting drug efflux, metabolism, and the antibiotic target. Some mutations increased the activity of pumps that remove antibiotics from the cell, while others altered bacterial metabolism and reduced membrane permeability, making it harder for the drug to enter. A duplication in the DNA gyrase subunit GyrB played a particularly important role in maintaining DNA function under antibiotic stress. Together, these results reveal how diverse genetic changes cooperate to generate ciprofloxacin resistance and provide insights that may help guide strategies to combat drug-resistant Salmonella infections.

DNA gyrase↗

PubMed2026

Activity shapes large herbivores' ecological influences.

The ecological effects of large herbivores are shaped by their spatial and temporal patterns of activity (i.e. where, when and how intensely they use specific locations). When large herbivores' ecological influences are perceived to be undesirable, the traditional approach has been to reduce their population size. This numbers-first logic assumes that ecological effects scale primarily with abundance. We argue that this framing provides an incomplete understanding of large herbivores' ecological impacts. Using African elephants (Loxodonta africana) as a well-documented case study, we show that ecological effects on plants, animals and ecosystem processes correlate more with spatio-temporal patterns of activity than with population size. In large, open systems characterized by strong gradients of water availability, forage quality, shade and risk, elephants concentrate into predictable hotspots while relaxing activity elsewhere, generating localized impacts and opportunities for recovery. By contrast, in small, fenced or fragmented landscapes, where movements are constrained, and gradients are weak, spatial self-regulation breaks down, producing homogenized use and widespread ecological effects. We contend that understanding where, when and under what constraints herbivores use space provides a more general and mechanistic basis for interpreting ecological influence than abundance alone, with implications that extend beyond elephants to large herbivores globally.

Animals↗

PubMed2026

Gene-environment interaction between perinatal oxytocin exposure and Pten mutation shapes epigenetic reprogramming of oxytocin signaling and behavior in mice.

Synthetic oxytocin (Pitocin) is the most commonly used pharmacologic agent for induction and augmentation of labor. Beyond its uterotonic effects, oxytocin plays a critical role in neurodevelopment and social behavior. Dysregulated oxytocin signaling has been implicated in autism spectrum disorder (ASD), raising concern that perinatal exposure to exogenous oxytocin may have lasting neurodevelopmental consequences. This study aimed to determine whether offspring harboring a genetic predisposition for ASD are differentially impacted by perinatal oxytocin exposures, with a focus on long-term oxytocin signaling and autism-like behavior. Pregnant mice carrying offspring with heterozygous mutations in phosphatase and tensin homolog deleted on chromosome ten (Pten), a well-established monogenic risk factor for ASD, received continuous oxytocin versus phosphate-buffered saline (PBS) control via micro-osmotic pumps during late gestation. Wild-type (WT) offspring exposed to each treatment served as a secondary control. Adult offspring were assessed for oxytocin receptor (Oxtr) methylation in the frontal cortex and hippocampus, oxytocin expression in the hypothalamus, serum oxytocin levels, and were subject to a battery of social and anxiety-related behavior tests. Perinatal oxytocin exposure produced genotype-dependent effects in offspring. Epigenetic analyses revealed bidirectional remodeling of Oxtr methylation in the frontal cortex and hippocampus, with increased exon 1 methylation in WT mice and decreased methylation in Pten-mutant mice, resulting in significant genotype-treatment interactions. Hypothalamic oxytocin expression increased following treatment regardless of genotype, though baseline levels were higher in Pten-mutant mice. Neither oxytocin treatment nor genotype impacted long-term serum oxytocin levels. Behavioral outcomes were modest but context-specific: repetitive behaviors and cognition performance were unchanged, but oxytocin-treated Pten-mutant mice exhibited increased anxiety-like behavior alongside improved social memory. In contrast, oxytocin-treated WT mice showed reduced social novelty preference. Exploratory analyses suggested potential sex-dependent trends. Our findings support a model in which genetic susceptibility shapes the epigenetic encoding of early-life hormonal signals, thereby recalibrating oxytocin system function and downstream behavioral outcomes. Together, these data highlight the context-dependent effects of perinatal oxytocin exposure and argue against uniformly beneficial or detrimental effects, emphasizing the importance of gene-environment interactions in neurodevelopmental trajectories.

Animals↗

PubMed2026

Prenatal exome sequencing of fetuses with central nervous system anomalies based on prenatal ultrasound and magnetic resonance imaging diagnosis: A retrospective cohort study with a systematic review and meta-analysis.

INTRODUCTION: Fetal central nervous system (CNS) abnormalities have diverse etiologies, with genetic factors as a major contributor. Prenatal exome sequencing (ES) is a powerful tool for precise molecular diagnosis of CNS anomalies, but its diagnostic yield varies among studies. This study aimed to evaluate the additional diagnostic yield of prenatal ES compared with chromosomal microarray analysis (CMA) in fetuses with CNS anomalies detected by prenatal imaging. MATERIAL AND METHODS: We collected ES results from fetuses diagnosed with CNS anomalies by prenatal imaging (2019-2024) who had negative results. Subgroup analyses assessed phenotype-specific ES diagnostic yield for associated genes and variants. A systematic review and meta-analysis incorporating our data and published studies further explored the association between phenotype and diagnostic yield. RESULTS: In the cohort study of 219 cases, ES identified pathogenic/likely pathogenic single nucleotide variations in 36 cases (16%). The highest diagnostic yield of ES was in cases with multisystem malformations (25%, 14/55), followed by multiple CNS anomalies (15%, 2/13) and isolated CNS anomalies (13%, 20/151). The most commonly identified isolated CNS anomaly was agenesis of the corpus callosum (31%, 5/16). Neural tube defects with urogenital anomalies were associated with a positive ES finding in 57% (4/7) of cases. The meta-analysis of 989 cases from 22 studies showed a pooled diagnostic yield of ES of 27% (95% CI, 21%-34%). The highest diagnostic yield of ES was in cases of corpus callosum anomalies with facial abnormalities (75%, 8/11) and neural tube defects with urogenital malformations (80%, 12/15). The diagnostic yield of ES for three or more CNS abnormalities was 43% (95% CI, 31%-58%), significantly higher than that for only two abnormalities (10%, 95% CI, 4%-18%). No significant difference in diagnostic yield was found between cases identified by prenatal MRI combined with ultrasound (27%, 95% CI, 20%-36%) and those identified by ultrasound alone (25%, 95% CI, 17%-35%). CONCLUSIONS: ES provided a significantly higher diagnostic yield than CMA for fetal CNS abnormalities, with diagnostic yields varying by phenotype. The systematic review and meta-analysis confirmed that the complexity and combination of malformations are key factors associated with differences in ES diagnostic yield.

Humans↗

PubMed2026

[Study of a patient with azoospermia due to variant of MOV10L1 gene].

OBJECTIVE: To explore the clinical and genotypic characteristics of a patient with Sertoli cell-only syndrome (SCOS) due to variants of MOV10L1 gene. METHODS: A 27-year-old patient with Non-obstructive azoospermia (NOA) underwent routine semen analysis. Serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), progesterone (P), estradiol (E2), prolactin (PRL), and testosterone (T) were determined by chemiluminescence assays. Peripheral blood samples were collected for G-banded karyotyping analysis. Multiplex PCR fluorescence detection was used to screen for AZF gene microdeletions. Whole exome sequencing (WES) and Sanger sequencing were performed simultaneously. Testicular biopsy tissues were subjected to Hematoxylin-Eosin (HE) staining to assess seminiferous tubule cell composition, and MOV10L1 protein expression was detected by immunohistochemical staining. Bioinformatics tools were employed to predict the pathogenicity of variants and their impact on protein structure and function. This study was approved by the Medical Ethics Committee of the Guangdong Institute of Reproductive Sciences [Ethics No.: 2023(01)]. RESULTS: The patient's two semen analyses had failed to detect any sperm. Hormone tests indicated elevated FSH (22.32 mIU/mL) and PRL (397.6 mIU/mL), while T (3.68 nmol/L) and E2 (38.32 pmol/L) were reduced. Chromosomal karyotyping revealed 46,XY, and no AZF gene deletion was detected. WES and Sanger sequencing detected compound heterozygous variants of the MOV10L1 gene, including a c.345C>A (p.C115X) nonsense variant and a c.3323C>T (p.T1108I) missense variant, with the former being unreported previously. HE staining showed only Sertoli cells in the seminiferous tubules, confirming the diagnosis of SCOS. Immunohistochemical staining revealed absent MOV10L1 protein expression in the testicular tissue. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the c.345C>A (p.C115X) was classified as a pathogenic variant (PVS1+PM2_Supporting+PP4), while the c.3323C>T (p.T1108I) was deemed variant of uncertain significance (PM2_Supporting+PP3_Supporting+PP4). Bioinformatics analysis demonstrated that c.345C>A (p.C115X) may cause premature termination of protein translation, while c.3323C>T (p.T1108I) may disrupt the hydrophobicity of the RNA helicase domain, reducing the active pocket volume and decreasing its affinity for MILI protein. CONCLUSION: This study has diagnosed a case of SCOS due to compound heterozygous variants of the MOV10L1 gene, which also enriched its mutational spectrum.

Humans↗