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PubMed2026

Studies on functional differentiation of xpr1a and xpr1b genes in zebrafish.

Xenotropic and polytropic retrovirus receptor 1 (XPR1) is known to be involved in various biological processes, including phosphate homeostasis, cellular signaling, brain and vascular mineralization, whereas its specific contribution to bone development remains incompletely characterized. Due to genome duplication in teleosts, zebrafish Danio rerio possess two paralogous genes of XPR1 namely xpr1a and xpr1b, whose functional divergence remains unclear. The amino acid sequence similarity between zebrafish xpr1a and xpr1b was 83.26%. In situ hybridization demonstrated overlapping localization in the head and spinal cord at 24-48 hpf, while diverged by 72 hpf, with xpr1a becoming restricted to the head while xpr1b persisted in both regions. CRISPR/Cas9 was used to generate xpr1a and xpr1b mutants. The xpr1a mutants are comparatively healthy, viable but with mild growth reduction, whereas the xpr1b mutants display high mortality, reduced body length and severe vertebral deformities. Interestingly, all the double mutants died at the embryonic stage. Moreover, to further investigate the molecular and regulatory mechanisms, we conducted comparative transcriptome analysis on bone and brain tissues from xpr1b+/+ and xpr1b-/- zebrafish. In bone tissue, 6749 DEGs were identified, comprising 3846 upregulated and 2903 downregulated genes. These DEGs were mainly enriched in the MAPK signaling pathway, Wnt signaling pathway, cysteine and methionine metabolism, and ECM-receptor interaction. RT-qPCR validated results showed that seven osteogenesis-related genes (col1a1a, sp7, runx2b, col1a2, col1a1b, alp1 and entpd5), and two phosphate homeostasis related genes (slc20a2 and pdgfba), which are essential for skeletal mineralization and phosphate homeostasis, exhibited significantly downregulated expression in bone tissue of xpr1b mutant zebrafish. These results highlight the pivotal role of xpr1b in regulating skeletal mineralization and phosphate metabolism, thereby elucidating the functional specialization of XPR1 paralogs while providing a theoretical basis for understanding bone developmental mechanism in teleost vertebrates.

Animals↗

PubMed2026

Genomic and One Health insights into Vibrio parahaemolyticus from environmental, seafood and clinical sources.

Vibrio parahaemolyticus is a leading cause of seafood-borne gastroenteritis worldwide, with climate warming facilitating its spread to high-latitude areas. In this study, we analyzed 212 genomes of environmental and seafood-associated isolates collected from seven cities in Zhejiang Province, China (2019-2024), alongside 228 clinical genomes from public databases. The 212 isolates were assigned to 172 sequence types (STs), with ST490 being the most frequent (5/212, 2.36%). Forty-four serotypes were identified, dominated by OL3:KUT (12.68%). High ST and serotype diversity were observed across different sample types and sources, with median pairwise single nucleotide polymorphisms (SNPs) ranging from 57,431 to 58,378, indicating comparable genetic diversity across groups. All isolates carried tlh and T3SS1 but lacked tdh and T3SS2. Resistance rates against ampicillin and cefazolin were 54.72% (116/212) and 44.34% (94/212), respectively, with multidrug resistance (MDR) detected in nine isolates, predominantly from seafood (7/9). A total of 63 distinct antimicrobial resistance genes (ARGs) spanning seven classes were identified. Isolates from aquaculture farms and wet markets exhibited greater resistance category diversity and higher ARG carriage than those from coastal or riverine sites. In contrast, the 228 clinical isolates harbored only 25 ARGs across two classes, with a significantly lower proportion of isolates carrying multiple ARG classes (0.44% vs. 6.13%, P < 0.001). Human isolates formed tighter phylogenetic clusters, although a minority were closely related to environmental/foodborne strains. Overall, our findings demonstrate the genetic diversity and resistance potential of V. parahaemolyticus across environmental, seafood, and clinical sources, highlighting the importance of the One Health approach to comprehensive public health risk assessment.

Vibrio parahaemolyticus↗

PubMed2026

Maternal obesity in rats results in male-specific increases in genome-wide DNA methylation in postnatal offspring liver.

Male-specific peripubertal DNA demethylation in the liver has been reported in mice. Here, we investigated whether it also occurs in rats, the influence of maternal obesity and whether DNA demethylation changes contribute to observed sex-specific effects of maternal obesity in offspring. Female rats were fed a high-fat, high-sugar 'cafeteria' (Caf) diet before mating with standard chow-fed males. The offspring liver methylome and transcriptome were examined. Body weight was higher in Caf-fed dams prior to mating, during gestation and at parturition. Male and female offspring from Caf-fed dams had lower birth weights but higher adult weights and adiposity than offspring from chow-fed dams. A comparison of DNA methylation in 3-week-old weaner males versus female siblings from chow-fed dams did not reveal the male-specific DNA demethylation that was previously reported in mice. However, strong maternal diet effects in male weaner offspring methylation were observed. A comparison of female weaners from chow- versus Caf-fed dams showed a range of differences, with 39% of differentially methylated regions (DMRs) having higher methylation in Caf offspring and 61% of DMRs having higher methylation in chow offspring. In stark contrast, 99% of maternal-diet-induced DMRs in male weaner offspring had higher methylation in offspring from Caf-fed dams. This suggests that maternal obesity induces widespread hypermethylation in the male offspring liver at weaning. However, a comparison with RNA sequencing data revealed limited transcriptional changes at this developmental stage or in adult offspring. While these data highlight how environmentally sensitive DNA methylation is in the male rodent perinatal period, these methylation changes may not be a major contributor to sex differences in developmentally programmed liver disease.

Animals↗

PubMed2026

Prevalence of POMC allele associated with obesity in feline population in Vietnam.

Feline obesity is an increasingly important health problem influenced by both genetic predisposition and husbandry practices. This study investigated the prevalence and phenotypic relevance of the feline proopiomelanocortin (POMC) c.28G > C (p.Gly10Arg) variant in a Vietnamese cat population and evaluated environmental factors associated with obesity. A total of 63 clinically healthy cats were classified as normal weight (body condition score [BCS] 5-6/9; n = 40) or obese (BCS ≥7/9; n = 23). Genotyping was performed using a newly developed PCR-restriction fragment length polymorphism assay and validated by Sanger sequencing. Ventral subcutaneous adipose tissue (VSAT) thickness was measured ultrasonographically as an objective indicator of adiposity. Genotyping revealed a high prevalence of the risk-associated C allele, with 45/63 cats (71.4%) carrying the GC genotype and 18/63 (28.6%) carrying the CC genotype, whereas the GG genotype was not detected, giving a Callele frequency of 64.3%. Obese cats had significantly greater body weight and VSAT thickness than normal-weight cats. Neuter status and ad libitum feeding were significantly associated with obesity, whereas diet type, housing, exercise frequency, and begging behavior were not. Although genotype distribution did not differ significantly between normal and obese cohorts, obese CC cats showed significantly greater VSAT thickness than obese GC cats, indicating an allele-dosage effect on adiposity. These findings suggest that the POMC c.28G > C variant is a useful risk-informative marker and that combining genetic screening with objective fat assessment may support earlier identification and prevention of feline obesity in Vietnam under routine laboratory conditions and guide personalized management strategies in practice.

Animals↗

PubMed2026

Development and Crossover Evaluation of an Artificial Intelligence-Assisted System for Solid Pancreatic Lesion Detection and Pancreatic Parenchyma Recognition in Endoscopic Ultrasonography (With Video).

BACKGROUND AND STUDY AIMS: Pancreatobiliary endoscopic ultrasonography (EUS) is technically demanding, and supervised training opportunities are limited. We developed an artificial intelligence (AI) overlay system for detecting solid pancreatic lesions (SPL) and recognizing pancreatic parenchyma (PP) and evaluated its effect on reader performance. PATIENTS AND METHODS: Across six centers, two deep learning-based models were trained using expert-annotated EUS frames. We then conducted a randomized, two-sequence, two-period crossover reader study in which eight endosonographers (five novices and three experts) interpreted image sets with and without AI assistance. The primary endpoint was superiority of sensitivity for SPL detection among novices; key secondary endpoints included specificity and PP recognition. RESULTS: From 118 patients, 120 SPL-positive/negative image sets and 160 PP-positive/negative image sets were constructed. Among novices, AI assistance improved SPL detection sensitivity (88.7% vs. 76.8%, p < 0.001) and accuracy (86.4% vs. 78.7%), while specificity met the predefined noninferiority criterion (84.2% vs. 80.5%, p < 0.001). For PP recognition, sensitivity increased numerically (86.3% vs. 83.3%) but did not meet the predefined superiority criterion (p = 0.095); specificity met the noninferiority criterion (87.8% vs. 81.0%), and accuracy increased from 82.1% to 87.0%. Among experts, sensitivity was maintained for both tasks, whereas specificity increased with AI assistance. CONCLUSIONS: AI assistance improved SPL detection among novice endosonographers. For PP recognition, sensitivity increased without reaching statistical superiority, whereas specificity met the predefined noninferiority criterion. These findings support a potential adjunctive role for AI in EUS interpretation.

Humans↗

PubMed2026

Generation of spCAS9 expressing human mesenchymal stem cell line to study gene function during osteoblast differentiation.

Human bone marrow-derived stromal cells (hMSCs) are a great resource for studying how genes influence cell fate and differentiation into various cell types like osteoblasts, adipocytes, and chondrocytes, among other cell types. However, genetic manipulation of primary hMSCs has been challenging due to their short lifespan and cellular senescence after limited passaging. Their low and unstable transfection efficiency also complicates gene delivery or inactivation, hindering long-term functional studies. The limited lifespan has been effectively solved by immortalizing hMSCs with telomerase reverse transcriptase (hMSCs-TERT). The use of these cells is ideal for functional studies of osteoblast and adipocyte differentiation through genetic manipulation, providing a stable and reliable model. Here, we have engineered a stable CAS9 expressing hMSC-TERT cell line (hMSC-TERTCAS9) via lentiviral transduction. The constitutive expression of spCas9 enables efficient and reproducible gene editing. We demonstrate the potential of these hMSC-TERTCAS9 cells for generating gene disruptions using plasmid delivery of guide RNAs as a fast and efficient strategy for targeted genome editing. The edited cells can be sorted and expanded as single cells to obtain homogenous clonal cell lines with mono- as well as bi-allelic gene deletions, a crucial step for producing reliable experimental results. We further validate this cell line as a powerful tool for studying gene function during hMSC proliferation and differentiation, providing 3 distinct examples of its utility. Through the generation of indels, single-cell sorting, and clonal selection, we have efficiently inactivated the vitamin D receptor and created both larger (256 nucleotides) gene disruptions in Forkhead box protein O1 and precise removals of a small genomic sequence (73 nucleotides) coding for microRNA MIR675. This novel hMSC-TERTCAS9 cell line represents a significant advancement, offering a stable, efficient, and versatile platform for advanced genetic studies, high-throughput screening, and the creation of reliable cellular disease models.

CRISPR-Cas9↗

PubMed2026

Climate and soil shape Daqu wheat quality and seed microbiome via rhizosphere taxa and microbial assembly.

The grain quality and seed microbiome of Daqu wheat are fundamental determinants of Daqu fermentation performance; however, the mechanisms by which cultivation environments influence these traits via rhizosphere microbial communities remain unclear. Bacterial and fungal communities across the bulk soil-rhizosphere-seed continuum of three wheat cultivars grown in four ecoregions were characterized using absolute quantitative amplicon sequencing. The rhizosphere microbiome was treated as a central intermediary, while the response variables were seed microbial diversity and grain-quality traits, including starch content, protein content, and grain hardness. Twelve physicochemical properties of soil and 11 climatic factors were integrated into a multidimensional association framework. Environmental conditions exerted stronger influences on both seed quality traits and microbial diversity than cultivar identity. Distinct regional signatures were also evident in rhizosphere microbiomes, with environmental gradients explaining community variation more effectively than geographic distance. Bacterial communities exhibited greater sensitivity to environmental fluctuations than fungi. Mantel analyses identified available nitrogen, precipitation, and atmospheric pressure as significant drivers of core rhizosphere taxa (P < 0.05). iCAMP revealed that stochastic processes predominantly governed rhizosphere bacterial assembly, whereas stochastic and deterministic mechanisms jointly shaped fungal assembly. Partial least squares path modeling further uncovered a rhizosphere-mediated environment-seed cascade, wherein sunlight intensity and duration, atmospheric pressure, and soil nitrogen directly or indirectly affected seed wet gluten content, grain hardness, and seed microbial diversity through their influences on rhizosphere microbiota. Rhizosphere bacterial diversity was negatively associated with seed bacterial diversity (path coefficient = -0.118, P < 0.05), indicating that rhizosphere communities may shape seed endophytic bacterial assemblages via environmental filtering and competitive interactions. Collectively, these findings elucidate how environments shape the quality and seed microbiomes of Daqu wheat, providing scientific guidance for optimal site selection and the standardized production of high-quality brewing wheat for industrial Baijiu.

Triticum↗

PubMed2026

Peripheral pain threshold, glycaemic status, and LAMP3 genetic variation: A community-based analysis.

Diabetic polyneuropathy is a common complication of diabetes, yet substantial inter-individual variation in peripheral pain perception suggests underlying genetic influences. This population-based study investigated clinical, metabolic, and genetic determinants of pain threshold using intraepidermal electrical stimulation in 906 participants from the Iwaki Health Promotion Project 2017. Genome-wide association analysis identified 12 loci showing suggestive associations, among which a missense variant in LAMP3 (rs482912) was prioritized as a biologically plausible candidate. Phenotype-stratified analyses showed that individuals carrying the CT or CC genotypes had lower PINT indices than those with the TT genotype, indicating reduced pain thresholds. Notably, the CC genotype retained an association with lower pain threshold using intraepidermal electrical stimulation under conditions of metabolic stress, including impaired glucose tolerance, elevated HbA1c, and obesity, whereas this association was attenuated in the presence of hypertension. Single-cell RNA sequencing analysis of human skin revealed that LAMP3-positive mature dendritic cells, enriched in immunoregulatory molecules, exhibited transcriptional enrichment of inflammatory, antigen-presenting, and nociception-related pathways, including NF-κB, JAK-STAT, cytokine signaling, and neuroimmune sensitization cascades. Autopsy-based skin analysis further demonstrated genotype-associated differences in dermal LAMP3-positive cell infiltration and CD8-positive T-cell abundance, while CD4-positive T-cell abundance and intraepidermal nerve fiber density remained unchanged across genotypes. Taken together, these findings suggest a potential association between LAMP3 variation and individual differences in peripheral pain threshold and provide biological context supporting a role for neuroimmune interactions in early sensory modulation under metabolic stress. Given the suggestive genetic evidence and indirect mechanistic data, these observations should be interpreted as exploratory and hypothesis-generating.

Humans↗

PubMed2026

Comparison of clinical efficacy and gut microbiota characteristics in children with ASD treated with fecal microbiota transplantation and ketogenic diet.

OBJECTIVE: Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and interaction, along with restricted, repetitive patterns of behavior. It is often accompanied by gastrointestinal dysfunction and gut microbiota dysbiosis. Fecal Microbiota Transplantation (FMT) and the Ketogenic Diet (KD) are interventions targeting the gut microbiota for ASD. METHODS: 30 participants were diagnosed with ASD according to DSM-5 and ADOS-2. ASD core symptoms were evaluated with CARS and ABC. Gut microbiota composition was analyzed by shotgun metagenomic sequencing. RESULTS: Both groups demonstrated significant improvements in core symptoms. In the FMT group, the mean CARS score significantly decreased from 34.87 to 33.53 (p < 0.01); in the KD group, it declined from 35.13 to 33 (p < 0.01). The mean ABC score reduced from 79.93 to 69.33 (p = 0.064) in the FMT group and from 63.07 to 42.73 (p < 0.01) in the KD group. Following the intervention, no statistically significant changes were observed in α-diversity or β-diversity within either group. LEfSe analysis revealed distinct post-intervention microbial signatures: FMT significantly enriched butyrate-producing taxa (Wujia chipingensis, Eubacterium sp. MSJ-33, and Butyrivibrio crossotus), while KD elevated Blautia massiliensis and decreased propionate metabolism -associated taxa (Veillonella sp. S12025-13 and Veillonella nakazawae). KEGG enrichment analysis revealed that KD enriched propionate metabolism (Fold enrichment = 3.747, q = 0.010) and aromatic compound degradation (Fold enrichment = 3.591, q = 0.010). CONCLUSIONS: Both interventions significantly improved clinical symptoms among children with ASD, potentially through distinct patterns of gut microbiota modulation. CLINICAL TRIALS NUMBER: NCT06348433 (03/21/2024).

Child↗

PubMed2026

Clinical and genetic features of Ph-negative myeloproliferative neoplasms with dual-driver gene positivity.

OBJECTIVES: To investigate the clinical laboratory characteristics and gene mutation features of dual-driver gene positivity in patients with Philadelphia chromosome-negative myeloproliferative neoplasm (Ph-negative MPN). METHODS: We conducted a retrospective analysis of clinical data and genetic test results from 203 newly diagnosed patients with Ph-negative MPN. Of these, 194 had single-driver gene positivity and 9 had dual-driver gene positivity. High-throughput sequencing was used to detect mutations in JAK2, CALR, and MPL. Clinical characteristics and gene mutation profiles were compared between the two patient groups. RESULTS: The incidence of dual-driver gene positivity was 4.4% (9/203), with the most common combinations being JAK2 with CALR (4 patients) and JAK2 with MPL (4 patients). Compared with the single-driver group, the dual-driver group had a significantly higher risk of bleeding [4.1% (8/194) vs. 33.3% (3/9), P = 0.008] and a higher proportion of uncommon mutations [3.6% (7/194) vs. 33.3% (3/9), P = 0.006]. No statistically significant differences were observed between the two groups regarding age, thrombosis incidence, splenomegaly, or routine blood test indicators. During follow-up, 1 patient in the dual-driver group died from cerebrovascular disease. No leukaemia transformation or disease-related deaths occurred among the remaining patients. DISCUSSION: The increased bleeding risk in dual-driver patients may be related to a higher proportion of CALR mutations, elevated platelet counts, and higher variant allele frequencies, though these findings require validation in larger cohorts due to the small sample size. The higher prevalence of uncommon mutations suggests a more complex mutational landscape in this subgroup. CONCLUSION: Patients with Ph-negative MPN and dual-driver gene positivity may have a higher risk of bleeding and a more complex gene mutation profile.

Humans↗

PubMed2026

Microbial allies in a cotton pest: A descriptive account of associated microbiota dynamics in Dysdercus cingulatus across development.

BACKGROUND: Hemipteran insects harbour several symbiotic partners, mainly bacteria, which play pivotal roles for hosts like dietary provision, support overall physiology, xenobiotic degradation and manipulate/regulate behaviour. Most of these symbionts usually reside and operate from the digestive tracts of the animals. Cotton is one of the major cash crops in India and Dysdercus cingulatus (D. cingulatus) though a secondary pest, is causing significant destruction of cotton bolls, poor lint quality and reduce oil content of seeds. Premature opening of cotton bolls often leads to bacterial and fungal infections, thus resulting in extensive economic loss worldwide. D. cingulatus is a hemimetabolous insect that comprises of developmental stages like egg, nymph (5 instar stages), and adult. The present work explored the ontogeny specific diversity in the associated microbiota and predicted their probable functional inputs in D. cingulatus. RESULTS: The data obtained using 16S rRNA gene sequencing (NovaSeq 6000) revealed presence of members of Proteobacteria (65.83%), Firmicutes (24%), Actinobacteria (10%) phyla throughout the ontogeny of D. cingulatus. Highest alpha diversity of these symbiotic bacteria was recorded in the third instar nymphs in contrast to rest of the developmental stages. Among all the observed genera, Stenotrophomonas, Hungatella and Glutamicibacter were predominant from egg to adult stages. MicFunPred, a tool used for predicting the probable functional inputs of these symbionts, hinted at their probable stage specific contribution in crucial biochemical pathways such as polyketide biosynthesis, ascorbate/aldarate metabolism, pentose phosphate and glyoxylate cycles, steroid hormone and peptidoglycan biosynthesis, and glycolysis/pyruvate metabolism. CONCLUSIONS: The primary investigations on the ontogenetic composition and diversity of associated microbiota, suggest dynamic shifts in D. cingulatus, concurrent with their probable functions/roles in the host development and metabolism. To the best of our knowledge, this is the first report on symbiotic microbiota variation across the developmental stages of D. cingulatus that provides preliminary descriptive observations that may guide future functional and experimental investigations into microbiota-based pest management.

Animals↗

PubMed2026

Acute Performance, Mechanical and Thermal Effects of Isometric Conditioning Versus Standardized Volleyball Pre-Training Activation in Highly Trained Male Players.

This study compared acute performance, neuromuscular, and thermal responses to a maximal isometric conditioning activity (ICA) versus a standardized volleyball pre-training activation (VPA) in highly trained male volleyball players, and to explore putative mechanisms underpinning post-activation performance enhancement (PAPE) considering training load. In a randomized crossover, 14 men (27 ± 3 y) completed two sessions: VPA (mobility/plyometric drills; 9 min), and ICA comprising 3×5×3-s maximal isometric back-squat contractions (knee angle 120°; 3-min inter-set rest). Countermovement jump (CMJ) height (primary), relative peak power (PP), RSImod, and contraction time (CT) were recorded pre and 3, 6, 9, and 12 min post. Rectus femoris muscle viscoelastic properties and skin surface temperature (SST) were assessed at matched time points. Analyses used repeated-measures ANOVA, responder analysis, correlations, and regression. Period×Sequence interactions favored ICA for CMJ and PP when delivered in Period 2 (lower training volume): ∆CMJ was higher under ICA versus VPA (p = 0.005, d = 1.20); PP likewise greater (p = 0.026, ηp2 = 0.35). ICA yielded more beneficial responders than VPA (9/14 vs 1/14; McNemar exact p = 0.021). In Period 2, reductions in rectus femoris muscle stiffness independently predicted CMJ gains (β_std = -0.495, p = 0.005), whereas SST changes did not (p = 0.974). RSImod and CT showed no differences. A brief, high-effort isometric squat protocol was associated with superior acute improvements in jump performance compared with a standard volleyball warm-up, but this advantage emerged specifically when the preceding training volume was reduced (Period 2), suggesting that residual fatigue from training may reduce the effects of PAPE. Gains align with neuro-mechanical rather than thermal mechanisms, supporting ICA as a practical, equipment-minimal priming strategy for elite volleyball.

Humans↗

PubMed2026

Variants in the interferon regulatory factor 5 gene confer genetic risk for systemic lupus erythematosus in a Han Chinese population.

BACKGROUND: Interferon regulatory factor 5 (IRF5), integral to interferon signaling pathways, has been identified as a susceptibility locus for systemic lupus erythematosus (SLE). Nevertheless, the relationship between IRF5 variants and SLE risk within the Han Chinese demographic remains inadequately characterized. MATERIALS AND METHODS: Genotyping of two functional single nucleotide variants (SNVs) in IRF5 was conducted in 167 individuals with SLE and 246 healthy controls utilizing sequence-specific primer polymerase chain reaction (PCR-SSP). Chi-square and Fisher's exact tests were employed to assess associations. RESULTS: The rs10954213 variant demonstrated a significant association with SLE susceptibility under the recessive model (GG vs. AG+AA, OR = 2.20, 95% CI: 1.30-3.75, p = 0.003, adjusted p [pc] = 0.030) and homozygous model (GG vs. AA, OR = 2.43, 95% CI: 1.36-4.42, p = 0.003, pc = 0.032). Similarly, the rs2004640 variant was associated with an increased risk of SLE across allelic (T vs. G, OR = 1.66, 95% CI: 1.22-2.26, p = 0.001, pc = 0.011), dominant (TG+TT vs. GG, OR = 1.77, 95% CI: 1.19-2.63, p = 0.005, pc = 0.047), and homozygous models (TT vs. GG, OR = 3.72, 95% CI: 1.58-8.78, p = 0.002, pc = 0.016). Haplotype analysis identified protective haplotype HT1 (A/G, OR = 0.54, 95% CI: 0.41-0.73, p < 0.001) and risk haplotype HT4 (G/T, OR = 2.51, 95% CI: 1.42-4.42, p = 0.001). CONCLUSIONS: These findings indicate that IRF5 gene variants substantially modulate susceptibility to SLE in the Han Chinese population. They hold potential as biomarkers for evaluating SLE risk and offer valuable perspectives into disease pathogenesis.

Adult↗

PubMed2026

Blood Metabolomic Signatures of 1-Hour Glucose Predict Cardiometabolic Risk.

BACKGROUND: Elevated 1-hour glucose levels during an oral glucose tolerance test strongly predict type 2 diabetes (T2D) and cardiovascular disease. We investigated whether the fasting blood metabolome predicting 1-hour glucose could be a target for improving β-cell function, long-term glycemic trajectories, and reducing the risks of T2D and coronary heart disease. We also investigated whether plasma microRNAs derived from key metabolic organs regulate changes in a metabolomic risk score (MRS) for predicting 1-hour glucose. METHODS: Untargeted blood metabolomics and a frequently sampled 75-g oral glucose tolerance test were performed in participants from the OmniCarb trial (n=162). In an independent weight-loss dietary intervention trial (POUNDS Lost [Preventing Overweight Using Novel Dietary Strategies]), temporal changes in MRS and plasma microRNAs measured by genome-wide sequencing were analyzed. In addition, associations of MRS at baseline and its 10-year changes with long-term risk of incident T2D and coronary heart disease were prospectively investigated in the NHS (Nurses' Health Study). RESULTS: We created a fasting blood MRS for predicting 1-hour glucose (Pearson r=0.8) and found significant associations with half-day (diurnal) postprandial glucose excursions and insulin secretion after 5-week controlled feeding interventions varying in carbohydrate amount and glycemic index. In the POUNDS Lost trial, diet-induced changes in MRSs were related to 2-year trajectories of glucose metabolism; circulating microRNAs regulating cardiometabolic abnormalities were pivotal factors influencing these changes. In the NHS, women in the top 20% of MRS had a multivariate-adjusted relative risk of 3.80 (95% CI, 2.22-6.51) for T2D and 1.48 (95% CI, 1.04-2.12) for coronary heart disease compared with those in the lowest 20%. In addition, 10-year increases in plasma metabolites related to 1-hour glucose were linearly associated with a higher risk of T2D. CONCLUSIONS: Our findings indicate that fasting blood metabolomic signatures predicting elevated 1-hour glucose reflect disease pathophysiology and could be targets for preventing T2D and coronary heart disease.

blood glucose↗

PubMed2026

Genomic diversity and thermal niches of Aspergillus molds disrupting rind formation of surface-ripened cheeses.

Filamentous fungi play important roles in the development of surface-ripened cheese microbial communities and contribute to the aesthetics and flavors of these products. Much is known about the diversity and ecology of desirable cheese fungi, but our understanding of the natural history of cheese spoilage molds is limited. The goal of this work was to characterize the genomic diversity of Aspergillus species contaminating artisan cheeses and to identify how the abiotic environment of cheese (the substrate itself and temperature) may constrain the growth of Aspergillus. Comparative genomics identified two main species of Aspergillus, A. westerdijkiae and A. ostianus, as the spoilage molds across three different facilities in the Northeastern United States that experienced contamination events. Multiple genomic types of A. westerdijkiae were found across the different cheese production facilities, indicating that these contamination events are not caused by a single clonal strain. All A. westerdijkiae isolates produced ochratoxin A, but concentrations varied greatly across strains. RNA-sequencing of A. westerdijkiae on nutrient-rich lab media (malt extract agar) versus cheese curd agar identified a suite of pathways enriched in expression on cheese, including degradation of amino and fatty acids. Experiments measuring growth over a range of temperatures identified that spoilage Aspergillus species have a higher optimal growth temperature compared to desirable fungal species in cheese rinds and are outcompeted by Penicillium species at temperatures lower than 15°C. Global fungal metabarcoding databases suggest that A. westerdijkiae is not normally found in natural habitats of the Northeastern United States, and it may be introduced to this region.IMPORTANCEOver the past decade, disruptive contamination events of Aspergillus spoilage molds have occurred at cheese production facilities in Massachusetts, Connecticut, and Vermont in the United States, causing aesthetic, flavor, and potential safety issues. Our work highlights independent introductions of different strains of A. westerdijkiae into multiple cheese facilities and suggests that temperature could be used to control the abundance of Aspergillus spoilage molds. Based on our analysis of the global distribution of A. westerdijkiae, it is not invading cheese facilities from local fungal populations and may be a contaminant in materials used for cheese production.

Aspergillus↗

PubMed2026

Developing low-carbon metered-dose inhalers: effects of propellant HFA-152a on mucociliary clearance and bronchoconstriction in two Phase 1 randomised trials.

BACKGROUND: To reduce the impact of respiratory care on climate change, metered-dose inhalers (MDIs) are being reformulated with low-global warming potential (GWP) propellants. Next-generation propellant hydrofluoroalkane (HFA)-152a has >90% lower GWP than HFA-134a. As part of the safety evaluation for HFA-152a, mucociliary clearance (MCC), bronchoconstriction and safety were compared with HFA-134a. METHODS: Two Phase 1, randomised, two-way crossover studies (NCT06506266/NCT06702462) were conducted. MCC study: healthy participants inhaled HFA-152a and HFA-134a in two 7-day sequences. MCC was quantified as area under radiolabelled particle retention time curve over 4 h (AUC0-4h) after nebulised 99mTc sulphur colloid, following each propellant. Bronchoconstriction study: patients with mild asthma inhaled single doses of HFA-152a and HFA-134a. Non-inferiority of HFA-152a versus HFA-134a was defined as percent change in FEV1 (litres), 15 min post dose (95% confidence intervals [CI]: lower limit >-10%, upper limit >0%). Both studies assessed safety. RESULTS: In 22 healthy participants, the impact on MCC did not differ between HFA-134a and HFA-152a (AUC0-4h geometric mean ratio [90% CI]: 1.00 [0.99, 1.01]). In 19 patients with mild asthma, neither HFA-152a nor HFA-134a induced bronchoconstriction (percent change in FEV1 at 15 min: -0.37% [HFA-152a] vs -0.60% [HFA-134a]); HFA-152a was non-inferior to HFA-134a (mean difference [95% CI]: 0.23% [-3.61, 4.07]). Adverse event (AE) rates were low and similar for both propellants in both studies; all AEs were mild, with no serious AEs or deaths. CONCLUSION: HFA-152a and HFA-134a had almost identical effects on MCC, neither induced bronchoconstriction, supporting MDI reformulation with the low-GWP propellant HFA-152a.

Humans↗

PubMed2026

Effects of acute hypoxia followed by reoxygenation on intestinal histomorphology, oxidative stress and hypoxia signaling biomarkers, and microbiota in pikeperch (Sander lucioperca).

In aquatic environments, natural and anthropogenic factors commonly reduce dissolved oxygen (DO) and trigger hypoxia, which threatens the health and survival of aquatic organisms. As an important economic fish species in China, pikeperch (Sander lucioperca) is extremely sensitive to hypoxia. However, there are relatively few reports on how hypoxia and reoxygenation affect its intestinal physiology and microbial community. Three treatment groups were set for pikeperch: normoxia (DO = 8.5 ± 0.5 mg/L), 48 h hypoxia (DO = 2.5 ± 0.1 mg/L), and reoxygenation (48 h hypoxia followed by 6 h reoxygenation at normal DO), to evaluate alterations in intestinal histopathology, tight junction gene expression, oxidative stress, hypoxia signaling molecules and intestinal microbiota composition. The results showed that hypoxia significantly decreased muscularis thickness by approximately 32.5% and reduced the expression of tight junction genes (Occludin, Claudin2, and ZO-2). Moreover, hypoxia significantly increased oxidative stress index levels (GSH-Px, CAT, and MDA), markedly upregulated the expression of Bax, Caspase3, and HIF-1α, while significantly downregulating the expression of Bcl-2, Egln1, and Egln2. Notably, reoxygenation elicited partial compensatory effects against these hypoxia-induced changes. 16S rRNA sequencing analysis revealed that hypoxic stress altered the intestinal microbial community composition of pikeperch and increased its diversity. In the hypoxia group, the abundance of the phylum Bacillota, along with the genera Halomonas and Acinetobacter, was significantly elevated, whereas in the reoxygenation group, the genus Lactobacillus increased approximately 180-fold. The results indicated that hypoxia caused intestinal oxidative damage, cell apoptosis, and intestinal microbiota dysbiosis in pikeperch, while short-term reoxygenation achieved partial recovery from these hypoxia-triggered intestinal injuries. The present research provides valuable references for in-depth exploration of the molecular mechanisms behind the response of pikeperch to acute hypoxia and reoxygenation stress, while also offering a novel perspective to understand the mechanism by which hypoxia impacts intestinal health in fish.

Animals↗

PubMed2026

"It was good because they have a relationship with us": A qualitative study on low-threshold buprenorphine treatment at syringe services programs.

INTRODUCTION: Syringe service programs (SSPs) reach people who inject drugs with opioid use disorder (OUD) and are novel "low-threshold" venues to initiate buprenorphine treatment. The study investigated patients' experiences with SSP-initiated buprenorphine treatment, which could aid in improving buprenorphine treatment delivery at SSPs. METHODS: The study included 12 participants who completed qualitative exit interviews after a randomized controlled trial of buprenorphine treatment at SSPs. In the parent study, participants received buprenorphine treatment through an onsite model at an SSP or enhanced referral to a community health center based on the randomization sequence. Most participants started taking buprenorphine at home. Exit interviews included participants from both study arms, and the semi-structured interview guide focused on their experiences with clinicians, experiences initiating buprenorphine, prior experiences with OUD treatment, and perceptions about continuing buprenorphine treatment. Four researchers iteratively read, coded, and discussed each transcript, then they derived recurring themes using thematic analysis. RESULTS: Participants were mostly male, middle-aged, and 50% identified as Latino. Four main themes related to buprenorphine treatment initiation: 1) Onsite treatment facilitated buprenorphine prescription, but some participants also expressed a need for additional support; 2) Precipitated withdrawal complicated participants' buprenorphine initiation in both arms; 3) Participants largely experienced the SSPs as affirming and welcoming; and 4) Developing strong relationships with healthcare providers was critical to successful buprenorphine treatment initiation. CONCLUSIONS: The SSP-based model provided rapid access to buprenorphine prescriptions, but precipitated withdrawal was a common complication. Some participants desired additional support and guidance when they started taking buprenorphine at home. The findings point to a "low-threshold, high-touch" approach where participants receive expedited access to buprenorphine providers at SSPs but also additional support throughout the initiation process to avoid and/or manage precipitated withdrawal. Despite some challenges, SSP-based buprenorphine treatment was highly valued by study participants.

Humans↗