PubMed Health⌕ Search

SEARCH · PubMed Health

Search PubMed Health

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 847 records · Page 47Linked to original sources
PubMed2026

Feedstock-specific effects of sulfur-rich vegetable fractions on food waste anaerobic digestion: Sulfide-associated redox perturbation and adaptive microbial reassembly.

Food waste (FW) anaerobic digestion (AD) is strongly affected by feedstock heterogeneity, yet the role of sulfur-rich vegetable fractions remains poorly defined. Here, garlic (GAR), Chinese cabbage (CHC), and cabbage (CAB) were used as representative sulfur-rich vegetables to assess their effects on methane production, redox status, and microbial function during FW AD. At equal volatile solids loading, GAR showed no significant effect, whereas CHC and CAB caused a biphasic response, with delayed methane accumulation and reduced cumulative yield followed by late-stage daily methane production 39.6% and 45.9% higher than the control, respectively. CHC and CAB promoted sulfide accumulation and elevated reactive oxygen species (ROS) during the early stage. Elevated ROS levels were associated with lower NADH/NAD+ ratios, reduced electron transport activity, and volatile fatty acid accumulation, collectively indicating a redox-perturbed state characterized by functional decoupling between acidogenesis and methanogenesis. Metagenomic analysis showed that this early disturbance was followed by functional reassembly of the community. Hydrolytic-acidogenic bacteria sustained fermentation, accompanied by enrichment of genes associated with PFOR-Rnf-mediated energy conservation and the ED and oxidative PPP pathways, while methanogenesis shifted toward acetoclastic and methylotrophic routes. Genome-resolved analysis attributed the genomic potential for PFOR-Rnf-mediated energy conservation to Aminobacterium and Defluviitoga MAGs, and showed that Methanosarcina possessed the broadest oxidative stress defense repertoire, supporting its dominance after ROS perturbation. These findings provide a mechanistic framework linking sulfur-rich feedstock heterogeneity to methane-production dynamics, involving sulfide-associated redox perturbation and subsequent microbial functional reassembly.

Energy conservation↗
PubMed2026

Temporal shifts in K-locus composition and expansion of dual-carbapenemase-producing ST11-KL62 Klebsiella pneumoniae: a retrospective genomic surveillance study.

OBJECTIVES: To characterize longitudinal changes in carbapenem-resistant Klebsiella pneumoniae (CRKP) and investigate the recent increase in dual-carbapenemase-producing ST11-KL62 isolates. METHODS: We retrospectively analysed 1,239 non-duplicate CRKP isolates recovered at a tertiary hospital in China during 2018-2025. Antimicrobial susceptibility testing, whole-genome sequencing, K-locus and resistance/virulence gene profiling, core-genome single-nucleotide polymorphism analysis, reference-guided plasmid comparison, conjugation and stability assays, and a murine lethality model were used. RESULTS: ST11 accounted for 936/1,239 isolates (75.5%). KL47 declined from 39/151 (25.8%) in 2018-2019 to 45/755 (6.0%) in 2024-2025, whereas KL62 increased from 3/151 (2.0%) to 147/755 (19.5%). Among 148 ST11-KL62 isolates, 13/148 (8.8%) co-harboured blaKPC-2 and blaNDM-1, of which 12/13 (92.3%) met the study's molecular definition of hypervirulent CRKP. Pairwise single-nucleotide polymorphism distances among local ST11-KL62 isolates ranged from 0 to 43 (median, 14), suggesting that clonal expansion may have contributed to their increase. Complete genome analysis of ZD872 located blaKPC-2, blaNDM-1, and major virulence-associated genes on distinct plasmids; related plasmid backbones were predicted in other isolates using short-read comparisons. ZD872 exhibited a hypervirulent phenotype in the murine model. CONCLUSIONS: The ST11 CRKP population underwent temporal shifts in K-locus composition, including expansion of a closely related ST11-KL62 subset carrying dual carbapenemases and hypervirulence-associated markers. These findings support integrating longitudinal genomic surveillance with local transmission analysis.

Carbapenem-resistant Klebsiella pneumoniae↗
PubMed2026

Detection of antibiotic heteroresistance in clinical microbiology: current and emerging methodologies.

BACKGROUND: Antibiotic heteroresistance (HR) is characterised by the coexistence of susceptible and resistant subpopulations within an apparently isogenic bacterial isolate. Because routine antimicrobial susceptibility testing (AST) primarily assesses the dominant population, HR may escape detection, potentially leading to discrepancies between laboratory susceptibility categorisation and the underlying bacterial population structure. OBJECTIVES: To provide a critical and practice-oriented evaluation of current and emerging methodologies for HR detection and to discuss their strengths, limitations, and potential for clinical implementation. SOURCES: Narrative review based on PubMed searches, complemented by screening of key reference lists and relevant EUCAST and CLSI documents. Peer-reviewed literature was prioritised. CONTENT: Phenotypic approaches, particularly population analysis profiling, remain the reference method for HR definition, but their labour-intensive workflows, long turnaround times, and limited standardisation restrict routine implementation. Alternative strategies, including modified AST assays, metabolic assays, and single-cell platforms, offer gains in speed or throughput but require broader validation. Molecular approaches such as quantitative PCR, droplet digital PCR, targeted deep sequencing, and whole-genome sequencing improve detection of minority resistance determinants. Emerging computational frameworks, including machine learning models integrating phenotypic and genomic data, represent a promising frontier for scalable HR prediction. IMPLICATIONS: Available evidence supports the clinical relevance of HR, although its association with adverse outcomes varies across bacterial species and antibiotic classes. Harmonised methodologies and clinically validated interpretive criteria are needed to support integration of HR assessment into routine diagnostics. Prospective multicentre studies and further standardisation, including engagement with EUCAST and CLSI, will be important to advance clinical implementation.

Antimicrobial resistance↗
PubMed2026

AISP position statement: Standardising biological sample collection and handling for advanced diagnostics and multi-omic analyses in pancreatic cancer.

The quality of biological samples is a major determinant of analytical reliability and translational relevance in patients with pancreatic ductal adenocarcinoma (PDAC). However, variability in specimen procurement, handling, transport, processing, and storage can substantially affect tissue integrity and the robustness of downstream analyses. This paper, promoted by the Pathology and Basic Science Task Force of the Italian Association for the Study of the Pancreas (AISP), brings together experts in pathology, molecular biology, translational research, medical oncology, and gastroenterology to provide practical recommendations for the collection, handling, and pre-analytical management of biological samples. Draft recommendations were discussed during dedicated working group meetings and approved by consensus among all authors, supported by key literature. The document identifies the biological specimen as the critical link between patient care, pathology, and research, and provides guidance for clinicians and professionals involved in sample procurement and processing. By addressing the requirements of different analytical platforms, including genomics, organoid generation, immunophenotyping, pharmacogenomics, and multiplex/spatial analyses, this paper aims to reduce pre-analytical variability, improve diagnostic accuracy, and enhance the clinical and translational value of molecular investigations in pancreatic cancer. Standardised procedures across centres may facilitate comparable data collection, support multicentre studies, and strengthen collaboration between clinicians, pathologists, and research laboratories.

Biobanking↗
PubMed2026

Assessing the potential of wastewater-based epidemiology to evaluate the impact of COVID-19 policy changes on stimulant use across 17 countries.

BACKGROUND AND AIMS: A limited number of studies have employed wastewater-based epidemiology (WBE) to assess the impact of specific COVID-19 public health directives on stimulant consumption. This study investigates the potential of WBE as a complementary information source to support decision-making, by examining drug use changes during the pandemic. METHODS: WBE data on stimulant use from 2019 through 2022 was obtained from 17 countries covering a total of 47 wastewater treatment plants worldwide. The Oxford Coronavirus Government Response Tracker stringency index was used to standardize the severity of the COVID-19 interventions across different countries. A multiple linear regression model was fitted for the population-normalized mass loads of amphetamine, cocaine (through its metabolite benzoylecgonine), MDMA, and methamphetamine to investigate whether changes in COVID-19 restrictions influenced stimulant use, controlling for possible week-weekend and spatial effects. RESULTS: In most locations, WBE suggests that stimulant use was not significantly affected by the COVID-19 interventions, or even increased under the stricter measures. Methamphetamine use showed the largest decrease with increasing policy stringency, with a negative linear relationship found in 19% of cities, followed by MDMA (18%), cocaine (15%) and amphetamine (6%). Social gathering restrictions mainly impacted cocaine and MDMA use, while methamphetamine consumption declined most under stringent travel restrictions. CONCLUSIONS: This study highlights the heterogeneous effects of the COVID-19 policy changes on stimulant use, even within countries. The ability of WBE to compile consecutive daily estimates proves to be particularly useful to assess the direct effect of specific policy changes on the consumption of different stimulants.

COVID-19 interventions↗
PubMed2026

Cerium dioxide nanoparticle exposure attenuates mobility-linked antibiotic resistome signatures across the soil-lettuce continuum.

Antibiotic resistance genes (ARGs) are contaminants of emerging concern in agricultural microbiomes. Their association with mobile genetic elements (MGEs) can enhance dissemination across soil-plant interfaces, creating potential environmental and food-chain exposure risks. However, how engineered nanoparticles modulate relative ARG abundance and mobility-linked resistome features in plant-associated microbiomes remains poorly understood. Here, we examined the effects of graded, experimentally elevated cerium dioxide nanoparticle (CeO2 NP) loadings in a soil-lettuce system by integrating compartment-resolved metagenomics, ARG-MGE co-occurrence analysis, putative host-reservoir profiling, transcriptomics, and functional assays. Metagenomic profiling identified 16 ARG types and 125 subtypes and revealed niche-dependent microbiome restructuring under CeO2 NP exposure. Rhizosphere relative ARG abundance showed a negative dose-associated trend, although overall inter-group differences were not significant, whereas leaf endophytes showed a weaker response. Relative MGE abundance decreased significantly in both compartments, and lower assembly-level ARG-MGE co-occurrence reflected fewer ARGs detected in MGE-associated genomic contexts, whereas fewer multi-ARG contigs suggested reduced ARG clustering and potential co-selection. Putative host-reservoir analysis associated key efflux determinants with bacterial families whose relative representation declined following CeO2 NP exposure. Transcriptomic profiling of representative putative ARG hosts revealed host-specific responses, including downregulation of genes involved in central metabolism and Sec-dependent trafficking. Complementary host assays showed reduced apparent envelope permeability and lower recovery of tetracycline-resistant recipient-identity colonies in the plasmid-associated host system. Together, under the tested elevated-loading conditions, CeO2 NP exposure was associated with lower relative ARG signals and weaker mobility-linked resistome features across the soil-lettuce continuum, providing mechanistic insight into nanoparticle-resistome interactions in soil-plant systems.

ARG dissemination↗
PubMed2026

Genome-wide identification of the expansin gene family in Rosa rugosa and overexpression of RrEXPA1 contributes to drought and salt stress tolerance in Arabidopsis.

The expansin (EX) gene family plays a crucial role in the growth and development of various plants, as well as responses to biotic and abiotic stresses. However, genome-wide analysis of the EX gene family and their functions in drought and salt stress tolerance has not been examined in Rosa rugosa. In this study, a total of 30 RrEX genes were identified and located on seven different chromosomes. Phylogenetic analysis classified these genes into four subfamilies: EXPA (24 members), EXPB (3 members), EXLA (1 member), and EXLB (2 members). The average amino acid length was 269.17 aa, with isoelectric points ranging from 4.79 to 9.97. Most members exhibited high aliphatic indices and protein stability, suggesting their adaptability to diverse environments. The synteny analysis provided insights into the evolution of the EX gene family in rose. Toxicity and autoactivation assays confirmed that BD-RrEXPA1 was non-toxic to yeast cells and lacked autoactivation activity, indicating its suitability for yeast two-hybrid screening. The transgenic Arabidopsis lines overexpressing RrEXPA1 improved seed germination and root length under abiotic stress. In addition, the overexpression lines showed reduced malondialdehyde (MDA) levels and increased chlorophyll content and superoxide dismutase (SOD) activity. These results suggest that RrEXPA1 may enhance stress tolerance by promoting root elongation and modulating physiological responses. This study provides important insights into the role of RrEXs in salt and drought stress and lays the foundation for further studies on the regulatory mechanisms of abiotic stress.

Drought stress↗
PubMed2026

Identification and validation of an alternatively spliced novel isoform of maspin that modulate genes involved in inflammatory and apoptotic pathways.

Maspin regulates cellular adhesion, migration, apoptosis, angiogenesis, and tumor suppression in a tissue and context-dependent manner. Its functional diversity is governed largely thorough extracellular matrix interactions, subcellular localization, and the reactive center loop (RCL), although the structural details are not well understood. To examine whether alternative splicing contributes to this heterogeneity, we analysed the SERPINB5 gene using a computational genomics approach and identified a novel 80 bp coding exon upstream of the first coding exon (E1). The alternatively spliced transcript was validated in human skin and esophagus by semi-nested touchdown PCR, quantitative real-time PCR, and Sanger sequencing. Recombinant B5N displayed a red-shifted fluorescence emission spectrum, indicating a more solvent-exposed conformation, which was supported by molecular dynamics simulations showing greater exposure of the nuclear localization signal (NLS) and the reactive center loop. Enzyme kinetic assays demonstrated concentration-dependent enhancement of tissue plasminogen activator (tPA) activity by both isoforms. In HaCaT cells, wildtype maspin produced stronger antiproliferative and anti-migratory effects, whereas B5N was only mildly antiproliferative. Annexin V/7-AAD staining revealed that wildtype maspin induced higher early apoptosis and cell death, while B5N produced lower overall cell death but a greater proportion of late apoptotic cells. RNA-seq of transfected HaCaT cells identified differentially expressed genes enriched in inflammatory, antiviral, and apoptotic pathways, which was validated by qPCR, and several of these were markedly upregulated in SARS-CoV-2 infected A549 cells. Thus, a novel N-terminally extended maspin isoform with differentially regulated gene profile is identified and validated in this study.

Apoptosis↗
PubMed2026

Cerebrospinal fluid infection caused by Mixta calida in a patient with sarcoma: Case report with whole-genome sequencing.

Mixta calida is a rare environmental Erwiniaceae organism with limited evidence of invasive human infection. We report cerebrospinal fluid infection in a 6-year-old girl with recurrent CIC-rearranged central nervous system sarcoma after neurosurgery, chemotherapy, stem-cell transplantation, and Ommaya reservoir access. Turbid cerebrospinal fluid showed severe neutrophilic inflammation and Gram-negative bacilli with leukocyte phagocytosis. Pure culture yielded an isolate identified by MALDI-TOF mass spectrometry. Four genomic 16S rRNA sequences showed 99.93% identity to the M. calida type strain, and whole-genome ANI was 99.59%. These findings support M. calida as a clinically significant opportunistic pathogen in immunocompromised patients.

Meningitis↗
PubMed2026

Genetic and biochemical screens identify MGAT1 as a druggable glycosyltransferase target in STK11-mutant lung cancer.

Checkpoint inhibitors are standard-of-care therapies for non-small cell lung cancer (NSCLC), but their efficacy is limited in tumors with STK11 mutations, highlighting the need for new therapeutic strategies. Here, we performed complementary in vivo and in vitro CRISPR-Cas9 functional genomic screens to identify genes whose loss restores sensitivity to anti-PD-1 therapy. We found that loss of MGAT1, a Golgi glycosyltransferase critical for the maturation of high-mannose N-glycans into hybrid and complex glycan structures, reversed resistance to anti-PD-1 treatment in syngeneic mouse tumor models harboring STK11 mutations. Parallel co-culture screens with antigen-matched CD8+ T cells further showed that disruption of N-glycosylation strongly sensitized tumor cells to T cell-mediated killing. Genetic rescue studies demonstrated that this immune-evasion phenotype depends on MGAT1 catalytic activity, supporting direct biochemical interrogation of the enzyme. Using purified human MGAT1 and a UDP-Glo™ glycosyltransferase assay, we established a tractable screening platform and performed a 500,000-compound biochemical high-throughput screen, identifying an initial hit (compound 1; IC50 = 197 μM). Subsequent medicinal chemistry optimization delivered progressively more potent analogs, including TNG-9333 (0.814 μM) and TNG-2673 (0.043 μM) and represented a >1000-fold improvement in biochemical potency from the starting hit. Crystal structures of human MGAT1 in apo, UDP-bound, UDP-GlcNAc-bound, and inhibitor-bound states, together with SPR and DSF analyses, revealed that this chemical series engages a previously unrecognized allosteric pocket and inhibits MGAT1 through a UDP-noncompetitive mechanism. Collectively, our work implicates N-glycosylation as a key mediator of immune evasion and establishes MGAT1 as a ligandable, structurally tractable target for small-molecule drug discovery.

CRISPR/Cas9 target discovery↗
PubMed2026

Functional identification of the key gene Eh-fadB in nicosulfuron degradation by Enterobacter hormaechei ES1 based on multi-omics and enzymatic characterization.

Nicosulfuron is a sulfonylurea herbicide with residues that pose ecological risks in agricultural soils. Here we elucidated the degradation mechanism of Enterobacter hormaechei ES1 through whole-genome sequencing, transcriptomics, metabolomics, gene knockout, heterologous expression, and soil bioremediation assays. Under nicosulfuron stress, ES1 upregulated antioxidant enzymes including SOD, POD, and CAT, along with glutathione synthesis, to scavenge excess reactive oxygen species. HPLC-TOF-MS identified degradation intermediates such as ADMP and ASDM, indicating initial cleavage of the sulfonylurea bridge. Integrated multi-omics prioritized Eh-fadB, encoding a fatty acid β-oxidation multifunctional enzyme, as a novel degradative gene. Targeted knockout of Eh-fadB reduced nicosulfuron degradation from 87.6% to 37.04%, while genetic complementation restored nearly full activity. Purified Eh-FadB directly converted nicosulfuron, with optimal performance at 30 °C and pH 5-6; its activity was enhanced by Na+ and Pb2+ but inhibited by Fe3+. Molecular docking and dynamics identified His-450 and Asn-427 as key residues for substrate binding. In contaminated soil, inoculation with ES1 reduced nicosulfuron content within 21 days and promoted recovery of dehydrogenase and urease activities. This study provides the first genetic and biochemical evidence that a FadB-type enzyme participates in nicosulfuron catabolism, supporting sulfonylurea bridge cleavage and its potential for soil bioremediation.

Eh-fadB↗
PubMed2026

Unraveling anaerobic indole degradation in an acclimated sludge consortium: Candidate pathways and microbial division of labor inferred from metagenomic and metatranscriptomic analyses.

Indole is a widespread nitrogen-containing heterocyclic compound in manure, sludge, and wastewater systems, yet the enzymes and microbial populations involved in its anaerobic transformation remain poorly resolved. Here, we established a long-term acclimated anaerobic sludge consortium and combined degradation assays, metabolite profiling, metatranscriptomics, and genome-resolved metagenomics to investigate the functional basis of anaerobic indole degradation. After 120 days of acclimation, the consortium stably degraded 100 mg/L indole, whereas skatole was not effectively removed under the same strategy, indicating substrate-specific adaptation of the microbial community. Metabolite profiling detected oxindole, dioxindole, isatin, and anthranilic acid, supporting a putative transformation route involving pyrrole-ring oxidation and ring cleavage toward anthranilate-like intermediates. Metatranscriptomic analysis identified 16,660 differentially expressed genes after indole addition, with strong transcriptional responses involving oxidoreductases, hydrolases, cofactor-dependent redox metabolism, aromatic-CoA-related metabolism, and methane metabolism-associated pathways. Transcriptional responses highlighted the xanthine dehydrogenase-like molybdenum-enzyme system and isatin hydrolase as candidate contributors to upstream indole transformation, whereas those of abmG-like, bcrC, and oah genes were consistent with possible anthranilic acid activation and downstream CoA-type processing. MAG-resolved analysis further suggested that these candidate functions may be distributed among populations affiliated with Bacteroidota, Chloroflexota, Desulfobacterota, and Methanobacterium. Together, these findings establish a stable anaerobic indole-degrading consortium and provide a testable functional framework for syntrophic interactions linking upstream indole transformation, aromatic-CoA metabolism, and methanogenesis-associated carbon flow.

Anaerobic degradation↗
PubMed2026

Re-evaluating the α/β ratio in 2026: A systematic review and quantitative reappraisal in the era of molecular radiobiology.

The linear-quadratic (LQ) model and its derived ratio, α/β, have served as the cornerstone of radiotherapy dose-fractionation decisions. The period from 2015 to 2026 has witnessed a substantial re-evaluation of this paradigm, driven by the clinical success of hypofractionation in prostate and breast cancer, stereotactic body radiation therapy (SBRT), and radiogenomics. A systematic review with narrative synthesis was conducted to evaluate quantitative estimates of α/β derived from clinical and preclinical studies over the last decade, updating classical assumptions using modern trial data. Extensive Phase III data in prostate cancer consistently define an α/β of 1.2 to 2.0 Gy. Microscopic models in breast cancer align with an α/β of ∼2.7 Gy. Conversely, lung SBRT data present a high modeled α/β driven by hypoxia artifacts. Genomic integration via the Genomic Adjusted Radiation Dose (GARD) reveals that α/β operates as a dynamic, patient-specific phenotype. In the molecular era, static α/β assumptions must be integrated with disease-specific kinetics, microenvironmental data, and genomic intrinsic radiosensitivity.

Hypofractionation↗
PubMed2026

Genome-wide CRISPRi screen in human iNeurons identifies novel negative mTOR regulator genes associated with focal cortical dysplasia.

Focal cortical dysplasia (FCD) is a common cause of focal epilepsy that typically results from brain mosaic mutations in the mTOR cell signaling pathway. To identify new potential FCD genes, we developed an in vitro CRISPRi screen in human neurons and used FACS enrichment based on the FCD biomarker, phosphorylated S6 ribosomal protein (pS6). Using whole-genome (110,000 gRNAs) and candidate (129 gRNAs) libraries, we discovered 6 new genes in which loss of function significantly increases pS6 levels: LRRC4, EIF3A, TSN, HIP1, PIK3R3, and URI1. Further analysis of the mTOR pathway showed that only two of the genes, PIK3R3 and HIP1, caused hyperphosphorylation throughout the AKT/mTOR/S6 signaling pathway. Importantly, potential pathogenic variants in these two genes have been reported in resected brain tissue from a single FCD patient each, supporting the predictive validity of our screen. Knocking down each of the 6 genes in iNeurons made mTOR signaling resistant to the loss of neurotrophic factor signaling, specifically GDNF; even without GDNF, pS6 levels remained comparable to GDNF-stimulated controls. Thus, we have identified negative regulators of neuronal mTOR signaling in the context of lost neurotrophic factor support. Our data expand the set of genes that are likely to regulate mTOR pathway signaling in neurons, provide biological confirmation for candidate genes identified in human tissue, and suggest additional targets for investigating somatic gene variants in resected FCD tissues. The identification of novel mTOR regulators using iNeurons also highlights the importance of genetic screening in disease-related cell types.

Brain mosaicism↗
PubMed2026

The dirigent protein MsDIR6 functions in drought tolerance and modulates reactive oxygen species scavenging and secondary metabolite biosynthesis in alfalfa.

Alfalfa (Medicago sativa L.) is a globally significant forage crop essential for ensuring global food security. However, soil water deficit leads to a substantial decline in its yield, posing a severe threat to sustainable forage production. Dirigent (DIR) proteins play important roles in lignan biosynthesis and plant stress responses. Here, we identified 52 MsDIR genes in alfalfa through a genome-wide analysis, and screened MsDIR6 as a key candidate gene associated with drought tolerance. The results of qRT-PCR showed that MsDIR6 transcription was significantly induced by drought stress in alfalfa. MsDIR6 was preferentially expressed in roots and leaves, and its protein was localized in the nucleus and plasma membrane. Heterologous expression of MsDIR6 in yeast improved tolerance to mannitol-triggered osmotic stress. Heterologous overexpression of MsDIR6 in Arabidopsis significantly increased seed germination rate, seedling survival rate, and antioxidant capacity under drought stress, while improving leaf water-holding capacity by regulating stomatal movement. In transgenic alfalfa hairy roots, MsDIR6 alleviated drought-induced growth inhibition and enhanced reactive oxygen species (ROS) scavenging mediated by the antioxidant defense system under drought stress. Transcriptomic analysis revealed that MsDIR6 activated key genes in the phenylpropanoid and flavonoid biosynthesis pathways, which are crucial for ROS scavenging during drought adaptation. Additionally, we observed elevated flavonoid and lignin contents in MsDIR6-overexpressing alfalfa. Collectively, our findings offer novel insights into alfalfa's drought tolerance mechanisms and identify MsDIR6 as a promising genetic resource for molecular breeding strategies to improve this vital forage crop.

Alfalfa↗
PubMed2026

Mapping the Immune cell-specific gene regulatory network in bipolar disorder: A framework from scTWMR to exploratory drug-target annotation.

BACKGROUND: Although the involvement of the immune system in the genetic susceptibility of bipolar disorder (BD) is widely acknowledged, the causal relationship between gene expression in specific immune cell subtypes and BD requires systematic elucidation. METHODS: We implemented an analytical framework integrating single-cell transcriptome-wide Mendelian randomization (scTWMR) with colocalization analysis. This approach utilized cis-expression quantitative trait loci (cis-eQTLs) derived from 14 distinct immune cell types as instrumental variables to interrogate BD genome-wide association study (GWAS) summary statistics (comprising 41,917 cases and 371,549 controls). Subsequent investigations encompassed functional enrichment analysis, protein-protein interaction (PPI) network construction, phenome-wide association study (PheWAS), and performed an exploratory drug-target annotation. RESULTS: Our analysis identified 33 gene-immune cell associations. Colocalization analysis provided robust evidence (PPH4 > 90%) for shared causal variants implicating the MAD1L1, APOM, and NFKBIL1 loci. Significantly enriched biological pathways included cell cycle regulation, circadian rhythm entrainment, and neuroinflammation. The PPI network revealed a core regulatory module centered on histone-encoding and immune-related genes. Exploratory drug-target annotation nominated compounds for further investigation for compounds targeting APOM, TMEM258, and NFKBIL1. CONCLUSION: This study systematically delineates a genetically supported regulatory network of immune cell-specific gene expression in BD, predominantly implicating CD8⁺ effector T cells, plasma cells, and B cells. The findings corroborate established pathological pathways while uncovering novel cell type-specific therapeutic targets, thereby providing a genetic framework for prioritizing candidate targets for future investigation.

Bipolar disorder↗
PubMed2026

Indoor Air Quality (IAQ) analysis and 16S rRNA gene sequencing of indoor air pollutants in a 3000-capacity religious auditorium.

A thorough molecular and environmental evaluation of microbial isolates and indoor air quality (IAQ) at a place of worship is presented in this work. The study used a dual-methodological approach, including systematic environmental monitoring to assess occupant health concerns and 16S rRNA gene sequencing for taxonomic identification. Four different bacterial isolates were successfully identified by molecular analysis using BLAST and phylogenetic reconstruction: Bacillus tropicus (A11), Leclercia adecarboxylata (A12), Acinetobacter sp. (A13), and Escherichia coli (A14). The evolutionary position of isolate A13 indicated possible horizontal gene transfer, underscoring the existence of flexible, opportunistic pathogens within the indoor environment, whereas isolates A11 and A14 demonstrated significant genetic stability. Concurrently, six sessions of air quality monitoring showed a thermally demanding environment, with humidity (56.00-70.51%) and temperatures (29.21-33.79 °C) continuously surpassing ASHRAE guidelines. The average pollutant concentrations are within WHO and USEPA safety criteria, however, there were outliers that may suggest sporadic pollutant penetration (outdoor) or resuspension of dust. The results demonstrate a clear relationship between increased chemical pollutants (TVOCs) and reduced thermal comfort. To reduce the congregation's acute respiratory and cardiovascular risks, optimal ventilation systems and source-control measures are urgently needed, as evidenced by the presence of clinically relevant microorganisms combined with dangerous pollution levels.

Analysis↗