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Biomedical subjects

Hao Wang

Publications and source records attributed to Hao Wang.

18 recordsLinked to original sources
PubMed2026

A Randomized Phase II Study of Combination Atezolizumab and Varlilumab (CDX-1127) with or without Cobimetinib in Previously Treated Unresectable Biliary Tract Cancer.

PURPOSE: The addition of MEK inhibition (MEKi) to programmed cell death ligand 1 (PD-L1) blockade improves progression-free survival (PFS) in patients with advanced biliary tract cancer. Although MEK inhibitors may increase tumor cell immunogenicity, they can impair T-cell priming/effector function, limiting combination efficacy. We hypothesized that the addition of a CD27 agonist could restore T-cell function and enhance antitumor immunity in this combination. PATIENTS AND METHODS: We conducted a randomized, phase II trial evaluating atezolizumab (840 mg, intravenously, days 1 and 15) in combination with the CD27 costimulatory monoclonal antibody [CDX-1127/varlilumab (3 mg/kg, intravenously, days 1 and 15)], with/without the addition of an MEK inhibitor [cobimetinib (60 mg, orally, daily, days 1-21, off days 22-28)] in unresectable biliary tract cancer following at least one metastatic therapy. Overall response rate (ORR) and PFS were coprimary endpoints. Treatment-related changes in CD8+ tumor-infiltrating lymphocytes (TIL) were the primary correlative outcomes. RESULTS: The trial was closed early following interim preplanned ORR analysis. At closure, 57 patients had been enrolled [n = 29 in the cobimetinib + atezolizumab + varlilumab (CAV) arm; n = 28 in the atezolizumab + varlilumab (AV) arm]. A majority (67%) had intrahepatic cholangiocarcinoma, and 32% were immunotherapy experienced. Both regimens were well tolerated without new safety signals. Objective responses were rare [0% (CAV); 3.8% (AV)]. The median PFS (mPFS) was 2.40 (CAV) and 1.84 (AV) months [hazard ratio (HR), 0.67; 95% confidence interval (CI), 0.38-1.18]. Among immunotherapy-experienced patients, the mPFS was 3.62 (CAV) and 1.84 (AV) months (HR, 0.54; 95% CI, 0.18-1.62). Treatment with CAV increased intratumoral CD8+ T-cell density compared with treatment with AV. CONCLUSIONS: The combinations of atezolizumab and varlilumab with/without cobimetinib were safe, but neither meaningfully improved outcomes in biliary tract cancer treated in the later lines. Correlative tissue studies validated preclinical work that MEKi increases CD8+ TILs.

Humans↗
PubMed2026

Epilepsy: Bridging Epidemiological Landscapes, Molecular Mechanisms, and Emerging Precision Therapeutics.

Epilepsy ranks among the most prevalent neurological disorders worldwide, and recent years have witnessed significant advancements in understanding its epidemiological features, pathophysiological mechanisms, diagnostic methodologies, and therapeutic approaches. This review systematically examines the epidemiology of epilepsy, highlighting pronounced regional and population-based disparities, particularly the substantial treatment gap observed in low-income countries. Regarding pathogenesis, epilepsy development involves aberrant ion channel function, neuroinflammatory processes, dysregulation of the mTOR signaling pathway, and genetic predispositions. Diagnostic innovations, including ultra-high field magnetic resonance imaging, artificial intelligence-enhanced electroencephalogram analysis, and liquid biopsy techniques, have markedly enhanced the precision of epileptogenic focus localization and etiological identification. Genetic investigations have uncovered numerous epilepsy-associated genes, thereby underpinning the advancement of targeted therapies. Therapeutically, novel antiepileptic drugs, neuromodulation modalities such as vagus nerve stimulation and deep brain stimulation, alongside gene therapy, have expanded treatment options for refractory epilepsy. Nonetheless, global epilepsy management continues to confront challenges including limited drug accessibility, social stigma, and pharmacoresistance. The future trajectory emphasizes individualized and precision medicine approaches, integrating genomics, biomarker discovery, and intelligent monitoring technologies to foster comprehensive improvements in epilepsy diagnosis and treatment.

epidemiology↗
PubMed2026

Modelling peak microbial pollution events caused by combined sewer overflows in a source-to-sea system.

Predicting peak microbial pollution events in downstream coastal bathing waters caused by combined sewer overflows (CSOs) is essential for protecting public health. In urban areas, wastewater effluents, CSOs, and surface runoff can contribute to elevated microorganism loads to downstream waters. These pressures are likely to be intensified by growing population density and more frequent heavy rainfalls due to climate change. This study developed a process-based model to simulate Escherichia coli (E. coli) emissions, transport, and fate from the initial sources to coastal beaches. A three-year retrospective simulation (2017-2019) shows that E. coli concentrations in CSO discharges varied widely across the catchment (4.6 - 7.3 (log10 CFU 100 ml-1)). 99th percentile E. coli concentrations (4.0 (log10 CFU 100 ml-1)) at the inland water outlet were dominated by local CSO emissions, whereas 90th percentile E. coli concentrations (3.6 (log10 CFU 100 ml-1)) reflected cumulative upstream contributions from both CSO and effluent emissions. With the simulation accuracy of 89%, the model reliably reproduced the E. coli dynamics on the downstream beach and showed strong performance in representing peak concentrations based on Complementary Cumulative Distribution Function (CCDF) analysis. The process-based model enables quantitative tracking of source contributions and identification of pollution hotspots, providing support for mitigation measures. The study lays down a source-to-sea modelling framework for representing pollution transport across the aquatic continuum and provides a transferable tool for microbial pollution forecasting and climate adaptation planning.

Climate projection↗
PubMed2026

Brucellar spondylitis is associated with disturbance in gut microbiota and histamine metabolism associated inflammation.

BACKGROUND: The pathogenesis of brucellar spondylitis (BLS) has traditionally been considered to be primarily limited to local osteoarticular lesions. With the proposal of the "gut-spine axis" concept, the role of intestinal microecological dysbiosis in inflammatory spinal diseases has attracted in an increase of attention. The overactivated inflammatory cytokine network not only mediates bone destruction and intervertebral disc damage, but also forms a bidirectional interaction with gut microbiota dysbiosis through the "gut-spine axis," collectively driving disease progression. However, the inflammatory mechanism by which gut microbiota participates in the pathological process of BLS remains largely unclear. METHODS: This study recruited 20 BLS patients and 20 healthy donors. Multi-omics analysis including metagenomics, untargeted metabolomics, and targeted short-chain fatty acids (SCFAs) analysis, were used to compare the structural differences in gut microbiota between the two groups and screen for signature differential bacterial species. Plasma levels of histamine and histidine decarboxylase were measured by ELISA to clarify the role of differential histidine metabolic pathway in the disease. Additionally, plasma levels of lipopolysaccharide (LPS) and inflammatory cytokines (IL-1β, IL-6, IL-10, IL-17A, TNF-α) were detected by ELISA. The correlation between gut microbiota and inflammatory indicators was further analyzed. RESULTS: Compared to the healthy control group, the α-diversity of the gut microbiota in BLS patients was significantly reduced, with the microbial community structure exhibiting increased homogeneity. Beta diversity analysis revealed significant differences, suggesting that disease progression is associated with an overall imbalance in the gut microbiota and the deterioration of its specific structural composition. At the phylum level, the abundances of Actinomycetota, unclassified_d_Viruses, and Fusobacteriota were significantly increased in the gut microbiota of BLS patients compared to the control group, while the abundances of Bacillota and Pseudomonadota were significantly decreased. Further analysis revealed that, compared to the control group, the generic abundance of Enterococcus was significantly increased, while the proportions of Blautia, Faecalibacterium, Ruminococcus, Agathobacter, Roseburia, Clostridium, Eubacterium, Alistipes and Anaerobutyricum were significantly decreased. At the species level, the abundances of Enterococcus sp and Enterococcus-faecium were increased, whereas Blautia sp, Ruminococcus sp, Faecalibacterium sp, Faecalibacterium prausnitzii, Agathobacter rectalis, Eubacterium sp, Agathobacter sp, and Roseburia sp were decreased. Furthermore, untargeted metabolomics revealed that metabolites were enriched in the histidine metabolic pathway, and the levels of SCFAs including butyrate, isobutyrate, valerate, and 4-methylvalerate in the intestinal contents were reduced in BLS. Functional KEGG profiling revealed that key KOs involved in butyrate synthesis (e.g., K00074, K00172, K01640) and transport were globally downregulated in the patient group, whereas histidine decarboxylase KOs (K01693, K11755, K19787) that convert histidine to pro-inflammatory histamine were significantly enriched. The loss of butyrate-producing symbionts led to SCFAs deficiency and mucosal barrier disruption, creating ecological niches for facultatively anaerobic Enterococcus, which further exacerbated local inflammation via proteolytic fermentation and histamine production. Compared with the control group, BLS patients showed decreased plasma levels of IL-10, while levels of IL-1β, IL-6, IL-17A, and TNF-α were increased, and LPS levels were elevated. In addition, significantly elevated plasma pro-inflammatory LPS levels in patients with BLS suggest disruption of intestinal integrity and permeability. Correlation analysis indicated a close relationship between gut microbiota and inflammation. CONCLUSION: BLS is associated with gut microbiota dysbiosis and alterations in microbial metabolites, which may be linked to inflammatory responses and histamine metabolism. The differential microbial taxa identified in this study could be developed into a stool-based non-invasive diagnostic panel to facilitate early differentiation of BLS from other spinal disorders. Furthermore, restoring gut microbial balance through probiotic supplementation or dietary modulation may represent a promising adjunctive strategy to enhance the efficacy of standard antibiotic therapy and reduce disease recurrence.

Humans↗
PubMed2026

Genome-wide epigenomic atlas and multi-omics responses of Eriocheir sinensis to natural extreme heat.

BACKGROUND: Global climate warming has led to increasingly frequent and prolonged extreme summer heat events, posing severe environmental challenges to aquaculture systems. Extreme summer heat can disrupt the performance of pond-cultured ectotherms. The Chinese mitten crab (Eriocheir sinensis) is an economically important freshwater crustacean, but coordinated molecular differences following contrasting natural summers remain incompletely characterized. RESULTS: We performed a comprehensive multi-omics analysis integrating meteorological monitoring, mRNA/lncRNA transcriptomics, small-RNA profiling of miRNAs, DNA methylomics, and LC-MS metabolomics in E. sinensis populations collected from Yancheng, China, between 2020 and 2024. Across the ten farms, survival was significantly lower in 2024, whereas yield and the proportion of large individuals showed nonsignificant downward trends. Gene-set analyses showed negative enrichment of cellular heat-response, protein-folding, oxidative-phosphorylation, and mitochondrial ATP-production terms in the 2024 cohort at the time of sampling. The integrated transcript annotation contained 72,240 lncRNAs and 63,833 mRNAs, and CpG was the predominant methylation context. Differential methylation analysis identified 73 regions and 185 cytosines, with hypomethylated events predominating within the significant subset. Metabolomic profiles differed between annual cohorts and mapped to carbohydrate, lipid, and amino-acid pathways. Cross-omics integration prioritized eight candidate genes-ADCY9, UNC79, UBN1, IFT52, ACO2, LOC126986070, LOC127001126, and LOC126997895-and qPCR reproduced the reported directions of expression for selected RNAs. CONCLUSION: This study provides the first integrative multi-omics framework for understanding chronic heat adaptation in E. sinensis. By linking transcriptomic, epigenomic, and metabolic remodeling, we elucidate the molecular mechanisms underlying energy imbalance, epigenetic reprogramming, and immune dysregulation during prolonged thermal stress. These findings offer valuable insights and genomic resources for breeding heat-tolerant crab strains and improving aquaculture resilience under ongoing climate change.

DNA methylation↗
PubMed2026

Spatial proteogenomic profiling uncovers sensitization strategies for antibody-drug conjugate in HER2-positive breast cancer.

Antibody-drug conjugates (ADCs) have transformed the treatment of HER2-positive breast cancer, yet resistance remains poorly understood. Using imaging mass cytometry, we profiled 157 regions of interest comprising 912,360 single cells from 47 HER2-positive/hormone receptor-negative breast cancers treated with SHR-A1811 in the FASCINATE-N trial. Spatial proteomic analyses identified two determinants of ADC response: elevated tumor-cell H3K27ac expression was associated with improved ADC efficacy, whereas collagen-positive fibroblasts mediated resistance. Combining ADC with the histone deacetylase inhibitor chidamide or the collagen-modulating agent losartan produced synergistic antitumor effects in preclinical models. These biomarkers and therapeutic vulnerabilities were independently validated in patients with advanced HER2-positive disease receiving trastuzumab deruxtecan. Moreover, based on these spatial features, we developed a clinically applicable ADC barrier prediction model that can be implemented using multiplex immunofluorescence. Taken together, our findings reveal actionable spatial determinants of ADC efficacy and suggest potential combination therapeutic strategies.

Humans↗
PubMed2026

Depth-dependent microbial succession and interspecies hydrogen transfer drive pit mud maturation in Chinese strong-flavor baijiu fermentation.

Microbial communities in fermentation pit mud play a key role in determining the quality of Chinese strong-flavor baijiu (CSFB). However, the ecological processes underlying pit mud maturation across spatial and temporal scales remain unclear. In this study, amplicon sequencing and metagenomic analyses were employed to investigate the taxonomic succession, community assembly, and metabolic functions of bacterial and archaeal communities during the transition from fresh pit mud (FPM) to new pit mud (NPM) and old pit mud (OPM). A pronounced depth-dependent succession pattern was observed, with 4 cm representing a critical ecological boundary separating distinct community structures and maturation trajectories. During surface-layer maturation, community assembly shifted from stochastic to deterministic processes, accompanied by homogeneous selection and increasing network complexity. In contrast, stochastic processes remained dominant throughout deep-layer maturation. Metagenomic analyses revealed a functional transition from lactate and acetate production, primarily associated with Lactobacillus in FPM and NPM, to butyrate and caproate production associated with Clostridium and Caproiciproducens in OPM. This functional transition was accompanied by enhanced amino acid metabolism, which was associated with the enrichment of Proteiniphilum and Aminobacterium. Notably, methanogen-mediated interspecies hydrogen transfer (IHT) emerged as a key ecological feature during pit mud maturation. In OPM, IHT networks primarily involving Methanobacterium and Methanosarcina linked methanogenesis with reverse β-oxidation through diverse hydrogen-transfer pathways, reinforcing metabolic interactions underlying caproate production. These findings provide new insights into the ecological mechanisms underlying pit mud maturation and offer a theoretical basis for the directed cultivation of high-quality pit mud in CSFB production.

Hydrogen↗
PubMed2026

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

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

Animals↗
PubMed2026

Cross-Ancestry Proteogenomic Analyses Identified New Therapeutic Insights for Ischemic Heart Disease.

BACKGROUND: Most drugs target proteins, and proteome-wide genetic analyses in diverse populations could discover potential novel and repurposed targets for improved prevention and treatment of ischemic heart disease (IHD) beyond statin therapy. OBJECTIVES: The purposes of this study were to use cis-acting single nucleotide polymorphisms (cis-pQTLs) identified for plasma proteins in East Asians and Europeans to discover and validate potential drug targets for IHD. METHODS: We measured plasma levels of 9,520 (Olink/SomaScan: 2,923/7,297) proteins in a case-cohort study of IHD (1,976 incident cases and 2,001 subcohort controls) in statin-free individuals in the prospective China Kadoorie Biobank (CKB). Genome-wide association studies identified 2,895 (Olink/SomaScan: 1,301/1,594) cis-pQTLs for these proteins in CKB. Two-sample Mendelian randomization (MR) and colocalization analyses assessed associations of all available cis-pQTLs for these proteins with IHD in East Asians (n = 29,319 cases), with further replication in Europeans (n = 181,522 cases) and comparison with findings in previous MR studies. RESULTS: In CKB observational analyses, a total of 959 (Olink/SomaScan: 426/533) proteins were associated at false discovery rate-corrected P < 0.05 with IHD after adjusting for major IHD risk factors. Two-sample MR analyses provided genetic support for 54 unique (Olink/SomaScan: 36/28) proteins in IHD etiology. Colocalization analyses confirmed shared gene-protein-IHD associations (posterior probability of hypothesis 4 [PPH4] &#x2265;0.8) for 15 unique (Olink/SomaScan: 10/10) proteins, including 8 lipid-related, 3 inflammation-related, 1 blood pressure-related, and 3 alcohol-related proteins in East Asians. In Europeans, MR analyses of 12 non-alcohol-related proteins showed directionally concordant results for 8 proteins, with 5 having strong colocalization evidence of shared gene-protein-IHD associations (PPH4 &#x2265;0.8), including 4 lipid-related (proprotein convertase subtilisin/kexin type 9, LPA, APOE, cadherin-1) and 1 systolic blood pressure-related (fibroblast growth factor 5) protein. However, 4 proteins showed directionally discordant MR results, including 2 lipid-related (APOA5, SORT1) and 1 inflammation-related (transforming growth factor beta 1) proteins with strong colocalization evidence of shared gene-protein-IHD associations (PPH4 &#x2265;0.8). Comparison with previous MR studies revealed little consistency across studies in the number and identity of target proteins for IHD beyond well-established lipid-related (low-density lipoprotein cholesterol, lipoprotein(a), and triglycerides) or inflammation-related (interleukin-6) protein targets. CONCLUSIONS: The findings support a role for lipid-driven chronic inflammation in IHD etiology, and treatment strategies simultaneously targeting multiple lipid and inflammation pathways should be prioritized for further research to improve drug treatment of IHD beyond statin therapy.

Aged↗
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 &#x3b1;-1,2-fucosyltransferase (&#x3b1;-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&#x202f;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

Multi-season analysis reveals hundreds of drought-responsive genes in sorghum.

Persistent drought affects global crop production and is becoming more severe in many parts of the world in recent decades. Deciphering how plants respond to drought will facilitate the development of flexible mitigation strategies. Sorghum bicolor L. Moench (sorghum), a major cereal crop and an emerging bioenergy crop, exhibits remarkable resilience to drought. To better understand the molecular traits that underlie sorghum's remarkable drought tolerance, we undertook a large-scale sorghum gene expression profiling effort, totaling nearly 1500 transcriptome profiles, across a 3-year field study with replicated plots in California's Central Valley. This study included time-resolved gene expression data from roots and leaves of two sorghum genotypes, BTx642 and RTx430, with different pre-flowering and post-flowering drought-tolerance adaptations under control and drought conditions. Quantification of genotype-specific drought tolerance effects was enabled by de novo sequencing, assembly, and annotation of both BTx642 and RTx430 genomes. These reference-quality genomes were used to construct a pangene set for characterizing conserved and genotype-specific expression. By integrating time-resolved transcriptomic responses to drought in the field across three consecutive years, we identified a set of 726 drought-responsive genes that responded similarly in all 3&#x2009;years of our field study. Functional enrichment analysis identified abiotic stress, secondary cell wall-related processes and metabolism as particularly affected under both types of drought stress. We also found that some glyoxylate cycle pathway genes, including malate synthase and isocitrate lyase, are differentially regulated particularly during post-flowering drought stress, implicating this pathway as potentially important for drought responsiveness. This expansive dataset represents a unique resource for sorghum and drought research communities and provides a methodological framework for the integration of multi-faceted time-resolved transcriptomic datasets.

Sorghum↗
PubMed2026

A Functionally Constrained Immune Ecosystem in Microsatellite-stable Colorectal Cancer Resolved by Single-cell and Exome Profiling.

BACKGROUND/AIM: Microsatellite-stable (MSS) colorectal cancer (CRC) generally responds poorly to immune checkpoint blockade, but some MSS tumors are T-cell rich. We examined whether such infiltration reflected effective immunity or functional immune constraint. CASE REPORT: A 77-year-old woman underwent resection of a mismatch repair-proficient (pMMR), MSS, low-mutational-burden CRC with a synchronous adenoma. Whole-exome sequencing of tumor, adenoma and adjacent normal tissue detected no shared high-confidence somatic mutations between tumor and adenoma within the sensitivity of this WES analysis and identified tumor-specific APC, KRAS and TP53 alterations. Tumor single-cell RNA sequencing yielded 7,569 cells, with T-lineage populations comprising 83.5%. Cytotoxic T cells showed cytolytic and dysfunction-associated features, regulatory T cells (Tregs) showed suppressive remodeling, and Th17 cells showed inflammatory/profibrotic programs. CellChat nominated stromal MIF/FN1-CD74/CD44 and extracellular-matrix communication with T-cell compartments. CONCLUSION: This molecular case report shows that T-cell abundance and immune effectiveness can be uncoupled in MSS CRC.

Humans↗
PubMed2025

Hologenomic insights into the molecular adaptation of deep-sea coral Bathypathes pseudoalternata.

Deep-sea coral ecosystems support biodiversity and nutrient cycling through interactions with symbionts. However, their molecular mechanisms remain unexplored. Here, hologenomic analyses of Bathypathes pseudoalternata are applied to uncover molecular adaptations underpinning host-symbiont interactions. Genomic evidence reveals that B. pseudoalternata exhibits adaptations in nutrient transport, immune response, and lysosomal digestion, reflecting its genomic adjustments for a stable symbiosis. Candidatus Nitrosopumilus bathypathes (78.43% &#xb1; 3.65%) is inferred to oxidize host-derived ammonia to synthesize amino acids and vitamins to provision the host. The presence of CRISPR-Cas and restriction-modification (R-M) systems suggests that Ca. Bathyplasma bathypathes and Ca. Thalassoplasma bathypathes (10.68% &#xb1; 2.99%) may protect the host from viral infections. Ca. Bathybacter bathypathes (8.39% &#xb1; 1.53%) is hypothesized to synthesize heme, lipoic acid, and glutathione, which serve dual functions as antioxidants and nutrients. These findings collectively provide insights into how the hologenome contributes to the survival of B. pseudoalternata in the extreme environment.

Animals↗
PubMed2025

Multi-omics analyses reveal DjTcf4 critical for proper timing of differentiation in planarian regeneration.

The blastema is key to forming complete tissues in regenerating Dugesia japonica (D. japonica). However, the dynamic changes in cellular compositions and transcription landscapes in blastema during regeneration are understudied. Here, through genome reannotation, 3D spatial transcriptome construction, single-cell RNA sequencing (scRNA-seq), and single-cell assay for transposase-accessible chromatin sequencing (scATAC-seq) analyses of changes in gene expression and chromatin structures, we delineate key transcription factors regulating the developmental trajectories of major cell clusters in the regenerating head. Importantly, we find that the T cell factor 4 (DjTcf4)-positive cells highly accumulate at wound areas, and its gene network is critical for the proper timing of development during regeneration in multiple progenitor cells. Depletion of DjTcf4 and its target genes leads to singular eye and/or dull tail phenotypes and delays regeneration. Taken together, we build multi-omics atlases in D. japonica and reveal the noncanonical function of the DjTcf4 network in developmental pattern formation, laying a foundation for studies of regeneration in D. japonica.

Animals↗
PubMed2025

Integrative omics of the genetic basis for wheat WUE and drought resilience reveal the function of TaMYB7-A1.

Improving wheat&#xa0;drought resilience and water use efficiency (WUE) is critical for sustaining productivity under increasing water scarcity. Here, we integrate genome-wide association&#xa0;study (GWAS), expression quantitative trait locus (eQTL) mapping, population-transcriptome analysis, and summary-data-based mendelian randomization (SMR), followed by functional validation using indexed EMS mutants and transgenic lines, to systematically identify key WUE regulators. GWAS across water conditions in 228 accessions identifies 73 quantitative trait loci (QTLs) for WUE-traits. Transcriptome profiling of 110 diverse accessions reveals 28 drought-responsive modules. eQTL mapping uncovers 146,966 regulatory variants, including condition-specific hotspots associated with key drought-related pathways. Integrative analysis underscores 85 high-confidence candidate genes, notably TaMYB7-A1. Overexpression of TaMYB7-A1 enhances photosynthesis, WUE, root development, and grain yield under drought condition by activating TaPIP2;2-B1 (water transport), TaRD20-D1 (stomatal regulation), and TaABCB4-B1 (root growth), reflecting reduced water loss and improved physiological resilience. Our study presents a comprehensive regulatory map and robust targets for wheat drought adaptation and resilient cultivar breeding.

Triticum↗
PubMed2025

A deep-sea hydrothermal vent worm detoxifies arsenic and sulfur by intracellular biomineralization of orpiment (As2S3).

The alvinellid worm Paralvinella hessleri is the only animal that colonizes the hottest part of deep-sea hydrothermal vents in the west pacific. We found P. hessleri accumulates exceptionally high level of toxic element arsenic (>1% of wet weight) and tolerated elevated concentrations hydrogen sulphide. Using advanced microscopy, elementary analysis, and genomics and proteomics approaches, we identified a previously unrecognized arsenic-sulfide biomineralization process in P. hessleri. Our data suggest that arsenic accumulates within epithelial cell granules, where it likely reacts with sulphide diffused inward from the hydrothermal vent fluid, resulting in the intracellular formation of orpiment (As&#x2082;S&#x2083;) minerals. In this "fighting poison with poison" manner, the highly toxic arsenic and sulphide were simultaneously detoxified in the form of orpiment minerals within the intracellular granules of the single layer of epithelial cells. This process represents a remarkable adaptation to extreme chemical environments. Our study provides new insights into understanding animals' environment adaptation mechanisms and the diversity and plasticity of biomineralization.

Animals↗
PubMed2025

A randomized pilot study of HPV16 L2E7E6 fusion protein vaccination site post-treatment for HPV16+ cervical cancer.

OBJECTIVE: Since anti-tumor immunity is enhanced by vaccination of mice adjacent to human papillomavirus type 16 (HPV16+) tumors, we examined whether HPV16 L2E7E6 fusion protein (TA-CIN) vaccination in the thigh of HPV16+ cervical cancer patients would be more immunogenic than their arm. METHODS: HPV16+ cervical cancer (stage IB1-IVA) patients, who had completed standard-of-care treatment within the past year and absent evidence of disease (NED), were enrolled in a pilot study (NCT02405221). Participants were randomized 1:1 to receive three 100&#xa0;&#x3bc;g TA-CIN monthly intramuscular immunizations either in the arm or thigh and followed for two years for safety (CTCAEv4.0), immune response, and recurrence. RESULTS: Fifteen patients were enrolled (median age 44, range 35-83&#xa0;years); one patient experienced a non-vaccine-related adverse event after one vaccination and withdrew. Treatment-related adverse events (n&#xa0;=&#xa0;8) were grade 1, primarily at the injection site, and self-resolved. No recurrence was observed. TA-CIN-specific antibody titers tended to be higher in thigh-vaccinated patients. Bulk TCRseq revealed significant increases in expanded and de novo T cell clones following thigh-vaccination compared with the arm. No correlation with prior treatment modality was observed. E6-, E7-, and L2-specific TCR clones expanded, although L2-specific T cell responses were predominant. One month post-vaccination, scRNAseq revealed significant expansion of MAIT and cytotoxic CD8+ T cells, and both expanded and novel TCR clonotypes were identified in the latter. CONCLUSIONS: Thigh or arm vaccination with TA-CIN was well tolerated, but the former elicited higher CD8 T cell and antibody responses in HPV16+ cervical cancer patients with NED after primary therapy.

Humans↗