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PubMed2026

Deciphering CD8+ T cell exhaustion in human cancers through single-cell and spatial transcriptomics.

Exhausted CD8+ T cells (Tex) within the tumor microenvironment (TME) represents a critical barrier limiting anti-tumor immune responses. Tex cells are characterized by upregulated inhibitory immune checkpoint receptors, reduced cytotoxicity, and functional heterogeneity. Their genomic features and regulatory networks remain poorly defined, and only a minority of patients respond to immune checkpoint blockade (ICB) therapy. Single-cell RNA sequencing (scRNA-seq), through high-resolution transcriptomic profiling, has revealed diverse Tex subpopulations, identified subpopulation-specific marker genes and regulatory pathways. Spatial transcriptomics has further mapped the spatial distribution of Tex and their interaction networks with immune cells, tumor cells, and stromal cells, elucidating the impact of spatial heterogeneity on Tex functionality. Current studies indicate that the exhausted state of Tex is dynamic and modifiable, with functional differences among subpopulations closely associated with tumor progression and therapeutic response. However, the genomic characteristics, epigenetic regulation, and spatial interaction mechanisms of Tex require further exploration. This review summarizes recent advances in high-resolution omics technologies for precisely dissecting Tex heterogeneity, functional features, and interactions with other cells. It emphasizes the central value of optimizing Tex-targeted tumor immunotherapy strategies, providing theoretical foundations and directional guidance for developing more effective anti-tumor immunotherapies.

Humans↗
PubMed2026

Ancient DNA and Human Physiology.

Ancient DNA (aDNA) enables the reconstruction of chronologically sampled genomes from ancient humans, animals, plants, pathogens, and microorganisms, as well as environmental DNA, providing a record of biological changes through time. Improvements in short and degraded DNA extraction methods and low-cost sequencing now enable the generation of broad, cross-regional datasets that expand evolutionary analyses from past population demography to biological mechanisms. By tracking temporal shifts of allele frequencies, integrating functional genomics resources (e.g., gene expression, chromatin structure variation), modeling population demography to separate selection from genetic drift, and aligning genetic changes with archaeological, cultural, and climatic data, aDNA has the potential to link sequence variation to physiological function within their temporal and environmental contexts. In this review, we summarize illustrative case studies from aDNA research spanning complex traits, dietary adaptations, and responses to pathogens and other environmental changes, showing how human biology has evolved under multiple selective pressures through time. These dated signals help triage experimental work and expose mechanisms that are rare or absent in living cohorts. Although some challenges remain, such as geographic and temporal sampling disparities, limitations in data resolution and variant detection, and genotype-phenotype uncertainties, rapid methodological progress and stronger ethical frameworks are expanding what can be inferred, making aDNA a promising tool for refining physiological pathways, their timing, and their drivers.

Humans↗
PubMed2026

Parent-of-origin effects on allelic expression bias in interspecific poplar hybrids.

In hybrid plants, phenotypic outcomes are governed by interactions between the two parental genomes. However, the mechanisms underlying the interplay of divergent regulatory networks from these genomes remain poorly understood. In this study, we compared gene-level and allele-specific expression patterns, as well as differentially enriched pathways between F₁ and complex backcross (CBC) lines derived from a natural interspecific hybrid population of Populus fremontii (Pf) and P. angustifolia (Pa). Metabolic differences between Pf and Pa which exhibit low and high levels respectively of phenylpropanoid-derived condensed tannins were leveraged. Using individualized transcriptome references, differential expression and clustering analyses revealed CBC-biased and F₁-biased expression for genes involved in phenylpropanoid metabolism and photosynthesis, respectively. Biased expression of these genes at the allele level was also observed in F1. At the whole-transcriptome level, Pa-biased genes predominated in F₁ hybrids, and Pa alleles displayed more conserved expression patterns than Pf alleles across examined samples. Further analyses indicated that allelic expression bias was significantly associated with parental origin, which could be driven by sequence variations in cis-regulatory elements and differences in CpG island length. Our findings demonstrate strong parent-of-origin effects on divergent regulatory networks governing gene expression in poplar hybrids and provide clues for strategic parental selection tailored to specific metabolic pathways of interest.

cis-regulation↗
PubMed2026

Engineering bubble structures as Cas12a activators for highly sensitive monitoring of WRN helicase function.

The Werner syndrome helicase (WRN) is a critical synthetic lethal target in microsatellite instability cancers, essential for resolving complex genomic structures like replication bubbles and R-loops. However, strategies to simultaneously discriminate WRN activity on DNA versus DNA-RNA substrates in living cells are lacking. Here, we developed a structure-specific CRISPR/Cas12a biosensing strategy to visualize WRN functional activity by engineering bubble-structure probes. These probes were rationally designed to structurally mimic DNA replication bubbles and R-loop associated DNA-RNA hybrids. Upon specific unwinding by WRN, the probes release a sequestered activator strand that triggers Cas12a trans-cleavage, effectively converting the unwinding event into an amplified fluorescent signal. This assay achieves low picomolar sensitivity (LODs: 5.6-6.0 pM) and exceptional selectivity against homologous RecQ helicases. Uniquely, this strategy enables the parallel quantification of WRN activity on both substrate types, providing insights into distinct WRN-mediated pathways for resolving genomic stress. We further demonstrated the strategy's utility by visualizing endogenous WRN dynamics in living cells and profiling the efficacy of small-molecule inhibitors. This work offers a powerful molecular toolkit for dissecting WRN biology and facilitating high-throughput drug screening in targeted cancer therapy.

Werner Syndrome Helicase↗
PubMed2026

The Thyroid-Brain Network: Exploring Inflammation, Immune Mechanisms and Common Triggers in Thyroid-Related Neurological Dysfunction.

Autoimmune thyroid diseases (AITD), including Hashimoto's thyroiditis and Graves' disease, represent the most prevalent endocrine disorders worldwide, affecting hundreds of millions with profound but often under recognized neurological consequences. There are emerging lines of evidence establishing inflammation and immunity as the critical missing link connecting peripheral thyroid dysfunction to central nervous system manifestations. Thyroid hormones function as essential neuromodulators governing neurodevelopment, synaptic plasticity, and cognitive processing through integrated genomic and non-genomic mechanisms, with region-specific cerebral metabolic disturbances correlating with distinct neuropsychiatric symptoms. The immunological perspective reveals that AITD propagates neuroinflammation through convergent pathways: molecular mimicry enabling cross-reactivity between thyroid and neural antigens, cytokine-mediated disruption of neurotransmitter metabolism, HMGB1-driven glial activation, and blood-brain barrier compromise facilitating immune cell infiltration. The thyroid-gut-microbiota axis emerges as a critical mediator wherein dysbiosis perpetuates both thyroid autoimmunity and neuroinflammation through impaired serotonin precursor availability and increased intestinal permeability. Mitochondrial dysfunction represents an energetic common denominator, as thyroid hormone dysregulation directly impairs oxidative phosphorylation, producing region-specific cerebral metabolic disturbances. Simultaneous compromise of monoamine systems, cholinergic signaling abnormalities, and glutamate excitotoxicity creates a particularly toxic neurochemical state in untreated thyroid dysfunction. Common triggers such as psychological stress, gut dysbiosis, and mitochondrial impairment may activate interconnected pathways that simultaneously compromise thyroid and brain function, revealing that these disorders share fundamental mechanistic origins. These insights have been discussed in the current review to enhance the understanding of thyroid-brain function, the core mechanisms and consequences of functional deficits.

Journal Article↗
PubMed2026

Hydroxyl Radical Inactivation of Vesicle-Cloaked and Free Murine Norovirus: Linking Biomolecular Oxidation to Lifecycle Disruption and Infectivity Loss.

Hydroxyl radicals (•OH) play a central role in inactivating human viruses during advanced oxidation processes for water and wastewater treatment, solar disinfection, and natural attenuation in sunlit aquatic environments. Human norovirus, a leading cause of gastroenteritis, is efficiently transmitted through water and exhibits strong environmental persistence. The recent discovery of vesicle-cloaked virus clusters (viral vesicles) further challenges water treatment and reuse, particularly for norovirus elimination. We investigated •OH inactivation kinetics and mechanisms of murine norovirus 1 (MNV-1), a human norovirus surrogate, in free-virus and vesicle-cloaked forms. •OH rapidly inactivated both MNV-1 vesicles and free MNV-1 with second rate constants of ∼1010 M-1 s-1; however, the vesicle membrane provided a 2.24-fold protective effect to cloaked MNV-1, resulting in slower inactivation kinetics than those of free MNV-1. •OH oxidized viral capsid proteins and genomes together with vesicle proteins and lipids, resulting in impaired CD300lf receptor and cell-based binding, disrupted genome replication, and diminished viral assembly. Despite these biochemical and functional impairments, most vesicle structures remained largely intact following •OH exposure. This study establishes a quantitative framework linking biomolecular damage to viral infectivity loss through functional impairment and lifecycle disruption, providing mechanistic insights into advance water disinfection strategies and public health protection.

Norovirus↗
PubMed2026

Pharmacogenomic and drug interactions risk in cardio-oncology: A precision medicine perspective for India.

Cardio-oncology patients may face complex treatment regimens due to the concurrent existence of cancer and cardiovascular disease, leading to a considerable polypharmacy burden. This significantly increases the prospect of drug-drug interactions (DDIs) and gene-drug interactions. The majority of these interactions arise from comparable pharmacokinetic and pharmacological pathways associated with drug transporters and cytochrome P450 enzymes. The significance of pharmacogenomics in tailored treatment strategies are emphasised by the fact that genetic variability enhances individual differences in drug response, safety, and efficacy. This narrative review focus on the effects of key genetic polymorphisms (e.g., DPYD, CYP2C19, and CYP2C9) on the metabolism and efficacy of commonly prescribed anticancer and cardiovascular medications such as fluoropyrimidines, clopidogrel, and warfarin. In addition it explore the role of pharmacogenomic variants on drug-drug interactions within the field of cardio-oncology. The study ultimately emphasizes the necessity of precision medicine in India to address the genetic diversity and underrepresentation in global genomic databases. The absence of pharmacogenomic testing, infrastructural deficiencies, financial constraints, and insufficient clinical integration hinder the widespread use of this technology in India. The Genome India Project and other national initiatives establish the foundation for pharmacogenomic-guided therapy. Utilizing genetic data, together with artificial intelligence-based predictive tools, for clinical decision-making may enhance medication safety and yield optimal outcomes in Indian cardio-oncology patients.

Humans↗
PubMed2026

UNCX/SIN3A-Mediated H4K8 decrotonylation suppresses FOXO3 to drive TNBC progression and docetaxel resistance.

Triple-negative breast cancer (TNBC) remains a clinically challenging subtype characterized by aggressive behavior and limited treatment options. Though docetaxel remains a cornerstone chemotherapy for TNBC, the frequent emergence of resistance highlights the urgent need to identify novel therapeutic targets. In this study, we report that uncoordinated homeobox (UNCX) is upregulated in docetaxel-resistant breast cancer cells, genomically amplified in breast cancer, and associated with poor survival in breast carcinoma patients. Functional studies revealed that UNCX promotes breast cancer cell proliferation, migration and reduces the docetaxel sensitivity. Mechanistically, UNCX functions as a transcriptional repressor by recruiting the SIN3A complex. Genome-wide profiling indicated that the UNCX/SIN3A complex directly binds to the promoters of tumor-suppressor genes including FOXO3, and represses their transcription by removing histone H4K8 crotonylation (H4K8cr). Additionally, the UNCX/SIN3A complex enhances FOXO3 phosphorylation and inhibits its nuclear translocation, further inhibiting its activity. Notably, SIN3A knockdown, FOXO3 overexpression, or crotonylation restoration effectively reverses UNCX-induced malignant phenotypes. These findings collectively establish the UNCX/SIN3A-H4K8cr-FOXO3 axis as a pivotal epigenetic regulator of TNBC progression and chemoresistance, revealing new avenues for targeted therapeutic development against this aggressive breast cancer subtype.

Humans↗
PubMed2026

Emergence of an optrA-positive Enterococcus faecalis ST699 lineage in animal-derived foods in Beijing, China.

Enterococci from animal-derived foods are key reservoirs for antimicrobial resistance (AMR) in the food chain. However, comparative genomic studies investigating the distribution of the oxazolidinone resistance gene optrA among food- and human-derived Enterococci remain limited. This study assessed linezolid-resistant Enterococci from retail meat and healthy humans in Beijing, China (2023-2024). Among 87 isolates, E. faecalis and E. faecium predominated. Food-derived isolates showed broader resistance profiles than human isolates. Fourteen optrA-positive strains were identified, accounting for 92.9% of food isolates. optrA frequently co-localized with erm(A), ant(9)-Ia, and fexA on Tn554-family transposons, suggesting a potentially transferable multidrug resistance module. Notably, an optrA-positive E. faecalis ST699 clone was identified for the first time in Chinese retail meat. This clone formed a distinct lineage and carried a complete Tn554-optrA island. A representative ST699 isolate exhibited enhanced fitness and virulence potential in the Galleria mellonella model. These findings highlight animal-derived foods as important reservoirs of linezolid-resistant Enterococci and provide genomic evidence consistent with their role as potential sources of optrA-mediated resistance. The emergence of a multidrug-resistant E. faecalis ST699 clone with enhanced fitness characteristics underscores the need for continued surveillance of foodborne antimicrobial resistance within the One Health framework.

Enterococcus faecalis↗
PubMed2026

Viral replication through phase separation: Cytosolic and nuclear condensates.

Replication of many RNA and DNA viruses occurs within specialized intracellular hubs organized as membraneless biomolecular condensates (BCs) driven by liquid-liquid phase separation. As obligate intracellular parasites, viruses depend on the host cell machinery to complete their replication cycles and therefore actively remodel the intracellular environment to favor viral genome replication, transcription, and assembly. Cytosolic and nuclear phase-separated replication compartments (RC) provide concentrated and dynamic platforms that promote efficient interactions between viral genomes and viral or host proteins essential for infection. The formation of viral replication BCs is typically facilitated by viral proteins enriched in intrinsically disordered regions and low-complexity domains, which enable multivalent interactions with viral nucleic acids and cellular factors. These interactions are mediated by diverse biophysical forces, including hydrophobic and π interactions, hydrogen bonding, molecular crowding, and osmotic effects. Throughout infection, viral BCs remain highly dynamic, allowing continuous exchange of components and functional maturation of replication hubs. Their properties and activities are further regulated by post-translational modifications of viral and host proteins, such as phosphorylation, acetylation, and methylation. In this review, we summarize current evidence supporting liquid-liquid phase separation as a central organizing principle of viral RCs. We focus on representative RNA and DNA viruses that replicate in the cytosol or nucleus, highlighting virus-specific strategies, conserved mechanisms, and the consequences of BC formation for viral replication efficiency, host antiviral responses, and therapeutic intervention.

Phase Separation↗
PubMed2026

Age-related differences in semen quality in Holstein-Friesian bulls: a paired within-bull comparison of early and mature reproductive stages.

Genomic selection has changed dairy cattle breeding by increasing the use of young bulls for artificial insemination and shortening the reproductive lifespan of sires. Under these conditions, semen quality at the beginning of commercial use has become an important practical issue. Semen samples from 39 fertile Holstein-Friesian bulls used for commercial AI were collected between 2013 and 2016, during the introduction of genomic selection in Poland. This paired within-bull study compared semen collected from the same bulls at an early reproductive stage (13-20 months; young bulls, YB) and at full maturity (5-6 years; mature bulls, MB). The evaluation included conventional ejaculate traits, CASA-derived motility and kinematic descriptors, mtDNA copy number, and mitochondrial content per sperm cell. Importantly, all ejaculates met the quality requirements for commercial insemination. Ejaculate volume, sperm concentration, mitochondrial DNA copy number, and mitochondrial content did not differ significantly between age groups. The CASA-derived sperm movement profile, in contrast, differed with age. Semen from young bulls showed a higher proportion of progressively motile spermatozoa, whereas semen from mature bulls showed higher velocity-related parameters, including VSL, VCL, and STR. These findings indicate that bull age mainly affected sperm movement characteristics rather than semen output or mitochondrial content. Overall, the results support the use of young bulls in artificial insemination programs and show that age-related differences in semen quality are expressed mainly through changes in the post-thaw sperm motility and kinematic profile.

Animals↗
PubMed2026

Distinct cell morphotypes of Aureobasidium melanogenum ZN exhibit differential functional profiles in promoting maize growth.

Black yeast-like fungi of the genus Aureobasidium exhibit morphological plasticity, but whether distinct cellular states within the same genetic background are associated with different plant growth-promoting functions remains unclear. Here, yeast-like cells (YL), swollen cells (SC), and chlamydospores (CH) of Aureobasidium melanogenum ZN were characterized. YL was associated mainly with siderophore production and laccase activity, SC with extracellular polysaccharide accumulation, and CH with phosphate mobilization and higher ammonia and IAA production. Whole-genome and comparative genomic analyses revealed a shared repertoire related to nutrient acquisition, auxin-associated metabolism, extracellular oxidation, and carbohydrate remodeling, with expansions in nutrient- and cell-surface-related gene families. Transcriptomic and metabolomic analyses showed distinct deployment of these capacities, with CH exhibiting broad reprogramming of tryptophan-associated, nitrogen, phosphate, central-carbon, and amino-acid metabolism. In maize, CH at the optimal inoculation concentration of 105 CFU·mL-1 produced the strongest growth promotion, increasing plant height, dry biomass, root length, root surface area, and root volume by 58.6%, 365.1%, 191.0%, 194.3%, and 222.4%, respectively. Consistent with this pronounced growth phenotype, maize root transcriptomics showed coordinated CH-induced responses involving root development, nutrient transport, redox regulation, and root-interface remodeling. Root-zone tracking showed greater short-term stability and persistence of CH. These findings identify cellular state as an important functional dimension of Aureobasidium-plant interactions and provide a basis for developing fungal inoculants with defined beneficial cellular states.

Zea mays↗
PubMed2026

Complement component C4 and neuroimaging in psychiatry: A systematic review.

INTRODUCTION: Genomic, transcriptomic, and proteomic studies suggest that the complement system contributes to the pathophysiology of various psychiatric disorders partly through neurodevelopmental effects linked to C4A protein levels variations. We conducted a systematic review to characterize how brain micro- and macrostructure and connectivity vary with proxies of in vivo brain C4A protein levels in both psychiatric and general-population cohorts. METHODS: We used Medline, Web of Science, and Embase, and included all studies published before April 14, 2025. Inclusion criteria were: (1) inclusion of healthy controls and/or individuals with psychiatric disorders assessed according to recognized diagnostic manuals (DSM or ICD); (2) use of MRI-based neuroimaging; and (3) use of genomic, transcriptomic and/or proteomic approaches as proxies of in vivo brain C4A proteins levels. RESULTS: From 317 identified articles, 11 were included. Associations between C4A levels and brain structure were heterogeneous across regions. Only the mOFC, dlPFC, and entorhinal cortex were implicated in more than one study. Findings for the mOFC and dlPFC varied by the type of metrics and clinical status, whereas higher C4A levels were more consistently associated with smaller entorhinal cortex surface area and cortical thickness in pediatric, middle-aged, and older general-population cohorts. In addition, one study found higher genetically predicted C4A expression to be associated with higher TSPO levels. CONCLUSION: The limited number of available studies and their methodological heterogeneity make synthesis challenging. However, biological hypotheses such as excessive synaptic pruning or broader inflammatory effects on the brain may provide plausible explanatory frameworks for the reported associations.

Humans↗
PubMed2026

Lactylation-related immune-metabolic dysregulation defines prognostic and therapeutic stratification in lung adenocarcinoma.

BACKGROUND: Lactylation links lactate metabolism with inflammatory signaling and immune regulation in tumors. However, its cellular distribution and translational value in lung adenocarcinoma (LUAD) remain unclear. METHODS: Single-cell RNA-sequencing datasets GSE189357 and GSE171145 were integrated to characterize lactylation-related activity, intercellular communication, and malignant epithelial cell states in LUAD. Single-cell-derived lactylation-related differentially expressed genes were mapped to TCGA-LUAD and multiple GEO cohorts. Univariate Cox regression and machine learning algorithms were used to construct a lactylation-related prognostic signature (LRPS). The associations of LRPS with prognosis, immunotherapy response, drug sensitivity, genomic alterations, immune infiltration, and inflammation- and metabolism-related pathways were evaluated. KRT7 was further validated using virtual knockout analysis, spatial transcriptomics, and in vitro and in vivo experiments. RESULTS: lactylation-related transcriptional activity showed heterogeneous distribution across LUAD cell populations and was associated with altered cell-cell communication. In malignant epithelial cells, LRTS-high and LRTS-low states exhibited distinct metabolic, inflammatory, and tumor-related pathway activities. LRPS showed stable prognostic performance in TCGA-LUAD and multiple GEO cohorts and remained an independent prognostic factor. Low LRPS was associated with greater potential benefit from immunotherapy, whereas different LRPS groups displayed distinct drug sensitivity, genomic alteration, and immune microenvironment patterns. KRT7 was highly expressed in LUAD and associated with poor prognosis. KRT7 knockdown suppressed LUAD cell proliferation, migration, invasion, colony formation, and tumor growth in vivo. CONCLUSIONS: This study identifies lactylation-related immune-metabolic dysregulation as a clinically relevant feature of LUAD and develops a single-cell-guided LRPS for prognosis and therapeutic stratification. KRT7 emerged as an LRPS-related functional candidate with experimentally supported roles in malignant LUAD phenotypes.

Immunotherapy↗
PubMed2026

Upscaling Genotyping by Amplicon Sequencing With GBAS-GUI.

Genotyping by amplicon sequencing (GBAS) is a relatively low-cost approach for generating genotypic data compared with established genomic methods, making it highly scalable and particularly suitable for large-scale genetic monitoring projects. However, most existing analytical pipelines are either marker-specific, insufficiently scalable, or lacking efficient data management systems for the long-term integration of genotypic information, limiting the full potential of GBAS. Here, we address this gap by introducing GBAS-GUI (https://github.com/sonnenbe-dot/GBAS-GUI), a pipeline capable of generating GBAS-based genotypic data for a wide variety of loci at scale. GBAS-GUI integrates a graphical user interface with multiple checkpoints to improve accessibility and robustness. It implements multiprocessing architecture and a relational database that links genotypic data with associated sample metadata to enhance scalability and data management. The pipeline further enables marker screening through automated calculation of polymorphism information content (PIC) and implements a strategy to recover homologous genotypic information from paralogous loci with non-overlapping amplicon length ranges. Using multiple empirical datasets, we demonstrate substantial improvements in processing speed, database management and handling artefacts related to co-amplification of unspecific regions and duplicates of the same genomic region. We further show that incorporating the full sequence information captured by an amplicon increases marker information content beyond what is achievable with length-based genotyping alone and expands the analytical versatility of GBAS. Overall, GBAS-GUI provides a robust, scalable and versatile framework that unlocks the potential of GBAS for large-scale population genetic and phylogeographic studies.

Genotyping Techniques↗
PubMed2026

Overcoming Immunological Barriers in MSC-Derived Insulin-Producing Cells through CRISPR-Based Hypoimmunogenic Engineering and Translational Perspectives for Type 1 Diabetes.

Mesenchymal stromal cell (MSC)-derived insulin-producing cells (IPCs) represent an emerging strategy for β-cell replacement in type 1 diabetes mellitus (T1DM) owing to their differentiation potential, intrinsic immunomodulatory properties, and lower tumorigenic risk compared with pluripotent stem cell-derived platforms. However, accumulating evidence indicates that differentiation-associated immunogenicity, context-dependent immune recognition, and recurrent autoimmune responses may substantially limit long-term graft survival and therapeutic durability following transplantation. This review critically examines the immunological barriers associated with MSC-derived IPCs, including altered MHC expression, susceptibility to alloimmune and autoimmune-mediated rejection, and potential reactivation of autoreactive immune memory. We discuss the application of CRISPR-based hypoimmunogenic engineering strategies targeting antigen presentation pathways, NK-cell activation, and immune checkpoint modulation to generate more immune-evasive MSC-derived IPCs while preserving β-cell functionality. By integrating insights from T1DM immunopathogenesis, MSC biology, genome editing, and translational immunology, we propose a framework linking immune engineering with controlled differentiation, functional maturation, and long-term safety evaluation. In parallel, we comparatively position MSC-derived IPCs alongside clinically advancing iPSC-derived β-cell platforms to highlight their distinct translational niche, including potential advantages related to safety, immunomodulatory capacity, manufacturing accessibility, and scalability, while acknowledging the superior functional maturity and clinical progression currently demonstrated by iPSC-derived systems. Finally, we discuss key translational challenges, including genomic stability, immune-evasion durability, GMP-compliant manufacturing, and the need for rigorous functional and immunological benchmarking prior to clinical application of hypoimmunogenic MSC-derived IPC therapies in T1DM.

Humans↗
PubMed2026

Immune dysregulation in depression and psychosis: summary of current evidence and future perspectives.

Despite compelling epidemiological, genetic and cellular evidence linking immune dysregulation to depression and schizophrenia (and other psychotic disorders), causality remains contested and no immune biomarker has yet demonstrated robust clinical utility. Emerging methodological approaches - from target trial emulation on observational data to functional genomics - offer a potential path towards precision immunopsychiatry and stratified immunomodulatory treatment.

Neuroimmunology↗
PubMed2026

Development and protective efficacy of a live attenuated vaccine candidate against goose astrovirus.

Goose astrovirus (GAstV) is a significant pathogen affecting goslings by inducing visceral gout, yet no commercial vaccine is currently available. This study involved the serial passaging of the GAstV-GXNN strain in LMH cells to investigate alterations in viral replication, genomic stability, and pathogenicity, as well as to assess the potential of a vaccine candidate. The findings indicated that the viral titer increased progressively with each passage, reaching 107.35 TCID50/mL by the 120th passage (GAstV-GXNNP120). Whole-genome sequencing revealed the presence of 6, 19, 26, and 28 nucleotide mutations at the 30th, 60th, 90th, and 120th passages, respectively. Pathogenicity assays demonstrated a reduction in virulence with successive passages, culminating in the complete attenuation of GAstV-GXNNP120, which did not induce clinical signs or lesions in one-day-old goslings. Following five successive passages in goslings, the attenuated strain exhibited stable genetic characteristics without any reversion to virulence. Goslings aged one day, inoculated with GAstV-GXNNP120 at dosages ranging from 102.0 to 105.0 TCID50, developed neutralizing antibodies by the third day post-vaccination. Antibody levels increased in a dose-dependent manner, peaking at day 21 and remaining elevated through day 42. Challenge experiments utilizing the virulent GAstV-GXNN strain revealed that groups vaccinated with doses of 103.0 TCID50 and above achieved complete protection. These groups exhibited no clinical symptoms or pathological damage post-challenge, and both tissue viral loads and virus shedding levels were significantly reduced compared to the control group. Consequently, the minimum effective vaccination dose was established at 103.0 TCID50. These results provide a crucial foundation for the development of a live attenuated GAstV vaccine.

Animals↗