Genes & genomics最新文献

Background: Hepatocellular carcinoma (HCC) is notable for its marked molecular heterogeneity and poor response to systemic therapy. Targeted next-generation sequencing (NGS) has facilitated the profiling of somatic alterations in HCC. However, the interpretation of panel-based genomic features such as tumor mutational burden (TMB), copy number alterations, and candidate gene fusions remains challenging, particularly in HBV-endemic Asian populations.

Objective: To explore the somatic mutation landscape of HCC using a targeted sequencing panel in a regional cohort and to descriptively assess its associations with clinicopathological characteristics.

Methods: We conducted a 671-gene targeted NGS panel covering approximately 2.5 Mb of coding regions on tumor-normal paired samples from 40 patients with HCC and integrated the mutational profiles with clinicopathological data. We analyzed somatic mutations, copy number variation signals, and candidate fusion events. We performed functional enrichment analyses and comparative analyses with the Cancer Genome Atlas (TCGA) cohort. Survival analyses were conducted in an exploratory manner.

Results: TP53 was the most frequently mutated gene (55%) and its mutation status was associated with hepatitis B virus infection, higher Edmondson-Steiner grade, and microvascular invasion. Panel-derived TMB values were evaluated descriptively, and exploratory survival analyses suggested potential differences between patient subgroups. Two candidate in-frame fusion signals, KIT-PDGFRA and ROS1-FBXL17, were detected in individual samples based on targeted DNA sequencing. Functional enrichment analyses indicated that mutated genes were mainly associated with cancer-related biological processes.

Conclusions: This study provides an exploratory overview of somatic alterations detected by a targeted sequencing panel in a regional HCC cohort. Given the limitations inherent to panel-based analyses and the lack of independent validation, these findings should be interpreted cautiously and primarily serve as a reference for future large-scale and experimentally validated studies aimed at refining precision oncology strategies in HCC.

Background: Some plant RNA viruses in the family Betaflexiviridae encode a nucleic acid-binding protein (NABP), which enhances viral infectivity. Until recently, Salvia divinorum RNA virus 1 (SdRV1) was the only known member of the genus Citrivirus to encode a NABP.

Objective: This study aimed to identify novel Betaflexiviridae genomes encoding NABPs and to investigate their evolutionary origins through comparative and phylogenetic analysis.

Methods: Publicly available plant transcriptome datasets were screened to identify Betaflexiviridae-like viral sequences. Twelve viral genome contigs corresponding to ten distinct viruses were assembled and annotated. Phylogenetic trees were constructed using replicase and NABP protein sequences.

Results: Six putative novel species were identified within the genera Citrivirus, Prunevirus, and a potential new genus. Aquilaria sinensis virus 1 (AquSiV1) encoded a NABP, making it the second known Citrivirus with a putative copy of this gene. Hippophae rhamnoides virus 1 (HipRhV1), which also encoded a NABP, formed a distinct lineage, possibly representing a novel genus. Phylogenetic analysis of NABPs revealed topologies incongruent with the replicase phylogeny, suggesting recurrent, independent acquisition events.

Conclusion: These findings expand the known genomic and taxonomic diversity of the genera Citrivirus and Prunevirus, and support the hypothesis that NABP genes have been independently and repeatedly acquired within the family Betaflexiviridae.

Background: Adoptive cell therapies employing chimeric antigen receptors (CARs) have achieved remarkable success in hematologic malignancies, yet their efficacy in solid tumors remains limited due to the immunosuppressive tumor microenvironment (TME), which restricts immune cell infiltration and persistence. While CAR-NK cells provide potent cytotoxicity with a favorable safety profile, their tumor penetration is often suboptimal. In contrast, macrophages possess intrinsic tumor-homing and tissue-remodeling abilities that could help overcome these barriers.

Objective: This study aimed to develop a combinatorial innate-cell immunotherapy integrating nanobody-based mesothelin (MSLN)-targeting CAR-macrophages (CAR-Ms) with CAR-NK cells to remodel the TME and enhance antitumor immunity in pancreatic cancer.

Methods: Using a validated D3 nanobody CAR construct, CAR-Ms were generated from PMA-differentiated THP-1 monocytes and characterized for CAR expression, M1/M2 polarization, migration, phagocytosis, and cytokine secretion. CAR-NK cell migration and cytotoxicity were evaluated using conditioned media (CM) from CAR-M/tumor co-cultures. Synergistic antitumor activity was assessed in an orthotopic MSLN⁺ pancreatic ductal adenocarcinoma (PDAC) model.

Results: D3-CAR-Ms exhibited robust CAR expression (> 90%) and sustained an M1-like phenotype (CD86⁺HLA-DR⁺CD204⁻) even after tumor engagement. Functionally, they displayed enhanced migration and infiltration into MSLN⁺ PANC-1 spheroids, along with increased phagocytic and tumoricidal activity. Upon antigen engagement, CAR-Ms secreted high levels of CXCL9, which promoted CAR-NK chemotaxis, degranulation, and cytotoxicity. Sequential administration of CAR-Ms and CAR-NK cells in vivo led to marked tumor regression and durable responses without systemic toxicity.

Conclusion: Combinatorial nanobody-based CAR-M and CAR-NK therapy reprograms the TME and establishes a CXCL9-driven feed-forward loop between macrophages and NK cells, leading to synergistic innate immune activation and potent tumor control. This strategy provides a mechanistically grounded and translationally feasible framework for next-generation CAR-based immunotherapies targeting MSLN-expressing solid tumors.

Background: The Chinese mitten crab (Eriocheir sinensis) is a commercially important crustacean, highly valued in China and Korean peninsula for its nutritional benefits and delicate flavor. However, the aquaculture industry has been significantly impacted by hepatopancreatic necrosis disease (HPND), leading to substantial economic losses. The exact cause and molecular mechanisms underlying HPND remain poorly understood.

Objective: This study aimed to decipher the genetic and molecular basis of HPND through an integrative transcriptomic meta-analysis to identity consistent and disease related gene expression patterns.

Methods: Publicly available RNA-Seq datasets from three different studies were systematically integrated and analyzed. Differentially expressed transcripts (DETs) were identified through meta-analysis, followed by functional annotation and enrichment analyses of Gene Ontology and KEGG pathways.

Results: The meta-analysis identified 571 DETs, including 245 up-regulated and 326 down-regulated transcripts in diseased hepatopancreas. Functional enrichment revealed significant disruptions in the pathways of protein modification, lipid metabolism, and vesicle-mediated transport. These processes are crucial for immune functions including pathogen detection, antigen presentation, cytokine secretion, and metabolic adaptation to stress in the hepatopancreas. Moreover, we found 11 novel DETs (6 up-regulated and 5 down-regulated), highlighting the ability of meta-analysis to uncover low-abundance or context-specific genes that may escape detection in individual studies.

Conclusions: Our study provides valuable insights into the causes and pathogenic mechanisms of HPND, identifies novel genetic factors and gene markers for detection, and offers a deeper understanding of the disease, highlighting potential biomarkers for its prevention in E. sinensis aquaculture.

Background: Tinnitus is a complex neurological condition affecting 10-15% of adults worldwide, characterized by phantom auditory perception without external sound sources. While traditional investigations have focused on discrete auditory structures, emerging evidence suggests tinnitus involves broader alterations across central auditory regions.

Objective: This study employed transcriptomic analysis to investigate molecular mechanisms underlying salicylate-induced tinnitus across multiple brain regions simultaneously.

Methods: Male C57BL/6 N mice received daily intraperitoneal injections of sodium salicylate (350 mg/kg) for five consecutive days to induce tinnitus-like behavior, assessed using gap-prepulse inhibition of acoustic startle reflex. RNA sequencing was performed on auditory cortex, inferior colliculus, and cochlear nucleus tissues. Differential gene expression analysis, weighted gene co-expression network analysis, and functional annotation were conducted to identify shared molecular signatures and pathways across auditory centers.

Results: Principal component analysis revealed region-specific transcriptomic changes following salicylate treatment. Differential gene expression analysis identified Depp1 and Angptl4 as consistently upregulated genes across multiple brain regions, particularly within the inferior colliculus and cochlear nucleus. Weighted gene co-expression network analysis revealed a 215-gene module increased across all auditory regions in tinnitus mice, with functional annotation indicating enrichment for vasculature-related biological processes. Depp1 emerged as a central hub gene linking oxidative stress responses to autophagy mechanisms.

Conclusion: This study shows that tinnitus pathology involves not only neuronal hyperactivity but also oxidative stress, neuroinflammation, and autophagy in the central auditory pathway. Depp1 acts as a molecular hub linking redox imbalance to cellular clearance, highlighting its potential as a therapeutic target and offering new insights for intervention.

Therapeutic resistance remains a major challenge in the management of urologic cancers, including renal cell carcinoma (RCC), bladder cancer (BC), and prostate cancer (PCa). Recent advances highlight the tumor microenvironment (TME) as a critical determinant of treatment failure across various modalities, such as androgen deprivation therapy (ADT), VEGF-targeted therapies, and immune checkpoint inhibitors (ICIs). This review summarizes how distinct TME components-such as cancer-associated fibroblasts (CAFs), extracellular matrix (ECM), immunosuppressive cells, and hypoxic conditions-promote resistance. CAFs drive oncogenic reactivation and epithelial-mesenchymal transition (EMT), while ECM stiffening hinders immune infiltration and facilitates pro-survival signaling. Immune evasion mechanisms include TGF-β-mediated T cell exclusion, regulatory T cell expansion, and adaptive checkpoint upregulation. Hypoxia and metabolic reprogramming further promote cancer stemness and immune suppression through HIF-2α activation, lactate accumulation, and acidification of TME. Targeting these resistance mechanisms requires a multifaceted approach. Promising strategies include ICI combination therapies with anti-angiogenics or TGF-β inhibitors, ECM-modulating agents, and hypoxia-targeted drugs. Novel approaches such as single-cell and spatial transcriptomics, organoid co-culture systems, and TME-derived biomarkers offer new opportunities for patient stratification and therapeutic development. Integrating TME biology into clinical practice is essential to overcome resistance and improve outcomes in urologic oncology.

Background: Demand for clean beauty ingredients is driving discovery of safe, effective, and sustainable actives. Microbes inhabiting polar deserts produce biomolecules adapted to stress, relevant to skin protection and regeneration.

Objective: To characterize taxonomic diversity and functional potential of Antarctic soil microbiomes from distinct biogeographic regions and identify microbial genes linked to cosmetic efficacy.

Methods: Public 16S rRNA amplicon datasets from NCBI SRA were compiled and classified into four Antarctic Conservation Biogeographic Regions: North Antarctic Peninsula, East Antarctica, South Victoria Land, and Transantarctic Mountains. Functional profiles were predicted using PICRUSt2 and analyzed for antioxidant, anti-aging, moisturization, skin-barrier, and regeneration pathways via KEGG Orthology terms.

Results: Analysis of 406 sequencing runs identified 54,523 amplicon sequence variants from 48 bacterial and 2 archaeal phyla. Actinobacteria dominated (36.1%), followed by Bacteroidetes (13.0%) and Proteobacteria (10.5%). East Antarctica exhibited highest diversity (Shannon index mean 8.97) and evenness (0.87), with region-distinct communities. Functional prediction revealed enriched antioxidant defense, skin-barrier maintenance, moisturization, and photoprotective genes. Taxonomic and functional ordinations partially decoupled, indicating functional convergence amid taxonomic divergence.

Conclusion: Antarctic soils are a rich source of microbial functions for cosmetic innovation, especially in East Antarctica. Multi-omics validation, strain isolation, and sustainable production may accelerate development of next-generation clean beauty actives compliant with access and benefit-sharing regulations.

Background: Echinoids, known as sea urchins, are a benthic family of marine invertebrates named for their spiny projections. Echinodermata translates from Greek to "Spiny Skin," yet in the laboratory setting, it is the embryos, not the spines, of these animals that are subjected to a wealth of molecular analyses.

Objective: In this study, we test the identity of genes expressed in the spines and identify conservation between four distant species.

Methods: We generated several transcriptomes de novo from four selected sea urchin species with a great diversity in size, color, and shape, representing 255 MYA of evolution (Strongylocentrotus purpuratus, Hemicentrotus pulcherrimus, Lytechinus variegatus, Eucidaris tribuloides). From de novo spine transcriptomes, we test for orthologous gene families, generating a wealth of orthogroups, as well as a species tree constructed from the available transcripts of only the spine.

Results: Core families of transcripts shared between all species, reveal that pathways involved in cell surface antigen-recognition, protein turnover, and cytoskeletal structure are each shared by diverse species of Echinoids. A basal branching species, Eucidaris tribuloides, contained a large number of unique transcripts, reflecting its unique spine morphology. When the spine transcriptome from Lytechinus variegatus was depleted of transcripts expressed elsewhere from the adult sea urchin, the resulting enriched spine transcriptomes were used for Orthofinder analysis, DEG analysis, and GO pathway analysis.

Conclusion: Regardless of species, the spines are an organ with an abundance of gene expression for sensory, structural, and defense functions, well attuned to its habitat in the benthos.

Background: Acute myeloid leukemia (AML) is a hematologic malignancy marked by blocked differentiation and uncontrolled proliferation. While miR-124 has been implicated as a tumor suppressor in various cancers, its functional role in AML remains unclear.

Objective: This study aimed to investigate the anti-leukemic effects of miR-124 and its regulatory mechanisms involving c-Myc and ROS signaling in AML.

Methods: AML cells were engineered to overexpress miR-124. Functional assays including flow cytometry, viability, and apoptosis analyses were conducted. ROS levels were measured, and c-Myc regulation was evaluated via western blotting, qPCR, ChIP, and pharmacological inhibition. Exosome-mediated delivery was also examined.

Results: miR-124 overexpression induced AML cell differentiation and apoptosis, accompanied by ROS accumulation and c-Myc downregulation. ROS induction suppressed c-Myc and activated the p21/p16/Rb axis, promoting cell cycle arrest. ChIP assays revealed that c-Myc binds the miR-124 promoter, indicating a negative feedback loop. Combination treatment with miR-124 and a c-Myc inhibitor enhanced anti-proliferative effects. Additionally, miR-124-containing exosomes reduced AML cell viability.

Conclusions: miR-124 acts as a tumor suppressor in AML by modulating a ROS-dependent c-Myc signaling pathway and inducing differentiation and apoptosis. These findings highlight miR-124 as a promising therapeutic and prognostic target in AML.