Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Transcriptomic analysis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 253 records · Page 14Linked to original sources
PubMed2025

An anti-androgen resistance-related gene signature acts as a prognostic marker and increases enzalutamide efficacy via PLK1 inhibition in prostate cancer.

BACKGROUND: Anti-androgen resistance remains a major clinical challenge in the treatment of prostate cancer (PCa), leading to disease progression and treatment failure. Despite extensive research on resistance mechanisms, a reliable prognostic model for predicting patient outcomes and guiding therapeutic strategies is still lacking. This study aimed to develop a novel gene signature related to anti-androgen resistance and evaluate its prognostic and therapeutic implications. METHODS: Anti-androgen resistance-related differentially expressed genes (ARRDEGs) were identified through transcriptomic analysis of enzalutamide- and dual enzalutamide abiraterone-resistant PCa cell lines from the GEO database. Functional enrichment analysis was performed to determine the biological roles of these genes. A prognostic gene signature was developed using univariate Cox regression, LASSO, and multivariate Cox regression models. The model was validated in independent PCa cohorts from The Cancer Genome Atlas (TCGA). Additionally, we assessed the correlation between the signature, immune infiltration, immune checkpoint expression, and drug sensitivity. The efficacy of PLK1 inhibition combined with enzalutamide was further explored using in vitro and in vivo experiments. RESULTS: We identified 304 ARRDEGs, from which three key genes (LMNB1, SSPO, and PLK1) were selected to construct a prognostic signature. This gene signature effectively stratified PCa patients into high- and low-risk groups, with the high-risk group exhibiting shorter recurrence-free survival and distinct immune characteristics. High-risk patients demonstrated elevated immune checkpoint expression (B7H3, CTLA-4, B7-1, and TIGIT), increased M2 macrophage infiltration, and enhanced sensitivity to chemotherapy and targeted therapy. Mechanistically, PLK1 inhibition potentiated the antitumor effect of enzalutamide by downregulating SLC7A11 and inducing ferroptosis, providing a potential therapeutic strategy to overcome anti-androgen resistance. CONCLUSION: We established a novel ARRDEGs-based prognostic signature that predicts PCa progression and response to chemotherapy and targeted therapy. The integration of this signature with immune profiling and drug sensitivity analysis provides a valuable tool for precision oncology in PCa. Our findings highlight the potential of PLK1 inhibition as a therapeutic strategy to enhance enzalutamide efficacy and overcome resistance.

Humans↗
PubMed2026

Transcriptomic insights into the molecular mechanism of antifouling agent-induced settlement inhibition in the Pacific oyster Crassostrea gigas.

Marine biofouling remains a persistent challenge to maritime industries and marine ecosystems worldwide. In this study, we systematically evaluated the acute toxicity, settlement inhibitory efficacy, and underlying molecular mechanisms of an N-oleyl-1,3-propanediamine-based antifouling agent using pediveliger larvae of the Pacific oyster Crassostrea gigas. The 96 h-LC50 of the agent was determined to be 0.81 mg/L, and exposure to 1.68 mg/L achieved complete larval settlement inhibition without inducing significant acute toxicity. Transcriptomic analysis identified 791 differentially expressed genes, dominated by downregulated genes associated with ribosomal function, translation, cell adhesion, and cytoskeletal organization. The agent exerts its inhibitory effect primarily through the global suppression of protein synthesis, disruption of cell-substrate adhesion and cytoskeletal integrity, and induction of proteotoxic stress responses. These findings reveal a multi-pathway molecular mechanism underlying antifouling agent-induced settlement inhibition in oyster larvae and provide key molecular biomarkers to support the development of eco-friendly antifouling technologies.

Animals↗
PubMed2026

Transcriptomic insights into the coordinated regulation of signaling, apoptosis, immunity, and metabolism during Sinonovacula constricta larval metamorphosis.

Metamorphosis is a critical ontogenetic transition for marine bivalves, marking the shift from planktonic to benthic lifestyles, where successful transformation dictates survival. The razor clam Sinonovacula constricta is economically important; however, low larval metamorphosis rates remain a major bottleneck in seedling production. To elucidate the mechanisms governing this process, we performed a comparative transcriptome analysis of S. constricta larvae at pre- and post-metamorphosis stages using Illumina sequencing. A total of 3701 differentially expressed genes (DEGs) were identified, including 3254 up-regulated and 447 down-regulated genes. Functional annotation of the respective top 20 significantly up-regulated and down-regulated DEGs indicated their potential pivotal roles in signal transduction (e.g., up-regulated: CAV1, CHRNA2; down-regulated: APP, NOTCH1), cellular proliferation and differentiation (e.g., up-regulated: TUBA, EGF1; down-regulated: KIF23, TTC25), transcriptional and epigenetic regulation (e.g., up-regulated: NFIL3; down-regulated: OVO, HMX1), substance transport (e.g., up-regulated: LRP2, LRP1B; down-regulated: SLC51A, Slc33a1), substance metabolism (e.g., up-regulated: CPK3, CYP26A1; down-regulated: RDMT1, ADAC), immunomodulation (e.g., up-regulated: CPN2, CRISP2), and protein homeostasis (e.g., up-regulated: HSP27, NAS-27). Functional enrichment analysis further revealed that DEGs were significantly enriched in pathways related to signal transduction and developmental regulation (e.g., Ras, TNF), cell death and homeostasis (e.g., apoptosis), immune responses (e.g., Toll-like receptor), energy metabolism (e.g., lipid), cardiovascular related (e.g., Fluid shear stress), cell junction and architecture (e.g., Tight junction), and infectious disease (e.g., measles). These results suggest a synergistic interplay between signaling, apoptosis, immunity, and metabolism during S. constricta metamorphosis. This study advances our understanding of marine bivalve metamorphosis and offers candidate genes for further mechanistic studies.

Animals↗
PubMed2026

Transcriptomic characterization of the intestine in Stichopus monotuberculatus under gradient temperature stress and HSP gene family-mediated molecular adaptation.

The increasing frequency of extreme temperature events under climate change poses a growing threat to the stability of tropical sea cucumber aquaculture. To characterize the molecular responses of the tropical sea cucumber Stichopus monotuberculatus to acute temperature stress, juveniles were exposed for 96 h to 15 °C, 20 °C, 25 °C, 30 °C, and 35 °C, followed by transcriptomic profiling of the intestine. By transcriptomic analysis, 2258, 634, 1618, and 2980 differentially expressed genes (DEGs) were identified at 15, 20, 30, and 35 °C compared to control, respectively. More DEGs were generally detected at temperatures further from 25 °C, with the 35 °C group showing the largest transcriptional response. Although cold and heat stress both affected metabolism and protein homeostasis, their enrichment profiles differed. At 15 °C, DEGs were mainly enriched in the spliceosome and p53 signaling pathways, highlighting RNA processing and p53 signaling as prominent features of the cold-stress response. At 35 °C, DEGs were mainly enriched in the PI3K-Akt signaling pathway, ubiquitin-mediated proteolysis, and mitophagy, indicating enhanced regulation of cell survival, protein turnover, and mitochondrial quality control. HSP genes also responded differently to cold and heat stress. Most HSP70 and HSP90 family members were downregulated at low temperatures, whereas HSP70 genes and small heat shock proteins were markedly upregulated at high temperatures. Overall, the intestinal transcriptome showed distinct responses to cold and heat stress. These results identify pathways and HSP genes potentially involved in the temperature response of S. monotuberculatus and provide useful information for evaluating temperature tolerance and defining suitable temperatures for its aquaculture.

Heat shock protein↗
PubMed2026

Uncovering the early and conserved molecular mechanisms of root nitrogen foraging in model and crops.

BACKGROUND: Nitrogen (N) foraging, the ability of plants to promote preferential root growth in N-rich patches of soil, is fundamental to the competitiveness and wellbeing of plants. A unique “split-root” system, where a heterogenous N environment stimulates root foraging, provides a powerful experimental model to study the mechanisms underlying root foraging in model (Arabidopsis) and/or crop plants. RESULTS: We used the split-root set up to capture early molecular events involved in systemic N-signaling after exposure to a heterogeneous N signal, through time-course transcriptomic analysis across shoots and roots of Arabidopsis. We found that a histone methyltransferase, SET DOMAIN GROUP 8 (SDG8), is necessary for root N-foraging, suggesting a previously unknown role for chromatin regulation in mediating the preferential root growth response to colonize N-rich patches. To determine if the underlying molecular mechanism is conserved in evolution, we compared the root foraging behavior from model-to-crop (Arabidopsis, tomato and maize). Our analysis showed the model and crop species shared a root N-foraging growth response, with some variation among specific genotypes. Interestingly, we observed both shared and distinct transcriptional responses to heterogenous N environments among these three species. CONCLUSIONS: Our study has generated insights into the molecular basis of root N-foraging, with the potential to improve nutrient use efficiency in crop plants in a heterogeneous field environment.

Crops, Agricultural↗
PubMed2026

Physiological and molecular responses of coelomocytes to low- to mid-frequency acoustic exposure in the sea urchin Strongylocentrotus intermedius.

Underwater noise is a widespread environmental pollutant in marine ecosystems, yet the effects of low- to mid-frequency acoustic exposure on immune physiology and molecular responses in echinoderms remain unclear. In this study, the sea urchin Strongylocentrotus intermedius was exposed to continuous pure-tone acoustic stimulation at 80, 125, 250, 500, 750, and 1000 Hz for 3 h. Results showed that acoustic exposure significantly affected redox homeostasis, energy metabolism, and immune function in S. intermedius coelomocytes: the antioxidant system and glutathione redox balance were altered, as indicated by increased superoxide dismutase (SOD) and catalase (CAT) activities, elevated reduced glutathione (GSH) content, and a higher GSH/GSSG ratio; glycolysis-related enzyme activities were enhanced, with increased pyruvate kinase (PK) activity under 125-500 Hz exposure and elevated hexokinase (HK) activity at 250 Hz; and immune function was impaired, as shown by increased coelomocyte mortality, reduced phagocytic activity, and inhibited acid phosphatase (ACP) and alkaline phosphatase (AKP) activities, whereas respiratory burst activity showed no significant change. Among all treatments, 250 Hz induced the most pronounced physiological responses. Transcriptomic analysis of coelomocytes from the 250 Hz group identified 663 differentially expressed genes, including 537 upregulated and 126 downregulated genes, mainly enriched in pathways related to apoptosis, phagosome, lysosome, glutathione metabolism, arachidonic acid metabolism, and carbohydrate metabolism. These findings indicate that low- to mid-frequency acoustic exposure can act as a physiological and molecular stressor to S. intermedius coelomocytes by affecting redox homeostasis, enhancing energy metabolism, and suppressing immune effector processes, with 250 Hz showing the strongest effect under the present exposure conditions. This study provides experimental evidence for evaluating the potential biological effects of low- to mid-frequency acoustic exposure on benthic echinoderms.

Animals↗
PubMed2025

Impact of polymorphisms on gene expression and splicing in response to exercise and diet-induced weight loss in human skeletal muscle tissues.

Weight loss through exercise and diet reduces the risk of type 2 diabetes, but the genetic regulation of gene expression and splicing in response to weight loss remains unclear in humans. We collected clinical data and skeletal muscle biopsies from 54 overweight/obese Asian individuals before and after a 16-week lifestyle intervention, which resulted in an average of ∼10% weight loss, accompanied by an ∼30% increase in insulin-stimulated glucose uptake. Improvements were observed in 118 of 252 clinical traits and six blood lipids. Transcriptomic analysis of paired skeletal muscle biopsies identified 505 differentially expressed genes enriched in mitochondrial function and insulin sensitivity. Thousands of muscle-specific expression/splicing quantitative trait loci (e/sQTLs) were detected pre- and post-intervention, including hundreds of lifestyle-responsive e/sQTLs. Notably, approximately 4.2% of eQTLs and 7.3% of sQTLs showed Asian specificity. Joint analysis with genome-wide association study (GWAS) identified 16 putative metabolic risk genes. Our study reveals gene-by-lifestyle interactions and how lifestyle modulates gene regulation in skeletal muscle.

Humans↗
PubMed2026

Dynamic and non-additive gene regulation shapes maize responses to simultaneous salt and cold stress.

Salt and cold stresses often occur together in nature and severely impact crop productivity, yet their transcriptional regulation remains poorly understood. Here, we conducted a time-series transcriptomic analysis of maize under salt, cold, and their combination at 0, 6, 12, and 24 h. Differential expression analysis revealed dynamic, condition-specific gene responses grouped into eight distinct temporal patterns. Promoter motif analysis of genes within each pattern identified 5-39 significantly enriched motifs, with over 40% lacking known counterparts, suggesting the involvement of previously uncharacterized cis-regulatory elements in stress-responsive transcriptional regulation. By comparing combined stress responses to the sum of single-stress effects, we found that about 74% of DEGs showed non-additive patterns, suggesting that combined stress triggers a distinct transcriptional program. Evolutionary analysis showed that additive DEGs tend to be more recently evolved, subject to weaker purifying selection, and enriched in transposed duplications, contrasting with the stronger constraint observed in non-additive DEGs. WGCNA identified 24 co-expression modules, among which 65 hub DEGs were detected in modules significantly correlated with specific stress conditions. Furthermore, we reconstructed 228, 20, and 200 sequential transcription factor cascades spanning 6 h, 12 h, and 24 h under cold, salt, and combined stress, respectively, with no cascade shared across all three conditions. Together, these results reveal that maize responses to combined salt and cold stress are largely non-additive and temporally dynamic, with distinct evolutionary patterns underlying different response types, offering insights and candidate regulators for enhancing crop stress resilience.

Zea mays↗
PubMed2024

Role of the Pseudomonas plecoglossicida fliL gene in immune response of infected hybrid groupers (Epinephelus fuscoguttatus ♀ × Epinephelus lanceolatus ♂).

Pseudomonas plecoglossicida, a gram-negative bacterium, is the main pathogen of visceral white-point disease in marine fish, responsible for substantial economic losses in the aquaculture industry. The FliL protein, involved in torque production of the bacterial flagella motor, is essential for the pathogenicity of a variety of bacteria. In the current study, the fliL gene deletion strain (ΔfliL), fliL gene complement strain (C-ΔfliL), and wild-type strain (NZBD9) were compared to explore the influence of the fliL gene on P. plecoglossicida pathogenicity and its role in host immune response. Results showed that fliL gene deletion increased the survival rate (50%) and reduced white spot disease progression in the hybrid groupers. Moreover, compared to the NZBD9 strain, the ΔfliL strain was consistently associated with lower bacterial loads in the grouper spleen, head kidney, liver, and intestine, coupled with reduced tissue damage. Transcriptomic analysis identified 2 238 differentially expressed genes (DEGs) in the spleens of fish infected with the ΔfliL strain compared to the NZBD9 strain. Based on Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, the DEGs were significantly enriched in seven immune system-associated pathways and three signaling molecule and interaction pathways. Upon infection with the ΔfliL strain, the toll-like receptor (TLR) signaling pathway was activated in the hybrid groupers, leading to the activation of transcription factors (NF-κB and AP1) and cytokines. The expression levels of proinflammatory cytokine-related genes IL-1β, IL-12B, and IL-6 and chemokine-related genes CXCL9, CXCL10, and CCL4 were significantly up-regulated. In conclusion, the fliL gene markedly influenced the pathogenicity of P. plecoglossicida infection in the hybrid groupers. Notably, deletion of fliL gene in P. plecoglossicida induced a robust immune response in the groupers, promoting defense against and elimination of pathogens via an inflammatory response involving multiple cytokines.

Animals↗
PubMed2026

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

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

Animals↗
PubMed2026

Molecular and immune profiling of HER2-low, HER2 ultra-low, and HER2-null male breast cancer.

BACKGROUND: HER2 expression is described along a biological continuum from null to positive and serves as a critical biomarker for therapeutic guidance in breast cancer (BC). While HER2-low and ultra-low categories have emerged as actionable targets for antibody-drug conjugates (ADCs) in female BC, their molecular and immune characteristics remain largely unexplored in male breast cancer. METHODS: We profiled 214 male breast tumors using next-generation sequencing and whole-transcriptome sequencing to assess mutational, transcriptomic, and immune landscapes. Tumor mutational burden (TMB) was defined as high if > 10 mutations/Mb. Immune cell fractions were inferred using Quantiseq deconvolution. RESULTS: Among 214 samples, 66 (30.8%) were HER2-null, 53 (24.8%) HER2 ultra-low, 80 (37.4%) HER2-low, and 15 (7.0%) HER2-positive. HER2 ultra-low tumors exhibited a higher prevalence of PIK3CA mutations (39.2% vs 22.6%, p ≤ 0.05) compared to HER2-null. No significant differences were observed in TMB-high frequency or PD-L1 expression across subgroups. Immune composition differed primarily between HER2-null and HER2-expressing subgroups: HER2-ultra-low tumors showed higher B-cell infiltration, whereas HER2-null tumors were enriched in neutrophils. Transcriptomic analysis revealed upregulation of selected stemness-associated genes (NANOG, KLF4, POU5F1) and CEACAM1 in HER2-null tumors, while HER2-low and HER2-ultra-low tumors were largely similar across most molecular and immune readouts in this cohort. CONCLUSIONS: HER2-null male breast cancer appears to represent the most biologically divergent subgroup within the HER2-negative spectrum, whereas HER2-low and HER2-ultra-low tumors were largely similar in this cohort. These findings support further investigation of HER2-null disease as a distinct biological state and provide hypothesis-generating data for biomarker development in this rare population.

Male↗
PubMed2026

Integrating transcriptomics and metabolomics reveals the molecular landscape of sperm maturation driven by regional differentiation in the epididymis of Guizhou-Guiqian semi-fine wool sheep.

Epididymal regionalized differentiation is crucial for sperm maturation. However, little is known about the synergistic remodeling mechanisms of different epididymal segments at the transcriptional and metabolic levels during sexual maturation in ruminants (especially sheep). We investigated the caput, corpus, and cauda epididymidis of pre-pubertal (2-month-old) and post-pubertal (7-month-old) Guizhou-Guiqian semi-fine wool sheep using histology, RNA sequencing, and metabolomics. Post-pubertal tissues exhibited increased luminal diameters, cilia lengths, and abundant cauda spermatozoa. Transcriptomic analysis revealed increasing differentially expressed genes (DEGs) along the caput-corpus-cauda axis (4642, 6103, and 7698 DEGs, respectively). Metabolomics detected 786 unique differentially accumulated metabolites (DAMs). Region-specific analysis showed that in the caput, up-regulated pathways (fructose/mannose metabolism; HK2, ALDOA, HKDC1) provide energy and substrates for initial sperm motility. In the corpus, down-regulated genes associated with extracellular matrix and tight junctions suggested epithelial barrier remodeling to establish an immune-tolerant microenvironment. The cauda specifically up-regulated the pentose phosphate pathway (FBP1, GPI) and glutathione metabolism, maintaining redox homeostasis for long-term sperm storage. Additionally, glycerophospholipid metabolism was enriched across all segments, where PEMT, AGPAT5, and LCAT likely regulate sperm plasma membrane fluidity. In conclusion, during sexual maturation, the caput drives energy metabolism and glycosylation, the corpus establishes immune tolerance, and the cauda maintains antioxidant homeostasis. The glycerophospholipid network throughout the across all epididymal segments synergistically remodels sperm membrane. This study reveals the underlying multi-omics regulatory mechanisms of epididymal functional differentiation, providing a theoretical basis for elucidating the molecular mechanisms of sperm maturation in this breed and for the molecular breeding of early reproductive performance in rams.

Animals↗
PubMed2025

A Functionally Conserved yet Dynamically Evolving Toolkit Underpinning Molluscan Biomineralization: Insights From Shell and Radula.

The molluscan shell and radula constitute pivotal molluscan innovations, each characterized by distinct functions and diverse forms, regulated by the highly specific biomineralization regulatory networks. Despite their paramount importance, the conserved components and adaptive evolutionary processes governing these regulatory networks remain unresolved. To address this knowledge gap, we advocate for the integration of data from less-explored lineages, such as Scaphopoda, as an essential step. This study presents the inaugural comprehensive transcriptome analysis of Pictodentalium vernedei, a representative species of Scaphopoda distinguished by a unique and evolutionarily conserved shell morphology and radula structure. Furthermore, comparative transcriptome/genome analyses are employed to unravel the conservatism and evolutionary innovation of the involved biomineralization regulatory elements. Our findings underscore the central role of secretomes in governing biomineralization processes, and we identified a fundamental set of 26 domains within molluscan secretomes, forming an essential functional protein domain repertoire necessary for the transformation of inorganic ions into biomineralized structures. This core biomineralization toolkit has undergone independent expansion and lineage-specific recruitment, giving rise to novel, modular domain architectures. This may be essential for the functional specialization and morphological diversification of shell and radula structures. These evolutionary processes are driven by the independent co-option of ancient genes and the emergence of novel de novo genes. This comprehensive investigation not only contributes insights into the evolution of molluscan biomineralization structures but also establishes avenues for further scholarly exploration.

Animals↗
PubMed2026

Environmental benzene exposure induces a conserved neutrophil degranulation program across species.

Immune systems have evolved under constant pressure from pathogens and environmental challenges, leading to the emergence of conserved defense mechanisms across diverse organisms. Evidence indicates that environmental exposures perturb immune regulatory networks, particularly during development, when transcriptional programs governing hematopoiesis, immune cell differentiation, and inflammatory signaling are highly dynamic and sensitive to external stressors. Volatile organic compounds represent an important but incompletely understood source of immunological perturbation. Among these, benzene is a ubiquitous environmental contaminant associated with hematotoxicity and immune dysregulation; however, transcriptional responses to environmentally relevant low-level exposures during development remain poorly characterized. To determine whether benzene exposure engages conserved cross-species immune regulatory pathways, we performed a comparative transcriptomic analysis integrating developmental tissues from 3 vertebrate systems: human placenta, murine placenta, and zebrafish larvae. Bulk RNA sequencing datasets were analyzed to identify transcriptional responses associated with benzene exposure in experimental models (≤5 ppm) and with benzene adduct levels in maternal plasma for human samples. Because placental gene expression exhibits strong sexual dimorphism, murine datasets were stratified by fetal sex. Pathway- and network-level analyses were used to identify conserved biological responses. We observed a striking convergence on activation of innate immune pathways associated with neutrophil degranulation, IL-8 signaling, and Rho GTPase-mediated inflammatory responses. Further, network analyses identified CXCL8 and ERK1/2 as shared regulatory hubs linking transcriptional responses across datasets. Together, these findings uncover an evolutionarily conserved innate immune signature associated with benzene exposure during vertebrate development, suggesting that environmental chemical perturbations may disrupt fundamental immune regulatory programs across species.

Animals↗
PubMed2025

Adaptive Evolution for Freshwater Adaptation in Coilia nasus by Directional Selection on Osmoregulation Genes.

The molecular mechanisms underlying the adaptation to freshwater habitats in fish of marine origin remain unclear. Grenadier anchovies, such as Coilia nasus, originate from marine environments and include both anadromous and freshwater-resident conspecifics, making them ideal for studying adaptive evolution from marine to freshwater habitats. We conducted a comparative population genomic and transcriptome analysis of two distinct C. nasus lineages, one anadromous and the other freshwater-resident, collected from mainstream and estuarine regions of the Yangtze River, China. By genome-wide genotyping of the anadromous and the freshwater-resident populations, we observed significant divergence in osmoregulation, energy metabolism, and immune response pathways associated with ecological adaptation and energy expenditure for migration. Some ion transport genes such as CAMK1, ATP1α3, KCNJ1 and SLC30A2 were identified that may contribute to freshwater adaptation. Notably, numerous mineralocorticoid signalling genes (e.g., NR3C2, SGK1, ATP1α3, KCNJ1) exhibit dynamic change between the anadromous and freshwater populations, suggesting an important role for the hormone cortisol in regulating salinity acclimation in euryhaline fish. Among these genes, the ion channel ATP1α3 experienced adaptive amino acid substitutions (Val317Ile and Thr329Ser), which appear to be evolutionary hotspots across migratory species based on ortholog comparisons. These variants may facilitate sodium/potassium transport and highlight salinity tolerance as a key driver of divergence in anadromous fish transitioning to freshwater. These results enhance our understanding of the genetic basis underlying freshwater adaptation for an anadromous fish across osmotic boundaries.

Animals↗
PubMed2026

Transcriptomic insights into thermal stress reveal physiological trade-off between thermal stress adaptation and reproductive investment in Spodoptera litura.

Spodoptera litura, a highly polyphagous lepidopteran pest, poses a major threat to agricultural productivity due to its remarkable adaptability to diverse environmental conditions. Although heat stress is known to trigger transcriptional reprogramming in insects, the molecular mechanisms underlying thermal stress responses in S. litura remain poorly understood. In the present study, fourth-instar larvae were exposed to acute heat stress (44 °C) and compared with control conditions (27 ± 1 °C) to investigate heat-induced transcriptional alterations affecting physiology and reproduction. High-quality RNA-Seq data achieved more than 80% mapping efficiency, with a total of 15,782 transcripts were identified. Transcriptome analysis of S. litura larvae showed 323 differentially expressed genes (DEGs), of which 262 genes were significantly upregulated and 61 were downregulated in heat-stressed larvae compared to the control group. The DEGs were associated with stress response, reproduction, signalling, proteostasis, detoxification, oxidative stress, metabolism, development, and chromatin regulation. Heat shock proteins genes, including HSP70, HSP90, and HSP27, together with co-chaperones such as TRET-1, STIP1, and Starvin, were strongly upregulated, indicating enhanced cellular protection against protein damage and oxidative stress under heat stress. Conversely, key reproductive and cell cycle-related genes, including BARR, CAPD2, FEO, CDK2 and MORULA, were significantly downregulated, suggesting reproductive impairment and developmental arrest. RT-qPCR validation corroborated the RNA-Seq findings, demonstrating a heat-induced physiological trade-off that prioritizes survival over reproduction. Consistent with these molecular responses, heat-stressed insects exhibited marked reproductive impairment, including significant reductions in gonadosomatic index, eupyrene sperm bundle count, mating frequency, mating success, female calling behaviour, copulation duration, fecundity, and egg fertility. Collectively, these findings provide comprehensive insights into the molecular basis of thermal adaptation in S. litura and demonstrate that acute heat stress compromises reproductive fitness while activating conserved stress-response pathways that promote short-term survival.

Animals↗
PubMed2026

Spatial Mapping of the Precancer-to-Cancer Transition in Breast and Prostate.

UNLABELLED: Breast and prostate cancers are both hormone-driven adenocarcinomas that undergo analogous invasion programs. Using lightsheet microscopy on intact tumors, we identified transitional junctions between precancerous and invasive regions. We then developed a multimodal serial-section workflow integrating volumetric reconstruction with spatial transcriptomics. Analysis of 319 spatial assays from 51 cases revealed gene expression features and novel structural insights defining the shift from precancer to invasive disease. In breast cancer, loss of MGP and PLAT was associated with invasive transition and promoted tumorigenesis in functional assays. In prostate cancer, GDF15, ALDH1A3, ANPEP, and FASN were upregulated along invasive progression, and their knockdown in PC-3 cells suppressed proliferation and migration. Enrichment of tumor-associated macrophages (SPP1+ and MS4A6A+) along non-triple-negative breast cancer breast cancer transitions highlights immune involvement as a potential driver of invasiveness. SIGNIFICANCE: Our method of defining precise spatial locations of invasive transition allows for the direct interrogation of transition drivers, presenting new therapeutic targets for the two most prevalent cancers and providing a framework for studying spatially defined mechanisms of tumor progression. See related commentary by Jing and Li, p. 1720.

Humans↗
PubMed2026

A Cooperative Release of Mitochondrial DNA From Platelets and Neutrophils Drives an Interferon Signature in Systemic Sclerosis.

OBJECTIVE: Mitochondria are organelles with a hypomethylated circular genome. Mitochondrial DNA (mtDNA) in the systemic circulation has been implicated in inflammation. This study investigates the role of circulating DNA in systemic sclerosis (SSc) and the cellular mechanisms governing its release. METHODS: Total DNA was isolated from the plasma of healthy controls (HCs) and patients with SSc. Copy numbers were analyzed for mtDNA (ATP-6) and GAPDH abundance by quantitative real-time polymerase chain reaction. mtDNA was isolated from HCs and patients with SSc. Neutrophils and platelets were incubated with the plasma and mtDNA of patients with SSc, and neutrophil extracellular trap (NET) formation was assessed by SytoxGreen and immunostainings. Platelets were tested for mtDNA release propensity. DNA oxidation was evaluated by MitoSOX Red staining in vitro and 8-OHdG enzyme-linked immunosorbent assay (ELISA) of patient plasma. Plasma interferon (IFN) type 1 and chemokine (C-X-C motif) ligand 4 (CXCL4) were measured by ELISA. IFN signaling activation capacity was evaluated using THP-1 reporter cells and confirmed by a whole blood bulk RNA transcriptomic analysis. RESULTS: Median plasma mtDNA levels were 152-fold higher in patients with SSc compared with HCs, whereas nuclear DNA levels were similar. mtDNA from SSc plasma was highly oxidized. SSc-derived mtDNA efficiently promoted its own release by NETosis, most potently in the neutrophils of patients with SSc and by platelet activation. Oxidized mtDNA from SSc platelets in complex with CXCL4 further stimulated mtDNA release in both neutrophils and platelets. mtDNA plasma concentrations correlated with type I IFN concentrations in the blood of patients with SSc, and SSc blood exhibited elevated IFN-stimulated gene expression. SSc plasma-derived mtDNA-induced IFN signaling and NET formation via endosomal Toll-like receptors, cyclic GMP-AMP synthase/stimulator of IFN genes, and the JAK/STAT pathway. The type I IFN pathway further promoted NETosis and mtDNA release because IFN receptor and JAK inhibition antagonized the proNETotic effects of IFN. CONCLUSION: SSc plasma is characterized by highly abundant mtDNA, which drives feedback loops amplifying its own release from both neutrophils and platelets. Thus, mtDNA contributes to inflammation and tissue damage in SSc.

Humans↗