Adipose resident immune cells are vital contributors to adipose dysfunction in metabolic diseases. While current research has focused on immunogenic heterogeneities, investigations into metabolic heterogeneity are needed to reveal the diverse responses to metabolic perturbations. This study dissected and profiled the metabolic activities of 9243 resident immunocytes from visceral adipose tissue. Clustering analysis revealed seven metabolic patterns with diverse functions. Differential analysis showed that these metabolic patterns exhibit heterogeneous responses to systemic metabolic reductions paralleling a type 2 diabetes-associated trajectory. Graph theory analysis of correlation networks further delineated that impaired capacities to catabolize complex lipids with peroxisomes and degrade amino acids are core metabolic defects regulating resident immune cell functions in type 2 diabetes. Collectively, these results unveiled the role of metabolic heterogeneity in the diverse responses of resident immunocytes to metabolic perturbations, with lipid and amino acid catabolic defects as core metabolic factors contributing to type 2 diabetes.

Obesity-related glomerulopathy (ORG) is a kidney disorder associated with obesity, where dysbiosis of the gut microbiota and disturbances in lipid metabolism play crucial roles in its development. However, the exact mechanisms by which imbalances in gut microbiota influence lipid metabolism and contribute to the pathogenesis of ORG are still not fully understood.

Heat stress has deleterious effects on flowering and yield of Tartary buckwheat. In this study, we compared the transcriptomes between thermo-sensitive MQ and adaptive KQ and XQ, in leaves and inflorescences. Compared with adaptive KQ and XQ, flowering genes like FtFT1, FtFT3 and MADS-Box, and developmental genes like PIF3, CIB1, CLAVATA3, YABBY, and HY5 were repressed in thermo-sensitive MQ leaf and inflorescence. Higher proportions of HSPs and HSFs were induced in thermo-sensitive MQ leaf and inflorescence. By using long-read sequencing, we identified DAS events on circadian clock, floral development and heat stress related genes between thermo-sensitive MQ and adaptive XQ. We found the DAS events on PIF, LHY, MADS-Box AGAMOUS and HSF genes generated malfunctional proteins. We speculated that the DAS events on key floral development and heat stress related genes may influence expressions of downstream flowering genes, thus leading to the flowering retardation in thermo-sensitive rice Tartary buckwheat.

Tilletia laevis is a fungal pathogen that causes the severe wheat disease known as common bunt, which is widespread in wheat-growing areas worldwide. Nevertheless, insufficient genome data hinders research at the molecular level. In this study, we reported a high-quality whole genome assembly of T. laevis isolated from China utilizing the integration of Illumina and PacBio sequencing technologies. The genome assembly consisted of 40 contigs with a total length of 38.09 Mb, a contig N50 of 1.50 Mb, and a maximum contig length of 2.61 Mb. The genome encoded 10,682 genes, with a notable enrichment of metabolism-related genes identified by functional annotations. The comparative genomic analysis was conducted between this assembly and closely related Tilletia strains, revealing its evolutionary trajectory. Overall, the genome assembly is currently the most continuous genome for T. laevis, facilitating future research on the pathogenic mechanism and control of this pathogen.

Pterygium was a common progressive ocular disease with unclear pathogenesis. The aim of this study was to identify biomarkers associated with the integrated stress response (ISR) in pterygia and explore the underlying molecular mechanisms.

Spermatogenesis is a highly regulated biological process involving various cell types, making the accurate identification and classification of different cell populations challenging. Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool for resolving cellular heterogeneity at high resolution. In this study, 10× Genomics Chromium™ scRNA-seq was employed to analyze 15,826 testicular cells from three 6-month-old sexually mature Hu sheep, and a high-resolution single-cell transcriptomic atlas was generated. Specifically, six somatic cell subtypes and five germ cell subtypes were identified, which revealed the differentiation trajectory of spermatogenesis. Notably, pseudo-time analysis suggested that Leydig cells and peritubular myoid cells may originate from a common progenitor lineage in sheep. Highly expressed genes were enriched in pathways such as cAMP signaling, PI3K-Akt, and ECM-receptor interaction. Furthermore, immunohistochemical analysis validated specific marker proteins for certain cell types. Collectively, these findings provide novel insights into spermatogenesis and serve as a valuable reference for the in vitro culture of male germ cells.

Gene expression is a dynamic phenotype influenced by tissue-specific regulatory mechanisms, which can modulate expression directly or indirectly through cis or trans factors. Identifying genetic variants in these regulatory regions can improve both expression quantitative trait locus (eQTL) mapping and gene expression prediction. Whole genome sequences offer the possibility for enhanced eQTL mapping accuracy, but detecting causal variants remains challenging. Here, we evaluate the potential added-value of integrating tissue-specific epigenetic annotations, such as chromatin accessibility and methylation status, into within-breed genomic predictions of expression for three pig breeds. Functional annotations from early developmental stages improved eQTL mapping interpretability as shown by the enrichment of trait-relevant QTLs. However, despite the use of functional annotations, predictions across breeds remain challenging due to differences in genetic architectures. Our work contributes to the understanding of gene expression regulation in livestock and highlights the value of functional annotations, despite continued challenges for predictions across breeds.

Grain size critically determines both yield and quality in crops. This study systematically investigated two distinct qingke varieties with contrasting grain sizes through integrated dynamic phenotyping, transcriptomics, and weighted gene co-expression network analysis (WGCNA). Key observations indicated that statistically significant differences in grain length and width between the two qingke varieties became apparent from 13 DAF. Transcriptome sequencing (RNA-seq) analysis revealed a peak in the number of differentially expressed genes (DEGs) at 13 days after flowering, indicating that gene expression patterns during this stage might regulate the establishment of grain length and width morphology. These DEGs were likely key regulators of grain dimensions. WGCNA analysis identified a highly correlated brown module enriched with MAPK pathway genes, which showed significant associations with grain size (length, width, thickness) and weight. Functional analysis of the MAPK pathway candidate gene HvPR1 demonstrated that its over-expression in barley significantly increased thousand-grain weight (TGW) while reducing grain hardness (GH), thereby uncovering a previously uncharacterized regulatory role in grain development. The observed reduction in grain hardness in over-expression lines was primarily attributed to decreased lignin and cellulose content. These results provide critical genetic resources and novel mechanistic insights to support precision breeding strategies for qingke and other cereal crops.

Rainbow trout (Oncorhynchus mykiss) is one of the most widely farmed salmonid species globally. To investigate the mechanisms regulating muscle fat content and enhancing tolerance to high-lipid diets, transcriptomic changes in muscle tissues (myotomes and myosepta) were analyzed after treatment with an elevated dietary lipid level (30 %). The results revealed that myotomes and myosepta employed distinct strategies to maintain lipid homeostasis under elevated dietary lipids. Myotomes suppressed lipid deposition by upregulating lipoic acid synthesis to enhance lipolysis and reducing lipoprotein sialylation, while myosepta inhibited lipid storage through AMP metabolism modulation in adipocytes and the decreased function of phosphatidylinositol-4-phosphate (PI4P) binding. Beyond these tissue-specific strategies, both myotomes and myosepta also adopted some common approaches against lipid surplus. The downregulation of GFRAL4 balanced energy acquisition, and MBLH2-mediated lipolysis prevented ectopic deposition. Crucially, miRNAs coordinated tissue-specific and systemic adaptations to dietary lipid fluctuations mainly by targeting key genes involved in lipid metabolism pathways. Overall, these findings identified potential protein targets and regulatory pathways for regulating myoseptal fat content to improve meat flavor attributes, and elucidated the metabolic adaptation mechanisms of triploid rainbow trout to high-lipid diets.

Despite the integrative function of miRNAs and genes in chicken embryonic gonadal sex differentiation, their roles remain poorly understood. Here, we used RNA-seq to analyze 12 gonadal samples from embryonic days 5 (E5) and 9 (E9). Our analysis of miRNA and mRNA expression during this key developmental stage revealed five DEmiRNAs and 235 DEmRNAs consistently associated with left-right asymmetry in female gonads in both F5L vs F5R and F9L vs F9R comparisons. The interaction between DEmiRNAs and target DEmRNAs was analyzed in relation to the left-right asymmetry of embryonic gonadal development at E5 and E9 in chickens. The KEGG pathway enrichment analysis revealed that several significant pathways were involved. These include the complement and coagulation cascades, tight junctions, and synthesis and secretion of aldosterone. Differentially expressed miRNAs and target genes at embryonic days 5 and 9 reveal key molecular mechanisms driving gonadal sex differentiation in chickens.

Glioma, one of the most common types of primary brain tumors, presents considerable challenges due to its poor prognosis. Emerging research has demonstrated a strong connection between Centromere Protein M(CENPM) and tumor progression. However, the precise role of CENPM in glioma remains poorly understood. This study delves into the involvement of CENPM in glioma progression. Data analysis revealed that heightened CENPM expression correlates with worse patient outcomes and is highly expressed in glioma. In vitro experiments showed that reducing CENPM expression inhibits glioma cell proliferation and induces G0/G1 phase cell cycle arrest. Furthermore, RNA-seq and Western Blot analyses demonstrated that CENPM activates the PI3K/AKT signaling pathway in glioma cells. In vivo experiments confirmed that knocking down CENPM leads to reduced tumor growth in glioma models and improves the prognosis of tumor-bearing mice. This study underscores the critical role of CENPM in glioma and sheds light on potential therapeutic strategies.

Aldosterone-producing adenoma (APA) is a significant cause of primary aldosteronism, however, its cellular heterogeneity remains unclear. We performed single-cell RNA sequencing on adrenal tissues from three APA patients and three controls. We identified CAPS zona glomerulosa (ZG)-like cells in APA with upregulated lipogenesis, oxidative phosphorylation, and mTOR signaling, indicating metabolic reprogramming. Pseudotime analysis revealed disrupted differentiation and aberrant CYP11B1, CYP11B2, and SULT2A1 expression. Oncogenic Myc, Wnt, and G2/M pathways were activated in ZR-like clusters. APA showed immune infiltration (B cells, CD8 T cells, M1 macrophages), angiogenic activation (VWF endothelial cells), and fibroblast-driven stromal remodeling via Hedgehog signaling. Our study provides a comprehensive single-cell atlas of APA, uncovering key tumorigenic mechanisms and identifying potential biomarkers (e.g., CAPS, VWF, UPK3B) and therapeutic targets, including mTOR and Hedgehog/Wnt pathways. These findings advance the genomic understanding of adrenal tumors and support precision medicine development.

Aging is an important pathological basis of age-related diseases. However, the similarities and differences among different types of senescent cells of different species and their role in normal homeostasis are poorly understood. Herein, in order to comprehensively map age-related transcriptome changes in multiple tissues of vertebrates during the ageing process, we analyzed 581 samples from 54 aging transcriptome datasets spanning 4 species including Homo sapiens, Mus musculus, Rattus norvegicus and Danio rerio, and identified the novel age-related differentially expressed genes, and obtained specific enriched expression of age-related pathways. Protein-protein interactions of differentially expressed genes in different species with the PTPRC or CD45 as the core were predicted. Through this study, we screened the key biomarkers and signaling pathways that regulate the aging process of tissues and organs in multiple species, which is of great significance for improving age-related tissues and organs by identifying senescent cells.

Freezing stress (FS), especially during germination, severely impacts the growth, development, productivity, and distribution of alfalfa (Medicago sativa L.). Exogenous salicylic acid (SA), a signal molecule involved in abiotic stress responses, effectively improves the FS response of seeds. We investigate changes in seedling phenotype and hormone contents, and perform transcriptome analyses to identify how SA may improve the FS response in alfalfa during germination. Compared with control values, after 16 h FS, exogenous SA promotes seedling lengthening, and increases endogenous contents of jasmonic, abscisic, and gibberellic acids, and decreases indole-3-acetic acid (IAA), and zeatin; after 24 h FS, contents of SA, IAA, and gibberellic and abscisic acids increased, and JA and zeatin content decreased. Phytohormone biosynthesis and signaling pathways genes were induced by SA after FS. Weighted correlation network analysis suggests that GH3.1 and HSP70 play important roles in SA regulation of FS. We report a possible working model, where exogenous SA inhibits GH3.1 expression to decrease IAA content, causing TIR1 to negatively regulate expression of AUX/IAA and auxin response related genes to suppress the IAA signaling pathway, and for TIR1 to repress the SA signaling pathway after FS. For the NPR1-dependent pathway, NPR1 could bind to TGAs to regulate expression of PR1 genes to defend against FS. For the NPR1-independent pathway, superoxide dismutase, ascorbateperoxidase, glutathione-S-transferase, heat shock protein, alternative oxidase, and late embryogenesis abundant encoded genes were induced following FS.

The Chinese longsnout catfish (Leiocassis longirostris) is an important freshwater aquaculture species, and the selective breeding of fast-growth and hypoxia tolerance population will have a positive impact on its industry. In order to promote the breeding process of Chinese longsnout catfish, construction of the genetic linkage map and identification of molecular markers associated with fast-growth and hypoxia tolerance is critical for the marker-assisted selection (MAS) of Chinese longsnout catfish. In the present study, whole-genome resequencing was used to construct a high-density genetic linkage map of the Chinese longsnout catfish. The map containing 2946 bin markers was distributed over 26 linkage groups (LGs) with a total genetic coverage of 1980.76 cM and an average density of 0.67 cM. Based on the genetic map, quantitative trait locus (QTL) mapping results suggested that 17 QTLs associated with growth traits and 1 QTL associated with hypoxia tolerance were identified in eight LGs with the phenotypic variability explained (PVE) ranged from 5.1 % to 9.3 %. Four SNP loci from these QTLs were associated with the phenotypic traits validated by Kompetitive Allele Specific PCR or Sanger sequencing. In addition, the expression of three candidate genes for growth traits and five candidate genes for hypoxia tolerance was examined in different growth speed populations and the process of hypoxia exposure and reoxygenation, respectively. The high-density genetic linkage map and QTLs for growth traits and hypoxia tolerance obtained in the present study could further provide the basis for genetic breeding and molecular marker-assisted breeding of Chinese longsnout catfish.

The Magnoliaceae family represents one of the most ancient angiosperm lineage and provides key insights into early flowering plant evolution. Woonyoungia septentrionalis is an endangered dioecious tree endemic to the karst regions of Southwest China, with small and fragmented populations threatened by habitat loss and low reproductive success. Here, we generated a high-quality chromosome-scale genome assembly of W. septentrionalis with an assembled genome size of 2.62 Gb and 98.9 % completeness based on BUSCO. Repetitive elements occupy 81.23 % of the genome, dominated by long terminal repeat retrotransposons. Ks-based analysis revealed an ancestral whole-genome duplication event around 65 Mya shared with Magnolia species. Phylogenomic analyses indicated that W. septentrionalis represents the earliest diverging lineage within Magnolia sensu lato, reflecting its distinct evolutionary position. Comparative and transcriptomic analyses identified gene family expansions and sex-biased regulatory networks, including hub genes such as MCM2-MCM7, and transcription factors SPL, TCP, and ERF, which may be involved in floral organ differentiation and dioecy formation. This reference genome provides a valuable resource for exploring the molecular basis of reproductive specialization and evolutionary diversification in Magnoliaceae, and supports conservation efforts for this endangered species.

Neutrophil extracellular traps (NETs) are a kind of DNA reticular structure that can capture and kill pathogenic microorganisms. NETs are closely related to the progression of tumors, but the role of NETs in the immunotherapy of lung adenocarcinoma (LUAD) remains unclear. We constructed a NETs-related prognosis signature based on ATG7, BST1, CEACAM3 and TNFRSF10C, and the prognosis of LUAD patients in the NET-high group was worse than NET-low group. At the same time, we constructed a nomogram to improve the validity of NETs-related signature and achieved good results in external datasets. The NET-high group was associated with a higher mutation burden, higher TIDE predicted MSI score and a poorer immunotherapy outcome. Finally, we found that MEK inhibitors (selumetinib and trametinib) were more sensitive in the NET-high group and can inhibit the invasion and migration of LUAD cells. The NETs-related signature was able to predict the prognosis and immunotherapy outcome of LUAD patients.

Cultivation regimes significantly modulate flavonoid metabolism in rice panicles. Metabolomic analysis identified 257 flavonoids, with high-density planting (T0-T3) enhancing total diversity compared to conventional sparse planting (CK). The zero‑nitrogen high-density regime (T0) yielded the highest number (254). Differential analysis revealed 226 metabolites (DFMs), showing distinct correlations: nitrogen rate negatively correlated with 5 DFMs, phosphorus/potassium positively with 11 DFMs, and planting density correlated with 20 DFMs (11 positive, 9 negative). Transcriptomics identified 149 differentially expressed genes (DEGs) enriched in flavonoid pathways. Integration analysis established regulatory networks linking cultivation factors, key DFMs (e.g., kaempferol glycosides), and DEGs (notably 4CL, CHI). Crucially, optimized density (20.8 hills/m) combined with balanced NPK (150-45-60 kg/hm) and delayed nitrogen application (T3) synergistically enhanced functional flavonoids like kaempferol-3-O-galactoside, providing a strategy for high-quality rice production.

By combining transcriptome sequencing with single-cell transcriptomic analysis of the tumor microenvironment, we aim to elucidate the molecular mechanisms underlying SerpinB2 (plasminogen activator inhibitor type 2, PAI-2) in regulating glioma cell proliferation.

Beer spoiling bacteria represent a major concern for the brewing industry. Anaerobic spoilers of the genus Megasphaera are especially dreadful. Until now, the genome analysis of Megasphaera spp. was limited to mammal-associated species, yet beer borne Megasphaera species and their abilities to tolerate the multiple high stress factors in their niche were broadly overlooked. This study is the first to carry out an in silico genome comparison of ten strains from three different beer spoiling Megasphaera species (M. cerevisiae, M. paucivorans and M. sueciensis). We experimentally show a hitherto unseen resilience of beer spoiling Megasphaera strains, which can grow in lager beer with an isoα-acids content of up to 120 IBU, an ethanol concentration of up to 7.0 % (v/v) and at pH 4.0. The genomes revealed genes appearing to aid survival in the harsh brewing environment mainly comprised of hop, ethanol and acid stress.

Endometriosis (EMS) is a chronic disease characterized by unclear etiology, influenced by various genetic and environmental factors, with no definitive biomarkers available for early screening. Recent studies suggest that the abdominal microbiome and its metabolites, shaped by the host's genetic composition and environmental exposures, play significant roles in the pathogenesis and regulation of EMS. This study aims to integrate microbiome and metabolomics analyses to identify bacteria and metabolites critical to the progression of EMS. Multi-omics characterization was performed on pelvic cavity washings (PCW) from 7 EMS patients and 8 matched controls using 16S rRNA gene sequencing and liquid chromatography-mass spectrometry (LC-MS). A validation cohort of 42 EMS patients and 42 controls was assessed for clinical measures. Metabolomics revealed 7 metabolites across 12 metabolic pathways, with three uniquely distinguished in the endometriosis group. Microbial diversity analysis identified 2471 operational taxonomic units (OTUs), showing significant compositional disparities between groups. Notably, Pseudomonas enrichment in PCW was associated with advanced disease progression, especially in stage III and IV EMS, characterized by extensive pelvic adhesions and larger lesion sizes. Our findings highlight Pseudomonas as a potential biomarker for EMS severity, advancing the understanding of its pathogenesis and offering promising implications for non-hormonal therapeutic strategies. KEY MESSAGE: Comprehensive analyses show significant interactions between Pseudomonas and its metabolite guanylate in endometriosis patients. Increased Pseudomonas levels correlate with larger lesions and more severe pelvic adhesions, suggesting it may serve as a biomarker and potential driver of disease severity, informing new preventive strategies and non-hormonal treatments.