Search Results (10,009)

Paraleyrodes minei is an invasive alien species in China, representing a new record for Yunnan Province and a new sugarcane pest. The mitochondrial genome of P. minei was sequenced using the Illumina NovaSeq 6000 sequencing platform. The genome sequence was assembled and annotated, and its structural characteristics and nucleotide composition were analyzed. A phylogenetic tree of 18 species in the family Aleyrodidae was constructed using maximum likelihood (ML) and Bayesian inference (BI) methods to analyze the phylogenetic relationship of P. minei within the family Aleyrodidae. The results indicated that the mitochondrial genome of P. minei was 18,774 bp in length and contained 13 protein-coding genes (PCGs), 22 transfer RNA (tRNA) genes, 2 ribosomal RNA (rRNA) genes, and 1 non-coding control region. The A+T content of the mitochondrial genome of P. minei was 80.93%, indicating a marked A+T preference. ATN was used as the start codon for the PCGs, and TAA, TAG, TA, and T were used as the stop codons. In the secondary structure of tRNA, the TΨC arm was missing in trnA, trnC, and trnG, and the DHU arm was missing in trnS1 and trnS2, with G-U base mismatches present. The phylogenetic tree revealed that the 18 species of 10 genera in the two subfamilies of the family Aleyrodidae clustered into two major branches: the subfamilies Aleyrodinae and Aleurodicinae. All 10 genera were monophyletic groups; among them, the genus Paraleyrodes and the genus Aleurodicus formed a sister relationship, and both belonged to the subfamily Aleurodicinae. This study represents the first successful sequencing of the mitochondrial genome of P. minei, as well as the first mitochondrial genome of the genus Paraleyrodes, laying the foundation for the control of P. minei and the analysis of phylogenetic relationships among various genera of the family Aleyrodidae. Full article

Venous thromboembolism (VTE) significantly impacts lung adenocarcinoma outcomes, yet current predictive tools lack precision. We investigated plasma extracellular vesicle (EV) mRNA as a liquid biopsy source to identify a pro-thrombotic molecular profile in VTE patients. Within a prospective cohort of 260 patients, we performed a retrospective nested case–control study, matching 10 VTE cases with 11 thrombosis-free controls. Plasma EV-RNA was analyzed via high-throughput sequencing. Differentially expressed genes (DEGs) were integrated with functional enrichment and explored across public non-cancer VTE datasets, buffy coat samples, and cell lines. RNA-seq identified 483 DEGs within the VTE patient EV compartment, predominantly linked to neutrophil degranulation (NETosis), inflammation, and coagulation. We identified a set of EV-associated candidate genes (SELP, ELANE, MYL9, DNASE1L3) distinguishing cancer-associated thrombosis from non-malignant VTE, along with transcripts (TFPI, FCGR2A) selectively enriched within the EV compartment relative to circulating blood cells. P-selectin (SELP) was the only significantly increased marker, providing the strongest complementary support at the protein level. This molecular state was detectable prior to the occurrence of VTE. Plasma EVs capture a multicellular mRNA profile, reflecting the systemic immunothrombotic activation in lung adenocarcinoma. Despite sample size limitations, these findings should be considered exploratory and hypothesis-generating, but they suggest the EV-derived mRNA in combination with circulating markers such as SELP may provide a framework for future studies aimed at improving risk stratification. Full article

Background: Sarcopenia is an age-related disorder characterized by loss of muscle mass, strength, and function, driven by oxidative stress, chronic inflammation, and protein imbalance. Broccoli-derived peptides (BDP) exert anti-inflammatory and myofiber-protective effects, while leucine regulates energy metabolism and redox balance. Methods: We established a D-galactose aging mouse model and treated mice with BDP alone, leucine alone, or their combination for 8 weeks. Lean mass, muscle index, grip strength, endurance, and treadmill capacity were detected, and atrophic, disorganized myofibers were observed through histology. RNA-seq was applied to screen differential signaling pathways, and qPCR was used to verify related gene expression levels. Results: D-galactose caused marked deficits in lean mass, muscle index, grip strength, endurance, and treadmill capacity, accompanied by atrophic and disorganized myofibers. Single BDP or leucine partially reversed these deficits, but the combination produced the most robust improvements. RNA-seq revealed that BDP enriched actin, chemokine, and TNF pathways; leucine enriched Apelin and ECM pathways; while the combination uniquely regulated MAPK signaling. qPCR confirmed that co-administration optimally upregulated myogenic drivers (Myod1, Myog, Mef2c), suppressed catabolic/inflammatory mediators (Mstn, Tnf, Cxcl10), and restored metabolic/adhesive regulators (Sirt3, Aplnr, Icam1). Conclusions: BDP and leucine show superior efficacy in ameliorating sarcopenia, through multimodal regulation of multiple signaling pathways, offering a promising plant-based nutritional strategy against age-related muscle decline. Full article

Dengue virus (DENV) and chikungunya virus (CHIKV) co-circulate in many regions and present with overlapping clinical features, which complicate accurate diagnosis and disease management. This study develops an integrative transcriptomic framework to identify robust host gene signatures that distinguish between dengue, chikungunya, and healthy states. Publicly available RNA sequencing (RNA-seq) datasets derived from human blood samples were analyzed using a cross-validation design to ensure robustness and prevent information leakage. Differential expression analysis was performed independently within each dataset using the Generalized Linear Models with Quasi-Likelihood F-tests and Magnitude–Altitude Scoring (GLMQL-MAS) framework, followed by Cross-Magnitude–Altitude Scoring (Cross-MAS) integration to identify shared and virus-specific gene signatures. A strict consensus approach across folds was applied to derive reproducible gene sets. These signatures were used for dimensionality reduction and multinomial logistic regression to evaluate classification performance. A small subset of selected genes showed strong discriminative performance within the cross-validation framework, with test balanced accuracy reaching 0.97, which improved upon models using all genes. Biologically, both infections exhibited a shared antiviral response characterized by interferon signaling and innate immune activation. However, distinct virus-specific patterns were identified. Dengue infection was associated with cell-cycle and DNA replication pathways, while chikungunya infection showed stronger enrichment of inflammatory and immune signaling pathways, including NF-kappaB and Toll-like receptor signaling. Overall, this study provides a cross-validation-based framework for integrative transcriptomic analysis and identifies compact, reproducible host-response signatures with strong discriminative signals in the analyzed cohorts. These signatures require validation in larger independent cohorts before any clinical or diagnostic application. Full article

Soil salinity is a major constraint on global wheat productivity, yet the genetic and molecular determinants of root system architecture (RSA) adaptation under salt stress remain poorly characterized. We integrated a genome-wide association study (GWAS) of 566 wheat accessions with comparative RNA-seq transcriptomics to identify the genetic and transcriptional determinants of RSA adaptation under 200 mM NaCl. GWAS identified a candidate locus on chromosome 7B harboring TaIAO, which encodes a protein with predicted aldehyde oxidase-like activity consistent with a role in tryptophan-dependent auxin biosynthesis. Accessions carrying the favorable CC allele exhibited significantly greater root volume retention than those carrying the GG genotype (p < 0.001). Comparative RNA-seq revealed that the salt-tolerant Sarajevo 1 exhibited coordinated transcriptional repression of three distinct modules—cell wall expansion (TaExpansin), auxin redistribution (TaPIN-like), and stress-associated ROS defense (TaPOD1)—whereas the sensitive genotype CI 17260 aberrantly induced or incompletely repressed these modules under stress. ELISA-based IAA quantification, ROS imaging, and qRT-PCR analysis provided independent physiological and transcriptional support for these patterns. These findings support a two-tier adaptive model in which constitutive genetic variation at the TaIAO locus may contribute to a developmental baseline, coupled with coordinated stress-responsive transcriptional repression of energy-consuming modules, providing promising targets for marker-assisted breeding of salt-tolerant wheat. Full article

Autoimmune myocarditis frequently progresses to inflammatory cardiomyopathy through dysregulated immune–stromal interactions. This study employs single-nuclei RNA-sequencing (snRNA-seq) to profile 46,233 cardiac nuclei from the experimental autoimmune myocarditis (EAM) mouse model at four timepoints: day 0 (healthy), day 14 (inflammation), day 21 (acute inflammation), and day 40 (late cardiac remodelling). Single-nuclei RNA profiling identified 18 transcriptionally distinct cell populations. Global cell–cell communication analysis revealed a dramatic peak of intercellular signalling at day 14 (5907 interactions), with fibroblast subpopulations and macrophages as dominant hubs, followed by partial resolution at day 21 (2264 interactions) and renewed remodelling at day 40 (4862 interactions). Subclustering of the macrophage compartment identified five subpopulations: Mac-TLF, Mac-MHCII, Mac-rMHCII, Mac-ResL, and Classical Monocytes. Tissue-resident macrophages (Mac-TLF, CCR2-) dominated at healthy state (~55%) but were rapidly depleted at day 14, coinciding with a dramatic influx of recruited CCR2⁺ macrophages (Mac-rMHCII), which expanded to over 70% of the compartment and maintained dominance through day 40. At inflammation (day 14), the expanded Mac-rMHCII subpopulation displayed a strongly pro-inflammatory signature (Il1b, Ankrd1, Stat2, Parp14, Apoe), and the overall macrophage compartment was enriched for cytokine response, Fc-gamma receptor, and Notch signalling pathways, while downregulating homeostatic and mitochondrial metabolic programmes, potentially contributing to impaired efferocytosis and cardiomyocyte dysfunction. Macrophage-centred communication networks expanded markedly at day 14 (1047 interactions), with resting fibroblasts (FB-R) as the primary signalling partner, driving pro-inflammatory stromal activation marked by upregulation of Ccl2, Ccl7, and Csf2. Intra-macrophage subcluster communication also intensified at this timepoint (447 interactions). These findings delineate the temporal and functional heterogeneity of cardiac macrophages during EAM progression and identify key immune–stromal interactions driving pathological cardiac remodelling. The coexistence of pro-inflammatory and transitional reparative macrophage subsets highlights the limitations of broad immunosuppression and supports precision strategies targeting CCR2-mediated recruitment, the SPP1 signalling axis, and macrophage–fibroblast crosstalk as therapeutic avenues in myocarditis and its progression. Full article

In addition to its role in energy storage, adipose tissue contributes substantially to energy metabolism, endocrine regulation, and inflammatory processes. Sujiang pigs, a hybrid breed approved by the National Livestock and Poultry Genetic Resources Committee of China as a new national breed in 2013, possess a genetic predisposition for substantial fat deposition, making them an ideal model for investigating the mechanisms underlying adipose tissue accumulation. In this study, back fat (BF; subcutaneous adipose tissue), greater omentum (GOM; visceral adipose tissue), and mesenteric adipose tissue (MAD; visceral adipose tissue) were collected from three 6-month-old male Sujiang pigs for RNA-seq analysis. Comparative analyses identified 3005 differentially expressed genes (DEGs) between BF and GOM, 975 DEGs between BF and MAD, and 892 DEGs between GOM and MAD. To validate the reliability of the sequencing data, five DEGs were randomly selected for RT-qPCR verification. The DEGs were further subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. By integrating protein–protein interaction (PPI) networks with bioinformatics analyses, we identified candidate genes potentially associated with lipid metabolism (e.g., WNT9A, WNT5A, and PDGFRA) and inflammatory responses in adipose tissue (e.g., CSF1R, C1QB, and CD4). These findings indicate potential molecular differences between porcine visceral and subcutaneous adipose tissues and may serve as a reference for further studies on the molecular regulation of adipose tissue metabolism. Full article

This study investigated generation-specific heterosis in Chinese Simmental × Chinese Holstein crossbred cows by comparing lactation performance, reproductive performance, hematological traits, and blood transcriptomic profiles among Chinese Simmental (SIM), Chinese Holstein (HOL), F1 crossbreds, and first-generation backcrosses (BC1). Lactation analysis was based on 17,005 valid records, reproductive analysis was based on 5481 valid records, and transcriptomic analysis was conducted using blood samples from 31 cows. F1 showed the most favorable reproductive profile, whereas BC1 showed relatively strong milk-yield performance. Hematological analysis revealed group-level differences in leukocyte-related indicators. Main-text transcriptomic interpretation focused on SIM, F1, and BC1 comparisons because the HOL RNA-seq group included only three samples. These comparisons suggested that F1-related DEGs were mainly associated with immune and inflammatory processes, whereas BC1-related DEGs showed broader immune- and metabolism-related enrichment patterns. Candidate-gene expression heterosis and d/a-ratio analyses are presented as exploratory supplementary results with bootstrap uncertainty estimates because qPCR validation was not available. Overall, these results indicate that heterosis in this crossbreeding system is generation-specific rather than uniform. The integration of phenotypic and blood transcriptomic analyses provides candidate pathways and associated systemic expression patterns for future validation rather than definitive mechanistic evidence. Full article

Background/Objectives: West Nile virus (WNV) remains a significant threat to human health, with no approved antiviral treatments or vaccine available. A better understanding of the molecular mechanisms governing flavivirus–host interactions is needed to identify host regulatory pathways involved in infection. This study aimed to investigate how WNV infection remodels the host miRNA–mRNA regulatory landscape. Methods: WNV-induced changes in host miRNA expression in HEK-293 cells were profiled using miRNA-Seq. Transcriptome-wide host gene expression changes in WNV-infected cells were analysed using RNA-Seq. Gene Ontology and pathway enrichment analyses were conducted using DAVID. Integrated miRNA–mRNA network reconstruction was performed using Cytoscape based on the experimentally validated miRNA–mRNA interactions in miRNet database. Results: WNV infection induced global changes in host miRNA expression, with pathogenic NY99 and non-pathogenic Kunjin strains of the virus producing overlapping and strain-specific alterations in the miRNA landscape. Transcriptome analysis showed strong induction of interferon-related responses and activation of NF-κB and MAPK signalling pathways in the infected cells. In contrast, pathways associated with RNA processing, splicing, and proteasomal degradation were downregulated. Integrated miRNA–mRNA network analysis identified miR-197-3p, miR-301b-3p, miR-129-3p, miR-3662, and miR-128-5p as candidate regulatory hubs involved in WNV-induced transcriptome remodelling. These networks suggested that miRNA-mediated regulation may influence antiviral signalling, apoptosis, and RNA metabolism during infection. Conclusions: These findings suggest that WNV infection broadly remodels host miRNA–mRNA regulatory networks and identifies candidate miRNAs that may contribute to the regulation of antiviral and cellular stress responses. These predicted regulatory interactions provide a foundation for future experimental validation. Full article

While the cerebellar dopaminergic system is suggested to be implicated in neurodevelopmental disorders, especially autism spectrum disorder (ASD), the details of its disturbances remain unclear. We performed a comparative analysis of human (GTEx) and mouse (GSE144046, GSE144277) transcriptomes, complemented by RT-qPCR in DAT-KO rats, to identify dopaminergic gene associations in the normal cerebellum and neurodevelopmental disorder models. Pairwise dopaminergic gene correlations were generally weak, with a slight increase in interaction complexity in ASD models. However, weighted gene co-expression network analysis identified a robust gene module involving Comt, which was consistently associated with synaptic translation across mouse datasets. These associations reflect regulatory processes in the whole cerebellum, which is commonly represented in rodent studies but absent in human data, which are acquired in studies of cerebellar subregions. ASD modeling exerted contrasting effects: Cul3 haploinsufficiency increased the number of genes involved in the module with a decrease in connectivity, while Mbd5 haploinsufficiency led to module collapse. These findings confirm neurodevelopmental disorders as a heterogeneous condition where divergent backgrounds uniquely rewire cerebellar dopaminergic networks. Considering the cerebellum’s role in ASD and that some ASD medications target the dopamine system, further investigation of these identified trends may support the development of more personalized therapeutic approaches. Full article

Bone remodeling relies on a balance between osteoclast-mediated resorption and osteoblast-mediated formation. Roxadustat, a hypoxia-inducible factor prolyl hydroxylase inhibitor, promotes osteoblast differentiation but its effects on osteoclasts remain unclear. This study investigated roxadustat’s impact on osteoclast differentiation and function in vitro using primary murine bone marrow-derived mononuclear cells differentiated with M-CSF and RANKL. Cell viability, TRAP staining, bone resorption assays, RNA-seq, flow cytometry, immunofluorescence, Western blot for p27, and rescue experiments with the cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitor abemaciclib were performed. Roxadustat suppressed osteoclast differentiation and resorption without cytotoxicity in a concentration-dependent manner. RNA-seq revealed enrichment of cell cycle pathways; although differentiation was inhibited, roxadustat paradoxically promoted osteoclast precursor proliferation, evidenced by increased Ki67 and decreased p27 expression. The inhibitory effects on osteoclastogenesis and resorption were partially reversed by abemaciclib. Given that terminal differentiation typically requires cell cycle exit, these findings suggest that roxadustat may inhibit osteoclast differentiation at least in part by disrupting this process, promoting precursor proliferation, and downregulating p27. Together with its known anabolic effects on osteoblasts, roxadustat might have dual therapeutic potential for bone disorders with renal anemia, such as osteoporosis in chronic kidney disease. Full article

Renal-resident macrophages (RMs) are essential regulators of kidney homeostasis and repair, yet the mechanisms governing RM niche regeneration after acute depletion remain poorly defined. To overcome these limitations, we have developed an inducible human CD59- intermedilysin (hCD59-ILY) ablation system, enabling rapid, specific, and reversible depletion of targeted macrophage populations, and subsequent replenishment of RMs, followed by longitudinal scRNA-seq analysis of kidneys at baseline and days 1, 3, and 7 post-ablation. RM ablation triggered a rapid and sustained upregulation of Cx3cl1, predominantly in proximal tubular epithelial cells (PTC1/PTC2), establishing a persistent chemotactic niche signal that coincided with macrophage repopulation. Regenerating RMs transitioned from inflammatory/stress-associated states toward metabolically active and proliferative phenotypes enriched in glycolysis, oxidative phosphorylation, MYC, and cell-cycle programs, with attenuation of canonical inflammatory pathways. Cell–cell communication analysis revealed an early burst of intercellular signaling at day 1, followed by progressive normalization, with fibronectin (Fn1), osteopontin (Spp1), chemokine (Ccl), and amyloid precursor protein (App) axes emerging as key mediators of niche restoration. Transcriptional network analysis identified a conserved regulatory module (Tfe3, Mitf, Hif1a, Myc, Gabpa, Rcor1) coordinating macrophage differentiation and regenerative programming, linking metabolic adaptation to lineage reconstitution. Sub-clustering revealed five dynamically shifting RM subsets with distinct inflammatory, remodeling, proliferative, and surveillance states, reflecting a hierarchical regeneration process. Functional validation using clodronate-mediated depletion in Secreted Phosphoprotein 1 (Spp1) (Opn)-deficient mice demonstrated impaired macrophage repopulation, establishing osteopontin as a critical regulator of RM regeneration. Together, these data define a coordinated epithelial–immune circuit in which Cx3cl1-driven chemotaxis, Spp1-dependent signaling, and a core transcriptional network orchestrate macrophage niche reconstitution and kidney repair following acute immune cell ablation. Full article

Phormia regina (Meigen, 1826) (Diptera: Calliphoridae), a necrophagous blow fly of significant forensic value, plays a crucial role in postmortem interval (PMI) estimation. The intra-puparial period of this species constitutes approximately half of its entire immature developmental duration. Therefore, precise aging of intra-puparial specimens is essential to improve the accuracy of PMI estimation. This study was performed at a constant 25 °C, examining intra-puparial morphology, histological sections, and body weight across different developmental stages. Additionally, full-length transcriptome profiling was conducted via a hybrid sequencing strategy combining PacBio single-molecule real-time (SMRT) sequencing and Illumina short-read next-generation sequencing (NGS). Morphological studies revealed the intra-puparial morphological characteristics, the reconstruction process of tissues and organs, and the continuous body weight loss during the intra-puparial period. Transcriptomic research identified a total of 425,349 full-length non-chimeric (FLNC) sequences. After redundancy removal, 84,852 transcript sequences were obtained, of which 46,325 transcripts were annotated. Using day-0 puparia (D0) as the control, differentially expressed gene (DEG) analysis was performed on samples from subsequent developmental stages (D1–D5), identifying 4242, 7964, 9509, 10,526, and 10,011 DEGs, respectively. Results from GO enrichment and KEGG pathway analyses provided reasonable explanations for the behavioral traits of different developmental stages. Eight candidate genes for intra-puparial development were screened, most of which were highly expressed at different time points during the intra-puparial period. Quantitative real-time PCR (qRT-PCR) results showed consistent gene expression trends with the RNA-seq data, confirming the reliability of the RNA-seq results. This study provides key morphological and molecular markers for P. regina in forensic PMI estimation. Full article

Background and Aims: TDF is a first-line antiviral for CHB with pleiotropic effects including immunomodulation and fibrosis regression, but its virus-independent mechanisms are unclear. This study delineates TDF’s direct molecular and metabolic landscape in vivo using multi-omics. Methods: Wild-type mice received TDF or vehicle for 4 months. Liver tissues underwent RNA-seq and targeted metabolomics, followed by integrative systems biology. Results: TDF caused no hepatotoxicity but induced transcriptomic reprogramming: broad upregulation of immune/inflammatory pathways and suppression of metabolic pathways. Metabolomics confirmed perturbations in amino acid and fatty acid homeostasis. Multi-omics revealed coordinated downregulation of arginine/proline, alanine/aspartate/glutamate, and phenylalanine metabolism, restricting fibrogenic amino acids. TDF also suppressed the TCA cycle (downregulating Idh, Sdh, and Mdh), suggesting a metabolic bottleneck that was associated with paradoxically accumulated succinate and oxoglutarate—immunomodulatory danger signals. Conclusions: This first integrated atlas shows TDF actively remodels the hepatic microenvironment independent of viral infection, bridging metabolic suppression with immune activation. These findings provide an immunometabolic framework that offers new perspectives for understanding the clinical application of TDF and identifies potential biomarkers for CHB therapy. explaining TDF’s clinical superiority and identifying potential biomarkers for CHB therapy. Full article

The Syrian golden hamster (Mesocricetus auratus) is a universally accepted model for visceral leishmaniasis (VL) due to its ability to mimic human disease pathology. Mus musculus (BALB/c) is preferred for evaluating pharmaceutical and immunological responses. This study focuses on the precise role of gene signatures in L. donovani-infected M. auratus and M. musculus, using transcriptomic analysis. Principal component analysis (PCA) revealed distinct clustering among the four groups (uninfected vs. infected spleen samples from M. auratus and M. musculus). After differential expression analysis, 2054 genes in M. auratus and 1108 in M. musculus were found to be differentially expressed, with 153 genes common to both species. Except for 31 genes, most of the commonly dysregulated genes show a similar expression pattern. Although Th1-mediated immune signaling was observed in both cases, the overexpression of LAG3 in both infected groups underscores the important role of T cell exhaustion. Immunological responses against parasite infection in M. auratus appear to be more aggressive, while M. musculus seems more intense. Interestingly, only the M. musculus-infected group shows overexpression of IL-10. Without a definitive role for IL-10, the overexpression of Tgm2, Clec7a, and Adora2b in both species may drive disease outcome. These findings elucidate the immunological mechanisms driving the pathogenesis of VL in rodent models. Full article