Search Results (791)

In marine aquaculture environments, microplastics (MPs) and cadmium (Cd) are widespread contaminants that may jointly affect host–microbe interactions. Here, we examined the combined effects of MPs (5 mg/L) and Cd (5 μg/L) on the intestinal microbial community of pearl oysters after a 48 h exposure, followed by a 5-day recovery period. Gut microbiota dynamics were characterized using 16S rRNA gene sequencing. Alpha diversity did not vary significantly, whereas beta diversity showed marked alterations in community composition among the different exposure treatments. LEfSe analysis revealed distinct microbial biomarkers and putative pathogens under each treatment: Sulfitobacter in the MPs-alone group; Vibrio and Candidatus_Megaira in the Cd-alone group; and Tenacibaculum, Roseibacillus, and Enterovibrio across different co-exposure and recovery groups. A brief recovery period partially decreased the abundance of certain pathogens (e.g., Vibrio), yet some taxa (e.g., Enterovibrio and Tenacibaculum) remained enriched. These results indicate that exposure to MPs and Cd, whether alone or in combination, disrupts gut microbial homeostasis in pearl oysters by reshaping community structure and promoting the proliferation of potential pathogens, with some disturbances persisting after exposure ceases. Generally, our findings will aid evaluation of the ecological risks of combined pollutants in marine aquaculture systems. Full article

Clostridium perfringens is one of the main causes of death in poultry with no vaccines approved for poultry at present. The appropriate adjuvant is critical for the development of vaccines in C. perfringens in poultry. Here, we utilized Levilactobacillus brevis for high-yielding selenium biotransformation and demonstrated that heat-inactivated nano-selenium Lactobacillus (HiSeL) is a safe, efficient, and chemically stable selenium immunopotentiator for C. perfringens vaccines. We evaluated the effectiveness of HiSeL as an immune adjuvant to modulate the efficacy of multi-epitope vaccine in mice. Subcutaneous immunization mice with HiSeL promoted high levels of specific IgG, modulated cytokine secretion, downregulated stress-related gene expression, and provided 100% protection against lethal challenge with C. perfringens. Surprisingly, we found that HiSeL can quickly and effectively induce SIgA production even by subcutaneous immunization. Transcriptome sequencing revealed the pivotal role of TGF-β and NF-κB signaling pathways in IgA immune responses in mice immunized with the HiSeL-adjuvanted multi-epitope vaccine. Collectively, our study provides proof-of-concept evidence that HiSeL functions as a potent adjuvant candidate for the multi-epitope vaccine in a murine model, offering new insights into the development of engineered postbiotic-based adjuvants. Full article

Background: Depression and Metabolic Dysfunction-Associated Steatotic Fatty Liver Disease (MASLD) are common chronic diseases, respectively. However, the causal and molecular links between them remain unclear. In order to explore whether depression contributes to an increased risk of MASLD and whether inflammation mediates this effect, we integrated multi-level evidence from the epidemiology of the National Health and Nutrition Examination Survey (NHANES), the genetics of GWAS, the transcriptomes of GEO, and single-cell RNA sequencing datasets. Methods: A multi-level integrative analysis strategy was used to validate this pathway. First, a cross-sectional epidemiological analysis based on NHANES data was used to reveal the association between depression and MASLD, and to explore the mediating role of inflammation and liver injury markers. Secondly, a two-sample Mendelian randomization analysis was used to infer the causal direction of depression and MASLD, and to verify the mediating effect of systemic inflammation and liver injury indicators at the genetic level. Then, the transcriptome co-expression network analysis and machine learning were used to screen the common hub genes connecting the two diseases. Finally, single-cell transcriptome data were used to characterize the dynamic expression of potential key genes during disease progression at cellular resolution. Results: Depression significantly increased the risk of MASLD, especially in women (OR = 1.39, 95%CI [1.17–1.65]). Parallel mediation analysis showed that high-sensitivity C-reactive protein (hs-CRP) (p < 0.001), γ-glutamyltransferase (GGT) (p < 0.001), and alkaline phosphatase (ALP) (p < 0.001) mediated this relationship. Mendelian randomization analysis confirmed the unidirectional causal effect of depression on MASLD, and there was no reverse association (β = 0.483, SE = 0.146, p = 0.001). Weighted gene co-expression network analysis and machine learning identified CD40LG as a potential molecular bridge between depression-associated immune modules and MASLD. In addition, single-cell data analysis revealed a stage-specific trend of CD40LG expression in CD4⁺ T cells during MASLD progression, while its receptor CD40 was also activated in B cells. In the female sample, CD40LG maintained an upward trend. However, the stability of this result is limited by the limited sample size. Conclusions: This study provides converging multi-omics evidence that depression plays a causal role in MASLD through inflammation-mediated immune signaling. The CD40LG-CD40 axis has emerged as an immune mechanism that transposes depression into the pathogenesis of MASLD, providing a potential target for the intervention of gender-specific metabolic liver disease. Full article

Precocious-fruiting Amomum villosum Lour. is characterized by early fruit set, rapid yield formation, and shortened economic return cycles, indicating strong cultivation potential. However, the molecular mechanisms underlying its flowering transition remain unclear. To elucidate the flowering mechanism of A. villosum, we used the Illumina NovaSeq X Plus platform to compare gene expression profiles in three tissues (Rhizomes, R; Stems, S; Leaves, L) during the vegetative stage and three tissues (Rhizomes and Inflorescences, R&I; Stems, S; Leaves, L) during the flowering stage of individual plants: VS-R vs. FS-R&I, VS-S vs. FS-S, and VS-L vs. FS-L. We obtained 52.5 Gb clean data and 789 million reads, and identified 2963 novel genes. The 3061 differentially expressed genes (DEGs, FDR ≤ 0.05 and |log2FC| ≥ 1) identified in the three comparison groups included six overlapping genes. The DEGs were enriched primarily in GO terms related to cellular process, metabolic process, binding, catalytic activity, and cellular anatomical entity, as well as multiple terms associated with development and reproduction. KEGG enrichment analysis revealed enrichment primarily in metabolic pathways, including global and overview maps, energy metabolism, and carbohydrate metabolism. Moreover, the most significantly enriched core pathways included metabolic pathways, photosynthesis, and carbon assimilation. Among all alternative splicing (AS) events, skipped exons (SEs) accounted for the largest proportion (59.5%), followed by retained introns (RI, 19.4%), alternative 3′ splice sites (A3SS, 10.7%), alternative 5′ splice sites (A5SS, 6.8%), and mutually exclusive exons (MXE, 3.6%). A preliminary set of 43 key DEGs was predicted, displaying spatiotemporal expression specificity and strong interactions among certain genes. Nine genes were further selected for RT-qPCR validation to confirm the reliability of the RNA-seq results. This study established a foundational framework for elucidating the flowering mechanism of precocious-fruiting A. villosum. Full article

The foraging environment is a critical source of microbes for wild birds, yet its role in shaping the gut microbiota of sympatric crane species remains poorly understood. This study investigated this relationship in the Yellow River Delta wetland by analyzing the microbial communities of paired foraging environments and fecal samples from Common Cranes (Grus grus) and White Cranes (Grus leucogeranus) via 16S rRNA gene sequencing. Significant inter-group differences in alpha diversity (ACE, Chao1, Shannon, Simpson) indicated strong environmental filtering effects. Beta diversity (PCoA) revealed pronounced segregation between foraging and fecal samples (PC1 = 25.0%), underscoring a significant microbial turnover between the environment and the gut. Dominant phyla included Proteobacteria (24.6–37.4%), Firmicutes (4.8–29.0%), and Actinobacteriota (12.4–23.3%). LEfSe identified genus-level biomarkers highly specific to sample type and host, including Ligilactobacillus (12.1% in Common Crane feces) and Cryobacterium (9.2% in White Crane feces). SourceTracker analysis indicated that >70% of gut microbial sources remained unknown, suggesting a vast uncharacterized environmental reservoir. Functional prediction highlighted group-specific adaptations, such as elevated amino acid transport metabolism in Common Cranes (9.8% vs. 7.1%; p < 0.05), potentially linked to local dietary resources. Our findings demonstrate that the gut microbiota of cranes is synergistically shaped by host-specific factors and the unique saline–alkaline foraging environment of the wetland. Full article

This study investigated the effects of varying levels and combinations of calcium (Ca) and magnesium (Mg) supplementation on the diversity, composition, and species differentiation of the rhizosphere soil bacterial community in rainfed maize, aiming to reveal their regulatory mechanisms on the rhizosphere micro-ecosystem. A field micro-plot experiment was conducted with seven treatments: low Ca (U), high Ca (V), low Mg (W), high Mg (X), low Ca and low Mg (Y), high Ca and high Mg (Z), and a control (K, no supplementation). The bacterial communities were analyzed using high-throughput sequencing of the 16S rRNA gene, and the data were processed using the QIIME2 pipeline, as well as multivariate statistical analyses, and LEfSe. The main results demonstrated that Ca and Mg supplementation significantly altered the rhizosphere bacterial community structure (beta-diversity). Analysis of Similarities (ANOSIM) indicated significant differences between treatments (R > 0.4, p < 0.01). LEfSe analysis successfully identified key biomarkers responsive to different treatments. For instance, high Ca treatment significantly enriched the genus Clostridium within the phylum Firmicutes, whereas high Mg treatment specifically enriched the genus Lysobacter. Furthermore, Ca-Mg interactions exhibited non-additive effects, and the coupled Ca-Mg supplementation treatments (Y, Z) formed unique species assemblages. As key environmental drivers, Ca and Mg supplementation specifically reshaped the rhizosphere bacterial community through “environmental filtering” in rainfed maize. This study provides a theoretical basis for understanding the microbiological pathways through which secondary element fertilizers influence soil health, offering practical implications for precisely managing rhizosphere micro-ecology through Ca and Mg supplementation to promote the sustainable development of dryland farming. Full article

Ovulation and granulosa cell luteinization are induced by ovulatory signals, including luteinizing hormone (LH) and human chorionic gonadotropin (hCG). Histone modifications enable rapid, signal-responsive transcriptional reprogramming. However, the effects of LH/hCG-induced histone modification changes on the mural granulosa cells (MGCs) function remain to be fully elucidated. By mining public datasets we integrated transcriptomic and histone-modification profiles of MGCs across the ovulatory interval and tracked LH/hCG-driven gene expression at three time points (0, 4, and 12 h after-hCG). During oocyte maturation, the 4 h LH-surge constitutes a critical window for meiotic resumption, during which many genes display rapid transcriptional changes followed by a return to baseline levels. Early-response genes are enriched for cell locomotion, inflammatory responses, the activation of signaling pathways, and histone modifications. Furthermore, LH/hCG-induced transcriptome remodeling is highly correlated with dynamic gains or losses of H3K4me3 and H3K27ac. Notably, we discovered for the first time that H3K27ac marks super-enhancers (SEs) that regulate LH/hCG-induced transcriptional activation in MGCs. Finally, through complementary in vitro and in vivo pharmacological inhibition, we demonstrate that LH/hCG governs oocyte maturation and ovulation by reshaping the MGC transcriptome via H3K4me3- and H3K27ac-dependent chromatin remodeling. In summary, our study advances the understanding of how gonadotropins regulate MGC function and oocyte maturation through histone-modification-mediated transcriptional control. Full article

Acute kidney injury (AKI) is defined as a quick and often reversible decline in renal performance, as shown by elevated creatinine or reduced urine volume. AKI is a common illness, particularly among hospitalized cases, and can be observed in up to 7% of hospital admissions and 30% of ICU admissions. This study was designed to explore the nephroprotective potential of eco-synthesized quercetin–selenium nanoparticles (QUR-SeNPs) against experimentally glycerol-induced rhabdomyolysis leading to AKI. Forty healthy adult male albino rats were employed in the experiment. Animals were randomly distributed equally into five groups: Control: orally administered with normal saline solution. GLY: orally administered with normal saline (0.9% NaCl) for 15 consecutive days, at day 14, animals of this group received a single dose of intramuscular (im.) injection of 50% glycerol (GLY) (10 mg/kg/day). GLY and quercetin (GLY&QUR): orally administered with quercetin daily for 15 days (50 mg/kg/day), at day 14, animals of this group received a single dose of im. injection of 50% glycerol (10 mg/kg/day). GLY&Na₂SeO₃: orally administered with sodium selenite daily for 15 days (0.5 mg/kg/day), at day 14, animals of this group received a single dose of im. injection of 50% glycerol (10 mg/kg/day). GLY&QUR-SeNPs: orally administered with selenium nanoparticles synthesized using quercetin daily for 15 days (0.5 mg/kg/day), at day 14, animals of this group received a single dose of im. injection of 50% glycerol (10 mg/kg/day). Oxidative stress, inflammatory, and apoptotic markers, in addition to histopathological, gene expression, and immunohistochemical analysis, were assessed for all groups. The results demonstrated that QUR-SeNPs effectively ameliorated renal functional, biochemical, and molecular disturbances through their synergistic antioxidant, anti-inflammatory, and anti-apoptotic potential, surpassing the effects of either quercetin or selenium alone. Biosynthesized selenium nanoparticles using QUR-SeNPs demonstrated remarkable nephroprotective activity by normalizing renal biomarkers, restoring antioxidant capacity, inhibiting inflammatory cytokines, and preventing apoptotic damage. The nanoparticle formulation exhibited superior efficacy to either QUR or Se alone, highlighting the synergistic interplay between selenium and quercetin through enhanced bioavailability, redox stability, and molecular targeting. Full article

The gut microbiota forms early in life and undergoes dynamic changes that are essential for host health and development. Although body condition is a key fitness-related trait and predictor of viability in many animal species, its association with gut microbiota, especially during early life stages in wild populations, remains poorly understood. In this study, we collected fecal samples and used 16S rRNA gene sequencing to investigate temporal shifts in gut microbiota of Japanese tits (Parus minor) across nestling stages (days 3, 6, 10, and 14 post-hatching, denoted as D3, D6, D10, and D14, respectively; n = 70, repeatedly sampled) and in adults (n = 25), and examined their association with nestling body condition. The results showed that nestlings harbored distinct microbial communities compared to adults, with the latter exhibiting higher relative abundances of Bacteroidota and Verrucomicrobiota (LMMs, p < 0.001 for both). LEfSe analysis identified Actinobacteriota as a biomarker for D14 nestlings and Bacteroidota for adults. Alpha diversity decreased from D3 to D14, with adults showing higher diversity than late-stage nestlings (D10–D14), but comparable diversity to early-stage nestlings (D3–D6). Beta diversity revealed clear separation between nestlings and adults, and within nestlings, early stages (D3–D6) differed significantly from D14. Nest effects also contributed to microbial structure. Time-lagged analyses showed that Firmicutes abundance at D6 positively predicted scaled mass index (SMI) at D10 (p = 0.002), whereas Proteobacteria negatively predicted SMI (p = 0.006). Overall, these findings highlight dynamic, stage-specific shifts in the gut microbiota of Japanese tits and suggest that microbial succession may influence nestling growth and physiological adaptation. Full article

Nocardia seriolae infection poses a serious threat to largemouth bass (Micropterus salmoides) aquaculture, owing to the lack of effective control strategies. This study investigated the antibacterial effects and underlying mechanisms of Macleaya cordata alkaloids—sanguinarine (SE) and chelerythrine (CHE)—against N. seriolae through integrated physiological and transcriptomic approaches. Results showed SE and CHE exhibited strong in vitro antibacterial activity, with minimum inhibitory concentrations (MICs) of 62.5 and 7.8 μg/mL, respectively. In vivo trials revealed that dietary supplementation with either alkaloid significantly enhanced the survival of infected fish, yielding relative percent survival (RPS) values of 34.5% for SE and 40.0% for CHE. Concurrently, both treatments reduced bacterial load and alleviated granulomatous pathology in multiple organs, including the liver, spleen, and kidney. Physiological analyses revealed severe damage to the cell envelope, as evidenced by increased membrane permeability and structural disintegration observed under transmission electron microscopy (TEM). Transcriptomic profiling identified 3708 and 5095 differentially expressed genes (DEGs) in the SE- and CHE-treated groups, respectively, with notable downregulation of key genes involved in peptidoglycan biosynthesis, the citrate cycle, oxidative phosphorylation, and the pentose phosphate pathways. These findings demonstrate that SE and CHE inhibit N. seriolae through a multi-target mechanism simultaneously disrupting cell envelope integrity and energy production, laying the groundwork for their development as eco-friendly aquaculture therapeutics. Full article

Despite advances in blood-based screening tests for colorectal cancer (CRC), most existing assays focus on DNA-based biomarkers, which predominantly reflect tumor-derived fragments released at later disease stages. In contrast, whole-blood transcriptomic profiling can capture systemic immune responses and tumor–host interactions, offering a complementary strategy for earlier disease detection. However, clinically validated whole-blood transcriptomic signatures remain limited. Here, we investigated a whole-blood RNA-based biomarker discovery strategy by integrating multi-cohort transcriptomic resources. Public GEO datasets (GSE164191 and GSE11545) were harmonized and analyzed, yielding 956 differentially expressed genes (DEGs). Multi-layer biological filtering incorporating PPI networks, transcription factors, CRC-related GWAS variants, whole-blood eQTL signals, DigSeE, and CoReCG disease associations refined these to 375 high-confidence transcripts (WB-PADs). In parallel, RNA-seq analysis of a Korean cohort (10 CRC vs. 10 controls) identified 217 DEGs (WB-K). Cross-dataset convergence highlighted seven overlapping transcripts, and five candidates (DLG5, CD177, SH2D1B, NQO2, and KRT73) were selected for validation. RT-qPCR in an independent clinical cohort (106 CRC and 123 healthy controls) confirmed four transcripts with significant discriminatory ability. A multivariable logistic regression model derived from the five-transcript signature achieved an AUC of 0.952 (95% CI 0.884–1.000), with sensitivities of 0.889 and 0.667 at fixed specificities of 90% and 95%, respectively, demonstrating strong applicability for screening-relevant thresholds. Notably, the model retained high accuracy in early-stage CRC (Stage I–II: AUC 0.929, 95% CI 0.868–0.989). Overall, this study provides a robust analytic framework for reproducible whole-blood RNA biomarker discovery and establishes a multi-gene signature with promising translational potential for minimally invasive and early CRC detection. Full article

Background: Nontuberculous mycobacterial pulmonary disease (NTM-PD) is a chronic respiratory infection primarily caused by Mycobacterium avium complex (MAC) and Mycobacterium abscessus. These species differ markedly in antibiotic susceptibility and treatment response, yet the contribution of the respiratory microbiome to this clinical variability remains unclear. To date, however, comparative analyses of microbiome differences between MAC-PD and M. abscessus-PD and their associations with disease severity are limited. Methods: We conducted microbiome analysis of sputum from 37 patients with NTM-PD. Patients were antibiotic-naïve and classified into MAC-PD (n = 29) and M. abscessus-PD (n = 8) groups. Disease severity was determined using radiologic extent on chest computed tomography. Bacterial communities were profiled by 16S rRNA gene sequencing, and differential taxa and predicted functional pathways were analyzed using LEfSe and KEGG orthology databases. Results: Distinct microbiome profiles were observed between MAC-PD and M. abscessus-PD. Three anaerobic species—Porphyromonas pasteri, Fusobacterium periodonticum, and Prevotella nanceiensis—were significantly enriched in M. abscessus-PD (LDA effect size > 3, p < 0.05). Functional biomarker analysis revealed significant enrichment of the cobalamin (vitamin B12) biosynthesis pathway in patients with severe disease, while the C19/C18 steroid hormone biosynthesis pathway was enriched in those with mild disease (p < 0.05). Conclusions: In conclusion, our study demonstrates distinct differences in the respiratory microbiome between MAC-PD and M. abscessus-PD and identifies specific functional pathways associated with disease severity in NTM-PD. These findings highlight the potential value of microbial metabolic signatures as biomarkers for disease assessment. Full article

Background/Objectives: Gestational diabetes mellitus (GDM) is associated with altered maternal gut microbiota and increased risk of large-for-gestational age (LGA) births. The contribution of gut microbiota to fetal overgrowth in GDM, independent of glycemic control, remains unclear. Methods: In this pilot longitudinal study, the gut microbiota of 18 women with GDM was followed from the second (2T) to the third trimester (3T). Maternal fecal samples were analyzed by 16S rRNA gene sequencing, and associations between microbial profiles and infant birth weight were examined. In addition, these associations were adjusted for pre-pregnancy body mass index (BMI) and gestational weight gain (GWG). Results: Maternal gut microbiota of LGA infants exhibited consistently lower microbial diversity, a reduced Bacillota/Bacteroidota ratio, and enrichment of pro-inflammatory taxa including Prevotella, Sutterella, and Bilophila. Short-chain fatty acids (SCFAs)-producing genera such as Acinetobacter, Odoribacter, Faecalibacterium, and Lachnoclostridium were depleted. Although Bilophila was identified as a third-trimester biomarker with LEfSE approach, its association with LGA disappeared after adjusting for BMI and GWG. Conversely, Nitrospirota, Polaromonas, Acinetobacter, and Aeromonas correlated negatively with LGA even after BMI and GWG adjustment. Conclusions: These findings suggest that specific maternal microbiota signatures, together with pre-pregnancy adiposity, influence fetal overgrowth in GDM and may serve as early biomarkers or targets for preventive interventions. Full article

Corneodesmosomes are specialized intercellular junctions that mediate adhesion between corneocytes in the stratum corneum (SC). The degradation of these structures is regulated by kallikrein-related peptidases (KLKs) and their inhibitors. This study aimed to elucidate the effects of Shotokuseki extract (SE), a substance rich in various trace elements, on molecules related to SC adhesion using a three-dimensional cultured human epidermis model. SE was applied to a three-dimensional epidermis model, and analyses were conducted on gene expression, protease activity, protein levels, and tissue structure. SE treatment significantly upregulated the mRNA expression of corneodesmosomal components (desmoglein1, desmocollin1, and corneodesmosin) and the major protease inhibitor serine peptidase inhibitor Kazal type 5. Concurrently, SE increased the mRNA expression of the trypsin-like protease KLK5,while significantly decreasing the mRNA expression and activity of the chymotrypsin-like protease KLK7. Although no significant changes were observed in the protein levels of corneodesmosomal components, histological analysis revealed that SE significantly increased the ratio of SC thickness to total epidermal thickness. These findings suggest that SE contributes to the homeostasis of the SC by simultaneously promoting the expression of genes encoding corneodesmosomal components, and regulating the balance of the protease/inhibitor system involved in their degradation. The selective suppression of KLK7 activity may appropriately regulate the final stage of desquamation, thereby stabilizing barrier function. Full article

Background: Normal spermatogenesis in Mongolian horses depends on the mitotic division of spermatogonia, two successive meiotic divisions, and the morphological transformation of spermatids into mature spermatozoa. The MEI1 gene is involved in the meiosis cycle and is required for normal chromosome association during meiosis. Previous studies have shown that alternative splicing of MEI1 may promote spermatogenesis in Mongolian horses. In this paper, the regulatory effects of different MEI1 alternative splicing events on Mongolian horse spermatogenesis are investigated. Results: In this study, two overexpressed lentiviral vectors with mutually exclusive exon (MXE) and skipped exon (SE) events of MEI1 were constructed and successfully used to infect Sertoli cells. After 72 h of viral infection, the expression of MEI1 was higher in the SE event than in the MXE event (p < 0.001), as shown by fluorescence quantification; transcriptomics and metabolomics were then used to screen and annotate the differential genes and metabolites, and 193 differentially expressed genes (comprising 109 genes, such as MEI1, and 84 genes with upregulated and downregulated expression, respectively) and 11,360 differentially expressed metabolites (comprising 7494 and 3866 metabolites with upregulated and downregulated expression, respectively) were screened. Differential genes and metabolites were mainly enriched in several metabolic pathways related to spermatogenesis. Differential genes such as IL31RA, ATP2B3, and CASQ2 were highly expressed in SE events, while IL11, PRLR, and CCR7 were highly expressed in MXE events. Metabolites such as folic acid and spermine were highly expressed during SE events, while citric acid and glutathione were highly expressed during MXE events. This suggests that both MXE and SE events of the MEI1 gene can promote the activity of the spermatogenesis signaling pathway. Conclusions: The MXE and SE splicing events of the MEI1 gene may influence spermatogenesis by regulating the expression of spermatogenesis-related genes and metabolites. These findings provide a theoretical foundation for further investigations into the regulatory mechanisms of different alternative splicing events in Mongolian horse spermatogenesis. Full article