生物学最新文献

The epitranscriptome, comprising post-transcriptional RNA modifications, has emerged as a pivotal regulator of gene expression in the female reproductive system. Among these modifications, 5-methylcytosine (m5C) stands out as a widespread and highly conserved mark whose roles in female reproductive health and disease are increasingly recognized but have not yet been systematically summarized. This review aims to synthesize current knowledge on the functions and regulatory mechanisms of m5C in female reproductive physiology and associated pathologies. We begin with a foundational overview of m5C, detailing its definition, biological functions, and the dynamic regulatory network of 'writers,' 'readers,' and 'erasers.' We then examine the critical roles of m5C in key physiological processes, including oogenesis and early embryonic development. Furthermore, we provide an in-depth analysis of the mechanistic involvement and clinical implications of m5C dysregulation in various gynecological diseases. By consolidating recent advances, this review seeks to establish a comprehensive framework for understanding m5C in the female reproductive system and to offer a valuable reference and theoretical basis for future research and therapeutic exploration.

Swine viral infections continue to impose major economic and animal-health burdens worldwide, with pathogens such as porcine epidemic diarrhea virus (PEDV), African swine fever virus (ASFV), and porcine reproductive and respiratory syndrome virus (PRRSV) causing recurrent outbreaks. Autophagy and ubiquitination are central degradative pathways that act as double-edged swords, serving both host defense and viral exploitation. In this narrative review, we synthesize recent advances showing how these pathogens manipulate ubiquitin - autophagy circuits while host cells counteract through selective autophagy. We propose an autophagy - metabolism - immunity triad that positions autophagy as a hub linking infection, metabolic reprogramming, and immune evasion. This integrated framework moves beyond the traditional view of autophagy as strictly antiviral or pro-viral. Deciphering how viruses hijack ubiquitin - autophagy axes reveals actionable therapeutic targets and translational opportunities for antivirals, adjuvants, and metabolic interventions to reduce the burden of swine viral diseases.

Ribosomal protein (RP) gene haploinsufficiency is a conserved form of ribosome dysfunction across species and underlies a class of disorders known as ribosomopathies. In Drosophila, RP gene haploinsufficiency manifests as the Minute phenotype, characterized by thinner and shorter mechanosensory bristles. The development of both bristles and proprioceptive campaniform sensilla (CS) is initiated by the bHLH proneural proteins Achaete (Ac) and Scute (Sc). By analysing genetic interactions between ac sc mutants and Minute mutants of varying severity, we identified a novel bristle-promoting effect that occurs only in the strongly affected Minutes in which the average bristle length is shorter than a threshold. This threshold-dependent effect also promotes ectopic CS formation in the strong Minutes. Transcriptomic analyses comparing the sensory organ - promoting and non-promoting Minutes revealed significant differences in stress-response pathways, including differentially elevated expression of the Xrp1-Irbp18 transcriptional dimer. Notably, mutation of Xrp1 suppresses the ectopic CS phenotype, indicating a positive regulatory role. These findings reveal a previously unrecognized threshold effect in RP gene haploinsufficiency, in which excessive Xrp1 activity promotes supernumerary sensory organ formation, suggesting a compensatory mechanism that modulates neurogenesis under severe ribosomal stress.

Vibriosis is the most important public health threat from seafood consumption and marine recreation. Pathogenic Vibrio spp. employ virulence factors, including hemolysins and secretion systems, frequently detected in human cases, but virulence data in northern and southern sea otters (Enhydra lutris kenyoni and E. l. nereis, respectively) are limited despite their potential as marine bioindicators. Genomic epidemiology was used to characterize virulence factors of Vibrio spp. genomes (n = 570), including V. alginolyticus (n = 55), V. diabolicus (n = 52), non-O1/O139 V. cholerae (n = 163), and V. parahaemolyticus (n = 287) collected in North America (2000-2019). Virulence factors of V. parahaemolyticus were compared between isolation sources: bivalves, environment, humans, and southern and northern sea otters. Hemolysins (tdh, trh) and type III secretion system 2 (T3SS2) gene prevalences were lowest in environmental isolates, while tdh and T3SS2 gene prevalences were higher in human and northern sea otter isolates than those from southern sea otters. A hemolysin allele (trh1) was detected almost exclusively in human and sea otter isolates. Despite V. parahaemolyticus genomic diversity, detected genomic clusters were comprised of highly related and tdh⁺/trh⁺ genomes from nonenvironmental sources including humans and sea otters. Observed pathology in Vibrio spp. positive sea otters frequently included septicemia, enteritis, and moderate-to-severe melena. Co-occurrence of T3SS2 and T6SS1 in V. parahaemolyticus was associated with pathological findings and ampicillin-susceptible genotypes, suggesting a trade-off between virulence and antimicrobial resistance. Based on these findings, V. parahaemolyticus undergoes selection pressures resulting in apparent expansion, i.e. genomic clustering, of tdh⁺/trh⁺ virulent strains infecting humans and sea otters.

Traditional antifungal drugs used against Candida albicans have several drawbacks, including the emergence of drug-resistant strains. In addition, developing novel antifungal agents requires long-term research and design. Drug repurposing, identifying and utilizing previously unknown functions of known drugs, such as antifungal activity, may be a quick method for mining efficient alternatives. Otilonium bromide (OB), an FDA-approved drug, is a quaternary ammonium compound used as a therapeutic drug for irritable bowel syndrome. We previously reported the inhibitory effect of OB against the spore germination of Cryptococcus neoformans. In this study, we found that the antifungal activity of OB against C. albicans was 2 μg/mL for both minimum inhibitory and fungicidal concentrations. OB could destroy the cell membrane and prevent C. albicans from undergoing yeast-to-hyphae transition, thus interfering with biofilm formation. Additionally, the efficacy of OB was abolished when iron ions were provided, suggesting that iron homeostasis was associated with the inhibition mechanism of OB. Interestingly, a therapeutic assay showed that OB demonstrated limited efficacy in reducing C. albicans burden in a murine systemic infection model. In summary, repurposing OB against C. albicans may facilitate the design of new antifungal drugs, and chemical modification could enhance the efficacy of OB to be more specific to fungal pathogens.

Foot-and-mouth disease virus (FMDV) can cause a severe infectious disease that primarily affects even-toed ungulates. FMDV is classified into the genus of Aphthovirus in the family Picornaviridae. FMDV's 3C protein is a nonstructural protein and, moreover, is a protease (3C^pro) that adopts a chymotrypsin-like fold and harbors a Cys-His-Asp catalytic triad. The 3C^pro plays crucial roles not only in cleaving the FMDV polyprotein but also in degrading various host proteins. Cleavage of the polyprotein contributes to generating different viral polypeptides. Degradation of host proteins possibly affects cellular signaling pathways, making FMDV impair innate immune responses. Here, we systematically reviewed FMDV 3C^pro concerning its multiple characteristics, including nucleotide and protein sequences, crystal structures, enzymatic activities, anti-3C^pro inhibitors, and more importantly, its functions in cleaving the viral polyprotein and host proteins. This review aims to provide a comprehensive insight into FMDV 3C^pro as a protease functioning in the course of viral propagation.

Exploring the role of key genes in colorectal cancer (CRC) progression to identify effective targets is highly practical. Previous studies have shown that miR-1276/ACTB plays an important regulatory role in CRC. In addition to miRNA, lncRNA also play a crucial role in tumour progression. However, there are currently no studies exploring the relationship between lncRNAs and miR-1276/LACTB. Analysis of the relationship between lncRNAs and miR-1276 using ENCORI database showed that lncRNA-LINC00852 bound to miR-1276 and inhibited its expression, thereby promoting LACTB expression, and miR-1276 upregulation weakened the ability of LINC00852 to promote LACTB expression. ENCORI and TCGA data also indicated that the expression of LINC00852 and LACTB in CRC was significantly downregulated, while miR-1276 expression was significantly upregulated. LINC00852 overexpression promoted E-cadherin expression, increased the activities of Caspase-3/8/9 and PARP, inhibited the expression of N-cadherin and Vimentin, and decreased the expression and secretion of MMP-2 and MMP-9. LINC00852 inhibited CRC cell viability, invasion and migration while promoting apoptosis. miR-1276 overexpression or LACTB knockdown significantly blocked the regulatory effect of LINC00852 on CRC cell biological function. Further xenograft mouse model confirmed that LINC00852 downregulated miR-1276 expression, enhanced the expression of LACTB and FDX1, increased tumour copper levels and inhibited tumour formation, indicating that the anticancer effect of LINC00852/LACTB may also be related to cuproptosis. However, LACTB knockdown blocked the inhibitory effect of LINC00852 on tumour formation. Therefore, LINC00852 inhibits CRC progression through miR-1276/LACTB, indicating that LINC00852/miR-1276/LACTB axis is an important pathway closely related to the occurrence and development of CRC.

Objectives: To systematically investigate the regulatory mechanisms of ferroptosis in renal tubular epithelial cells under high oxalate stress, focusing on identifying key upstream signaling pathways and their therapeutic potential.

Methods: We employed HK-2 cell cultures and Glyoxylate-induced mouse models of oxalate nephropathy. Multi-omics approaches including 4D-label-free proteomics, RNA-sequencing, and CUT&Tag were integrated to identify regulatory networks. Functional validation utilized genetic manipulation, pharmacological intervention, chromatin immunoprecipitation, and dual-luciferase reporter assays.

Results: High oxalate dose-dependently induced renal tubular ferroptosis and activated the Hippo pathway, leading to YAP1 phosphorylation and inactivation. Proteomic and multi-omics analyses identified YAP1 as a key regulator and SLC7A5 as its direct transcriptional target via TEAD1. High oxalate disrupted YAP1/TEAD1 binding to the SLC7A5 promoter, downregulating SLC7A5. Functional rescue confirmed that SLC7A5 loss mediated ferroptosis under YAP1 inhibition. Mechanistically, SLC7A5 downregulation restricted leucine availability and suppressed mTOR signaling, while leucine supplementation or mTOR reactivation reversed ferroptosis, demonstrating that SLC7A5 regulates ferroptosis via the leucine/mTOR axis.

Conclusion: We establish the Hippo-YAP1/TEAD1-SLC7A5 axis as a master regulatory pathway controlling oxalate-induced ferroptosis. This pathway represents a promising therapeutic target for oxalate nephropathy and provides fundamental insights into stress-responsive ferroptosis regulation in kidney disease.

Background: Interleukin-6 (IL-6) is a pleiotropic cytokine that participates in multiple metabolic disorders. IL-6 is well recognized to induce hepcidin expression and decreased serum iron through the JAK2/STAT3 pathway under inflammatory conditions. Targeted inhibition of IL-6 represents a potential therapeutic regimen for multiple diseases. The current study aimed to explore the physiological concentration of IL-6 in sustaining systemic iron homeostasis.

Methods: IL-6-knockout mice (IL-6-/-) were established in the current study. Western blot measured the expression of key iron-related proteins in liver, kidney, spleen and duodenum, as well as hepatic hepcidin mRNA expression. Serum iron and hematologic parameters were detected. ELISA and Masson's trichrome staining were performed to detect renal TGF-β1 expression and collagen deposition. Furthermore, bone marrow-derived and peritoneal macrophages were prepared to identify the iron recycling.

Results: Serum iron and tissue iron content were markedly elevated in IL-6-/- mice. Mechanistically, decreased renal erythropoietin (EPO) synthesis contributed to iron utilization, macrophage-mediated recycling of iron was markedly reduced, thereby resulting in systemic iron accumulation. However, IL-6-/- mice displayed increased Hepcidin expression via p-ERK activation and a significant reduction in duodenal iron uptake.

Conclusion: This study highlighted the critical role of IL-6 in iron homeostasis both in physiological and pathological situations.