生物学最新文献

Erianin, a natural bibenzyl compound, has recently garnered attention owing to its diverse biological activities. In the present study, we investigated the effects of Erianin on adipocyte differentiation, lipid metabolism, and mitochondrial respiration in murine 3T3-L1 cells. Cytotoxicity assays indicated that Erianin exhibited low toxicity towards preadipocytes at concentrations up to 200 μM. Treatment with 20 μM Erianin completely inhibited the differentiation of 3T3-L1 preadipocytes into mature adipocytes and reduced lipid droplets. Western blot analysis revealed that Erianin attenuated Akt and p38 MAPK signalling without inducing apoptosis, suppressed the expression of key pro-adipogenic transcription factors, C/EBPα and PPARγ during the early stages of differentiation. This suppression was accompanied by the downregulation of lipogenic enzymes, including acetyl-CoA carboxylase 1 (ACC1), fatty acid synthase (FASN), pyruvate carboxylase (PC) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). While early-stage differentiation was robustly inhibited, higher concentrations (≥25 μM) were required to suppress terminal differentiation of immature adipocytes. This late-stage inhibition was accompanied by decreased expression of PPARγ, PC, and HMGCR, with minimal effects on ACC1 and FASN, suggesting a more modest role for Erianin in terminal adipogenesis. Assessment of mitochondrial metabolism of 3T3-L1 cells following 24-hour treatment of Erianin showed that it modestly impaired ATP-linked respiration, maximal respiration, spare respiratory capacity and intracellular ATP levels while basal respiration was unaffected. Collectively, these findings indicated that Erianin predominantly targets early adipogenic differentiation and mitochondrial bioenergetics.

Streptococcus suis is a major cause of sepsis and meningitis in pigs, and zoonosis through the emergence of disease-associated lineages. The ability of S. suis to adapt and survive in host environments, such as blood and cerebrospinal fluid (CSF), is important for pathogenesis. Here, we used Transposon Sequencing (Tn-seq) coupled with Nanopore sequencing to identify conditionally essential genes (CEGs) for the growth of S. suis P1/7 in active porcine serum (APS) and CSF derived from choroid plexus organoids. To our knowledge, this is the first successful application of ONT to Tn-library screening, enabling rapid local runs and a publicly available analysis pipeline. Through comparative fitness analyses, we identified 33 CEGs that support growth in APS and 25 CEGs in CSF. These genes highlight the importance of pathways related to amino acid transport, nucleotide metabolism, and cell envelope integrity. Notably, the LiaFSR regulatory system and multiple ABC transporters were important for proliferation. We also identified several genes of unknown function as essential for growth, pointing to previously unrecognized genetic factors involved in S. suis adaptation during infection. These findings provide new insights into the genetic requirements for S. suis survival in host-like environments and a deeper understanding of its ability to adapt to distinct physiological niches.

Porcine enteric coronaviruses, including porcine deltacoronavirus (PDCoV), porcine epidemic diarrhea virus (PEDV), swine acute diarrhea syndrome coronavirus (SADS-CoV), and transmissible gastroenteritis coronavirus (TGEV), can cause acute diarrhea, vomiting, dehydration, and high mortality in suckling piglets. Recent studies revealing human PDCoV infections and the potential of SADS-CoV to penetrate human cell lines have heightened apprehensions about the zoonotic transmission risks of these viruses. While heparan sulfate (HS) serves as a receptor in PDCoV binding, the key host genes involved in HS biogenesis and the specific molecular mechanisms underlying this process have not been fully examined. Enzymes involved in HS biosynthesis, including SLC35B2, EXT1, and NDST1, were identified as critical host factors via the use of CRISPR-Cas9 knockout cells. Moreover, inhibition assays using heparin sodium, a competitive HS mimic, demonstrated dose-dependent reductions in PDCoV infection in vitro. Additionally, mitoxantrone, an HS-binding drug, reduced PDCoV infection. Furthermore, HS was confirmed to facilitate the entry of other porcine enteric coronaviruses (SeCoVs), including PEDV, SADS-CoV, and TGEV, underscoring the conserved role of HS in CoV pathogenesis. These insights contribute to the understanding of porcine coronavirus-host interactions and support the development of innovative antiviral interventions.

We employed single-cell RNA sequencing (scRNA-seq) of fine needle aspirates (FNAs) to describe the cells and communication networks characterizing granulomatous lymph nodes of TB patients. We uniformly identified several cell types known to characterize granulomas. Overall, we found the T cell cluster to be the most abundant. Other cell clusters that were uniformly detected, but that varied in abundance amongst the individual patient samples, were the B cell, plasma cell and macrophage/dendritic and NK cell clusters. When we combined all our scRNA-seq data from our current 19 patients, we distinguished T, B, macrophage, dendritic and plasma cell subclusters. The sizes of these subclusters also varied dramatically amongst the individual patients. In comparing FNA composition we noted trends in which T cell populations were negatively correlated with NK cell populations and with macrophage/dendritic cell populations. In addition, we discovered that the scRNA-seq pipeline detects Mtb RNA transcripts and associates them with their host cell's transcriptome, thus identifying individual infected cells. The number of infected cells also varies in abundance amongst the patient samples. CellChat analysis identified predominating signaling pathways amongst the cells comprising the various granulomatous lymph nodes, identifying several pathways involved in immune cell maturation, migration and adhesion.

Methicillin-resistant Staphylococcus aureus (MRSA) remains a major therapeutic challenge and poses a significant global health threat. Developing adjuvants to enhance the efficacy of existing antibiotics represents a promising strategy to address this issue. In this study, we evaluated auranofin as an adjuvant to potentiate the activity of linezolid against MRSA. Auranofin significantly increased MRSA susceptibility to linezolid, promoted intracellular linezolid accumulation, and suppressed the emergence of MRSA resistance to linezolid. Mechanistically, auranofin inhibited the Trx/TrxR system, inducing redox imbalance and reactive oxygen species (ROS) accumulation, which triggers DNA damage and transcriptional dysregulation. Auranofin synergized with linezolid to achieve dual inhibition of MRSA protein synthesis. Furthermore, auranofin downregulated the global regulator sarA, impaired SarA DNA-binding activity, and enhanced SarA phosphorylation, thereby attenuating SarA-mediated virulence factors (eg, adhesins and toxins) and biofilm formation. Importantly, auranofin fully restored anti-MRSA activity of linezolid in both Galleria mellonella and murine bacteremia models. Collectively, these findings identify auranofin as a promising adjuvant to linezolid and highlight its potential to improve therapeutic outcomes against invasive MRSA infections.

Porcine deltacoronavirus (PDCoV) is an emerging enteric coronavirus that causes acute diarrhea and high mortality in neonatal piglets. In this study, we isolated and characterized a novel PDCoV strain, CH/HLJ/20, from diarrheic piglets in Northeast China. Full-length genome sequencing and phylogenetic analysis revealed that CH/HLJ/20 belongs to the Chinese lineage but harbors distinct recombination signals within the S gene, with Korea/DH1/2017 and CHN/Tianjin/2016 identified as putative parental strains. Comparative analysis identified two unique amino acid substitutions (Q10H and N98K) within the receptor-binding domain (RBD) of the spike protein. Structural modeling and molecular docking revealed that the CH/HLJ/20 RBD retains binding compatibility with aminopeptidase N (APN) receptors from multiple species, including pig, human, dog, cat, and chicken, indicating broad host receptor adaptability. Docking simulations using sequence-reverted mutants suggested that these substitutions may slightly attenuate receptor-binding affinity, potentially influencing cross-species transmission. Notably, the N98K residue has been identified as a critical site involved in both APN binding and neutralizing epitopes, therefore, its mutation may influence receptor engagement and antigenic properties. In vivo virus infection experiments demonstrated that CH/HLJ/20 caused rapid disease onset and 100% mortality in neonatal piglets, with severe villous atrophy and high intestinal viral loads. These findings highlight the evolving genomic diversity, pathogenicity, and zoonotic potential of PDCoV, underscoring the critical importance of continuous viral surveillance, timely isolation and functional characterization of emerging strains, and enhanced understanding of cross-species transmission mechanisms to inform effective disease control and prevention strategies.

Pseudomonas aeruginosa is the leading cause of death in cystic fibrosis (CF) patients, yet the genetic mechanisms driving its fitness in the host remain poorly defined. Previously collected transcriptomic data of clinical samples showed that expression of the gene PA14_RS04555 (sirB2) is stimulated in the CF lung environment. In this work, we show that sirB2 is regulated by the global transcriptional regulators Vfr and AmrZ. Loss of sirB2 markedly enhanced P. aeruginosa pathogenicity, increasing virulence in Galleria mellonella, and promoting bacterial translocation and biofilm formation in a differentiated airway epithelial infection model. Deletion of sirB2 triggered the emergence of biofilm-proficient rugose small colony variants (RSCVs), driven by elevated c-di-GMP and increased Pel polysaccharide production when cultures were grown in static conditions. The RSCV phenotype depends on suppressor mutations in the wsp operon, possibly as a response to redox imbalance caused by the lack of sirB2 under oxygen-limited conditions. Indeed, the sirB2 mutant exhibited impaired fitness during anaerobic respiration when nitrate was the sole electron acceptor, in a manner independent of the ubiquinone pool. Our findings show that sirB2 inactivation promotes RSCV emergence and identify sirB2 as a novel genetic determinant of metabolic fitness under host-relevant conditions, thereby underscoring the role of redox balance in chronic CF infections.

DDX17 (DEAD-box RNA helicase 17) is an essential RNA helicase and regulatory ATPase in host cells, extensively involved in various cellular processes during viral infections, such as RNA splicing, transcriptional regulation, and post-transcriptional modification. DDX17 exhibits dual functionality in viral infections: it enhances the stability, packaging, and replication of viral RNA through interactions with viral ribonucleoprotein complexes, as evidenced in infections caused by influenza viruses and Hantaan virus (HTNV). Conversely, DDX17 can inhibit viral proliferation by disrupting viral RNA metabolism, as observed in hepatitis B virus (HBV) and Epstein-Barr virus (EBV) infections, where it suppresses replication by modulating viral RNA decapping and degradation. The dual role of DDX17 provides novel insights into host-virus interactions while also highlighting its significant potential as an antiviral therapeutic target. These findings are expected to establish a theoretical foundation for related research and offer valuable references for developing novel antiviral strategies.

Sindbis virus (SINV), a widely distributed alphavirus, is both a foundational model for viral replication studies and an underrecognized human pathogen. Despite its typically mild presentation, SINV can lead to prolonged joint pain and, in rare cases, neurological complications. This review explores SINV's molecular biology and clinical manifestations, particularly its role in causing Sindbis Fever - a self-limiting but potentially chronic arthritic disease. Molecular insights reveal mechanisms of immune evasion, neurovirulence, and persistent infection, highlighting SINV's potential for broader public health impact, especially under changing climatic conditions. This review also identifies key virulence determinants and discusses the virus's utility as a model for studying alphaviral encephalitis. Continued research is essential to better understand SINV pathogenesis and to prepare for potential outbreaks.