生物学最新文献

In response to stress, cells undergo gene expression reprogramming to cope with external stimuli. Cells utilize a conserved stress response mechanism called global downregulation of translation, leading to the storage of translationally repressed mRNAs in RNA granules. During oxidative stress induced by H2O2, genes responsible for combating oxidative stress, such as catalases, are strongly induced. However, the post-transcriptional regulatory events affecting these genes during H2O2 stress are not well-explored. Scd6, an RGG-motif-containing protein in yeast, acts as a translational repressor through its interaction with eIF4G1. This study identifies the role of Scd6 in oxidative stress response by regulating cytoplasmic catalase T1 (CTT1). We observe that peroxide stress induces the assembly of Scd6 puncta, which do not colocalize with P-bodies or stress granules. Scd6 overexpression increased sensitivity, while deletion enhanced tolerance to H2O2 treatment. Increased ROS accumulation and decreased Ctt1 protein levels were observed upon Scd6 overexpression due to translation repression of CTT1 mRNA. CTT1 mRNA interacts with Scd6. smFISH analysis and RNA immunoprecipitation studies reveal that localization of Scd6 to puncta upon peroxide stress reduces its interaction with CTT1 mRNA, allowing derepression. The role of Scd6 in peroxide stress response is conserved since the human homolog LSm14A also localizes to puncta upon H2O2 stress, and its overexpression reduces survival in response to peroxide stress. Overall, this study identifies a unique example of translation regulation whereby stress-induced localization of the translation repressor protein to puncta leads to derepression of the target mRNA.

Escherichia coli is a key pathogen in extraintestinal infections, including prosthetic joint infections (PJIs), which account for approximately 9% of all such cases. Despite its clinical relevance, the molecular pathogenesis of E. coli in PJIs remains poorly defined. This study investigated the clinical, phylogenetic, and virulence profiles of E. coli isolates from PJIs and compared them to isolates from bacteremic urinary tract infections (UTIs). A total of 13 isolates from each infection type were analyzed using whole-genome sequencing (WGS) to determine phylogenetic relationships, sequence types, and the presence of virulence genes. PJI isolates exhibited substantial genetic diversity, encompassing 10 sequence types, with ST131 and ST69 being the most frequent. Phylogroup B2 predominated (53.9%) among PJI isolates. Adhesion and biofilm-related genes, such as fimG/H, csg, and epaO, were highly prevalent in PJI isolates, supporting the role of biofilm formation in pathogenesis. Conversely, toxin-associated genes (e.g. pic and senB) were more frequently detected in UTI isolates. Notably, the matA gene, linked to biofilm enhancement, was significantly associated with microbiological failure in PJIs (75% vs. 0%, p = 0.02). Phylogenetic analyses revealed no clustering by infection type, suggesting that ExPEC strains share a versatile genomic background, enabling them to adapt to different infection environments. The study highlights the critical role of biofilm formation in PJIs and underscores the genetic adaptability of ExPEC strains, which lack distinct virulence profiles specific to PJIs. However, the small number of PJI isolates limits the generalizability of these findings and warrants confirmation in larger cohorts.

In the context of COVID-19, macrophages are primarily responsible for sensing and responding to the virus, significantly influencing disease outcomes. They are involved in early pathogen recognition, immune activation, and tissue repair. Heterogeneity and phenotypic plasticity of macrophages are dynamically shaped by microenvironmental cues, including metabolites, hypoxia, and pathogen-derived signals. Notably, emerging evidence underscores that cellular metabolism, particularly in macrophages, dictates immune responses to viral infection. This metabolic-immune crosstalk critically determines COVID-19 severity, ranging from viral clearance to hyperinflammation or fibrosis. In this review, we systematically dissect how cell-intrinsic metabolic nodes and extrinsic factors modulate macrophage effector functions, while illustrating the complications associated with macrophage metabolic dysregulation in SARS-CoV-2 infection. These mechanistic insights provide a rational foundation for therapeutic strategies targeting macrophage metabolism to rebalance immune responses and mitigate COVID-19 complications.

Tuberculosis, caused by Mycobacterium tuberculosis, is an infectious disease linked to high mortality and can stay in the host cell longer when inactive. Multiple factors are linked to disease prognosis, including microRNAs. It is a diminutive single-stranded RNA that regulates the expression of its target mRNAs. It consists of a brief nucleotide sequence, often 19-25 nucleotides in length, of non-coding RNA. It is also essential for early embryonic development, invasion, cell migration, apoptosis, and cell death. The review aims to analyse the transcriptome characteristics of various miRNAs in the tuberculosis prognosis. However, miR-155, miR-29, circ-miRNA, and lncRNAs regulate gene expression. In TB patients' serum exosomes, miRNA-146 expression was noticeably higher than in healthy individuals. Drug-resistant tuberculosis was related to miR-548 m, miR-631, miR-328-3p, and miR-let-7e-5p, as well as let-7b-5p, miR-30a-3p, IL-27, and CXCL9/10/11 in TB patients' lesion tissue and peripheral blood. Therefore, further miRNA research will focus on TB progression.

Objectives: Acid-sensing ion channel 1a (ASIC1a) functions as an extracellular acid sensor, with its activation frequently associated with age-related diseases. We aim to investigate the expression pattern of ASIC1a in the ferroptosis of degenerated nucleus pulposus (NP) tissues and NP cells (NPCs), and explore whether ASIC1a-mediated calcium influx regulates ferroptosis in NPCs through the calcium/calmodulin pathway during intervertebral disc degeneration (IVDD).

Methods: We use NP tissues, NPCs, and Transcriptome sequencing to investigate the effects and mechanism of ASIC1a in ferroptosis during the progression of IVDD.

Results: Elevated expression of ASIC1a was associated with the progression of ferroptosis in human degenerated NP tissues. Meanwhile, the expression of ASIC1a remarkably increased as acid-induced ferroptosis progressed in human NPCs. Besides, transcriptomic analysis identified that inhibition of ASIC1a attenuates ECM degradation and ferroptosis. We then confirmed the overexpression of ASIC1a promoted the progression of ferroptosis and ECM degradation in human NPCs in vitro. Moreover, the ferroptosis of NPCs induced by ASIC1a overexpression was ameliorated by the treatment of BAPTA-AM (the intracellular calcium chelator) or calmidazolium (the calmodulin antagonist). ASIC1a mediated acid-induced ferroptosis via calcium/calmodulin signaling in human NPCs. The in vivo study further indicated that the inhibition of ASIC1a activation ameliorated the IVDD by suppressing ferroptosis in the rat model.

Conclusion: This study demonstrated that ASIC1a increased as ferroptosis progressed in human NP tissues and human NPCs. The acid-induced ASIC1a upregulation caused increased calcium levels and contributed to the ferroptosis in NPCs partially mediated by calcium/calmodulin signaling.

Camellia oleifera is an important economic woody oil plant in many Asian countries, and the anthracnose caused by Colletotrichum fructicola is prevalent in its cultivation regions, causing significant losses annually. We previously found that CfGcn5-mediated H3 acetylation governs virulence of C. fructicola. To further elucidate the regulatory mechanism of CfGcn5, we carried out mass spectrometry analysis for CfGcn5-interacting proteins and identified CfAda3 protein for functional analysis. We found that CfAda3 was mainly localized in nucleus and cooperated with CfGcn5 to acetylate H3K18 for global gene transcription. Targeted gene deletion revealed that CfAda3 is involved in growth and conidiation. Similar to ΔCfgcn5 mutant, the ΔCfada3 mutant is defective in conidial germination, appressorial formation, autophagy, and in the response to environmental stresses. These combined effects result in its non-virulence on C. oleifera. In addition, we provided evidence showing that both NLS region and ADA3 domain are required for the localization and function of CfAda3. Moreover, we indicated that the interaction with CfGcn5 is essential but not sufficient for the normal localization and full function of CfAda3. Taken together, our studies not only illustrate the prominent roles of CfAda3 in growth, development, and virulence but also highlight how CfAda3 functions together with CfGcn5 in C. fructicola.

Peronophythora litchii is an oomycete pathogen responsible for litchi downy blight, a significant threat to global litchi production. Autophagy, a conserved degradation pathway crucial for the growth, development, and pathogenicity of phytopathogenic organisms, remains an area of active investigation. In this study, we characterized the function of the Atg26 homolog PlAtg26b in P. litchii. Using the CRISPR/Cas9 genome editing system, we generated PlATG26b knockout mutants and determined that PlAtg26b localizes to mitochondria under stress conditions. Although deletion of PlATG26b did not impair selective autophagy, it markedly reduced Atg8-PE synthesis, vegetative hyphal growth, asexual and sexual reproduction, and zoospore release. Furthermore, PlATG26b-deficient mutants exhibited significantly reduced virulence on litchi fruits and leaves. Collectively, our findings demonstrate that PlAtg26b plays a pivotal role in the biological development and pathogenicity of P. litchii.

Transfer messenger RNA (tmRNA), a key component of the trans-translation system, plays an essential role on the virulence of pathogenic bacteria. However, the upstream regulatory mechanisms that regulate tmRNA expression remain largely unexplored. In this study, AraC superfamily regulator (AsfR) was found to directly interact with the promoter of ssrA gene, which encodes tmRNA. Co-transformation of the reporter construct, consisting of tmRNA promoter fused to enhanced green fluorescent protein (eGFP), alongside an AsfR expression vector, resulted in increased fluorescence, indicating that AsfR positively regulates mRNA expression. Consistently, the transcription level of tmRNA was significantly decreased in ΔasfR compared with WT of A. veronii by quantitative real-time PCR (RT-qPCR) analyses. The ΔasfR and ΔtmRNA mutants exhibited significantly reduced motility and biofilm formation. Reduced transcription of the flagellar gene fliE in both mutants suggests that the AsfR/tmRNA axis may regulate these processes via fliE. Furthermore, deletion of asfR and tmRNA impairs oxidant resistance and pathogenicity, resulting in growth inhibition in A. veronii. This study elucidates the regulatory role of the AsfR-tmRNA pathway in flagellar motility, biofilm formation, and antioxidant capacity, all of which contribute to bacterial virulence and provide potential targets for the treatment of bacterial infections.

Microsporidia, ubiquitous obligate intracellular parasites infecting a wide range of hosts from humans to economically vital animals, employ transovarial transmission (TOT) as their primary vertical transmission mode. Despite its significance, the mechanisms underpinning microsporidian TOT have remained elusive. This study comparatively analyzed the TOT in two distinct systems: Nosema pernyi infecting wild tussah Antheraea pernyi, and Nosema bombycis infecting domestic silkworms Bombyx mori and crop pests Spodoptera litura and Helicoverpa armigera. Our findings reveal that both parasites share a conserved invasion sequence targeting ovariole sheath cells, follicular cells, nurse cells, and ultimately oocytes. Notably, infection of follicular and nurse cells consistently precedes oocyte invasion, suggesting a strategic utilization of these cells for efficient transmission. Contrasting patterns were observed between the two parasites: while N. bombycis exhibits lower infection rates and produces mature spores in both oocytes and nurse cells, N. pernyi displays higher parasite loads with proliferative stages predominant throughout infection. A critical innovation emerges from our RNA interference experiments, where knockdown of host vitellogenin (Vg) significantly reduced microsporidian loads, identifying Vg as a conserved molecular facilitator in TOT. These findings not only elucidate the evolutionary conservation of vertical transmission mechanisms among microsporidia but also pinpoint Vg as a promising target for intervention against these pathogens. This research advances our understanding of vertical transmission of fungal parasites and offers novel avenues for disease control.

The transplantation of neural progenitor cells derived from induced pluripotent stem cells (iPSCs) has therapeutic potential for the treatment of neurological diseases. However, the functional integration of transplanted iPSC-derived neurons into host neural networks remains controversial. Optogenetic and chemogenetic tools offer the means to assess such integration. However, constructing modifiable iPSC-derived neurons requires efficient gene editing. Here, we used CRISPR/Cas9 (targeting the AAVS1 safe harbor) and PiggyBac transposon systems to insert optogenetic and chemogenetic receptors (ChR2/hM4Di) into human iPSCs. While both systems successfully integrated genes into the genomes of HEK293T cells and iPSCs, receptor expression was detected only in HEK293T cells. Bisulfite sequencing revealed extensive methylation of the TRE3G BI promoter (95.3-98.2%) in iPSCs, in contrast to low methylation (5.9%) in HEK293T cells. For PiggyBac, the methylation of CMV/EF1α promoters in iPSCs exhibited integration site-dependent variability (0-95.2%). Notably, even hypomethylated clones failed to show gene expression, suggesting that additional regulatory mechanisms, such as histone modifications or chromatin remodeling, may contribute to transcriptional silencing. Differentiation into neural stem cells does not reverse methylation nor restore protein expression. Our findings demonstrate that the CRISPR/Cas9 and PiggyBac systems enable the integration of optochemical receptor genes into iPSCs. However, promoter methylation or other epigenetic and non-epigenetic gene-silencing mechanisms could pose barriers to efficient protein expression from the integrated transgene in iPSCs.