Science China Life Sciences最新文献

Botrytis cinerea and Sclerotinia sclerotiorum, two closely related necrotrophic fungal pathogens, secrete large amounts of oxalic acid (OA) into the plant apoplast to suppress host immunity, though the underlying mechanisms remain unclear. Here, we demonstrate that OA-induced virulence in Arabidopsis thaliana depends on CERK1, a coreceptor critical for fungal chitin-triggered immunity. Mass spectrometry analysis identified a site-specific deamidation at three asparagine residues (Asn70, Asn205, and Asn216) in CERK1's extracellular domain. Among these, only the deamidation-deficient N70A mutation impaired chitin-induced MPK4 activation, a process proven essential for plant resistance against both pathogens. OA treatment phenocopied the N70A mutation by suppressing chitin-elicited MPK4 activation. Consistently, acidic conditions mimicking the OA-acidified infection niche directly inhibited Asn70 deamidation. Notably, the N70A mutation of CERK1 triggered EDS1-dependent autoimmunity associated with senescence, which was mutually suppressed by the previously reported autoimmunity induced by the cerk1-4 (L124F) mutation. Our findings reveal that fungal OA dampens chitin-triggered immunity by exploiting pH-dependent inhibition of CERK1 Asn70 deamidation, establishing a mechanistic link between pathogen-derived acidity, post-translational modification of host immune receptors, and suppression of host immunity. Our data also suggest that the functional integrity of CERK1 is monitored by an endogenous immune surveillance system.

Dynamic spatiotemporal regulation of genetic information flow underlies all cellular processes, yet our current understanding still largely relies on static measurements. Real-time, dynamic recording of genetic information flow along the central dogma is therefore essential to reveal both the processes and molecular mechanisms at play. Recent advances in live-cell imaging, single-molecule fluorescence, super-resolution microscopy, gene editing, and computational analysis have greatly enhanced our ability to visualize genetic information flow across spatial and temporal scales. This review synthesizes the historical development, underlying principles, and technical implementations of dynamic DNA and RNA imaging approaches, comparing their capabilities, limitations, and optimal applications. We highlight key biological insights afforded by these methods-including chromatin dynamics, transcriptional bursting, RNA processing and transport, and localized translation-and discuss how multimodal integration with orthogonal biochemical and genomic techniques strengthens mechanistic interpretation. Finally, we identify current challenges and necessary breakthroughs. A deeper understanding of the fundamental principles governing dynamic genetic information flow could pave the way for deciphering the operational principles of non-equilibrium complex systems, thereby unlocking the organizational logic of complex living systems.

Increasing evidence has established the gut microbiota as a central driver of BA modification. Gut microbiota is involved in extensive BA modifications through various processes, including deconjugation, 7α-dehydroxylation, oxidation, epimerization, as well as emerging pathways like re-conjugation and succinylation. This review examined these microbial transformations, delineating the specific microbial species and metabolic enzymes involved. Focusing on the association between microbial modified BAs and human physiology, we investigated the existing therapeutic strategies targeting the microbiota-BA axis. These strategies can be categorized into two main domains: regulation of microbial composition (e.g., probiotics, FMT) and BA modifications (e.g., enzyme inhibitors). BA receptors, including canonical receptors (FXR, TGR5) and non-canonical (PXR, CAR, VDR, S1PR2, RORγt) receptors, further mediated the effects of BAs on various physiological functions, such as BA homeostasis, intestinal barrier integrity, and immune responses. We also summarized emerging tools, such as reverse metabolomics, source tracking algorithms, and organoid models, which facilitated knowledge discovery of novel BA modifications and their biological roles. Collectively, this review offers a comprehensive perspective on microbial BA modifications and underscores the significant potential of the gut microbiota-BA axis for disease management.

Obesity is a major pathological factor that induces insulin resistance and consequent type 2 diabetes through multiple mechanisms. Inactivation of the insulin receptor (INSR) contributes to the development of insulin resistance, whose protein level is down-regulated in obesity through as yet-undefined mechanisms. Here we show that the E3-ligase TRAF6 is a critical regulator of INSR maturation, whose inactivation prevents palmitic acid- or high-fat diet-induced diminution of the INSR. Consequently, genetic inactivation of TRAF6 enhances insulin signaling that further increases muscle glucose uptake and inhibits hepatic gluconeogenesis. TRAF6 inactivation increases the proprotein convertase FURIN that controls the processing of pro-INSR to mature INSR. Mechanistically, TRAF6 associates with the Golgi apparatus, where it ubiquitinates the cytosolic tail of FURIN, leading to its lysosomal degradation. This TRAF6-FURIN axis also regulates cholesterol metabolism via PCSK9 processing in the circulation. Collectively, our results reveal a critical role of TRAF6 in regulating proprotein processing and have therapeutic implications for metabolic control.

Zika virus (ZIKV) has emerged as a global health priority due to its association with severe congenital abnormalities, including microcephaly and neonatal mortality in infants born to infected mothers. In adults, ZIKV infection is epidemiologically linked to Guillain-Barré Syndrome (GBS). These clinical manifestations prompted the World Health Organization (WHO) to declare ZIKV a Public Health Emergency of International Concern (PHEIC). The antibody-dependent enhancement (ADE) phenomenon further complicates vaccine development and therapeutic strategies. While substantial progress has been made in elucidating ZIKV biology through multidisciplinary approaches, no vaccines or therapies have been clinically approved. This review examines ZIKV-associated risks by analyzing transmission dynamics, viral architecture, and cellular entry mechanisms, and proposes evidence-based prevention and management strategies.