Science China Life Sciences最新文献

Endothelial-to-mesenchymal transition (EndMT) constitutes a transdifferentiation phenomenon during which endothelial cells (ECs) progressively acquire mesenchymal traits. Mounting evidence has established that EndMT holds a central and indispensable position in angiogenesis. Partial EndMT, an intermediate stage of ECs within the EndMT cascade, is intimately regulated by numerous enzymes. Among them, sirtuin 6 (SIRT6), a member of the sirtuin family of NAD⁺-dependent deacetylases, has been reported to be involved in the repair of cardiovascular injury; however, the SIRT6-mediated molecular mechanism inpartial EndMT has hitherto remained largely unelucidated. In the present study, SIRT6 can regulate EndMT elicited by TGF-β and maintain a partial EndMT state. Subsequently, through conducting proteomic data analysis and performing verification using molecular biology techniques, we found that SIRT6 promoted EndMT via the upregulation of RREB1/Snail; simultaneously, SIRT6 directly targeted Sp1 to augment the expression of STC1 which in turn acetylated Smad7 to inhibit phosphorylation of Smad2/3, decreasing the formation of phosphorylated Smad2/3 and Smad4 to curtail excessive EndMT. Finally, in the model of murine hindlimb ischemia, the overexpression of Sirt6 could increase capillary density and promote the recovery of blood flow, effects that were partially abrogated by siRREB1 or recombinant STC1. These results of in vivo animal experiments are consistent with the previous conclusions of in vitro cell experiments. Collectively, our findings demonstrated that SIRT6 orchestrated a beneficial balance of the EndMT response to promote angiogenesis and mitigate ischemic injury, thereby providing a potential therapeutic target related to EndMT for ischemic diseases.

Accurate genome assembly from metagenomic sequencing data remains challenging, particularly in mixed infections involving multiple pathogens, due to data complexity and contaminant sequences. Here, we present GMW (Genomic Microbe-Wise), a novel computational tool that improves pathogen genome assembly accuracy and enhances contaminant removal capabilities by simplifying the post-assembly graph. GMW leverages community detection algorithms, sequence similarity analysis, and coverage patterns to resolve strain mixtures and improve assembly accuracy. Using datasets of influenza A virus subtypes, we demonstrate GMW's ability to disentangle mixed infections and reconstruct complete viral genomes with high precision. Additionally, GMW outperforms traditional sequence similarity methods in classifying target contigs from contaminants. This tool also provides interactive visualization modules to streamline the inspection of assembly outputs, including simplified representations of complex assembly graphs. By enhancing assembly quality and contamination filtering, GMW emerges as a versatile solution for applications in clinical diagnostics, microbial ecology, and pathogen surveillance.

Although the coupled blood and lymphatic vascular systems are crucial for mammalian homeostasis, they remain understudied in skeletal contexts. The blood vessel system orchestrates oxygen delivery and waste clearance, while the lymphatic network dynamically regulates interstitial fluid balance and immune surveillance. Their embryonic codevelopment allows for synergistic microcirculatory control. Recently, increasing evidence has highlighted the critical role of the blood and lymphatic vascular networks in bone tissue repair. This network effectively promotes and accelerates bone regeneration by spatiotemporally regulating inflammation, bidirectional molecular trafficking, and the secretion of angiocrine/lymphangiocrine factors. Current reviews predominantly address the blood and lymphatic vascular systems in isolation, thereby failing to provide system-level insights into their coordinated regulation during osseous regeneration. This review systematically elaborates on the relationship of the blood and lymphatic vascular systems in bone repair. Furthermore, we describe current tissue engineering studies targeting the blood and lymphatic vascular networks to accelerate bone injury repair and identify critical gaps in this research field. Thus, we aimed to construct a theoretical framework for the coregulation of blood and lymphatic vascular systems in the context of bone injury repair.

Surrogate reproduction offers a promising biotechnological approach for accelerating aquaculture breeding. Grass carp (Ctenopharyngodon idellus), a key freshwater species, faces significant constraints in breeding due to its prolonged sexual maturation of 5 years and huge body size. Here, we establish an ultra-fast breeding strategy to generate all-female grass carp within six months via surrogate production in tiny laboratory fish, zebrafish (Danio rerio). We identify and isolate female GSCs from juvenile ovaries of 3-month-old grass carp. Three months after transplantation into zebrafish larvae, the donor-derived female GSCs undergo ultra-fast spermatogenesis and differentiate into functional grass carp sperm carrying X chromosomes. Fertilization of wild-type grass carp eggs with this sperm yields all-female offspring. This work demonstrates that fish female GSCs with XX chromosomes can differentiate into functional sperm in a short time in zebrafish gonadal somatic niche, opening a new avenue for precision breeding and sex control in aquaculture species.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a highly prevalent and progressive liver condition that is increasingly recognized for its systemic cardiometabolic impacts. MASLD increases the risk of cardiovascular and renal complications mainly through shared mechanisms, such as insulin resistance, low-grade inflammation, oxidative stress, atherogenic dyslipidemia, and a procoagulant state. Although these interrelated processes drive multisystem damage, MASLD remains often underdiagnosed in cardiology and nephrology settings and is excluded from the recently proposed framework for cardiovascular-kidney-metabolic (CKM) syndrome. Increasing recognition of the bidirectional interconnections between MASLD, cardiovascular disease, and chronic kidney disease suggests the need for an expanded cardiovascular-kidney-liver-metabolic (CKLM) model. Integrating MASLD into this framework supports earlier identification using non-invasive screening tools, encourages coordinated multidisciplinary care, and highlights the potential of pharmacotherapies, such as glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter 2 inhibitors, with cross-organ benefits. This review aims to reframe MASLD within this broader multisystem context and explore the implications of its integration into an expanded CKLM framework, with the goal of improving clinical outcomes and addressing multimorbidity.