Science China Life Sciences最新文献

{"title":"New insights shed light on the enigma of genetic diversity and species complexity.","authors":"Zuobin Zhu, Conghui Han, Shi Huang","doi":"10.1007/s11427-023-2610-2","DOIUrl":"10.1007/s11427-023-2610-2","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2774-2776"},"PeriodicalIF":8.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142018419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid nanoparticle-mediated base-editing of the Hao1 gene achieves sustainable primary hyperoxaluria type 1 therapy in rats.","authors":"Dexin Zhang, Rui Zheng, Zhoutong Chen, Liren Wang, Xi Chen, Lei Yang, Yanan Huo, Shuming Yin, Dan Zhang, Jiaxin Huang, Xingang Cui, Dali Li, Hongquan Geng","doi":"10.1007/s11427-024-2697-3","DOIUrl":"10.1007/s11427-024-2697-3","url":null,"abstract":"<p><p>Primary hyperoxaluria type 1 (PH1) is a severe hereditary disease, leading to the accumulation of oxalate in multiple organs, particularly the kidney. Hydroxyacid oxidase 1 (HAO1), a pivotal gene involved in oxalate production, is an approved target for the treatment of PH1. In this study, we demonstrated the discovery of several novel therapeutic sites of the Hao1 gene and the efficient editing of Hao1 c.290-2 A in vivo with lipid nanoparticles (LNP) delivered adenine base editing (ABE) mRNA. A single infusion of LNP-ABE resulted in a near-complete knockout of Hao1 in the liver, leading to the sustainable normalization of urinary oxalate (for at least 6 months) and complete rescue of the patho-physiology in PH1 rats. Additionally, a significant correlation between Hao1 editing efficiency and urinary oxalate levels was observed and over 60% Hao1 editing efficiency was required to achieve the normalization of urinary oxalate in PH1 rats. These findings suggest that the LNP-mediated base-editing of Hao1 c.290-2 A is an efficient and safe approach to PH1 therapy, highlighting its potential utility in clinical settings.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2575-2586"},"PeriodicalIF":8.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted genome duplications by amplification editing (AE).","authors":"Chao Sun, Caixia Gao","doi":"10.1007/s11427-024-2712-5","DOIUrl":"10.1007/s11427-024-2712-5","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2786-2788"},"PeriodicalIF":8.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bactericidal ability of target acidic phospholipids and phagocytosis of CDC42 GTPase-mediated cytoskeletal rearrangement underlie functional conservation of CXCL12 in vertebrates.","authors":"Yanqi Zhang, Ning Xia, Yazhen Hu, Wentao Zhu, Chunrong Yang, Jianguo Su","doi":"10.1007/s11427-023-2625-7","DOIUrl":"10.1007/s11427-023-2625-7","url":null,"abstract":"<p><p>Chemokine CXCL12 plays a crucial role in both direct bactericidal activity and phagocytosis in humans. However, the mechanisms and evolutionary functions of these processes in vertebrates remain largely unknown. In this study, we found that the direct bactericidal activity of CXCL12 is highly conserved across various vertebrate lineages, including Arctic lamprey (Lampetra japonica), Basking shark (Cetorhinus maximus), grass carp (Ctenopharyngodon idella), Western clawed frog (Xenopus tropicalis), Green anole (Anolis carolinensis), chicken (Gallus gallus), and human (Homo sapiens). CXCL12 also has been shown to promote phagocytosis in lower and higher vertebrates. We then employed C. idella CXCL12a (CiCXCL12a) as a model to further investigate its immune functions and underlying mechanisms. CiCXCL12a exerts direct broad-spectrum antibacterial activity by targeting bacterial acidic phospholipids, resulting in bacterial cell membrane perforation, and eventual lysis. Monocytes/macrophages are attracted to the infection sites for phagocytosis through the rapid production of CiCXCL12a during bacterial infection. CiCXCL12a induces CDC42 and CDC42 GTPase activation, which in turn mediates F-actin polymerization and cytoskeletal rearrangement. The interaction between F-actin and Aeromonas hydrophila facilitates bacterial internalization into monocytes/macrophages. Additionally, A. hydrophila is colocalized within early endosomes, late endosomes and lysosomes, ultimately degrading within phagolysosomes. CiCXCL12a also activates PI3K-AKT, JAK-STAT5 and MAPK-ERK signaling pathways. Notably, only the PI3K-AKT signaling pathway inhibits LPS-induced monocyte/macrophage apoptosis. Thus, CiCXCL12a plays key roles in reducing tissue bacterial loads, attenuating organ injury, and decreasing mortality rates. Altogether, our findings elucidate the conserved mechanisms underlying CXCL12-mediated bactericidal activity and phagocytosis, providing novel perspectives into the immune functions of CXCL12 in vertebrates.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2713-2729"},"PeriodicalIF":8.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of the RXRA-PPARα-FABP4 signaling pathway alleviates vascular cellular aging by an SGLT2 inhibitor in an atherosclerotic mice model.","authors":"Weiwei Zhang, Linghuan Wang, Yujia Wang, Yan Fang, Ruihua Cao, Zhiyi Fang, Dong Han, Xu Huang, Zhenghui Gu, Yingjie Zhang, Yan Zhu, Yan Ma, Feng Cao","doi":"10.1007/s11427-024-2602-7","DOIUrl":"10.1007/s11427-024-2602-7","url":null,"abstract":"<p><p>Atherosclerosis is the pathological cause of atherosclerotic cardiovascular disease (ASCVD), which rapidly progresses during the cellular senescence. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce major cardiovascular events in patients with ASCVD and have potential antisenescence effects. Here, we investigate the effects of the SGLT2 inhibitor dapagliflozin on cellular senescence in atherosclerotic mice. Compared with ApoE^-/- control mice treated with normal saline, those in the ApoE^-/- dapagliflozin group, receiving intragastric dapagliflozin (0.1 mg kg^-1 d^-1) for 14 weeks, exhibited the reduction in the total aortic plaque area (48.8%±6.6% vs. 74.6%±8.0%, P<0.05), the decrease in the lipid core area ((0.019±0.0037) mm²vs. (0.032±0.0062) mm², P<0.05) and in the percentage of senescent cells within the plaques (16.4%±3.7% vs. 30.7%±2.0%, P<0.01), while the increase in the thickness of the fibrous cap ((21.6±2.1) µm vs. (14.6±1.5) µm, P<0.01). Transcriptome sequencing of the aortic arch in the mice revealed the involvement of the PPARα and the fatty acid metabolic signaling pathways in dapagliflozin's mechanism of ameliorating cellular aging and plaque progression. In vitro, dapagliflozin inhibited the expression of PPARα and its downstream signal FABP4, by which the accumulation of senescent cells in human aortic smooth muscle cells (HASMCs) was reduced under high-fat conditions. This effect was accompanied by a reduction in the intracellular lipid content and alleviation of oxidative stress. However, these beneficial effects of dapagliflozin could be reversed by the PPARα overexpression. Bioinformatics analysis and molecular docking simulations revealed that dapagliflozin might exert its effects by directly interacting with the RXRA protein, thereby influencing the expression of the PPARα signaling pathway. In conclusion, the cellular senescence of aortic smooth muscle cells is potentially altered by dapagliflozin through the suppression of the RXRA-PPARα-FABP4 signaling pathway, resulting in a deceleration of atherosclerotic progression.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2678-2691"},"PeriodicalIF":8.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting STING oligomerization with licochalcone D ameliorates STING-driven inflammatory diseases.","authors":"Yinghui Zhang, Yadan Liu, Bing Jiang, Lifan Chen, Jie Hu, Buying Niu, Jie Chang, Zisheng Fan, Jingyi Zhou, Yajie Wang, Dan Teng, Ning Ma, Xiaofeng Wang, Ruirui Yang, Mingyue Zheng, Sulin Zhang","doi":"10.1007/s11427-024-2703-6","DOIUrl":"10.1007/s11427-024-2703-6","url":null,"abstract":"<p><p>The development of STING inhibitors for the treatment of STING-related inflammatory diseases continues to encounter significant challenges. The activation of STING is a multi-step process that includes binding with cGAMP, self-oligomerization, and translocation from the endoplasmic reticulum to the Golgi apparatus, ultimately inducing the expression of IRF3 and NF-κB-mediated interferons and inflammatory cytokines. It has been demonstrated that disruption of any of these steps can effectively inhibit STING activation. Traditional structure-based drug screening methodologies generally focus on specific binding sites. In this study, a TransformerCPI model based on protein primary sequences and independent of binding sites is employed to identify compounds capable of binding to the STING protein. The natural product Licochalcone D (LicoD) is identified as a potent and selective STING inhibitor. LicoD does not bind to the classical ligand-binding pocket; instead, it covalently modifies the Cys148 residue of STING. This modification inhibits STING oligomerization, consequently suppressing the recruitment of TBK1 and the nuclear translocation of IRF3 and NF-κB. LicoD treatment ameliorates the inflammatory phenotype in Trex1^-1- mice and inhibits the progression of DSS-induced colitis and AOM/DSS-induced colitis-associated colon cancer (CAC). In summary, this study reveals the potential of LicoD in treating STING-driven inflammatory diseases. It also demonstrates the utility of the TransformerCPI model in discovering allosteric compounds beyond the conventional binding pockets.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2664-2677"},"PeriodicalIF":8.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rice GWAS-to-Gene uncovers the polygenic basis of traits.","authors":"Xianrong Xie, Qunjie Zhang, Yao-Guang Liu","doi":"10.1007/s11427-024-2716-5","DOIUrl":"10.1007/s11427-024-2716-5","url":null,"abstract":"","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2783-2785"},"PeriodicalIF":8.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Individual and joint exposures to PM_2.5 constituents and mortality risk among the oldest-old in China.","authors":"Yaqi Wang, Yang Yuan, Shaocai Mo, Fang Wang, Jing Wei, Yao Yao, Yi Zeng, Yunquan Zhang","doi":"10.1007/s11427-024-2718-9","DOIUrl":"10.1007/s11427-024-2718-9","url":null,"abstract":"<p><p>Cohort evidence linking long-term survival of older adults with exposure to fine particulate matter (PM_2.5) constituents remains scarce in China. By constructing a dynamic cohort based on the Chinese Longitudinal Healthy Longevity Study, we aimed to assess the individual and joint associations of major PM_2.5 constituents with all-cause death in Chinese oldest-old (.80 years) adults. Time-dependent Cox proportional hazards models were adopted to estimate death risks of long-term exposure to PM_2.5 constituents. Among 14,884 participants, totaling 56,342 person-years of follow-up, 12,346 deaths were identified. The highest mortality risk associated with an interquartile range (IQR) increase in exposure was 1.081 (95% confidence interval [CI]: 1.055-1.108) for sulfate (IQR=4.1 μg m^-3), followed by 1.078 (95% CI: 1.056-1.101) for black carbon (IQR=1.6 μg m^-3), 1.056 (95% CI: 1.028-1.084) for ammonium (IQR=3.2 μg m^-3), 1.050 (95% CI: 1.021-1.080) for nitrate (IQR=5.8 μg m^-3), and 1.049 (95% CI: 1.024-1.074) for organic matter (IQR=10.3 μg m^-3). In joint exposure, each IQRequivalent rise of all five PM_2.5 constituents was associated with an 8.2% (95% CI: 4.0%-12.6%) increase in mortality risk. The weight analysis indicated the predominant role of sulfate and black carbon in driving PM_2.5-related mortality. Octogenarians (aged 80-89 years) and rural dwellers were at significantly greater risk of mortality from individual and joint exposures to PM_2.5 constituents. This study suggests that later-life exposure to PM_2.5 constituents, particularly sulfate and black carbon, may curtail long-term survival of the oldest-old in China.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2692-2700"},"PeriodicalIF":8.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142473723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Crop antiviral defense: Past and future perspective.","authors":"Zhirui Yang, Guangyao Li, Yongliang Zhang, Fangfang Li, Tao Zhou, Jian Ye, Xianbing Wang, Xiaoming Zhang, Zongtao Sun, Xiaorong Tao, Ming Wu, Jianguo Wu, Yi Li","doi":"10.1007/s11427-024-2680-3","DOIUrl":"10.1007/s11427-024-2680-3","url":null,"abstract":"<p><p>Viral pathogens not only threaten the health and life of humans and animals but also cause enormous crop yield losses and contribute to global food insecurity. To defend against viral pathogens, plants have evolved an intricate immune system to perceive and cope with such attacks. Although most of the fundamental studies were carried out in model plants, more recent research in crops has provided new insights into the antiviral strategies employed by crop plants. We summarize recent advances in understanding the biological roles of cellular receptors, RNA silencing, RNA decay, hormone signaling, autophagy, and ubiquitination in manipulating crop host-mediated antiviral responses. The potential functions of circular RNAs, the rhizosphere microbiome, and the foliar microbiome of crops in plant-virus interactions will be fascinating research directions in the future. These findings will be beneficial for the development of modern crop improvement strategies.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2617-2634"},"PeriodicalIF":8.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142073761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Increase of PCSK9 expression in diabetes promotes VEGFR2 ubiquitination to inhibit endothelial function and skin wound healing.","authors":"Jian-Jun Gao, Fang-Yuan Wu, Yu-Jia Liu, Le Li, Yi-Jun Lin, Yue-Ting Kang, Yue-Ming Peng, Yi-Fang Liu, Chen Wang, Zhen-Sheng Ma, Yang Cao, Hong-Yu Cao, Zhi-Wei Mo, Yan Li, Jing-Song Ou, Zhi-Jun Ou","doi":"10.1007/s11427-023-2688-8","DOIUrl":"10.1007/s11427-023-2688-8","url":null,"abstract":"<p><p>Diabetic foot ulcers (DFUs) are a serious vascular disease. Currently, no effective methods are available for treating DFUs. Pro-protein convertase subtilisin/kexin type 9 (PCSK9) regulates lipid levels to promote atherosclerosis. However, the role of PCSK9 in DFUs remains unclear. In this study, we found that the expression of PCSK9 in endothelial cells (ECs) increased significantly under high glucose (HG) stimulation and in diabetic plasma and vessels. Specifically, PCSK9 promotes the E3 ubiquitin-protein ligase NEDD4 binding to vascular endothelial growth factor receptor 2 (VEGFR2), which led to the ubiquitination of VEGFR2, resulting in its degradation and downregulation in ECs. Furthermore, PCSK9 suppresses the expression and activation of AKT, endothelial nitric oxide synthase (eNOS), and ERK1/2, leading to decreased nitric oxide (NO) production and increased superoxide anion (O₂^._) generation, which impairs vascular endothelial function and angiogenesis. Importantly, using evolocumab to limit the increase in PCSK9 expression blocked the HG-induced inhibition of NO production and the increase in O₂^._ production, as well as inhibited the phosphorylation and expression of AKT, eNOS, and ERK1/2. Moreover, evolocumab improved vascular endothelial function and angiogenesis, and promoted wound healing in diabetes. Our findings suggest that targeting PCSK9 is a novel therapeutic approach for treating DFUs.</p>","PeriodicalId":21576,"journal":{"name":"Science China Life Sciences","volume":" ","pages":"2635-2649"},"PeriodicalIF":8.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141996360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}