期刊,中国科学:生命科学（英文版） 2024年卷12期_国家学术搜索

期刊信息/Journal information

中国科学:生命科学（英文版）

主　　编：周光召

出版周期：月刊

国际刊号：1674-7305

电子邮箱：sales@scichina.org

电　　话：010-64019820

邮政编码：100717

地　　址：北京东黄城根北街16号

中国科学:生命科学（英文版）/Journal Science China(Life Sciences)CSCDCSTPCDSCI

查看更多>>《中国科学》是中国科学院主办、中国科学杂志社出版的自然科学专业性学术刊物。《中国科学》任务是反映中国自然科学各学科中的最新科研成果，以促进国内外的学术交流。《中国科学》以论文形式报道中国基础研究和应用研究方面具有创造性的、高水平的和有重要意义的科研成果。在国际学术界，《中国科学》作为代表中国最高水平的学术刊物也受到高度重视。国际上最具有权威的检索刊物SCI，多年来一直收录《中国科学》的论文。1999年《中国科学》夺得国家期刊奖的第一名。

正式出版

收录年代

Optimizing ABA-based chemically induced proximity for en-hanced intracellular transcriptional activation and modification response to ABA

Zeng ZhouYue-Qi WangXu-Nan ZhengXiao-Hong Zhang...

2650-2663页

查看更多>>摘要：Abscisic acid(ABA)-based chemically induced proximity(CIP)is primarily mediated by the interaction of the ABA receptor pyrabactin resistance 1-like 1(PYL1)and the 2C-type protein phosphatase ABI1,which confers ABA-induced proximity to their fusion proteins,and offers precise temporal control of a wide array of biological processes.However,broad application of ABA-based CIP has been limited by ABA response intensity.In this study,we demonstrated that ABA-induced interaction between another ABA receptor pyrabactin resistance 1(PYR1)and ABI1 exhibited higher ABA response intensity than that between PYL1 and ABI1 in HEK293T cells.We engineered PYR1-ABI1 and PYL1-ABI1 into ABA-induced transcriptional activation tools in mammalian cells by integration with CRISPR/dCas9 and found that the tool based on PYR1-ABI1 demonstrated better ABA response intensity than that based on PYL1-ABI1 for both exogenous and endogenous genes in mammalian cells.We further achieved ABA-induced RNA m6A modification installation and erasure by combining ABA-induced PYR1-ABI1 interaction with CRISPR/dCas13,successfully inhibiting tumor cell proliferation.We subsequently improved the interaction of PYR1-ABI1 through phage-assisted continuous evolution(PACE),successfully generating a PYR1 mutant(PYR1m)whose interaction with ABI1 exhibited a higher ABA response intensity than that of the wild-type.In addition,we tested the transcriptional activation tool based on PYRm-ABI1 and found that it also showed a higher ABA response intensity than that of the wild type.These results demonstrate that we have developed a novel ABA-based CIP and further improved upon it using PACE,providing a new approach for the modification of other CIP systems.

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Targeting STING oligomerization with licochalcone D amelio-rates STING-driven inflammatory diseases

Yinghui ZhangYadan LiuBing JiangLifan Chen...

2664-2677页

查看更多>>摘要：The development of STING inhibitors for the treatment of STING-related inflammatory diseases continues to encounter significant chal-lenges.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 in-flammatory 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-/-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.

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Inhibition of the RXRA-PPARα-FABP4 signaling pathway alleviates vascular cellular aging by an SGLT2 inhibitor in an atherosclerotic mice model

Weiwei ZhangLinghuan WangYujia WangYan Fang...

2678-2691页

查看更多>>摘要：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 athero-sclerotic mice.Compared with ApoE-/-control mice treated with normal saline,those in the ApoE-/-dapagliflozin group,receiving in-tragastric 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)mm2 vs.(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.

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维普

Individual and joint exposures to PM2.5 constituents and mortality risk among the oldest-old in China

Yaqi WangYang YuanShaocai MoFang Wang...

2692-2700页

查看更多>>摘要：Cohort evidence linking long-term survival of older adults with exposure to fine particulate matter(PM2.5)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 PM2.5 constituents with all-cause death in Chinese oldest-old(≥ 80 years)adults.Time-dependent Cox propor-tional hazards models were adopted to estimate death risks of long-term exposure to PM2.5 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 IQR-equivalent rise of all five PM2.5 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 PM2.5-related mortality.Octogenarians(aged 80-89 years)and rural dwellers were at significantly greater risk of mortality from individual and joint exposures to PM2.5 constituents.This study suggests that later-life exposure to PM2.5 constituents,particularly sulfate and black carbon,may curtail long-term survival of the oldest-old in China.

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Novel DNA methylation markers for early detection of gastric cardia adenocarcinoma and esophageal squamous cell carcino-ma

Zhiyuan FanJiajie HaoFeifan HeHao Jiang...

2701-2712页

查看更多>>摘要：Gastric cardia adenocarcinoma(GCA)and esophageal squamous cell carcinoma(ESCC)present significant health challenges in China,often diagnosed at advanced stages with poor prognoses.However,effective biomarkers for early detection remain elusive.This study aimed to integrate methylome and transcriptome data to identify DNA methylation markers for the early detection of GCA and ESCC.In the discovery stage,we conducted Infinium MethylationEPIC array analysis on 36 paired GCA and non-tumor adjacent tissues(NAT),identifying dif-ferentially methylated CpG sites(DMCs)between GCA/ESCC and NAT through combined analyses of in-house and publicly available data.In the validation stage,targeted pyrosequencing and quantitative real-time RT-PCR were performed on paired tumor and NAT samples from 50 GCA and 50 ESCC patients.In the application stage,an independent set of 438 samples,including GCA,ESCC,high-and low-grade dysplasia(HGD/LGD),and normal controls,was tested for selected DMCs using pyrosequencing.Our analysis validated three GCA-specific,two ESCC-specific,and one tumor-shared DMCs,exhibiting significant hypermethylation and decreased expression of target genes in tumor samples compared with NAT.Leveraging these DMCs,we developed a GCA-specific 4-marker panel(cg27284428,cg11798358,cg07880787,and cg00585116)with an area under the receiver operating characteristic curve(AUC)of 0.917,effectively distinguishing between cardia HGD/GCA patients and cardia LGD/normal controls.Similarly,an ESCC-specific 3-marker panel(cg14633892,cg04415798,and cg00585116)achieved an AUC of 0.865 in distinguishing esophageal HGD/ESCC cases.Furthermore,integrating cg00585116,age,and alcohol con-sumption yielded a tumor-shared logistic model with good discrimination for two cancer/HGD(AUC,0.767;95％confidence interval,0.720-0.813).The mean AUC of the model after 5-fold cross-validation was 0.764.In summary,our study identifies novel DNA methylation markers capable of accurately distinguishing GCA/ESCC and HGD from LGD and normal controls.These findings offer promising prospects for targeted DNA methylation assays in future minimally invasive cancer screening methods.

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Bactericidal ability of target acidic phospholipids and phagocy-tosis of CDC42 GTPase-mediated cytoskeletal rearrangement underlie functional conservation of CXCL12 in vertebrates

Yanqi ZhangNing XiaYazhen HuWentao Zhu...

2713-2729页

查看更多>>摘要：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 per-foration,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 poly-merization 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.

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Versatile plant genome engineering using anti-CRISPR-Cas12a systems

Yao HeShishi LiuLong ChenDongkai Pu...

2730-2745页

查看更多>>摘要：CRISPR-Cas12a genome engineering systems have been widely used in plant research and crop breeding.To date,the performance and use of anti-CRISPR-Cas 12a systems have not been fully established in plants.Here,we conduct in silico analysis to identify putative anti-CRISPR systems for Cas12a.These putative anti-CRISPR proteins,along with known anti-CRISPR proteins,are assessed for their ability to inhibit Cas12a cleavage activity in vivo and in planta.Among all anti-CRISPR proteins tested,AcrVA1 shows robust inhibition of Mb2Cas12a and LbCas12a in E.coli.Further tests show that AcrVA1 inhibits LbCas12a mediated genome editing in rice protoplasts and stable transgenic lines.Impressively,co-expression of AcrVA1 mitigates off-target effects by CRISPR-LbCas12a,as revealed by whole genome sequencing.In addition,transgenic plants expressing AcrVA1 exhibit different levels of inhibition to LbCas12a mediated genome editing,representing a novel way of fine-tuning genome editing efficiency.By controlling temporal and spatial expression of AcrVA1,we show that inducible and tissue specific genome editing can be achieved in plants.Furthermore,we demonstrate that AcrVA1 also inhibits LbCas12a-based CRISPR activation(CRISPRa)and based on this principle we build logic gates to turn on and off target genes in plant cells.Together,we have established an efficient anti-CRISPR-Cas12a system in plants and demonstrate its versatile applications in mitigating off-target effects,fine-tuning genome editing efficiency,achieving spatial-temporal control of genome editing,and generating synthetic logic gates for controlling target gene expression in plant cells.

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维普

Dual activation of soybean resistance against Phytophthora sojae by pectin lyase and degraded pectin oligosaccharides

Guangzheng SunYeqiang XiaKuikui LiQinsheng Zhu...

2746-2760页

查看更多>>摘要：Phytophthora pathogens secrete numerous apoplastic effectors to manipulate host immunity.Herein,we identified a polysaccharide lyase 1 protein,PsPL1,which acts as an essential virulence factor of P.sojae infection in soybean.However,the overexpression of PsPL1 in P.sojae reduced infection and triggered enhanced immune responses in soybean.PsPL1 exhibited pectin lyase activity and degraded plant pectin to generate pectin oligosaccharides(POSs)with a polymerization degree of 3-14,exhibiting different levels of acetylation and methylation modifications.PsPL1 and the degraded pectin products triggered immune responses in soybean and different Solanaceous plants.The PsPL1-triggered immune responses required RSPL1,a membrane-localized leucine-rich repeat receptor-like protein,which is essential for Phy-tophthora resistance.Conversely,the PsPL1-degraded product-triggered immune responses depended on the membrane-localized lysin motif receptor-like kinase CERK1.This study reveals that the pectin lyase exhibits a dual immunogenic role during P.sojae infection,which activates plant resistance through different immune receptors and provides novel insights into the function of pectin lyase in host-pathogen interactions.

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维普

Neol represents a group of transcriptional repressors regulating the biosynthesis of multiple aminoglycosides

Yue LiXiangxi MengDong LiXiulei Xia...

2761-2770页

查看更多>>摘要：In general,the initiation or closure of antibiotic biosynthesis is determined by regulatory proteins,but most of their mechanisms of action remain unknown.The 2-deoxystreptamine-containing aminoglycosides(2-DOS AGs)form a unique category among antibiotics.Genomic analysis revealed that a group of hypothetical regulatory genes represented by neoI are widely distributed in the biosynthetic gene clusters(BGCs)of natural products from Streptomyces species,including several 2-DOS AGs.Only limited knowledge is available for the roles of NeoI-type regulators although neomycin and some of the related AGs have been developed as therapeutic drugs for decades.This study focuses on the functional determination of neoI and its homologues situated in the BGCs of six AGs.We found that the yield of neomycin in neoI disruption mutant(AneoI)increased by 50％compared to the wild-type(WT)strain((420.6±44.1)mg L-1),while it was partially restored by the complementation of neoI,demonstrating that NeoI acted as a repressor in neomycin biosynthesis.Further electrophoretic mobility shift assays(EMSAs)and DNase I footprinting assays indicated that NeoI could specifically bind to the promoter region between neoE and neoI with conserved nucleotides(5'-CVHYMRCHDKAGYGGACR-3'),as determined by site-directed mutagenesis.Interestingly,cross-bindings of the NeoI homologues from the six different BGCs to their corresponding DNA targets were manifested,and the five exogenous NeoI homologues could complement NeoI function of repressing neomycin biosynthesis.Our results suggested that NeoI-type regulators re-present widespread and conservative regulatory characteristics in the biosynthesis of 2-DOS AGs,which would be significant for optimizing the biosynthetic pathways of valuable commercialized aminoglycoside antibiotics.

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Advances in brain tumor therapy:from molecular diagnostics to novel treatments

Junwen ZhangRan MuFusheng Liu

2771-2773页

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维普