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cGAS-STING: mechanisms and therapeutic opportunities

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Science China life sciences 2025年

作者： Mengyuan Zhang Changxin Wu Defen Lu Xing Wang Guijun Shang Shanxi Medical University School and Hospital of Stomatology Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials The Key Laboratory of Medical Molecular Cell Biology of Shanxi Province Institutes of Biomedical Sciences Shanxi University College of life sciences Shanxi Agricultural University

The cGAS-STING pathway plays a crucial role in the innate immune system by detecting mislocalized double-stranded DNA(dsDNA) in the cytoplasm and triggering downstream signal transduction. Understanding the mechanisms by which cGAS and STING operate is vital for gaining insights into the biology of this pathway. This review provides a detailed examination of the structural features of cGAS and STING proteins, with a particular emphasis on their activation and inhibition mechanisms. We also discuss the novel discovery of STING functioning as an ion channel. Furthermore, we offer an overview of key agonists and antagonists of cGAS and STING, shedding light on their mechanisms of action. Deciphering the molecular intricacies of the cGAS-STING pathway holds significant promise for the development of targeted therapies aimed at maintaining immune homeostasis within both innate and adaptive immunity.

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Single-cell omics: experimental workflow, data analyses and applications

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Science China life sciences 2025年第1期68卷 5-102页

作者： Fengying Sun Haoyan Li Dongqing Sun Shaliu Fu Lei Gu Xin Shao Qinqin Wang Xin Dong Bin Duan Feiyang Xing Jun Wu Minmin Xiao Fangqing Zhao Jing-Dong J.Han Qi Liu Xiaohui Fan Chen Li Chenfei Wang Tieliu Shi Department of Clinical Laboratory the Affiliated Wuhu Hospital of East China Normal University (The Second People's Hospital of Wuhu City) Pharmaceutical Informatics Institute College of Pharmaceutical SciencesZhejiang University Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration (Tongji University) Ministry of EducationOrthopaedic DepartmentTongji HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Frontier Science Center for Stem Cells School of Life Sciences and TechnologyTongji University Translational Medical Center for Stem Cell Therapy and Institute for Regenerative Medicine Shanghai East HospitalBioinformatics DepartmentSchool of Life Sciences and TechnologyTongji University Research Institute of Intelligent Computing Zhejiang Lab Shanghai Research Institute for Intelligent Autonomous Systems Center for Single-cell Omics School of Public HealthShanghai Jiao Tong University School of Medicine National Key Laboratory of Chinese Medicine Modernization Innovation Center of Yangtze River DeltaZhejiang University Center for Bioinformatics and Computational Biology Shanghai Key Laboratory of Regulatory Biologythe Institute of Biomedical Sciences and School of Life SciencesEast China Normal University Beijing institutes of life Science Chinese Academy of Sciences Peking-Tsinghua Center for life sciences Academy for Advanced Interdisciplinary StudiesCenter for Quantitative Biology (CQB)Peking University Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases Women's HospitalZhejiang University School of Medicine Key Laboratory of Advanced Theory and Application in Statistics and Data Science-MOE School of StatisticsEast China Normal University

Cells are the fundamental units of biological systems and exhibit unique development trajectories and molecular features. Our exploration of how the genomes orchestrate the formation and maintenance of each cell, and control the cellular phenotypes of various organismsis, is both captivating and intricate. Since the inception of the first single-cell RNA technology, technologies related to single-cell sequencing have experienced rapid advancements in recent years. These technologies have expanded horizontally to include single-cell genome, epigenome,proteome, and metabolome, while vertically, they have progressed to integrate multiple omics data and incorporate additional information such as spatial sc RNA-seq and CRISPR screening. Single-cell omics represent a groundbreaking advancement in the biomedical field,offering profound insights into the understanding of complex diseases, including cancers. Here, we comprehensively summarize recent advances in single-cell omics technologies, with a specific focus on the methodology section. This overview aims to guide researchers in selecting appropriate methods for single-cell sequencing and related data analysis.

关键词： single-cell sequencing genome epigenome proteomics metabolomics multimodal spatial transcriptomics CRISPR screening

AZD1775 synergizes with SLC7A11 inhibition to promote ferroptosis

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Science China life sciences 2025年第1期68卷 204-218页

作者： Chen Xiong Hong Ling Yingdan Huang Hanzhi Dong Bangxiang Xie Qian Hao Xiang Zhou Fudan University Shanghai Cancer Center and institutes of Biomedical sciences Fudan University Department of Oncology Shanghai Medical CollegeFudan University Department of Breast Surgery Fudan University Shanghai Cancer CenterFudan University Department of Oncology First Affiliated Hospital of Nanchang University Beijing Institute of Hepatology Beijing Youan HospitalCapital Medical University Beijing Engineering Research Center for Precision Medicine and Transformation of Hepatitis and Liver Cancer Key Laboratory of Breast Cancer in Shanghai Fudan University Shanghai Cancer CenterFudan University Shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism (Ministry of Science and Technology)Institutes of Biomedical SciencesFudan University

Tumor suppressor p53-mediated cell cycle arrest and DNA damage repair may exert cytoprotective effects against cancer therapies, including WEE1 inhibition. Considering that p53 activation can also lead to multiple types of cell death, the role of this tumor suppressor in WEE1 inhibitor-based therapies remains disputed. In this study, we reported that nucleolar stress-mediated p53 activation enhanced the WEE1 inhibitor AZD1775-induced ferroptosis to suppress lung cancer growth. Our findings showed that AZD1775 promoted ferroptosis by blocking cystine uptake, an action similar to that of Erastin. Meanwhile, inhibition of WEE1 by the WEE1 inhibitors or si RNAs induced compensatory upregulation of SLC7A11, which conferred resistance to ferroptosis. Mechanistically, AZD1775 prevented the enrichment of H3K9me3, a histone marker of transcriptional repression, on the SLC7A11 promoter by repressing the expression of the histone methyltransferase SETDB1, thereby enhancing NRF2-mediated SLC7A11 transcription. This finding was also validated using the H3K9me3 inhibitor BRD4770. Remarkably, we found that the nucleolar stress-inducing agent Actinomycin D(Act. D) inhibited SLC7A11 expression by activating p53, thus augmenting AZD1775-induced ferroptosis. Moreover, the combination of AZD1775 and Act. D synergistically suppressed wild-type p53-harboring lung cancer cell growth both in vitro and in vivo. Altogether, our study demonstrates that AZD1775 promotes ferroptosis by targeting cystine uptake but also mediates the adaptive activation of SLC7A11 through the WEE1-SETDB1 cascade and NRF2-induced transcription, and inhibition of SLC7A11 by Act. D boosts the anti-tumor efficacy of AZD1775 by enhancing ferroptosis in cancers with wild-type p53.

关键词： p53 NRF2 SLC7A11 WEE1 AZD1775 ferroptosis nucleolar stress

Ketogenic diet and cancer:multidimensional exploration and research

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Science China life sciences 2025年

作者： Shiyun Wan Xiaoxue Zhou Feng Xie Fangfang Zhou Long Zhang The First Affiliated Hospital the Institutes of Biology and Medical Sciences Suzhou Medical College Soochow University School of Medicine Hangzhou City University life sciences Institute and State Key Laboratory of Transvascular Implantation Devices of the Second Affiliated Hospital of Zhejiang University School of Medicine Zhejiang University The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors The First Affiliated Hospital Jiangxi Medical College Nanchang University Cancer Center Zhejiang University

The ketogenic diet(KD) has attracted attention in recent years for its potential anticancer effects. KD is a dietary structure of high fat,moderate protein, and extremely low carbohydrate content. Originally introduced as a treatment for epilepsy, KD has been widely applied in weight loss programs and the management of metabolic diseases. Previous studies have shown that KD can potentially inhibit the growth and spread of cancer by limiting energy supply to tumor cells, thereby inhibiting tumor angiogenesis, reducing oxidative stress in normal cells, and affecting cancer cell signaling and other processes. Moreover, KD has been shown to influence T-cell-mediated immune responses and inflammation by modulating the gut microbiota, enhance the efficacy of standard cancer treatments, and mitigate the complications of chemotherapy. However, controversies and uncertainties remain regarding the specific mechanisms and clinical effects of KD as an adjunctive therapy for cancer. Therefore, this review summarizes the existing research and explores the intricate relationships between KD and cancer treatment.

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Tuning the porosity of {Co12IICo8III（μ3-OH）24（X）}11+ supramolecular frameworks by reaction time for D2/H2 separation

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Science China Chemistry 2025年

作者： Zhuozhou Xie Zhu Zhuo Zi-Ang Nan Qing Li Xiufang Li Zi-Xiu Lu Linzhe Lü Jin Liu Luyao Liu Wenjing Wang Wei Wang Daqiang Yuan You-Gui Huang State Key Laboratory of Structure Chemistry Fujian Institute of Research on the Structure of Matter Chinese Academy of Sciences University of Chinese Academy of sciences Xiamen Key Laboratory of Rare Earth Photoelectric Functional Materials Xiamen Institute of Rare Earth Materials Haixi InstitutesChinese Academy of Sciences State Key Laboratory of Physical Chemistry of Solid Surfaces Department of Chemistry College of Chemistry and Chemical EngineeringXiamen University

Systematicly tuning the porosities of porous materials is crucial for targeted gas mixture separation,yet it remains a longstanding *** a common strategy,altering the phenylene ring count in the organic building units has been exploited to adjust pore apertures in metal organic frameworks （MOFs） and covalent organic frameworks （COFs）,resulting in only a stepwise pore size variation of approximately 2.8?.Unlike MOFs and COFs,the porosities for supramolecular assembly frameworks are highly dependent on the packings of the molecular building units in the *** above strategy cannot be applied to supramolecular assembly frameworks and other strategies are required to adjust pore apertures in supramolecular frameworks,especially to achieve porous materials with the optimal pore size for D2/H2separation （～3?）.Here,we successfully modulate the porosity of supramolecular frameworks of[CoII1+12CoIII8L12（μ3-OH）24（X）]1clusters （L=mono-deprotonated 1-iminoisoindole-3-amine,X=ClO?4or Cl?） by controlling the duration of self-assembly *** simply adjusting the reaction time,we obtain three[CoII12CoIII8L12（μ3-OH）24（X）]11+supramolecular frameworks:[CoII12CoIII8（μ3-OH）24（ClO4）L12)]·（Cl）4·（HCO2）7（1）,[CoII12CoIII8L12（μ3-OH）24（Cl）]·（ClOI4）4·（Cl）6·（HCO2）·（H2O）10（2）,and[CoI12CoIII8L12（μ3-OH）24（Cl）]·（Cl）11·（H2O）12（3）.The different stacking patterns of the[CoII12CoIII8L12（μ3-OH）24（X）]11+clusters in these frameworks lead to significantly varied stabilities and *** 1 exhibits permanent porosity with interconnected channels and maintains stability under harsh *** contrast,compound 2 is nearly nonporous,and compound 3 becomes unstable upon *** pores of compound 1 show higher affinity to D2than H2,and the pore aperture diameter of compound 1 （～3.06?） meets the optimal porosity for D2/***,compound 1 demonstrates moderate D2/H2separation at 77 K (retention time:～7 min/g for D2/H2/Ne （10/10/80 vol%） in a flow of 5 mL

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Design and test of cesium atomic concentration detection system based on TDLAS*1

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Optoelectronics Letters 2025年第3期21卷 167-171页

作者： LIANG Lizhen LIU Shanhu WU Yong WEI Jianglong XIE Yahong Hefei institutes of Physical Science Chinese Academy of Sciences School of Science Shandong Jianzhu University School of Electronic and Information Engineering Anhui Jianzhu University

In order to better build the neutral beam injector with negative ion source (NNBI), the pre-research on key technologies has been carried out for the comprehensive research facility for fusion technology (CRFFT). Cesium seeding into negative-ion sources is a prerequisite to obtain the required negative hydrogen ion. The performance of ion source largely depends on the cesium conditions in the source. It is very necessary to quantitatively measure the amount of cesium in the source during the plasma on and off periods (vacuum stage).

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ICA-Net: improving class activation for weakly supervised semantic segmentation via joint contrastive and simulation learning

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Optoelectronics Letters 2025年第3期21卷 188-192页

作者： YE Zhuang LIU Ruyu SUN Bo School of Information Engineering Chengdu Aviation Vocational and Technical College School of Computer Science and Engineering Hangzhou Normal University Quanzhou Institute of Equipment Manufacturing Haixi Institutes Chinese Academy of Sciences

In the field of optoelectronics, certain types of data may be difficult to accurately annotate, such as high-resolution optoelectronic imaging or imaging in certain special spectral ranges. Weakly supervised learning can provide a more reliable approach in these situations. Current popular approaches mainly adopt the classification-based class activation maps (CAM) as initial pseudo labels to solve the task.

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Unveiling an ancient whole-genome duplication event in Stentor,the model unicellular eukaryotes

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Science China life sciences 2025年

作者： Weibo Zheng Chao Li Zhaorui Zhou Xiao Chen Michael Lynch Ying Yan School of life sciences Ludong University Key Laboratory of Evolution & Marine Biodiversity (Ministry of Education) and Institute of Evolution & Marine Biodiversity Ocean University of China Biodesign Center for Mechanisms of Evolution Arizona State University Marine College Shandong University

Whole-genome duplication(WGD) events are widespread across eukaryotes and have played a significant role in moulding the genetic architectures of diverse organisms. In the present study, the newly sequenced genome of a giant ciliated protist, Stentor roeselii, provides an opportunity for the analysis of the collinearity and retention of reciprocal best-hit genes between two Stentor species. As a main result, we have unveiled a previously undetected ancient WGD event shaping the genome of its congener, Stentor coeruleus, a model protist used in cytological and evolutionary studies. Genomes of two congeners, S. coeruleus and S. roeselii, are compared and analyzed, revealing that:(i)the former exhibits a much higher retention rate of colinear-gene pairs(28%) than does S. roeselii, and in S. coeruleus, 75% of genes that have a RBH hit in S. roeselii, have paralogs with high amino-acid identity, consistent with a WGD event in the lineage leading to S. coeruleus;(ii) the S. roeselii genome possesses extremely short intergenic regions, implying that the lengths of intergenic regions are under strong selection;(iii) the unique characteristics of introns may have been shaped in the common ancestor of heterotrichs;(iv) gene families that play a role in activities of multiple protein kinases and voltage-gated ion channels expanded rapidly in the ancestor of both taxa, possibly relating to the remarkable regenerative ability in Stentor. This study offers new insights into the evolutionary dynamics of ciliate genomes,with implications for understanding of the processes underlying the evolution of genomic complexity.

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The rising young scientist stars in China

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Protein & Cell 2016年第12期7卷 850-853页

作者： Hao Cheng Beijing institutes of life Science Chinese Academy of Sciences Beijing 100101 China

The Chinese government has devoted a great amount of effort to strengthen its scientific capacity, as an important national strategic aim. Increased funding support, improving scientific structure and administration combined with rapid economic growth has seen great achievements in science and technology by Chinese scientists over the past decade. China has now become an outstanding country with advanced developments in major disciplines, especially in biology.

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维普期刊数据库