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DNA bridging of FOXP3 ladder-like multimer: Unveiling a novel transcriptional regulation paradigm

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The Innovation 2024年第3期5卷 15-16页

作者： Ying Lu Lanfang Li Hanting Yang Bin Li Zuoyun Wang Key laboratory of Metabolism and Molecular Medicine of the Ministry of Education Shanghai Xuhui Central Hospital and School of Basic Medical SciencesFudan UniversityShanghai 200032China Institute for Translational Brain Research State Key Laboratory of Medical NeurobiologyMOE Frontiers Center for Brain ScienceDepartment of NeurologyZhongshan HospitalFudan UniversityShanghai 200032China Center for Immune-Related Diseases at Shanghai Institute of immunology Department of Immunology and MicrobiologyShanghai Jiao Tong University School of MedicineShanghai 200025China

In the latest issue of Nature,Zhang et *** a novel ladder-like structure of FOXP3-DNA interaction involving FOXP3 multimerization and remote DNA bridging through a combination of biochemistry,structural biology,cell biology,and bioinformatics analyses.1 In this commentary,we highlight their key findings and provide our insights into the research paradigm for further exploration of a novel transcriptional regulation mode as well as a therapeutic strategy from the structural aspects of the FOXP3 complex(Figure 1).

关键词： FOXP3 bridging

Reduced clinical severity during 2022 Shanghai Spring epidemic of SARS-CoV-2 omicron BA.2 variant infection——an integrated account of virus pathogenicity and vaccination effectiveness

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National Science Review 2024年第4期11卷 24-27页

作者： Xingyue Wu Yao Chen Kangli Cao Yao Shen Xueling Wu Yilin Yang Zhongshu Kuang Qingrun Li Zhenzhen Lu Yichen Jia Mian Shao Guorong Gu Xiangwei Wang Ye Yao Ying Wang Shaodie Chen Zhigao Yu Wei Wei Longfei Ding Lulu Lan Tianwen Gu Xiangyu Long Jian Sun Lingyu Xing Jiayuan Shen Yi Han Yue Luo Sucheng Mu Mengna Lin Xiaoyan Zhang Rong Zeng Jianqing Xu Guoping Zhao Lihong Huang Zhenju Song Department of Emergency Medicine Clinical Center for Bio-Therapy Department of Biostatistics and Department of UrologyShanghai Key Laboratory of Lung Inflammation and Injury Zhongshan Hospital Fudan University Department of Respiratory and Critical Care Medicine Shanghai Pudong Hospital Fudan University Department of Pulmonology Renji Hospital Shanghai Jiao Tong University School of Medicine Key laboratory of Systems Biology Center for Excellence in Molecular Cell Science Shanghai Institute of Biochemistry and Cell Biology Chinese Academy of Sciences Shanghai Public Health Clinical Center Fudan University Department of Biostatistics School of Public Health Key Laboratory of Public Health Safety of Ministry of Education and Shanghai Institute of Infectious Disease and Biosecurity School of Public Health Fudan University Shanghai Institute of immunology Department of Immunology and Microbiology Shanghai Institute of Virology Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of EducationSchool of Medicine Shanghai Jiao Tong University State Key laboratory of Genetic Engineering Fudan Microbiome CenterSchool of Life Sciences Fudan University Bio-Med Big Data Center Shanghai Institute of Nutrition and Health Chinese Academy of Sciences

The emergence of SARS-Co V-2 variant of concern omicron BA.2 led to high infection incidence rates as well as reduced severity of COVID-19 during the Shanghai Spring epidemic of 2022 [1]. We assessed the role of viral pathogenicity and the effectiveness of inactivated vaccines in a retrospective observational study including 10 258 confirmed COVID-19cases identified between April and June of 2022, from four COVID-19 designated hospitals located in two areas of Shanghai, namely the West Bund and the East Bund, where the populations’ demographic characteristics varied significantly (Table S1, Fig. S1).

关键词： REPLICATION

Cortical Organoid-on-a-Chip with Physiological Hypoxia for Investigating Tanshinone IIA-Induced Neural Differentiation

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Research 2024年第3期2023卷 457-468页

作者： Yue Zhi Yujuan Zhu Jinglin Wang Junqi Zhao Yuanjin Zhao Department of Rheumatology and immunology Nanjing Drum Tower HospitalClinical Medical College of Traditional Chinese and Western MedicineNanjing University of Chinese MedicineNanjing210023China State Key laboratory of Bioelectronics School of Biological Science and Medical EngineeringSoutheast UniversityNanjing210096China Shenzhen Research Institute Southeast UniversityShenzhen518038China

Cortical organoids represent cutting-edge models for mimic human brain development during the early and even middle stage of pregnancy, while they often fail to recreate the complex microenvironmental factors, such as physiological hypoxia. Herein, to recapitulate fetal brain development, we propose a novel cortical organoid-on-a-chip with physiological hypoxia and further explore the effects of tanshinone IIA (Tan IIA) in neural differentiation. The microfluidic chip was designed with a micropillar array for the controlled and efficient generation of cortical organoids. With low oxygen, the generated cortical organoids could recapitulate key aspects of early-gestational human brain development. Compared to organoids in normoxic culturing condition, the promoted neurogenesis, synaptogenesis and neuronal maturation were observed in the present microsystem, suggesting the significance of physiological hypoxia in cortical development. Based on this model, we have found that Chinese herbal drug Tan IIA could promote neural differentiation and maturation, indicating its potential therapeutic effects on neurodevelopmental disorders as well as congenital neuropsychiatric diseases. These results indicate that the proposed biomimetic cortical organoid-on-a-chip model with physiological hypoxia can offer a promising platform to simulate prenatal environment, explore brain development, and screen natural neuroactive components.

关键词： promoted herbal cutting

The m^(6)A regulator KIAA1429 stabilizes RAB27B mRNA and promotes the progression of chronic myeloid leukemia and resistance to targeted therapy

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Genes & Diseases 2024年第2期11卷 993-1008页

作者： Fangyi Yao Fangmin Zhong Junyao Jiang Ying Cheng Shuai Xu Jing Liu Jin Lin Jing Zhang Shuqi Li Meiyong Li Yanmei Xu Bo Huang Xiaozhong Wang Jiangxi Province Key laboratory of laboratory Medicine Jiangxi Provincial Clinical Research Center for Laboratory MedicineDepartment of Clinical LaboratoryThe Second Affiliated Hospital of Nanchang UniversityNanchangJiangxi 330006China

Chronic myeloid leukemia(CML)is a common adult *** the acute phase of the disease and the adverse effects of anti-cancer treatments can lead to a poor *** N6-methyladenine(m^(6)A)modification plays an important regulatory role in various physiological and pathological ***1429 is a known m^(6)A regulator,but the biological role of KIAA1429 in CML is *** this study,we observed that the m^(6)A levels and KIAA1429 expression were significantly up-regulated in patients with blast phase ***,KIAA1429 regulated the total level of RNA m^(6)A modification in the CML cells and promoted the malignant biological behaviors of CML cells,including proliferation,migration,and imatinib *** KIAA1429 in CML cells reduced the stability of RAB27B mRNA through the m^(6)A/YTHDF1 axis,consequently inhibiting CML proliferation and drug efflux,ultimately increasing the sensitivity of CML cells to ***,the knockdown of RAB27B also inhibited the proliferation and drug resistance of CML cells and promoted their ***,a recently developed anti-cancer agent,suppressed the expression of KIAA1429 and CML cell proliferation and promoted cell *** also inhibited the tumorigenesis of CML cells in *** combined use of rucaparib and imatinib enhanced the sensitivity of CML cells to *** study provides evidence that elevated KIAA1429 expression in the blast phase of CML enhances the stability of RAB27B mRNA through the m^(6)A/YTHDF1 axis to up-regulate RAB27B expression,thereby promoting CML *** exerts inhibitory effects on KIAA1429 expression and thus reduces CML progression.

关键词： Chronic myeloid leukemia KIAA1429 N6-methyladenine RAB27B Rucaparib YTHDF1

Coming of age:the formation and function of age-associated B cells

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Cellular & Molecular immunology 2024年第4期21卷 311-312页

作者： Ke Rui Nan Che Kongyang Ma Hejian Zou Fan Xiao Liwei Lu Department of laboratory Medicine Institute of Medical Immunology of Jiangsu UniversityAffiliated Hospital of Jiangsu UniversityZhenjiangChina Department of Rheumatology and immunology Nanjing First HospitalNanjing Medical UniversityJiangsuChina Centre for Infection and Immunity Studies School of MedicineThe Sun Yat-sen UniversityShenzhen518107GuangdongChina Department of Rheumatology Huashan HospitalFudan UniversityShanghaiChina Department of Pathology and Shenzhen Institute of Research and Innovation HKU Shenzhen HospitalThe University of Hong KongHong KongChina Centre for Oncology and immunology Hong Kong Science ParkHong KongChina

B cells are generated in the bone marrow during ontogeny and migrate to peripheral lymphoid organs,where they encounter antigens to elicit humoral *** the past decade,many novel B-cell subsets with distinct phenotypes and functions have been identified,and among these subsets,age-associated B cells(ABCs)were first characterized as a B-cell subset that accumulates with age[1].

关键词： organs lymphoid migrate

IL-17 induces NSCLC cell migration and invasion by elevating MMP19 gene transcription and expression through the interaction of p300-dependent STAT3-K631 acetylation and its Y705-phosphorylation

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Oncology Research 2024年第4期32卷 625-641页

作者： WEN GE YA LI YUTING RUAN NINGXIA WU PEI MA TONGPENG XU YONGQIAN SHU YINGWEI WANG WEN QIU CHENHUI ZHAO Department of immunology Nanjing Medical UniversityNanjing210000China Key laboratory of Immunological Environment and Disease Nanjing Medical UniversityNanjing210000China Department of Oncology The First Affiliated Hospital of Nanjing Medical UniversityNanjing210000China Jiangsu Key laboratory of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjing210000China

The cancer cell metastasis is a major death reason for patients with non-small cell lung cancer(NSCLC).Although researchers have disclosed that interleukin 17(IL-17)can increase matrix metalloproteinases(MMPs)induction causing NSCLC cell metastasis,the underlying mechanism remains *** the study,we found that IL-17 receptor A(IL-17RA),p300,p-STAT3,Ack-STAT3,and MMP19 were up-regulated both in NSCLC tissues and NSCLC cells stimulated with IL-17.p300,STAT3 and MMP19 overexpression or knockdown could raise or reduce IL-17-induced p-STAT3,Ack-STAT3 and MMP19 level as well as the cell migration and *** investigation revealed that STAT3 and p300 bound to the same region(−544 to−389 nt)of MMP19 promoter,and p300 could acetylate STAT3-K631 elevating STAT3 transcriptional activity,p-STAT3 or MMP19 expression and the cell mobility exposed to ***,p300-mediated STAT3-K631 acetylation and its Y705-phosphorylation could interact,synergistically facilitating MMP19 gene transcription and enhancing cell migration and ***,the animal experiments exhibited that the nude mice inoculated with NSCLC cells by silencing p300,STAT3 or MMP19 gene plus IL-17 treatment,the nodule number,and MMP19,Ack-STAT3,or p-STAT3 production in the lung metastatic nodules were all ***,these outcomes uncover that IL-17-triggered NSCLC metastasis involves up-regulating MMP19 expression via the interaction of STAT3-K631 acetylation by p300 and its Y705-phosphorylation,which provides a new mechanistic insight and potential strategy for NSCLC metastasis and therapy.

关键词： NSCLC cell migration and invasion IL-17 p300 STAT3 MMP19 Acetylation and phosphorylation

Microwave-Assisted Confining Growth and Liquid Exfoliation of sp^(3)-Hybrid Carbon Nitride Nano/Micro-Crystals

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Energy & Environmental Materials 2024年第6期7卷 399-408页

作者： Chenglong Shen Qing Lou Kaikai Liu Guangsong Zheng Runwei Song Jinhao Zang Xigui Yang Xing Li Lin Dong Chongxin Shan Henan Key laboratory of Diamond Optoelectronic Materials and Devices Key Laboratory of Material PhysicsMinistry of EducationSchool of Physics and Laboratory of Zhongyuan LightZhengzhou UniversityZhengzhou 450052China

As one promising carbon-based material,sp^(3)-hybrid carbon nitride has been predicted with various novel physicochemical ***,the synthesis of sp^(3)-hybrid carbon nitride is still limited by the nanaoscale,low crystallinity,complex source,and expensive ***,we have presented a facile approach to the sp^(3)-hybrid carbon nitride nano/micro-crystals with microwave-assisted confining growth and liquid ***,the carbon nitride nano/micro-crystals can spontaneously emerge and grow in the microwave-assisted polymerization of citric acid and urea,and the liquid exfoliation can break the bulk disorder polymer to retrieve the highly crystalline carbon nitride nano/*** obtained carbon nitride nano/micro-crystals present superior blue light absorption strength and surprising photoluminescence quantum yields of 57.96%in ethanol and 18.05%in solid *** experimental characterizations and density functional theory calculations reveal that the interface-trapped localized exciton may contribute to the excellent intrinsic light emission capability of carbon nitride nano/micro-crystals and the interparticle staggered stacking will prevent the aggregation-caused-quenching ***,the carbon nitride nano/micro-crystals are demonstrated to be potentially useful as the phosphor medium in light-emitting-diode for interrupting blue light-induced eye *** work paves new light on the synthesis strategy of sp^(3)-hybrid carbon nitride materials and thus may push forward the development of multiple carbon nitride research.

关键词： confining growth density functional theory liquid exfoliation luminescence sp^(3)-hybrid carbon nitride

Discovery of Trametinib as an orchestrator for cytoskeletal vimentin remodeling

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Journal of Molecular Cell Biology 2024年第3期16卷 24-34页

作者： Shuangshuang Zhao Zhifang Li Qian Zhang Yue Zhang Jiali Zhang Gaofeng Fan Xiaobao Cao Yaming Jiu Unit of Cell Biology and Imaging Study of Pathogen Host Interaction The Center for MicrobesDevelopment and HealthKey Laboratory of Molecular Virology and ImmunologyShanghai Institute of Immunity and InfectionChinese Academy of SciencesShanghai 200031China Guangzhou National laboratory Guangzhou 510005China University of Chinese Academy of Sciences Beĳing 100049China School of Life Science and Technology ShanghaiTech UniversityShanghai 201210China

The dynamic remodeling of the cytoskeletal network of vimentin intermediate filaments supports various cellular functions,including cell morphology,elasticity,migration,organelle localization,and resistance against mechanical or pathological *** available chemicals targeting vimentin predominantly induce network reorganization and shrinkage around the *** tools for long-term manipulation of vimentin network dispersion in living cells are still lacking,limiting in-depth studies on vimentin function and potential therapeutic ***,we verified that a commercially available small molecule,trametinib,is capable of inducing spatial spreading of the cellular vimentin network without affecting its transcriptional or Translational *** evidence confirmed its low cytotoxicity and similar effects on different cell ***,Trametinib has no impact on the other two cytoskeletal systems,actin filaments and the microtubule ***,Trametinib regulates vimentin network dispersion rapidly and efficiently,with effects persisting for up to 48 h after drug *** also ruled out the possibility that Trametinib directly affects the phosphorylation level of *** summary,we identified an unprecedented regulator Trametinib,which is capable of spreading the vimentin network toward the cell periphery,and thus complemented the existing repertoire of vimentin remodeling drugs in the field of cytoskeletal research.

关键词： vimentin intermediate filaments cytoskeleton small molecule network reorganization

Bioinspired 3D flexible devices and functional systems

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National Science Review 2024年第3期11卷 271-295页

作者： Xu Cheng Zhangming Shen Yihui Zhang Applied Mechanics laboratory Department of Engineering Mechanics Tsinghua University laboratory of Flexible Electronics Technology Tsinghua University

Flexible devices and functional systems with elaborated three-dimensional(3D) architectures can endow better mechanical/electrical performances, more design freedom, and unique functionalities, when compared to their two-dimensional(2D) counterparts. Such 3D flexible devices/systems are rapidly evolving in three primary directions, including the miniaturization, the increasingly merged physical/artificial intelligence and the enhanced adaptability and capabilities of heterogeneous *** challenges exist in this emerging research area, such as relatively poor controllability in the locomotion of soft robotic systems, mismatch of bioelectronic interfaces, and signal coupling in multi-parameter sensing. By virtue of long-time–optimized materials, structures and processes, natural organisms provide rich sources of inspiration to address these challenges, enabling the design and manufacture of many bioinspired 3D flexible devices/systems. In this Review, we focus on bioinspired 3D flexible devices and functional systems, and summarize their representative design concepts, manufacturing methods, principles of structure-function relationship and broad-ranging applications. Discussions on existing challenges, potential solutions and future opportunities are also provided to usher in further research efforts toward realizing bioinspired 3D flexible devices/systems with precisely programmed shapes,enhanced mechanical/electrical performances, and high-level physical/artificial intelligence.

关键词： bioinspired designs biomimetic 3D structures 3D flexible electronics 3D functional systems direct 3D manufacture 2D-to-3D assembly