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The Functional Redundancy of Neddylation E2s and E3s in Modulating the Fitness of Regulatory T Cells

Research 2024年第2期2023卷 373-387页

作者： Di Wu Yi Sun cancer Institute(key laboratory of cancer prevention and intervention China National Ministry of Education)of the Second Affiliated Hospital and Institute of Translational MedicineZhejiang University School of MedicineHangzhou 310029China cancer Center of Zhejiang University Hangzhou 310029China Zhejang Provincial Clinical Research Center for cancer Zhejang ProvinceChina key laboratory of Molecular Biology in Medical Sciences Zhejang ProvinceChina Research Center for Life Science and Human Health Binjiang Institute of Zhejiang UniversityHangzhou 310053China

Neddylation is necessary for activation of Cullin-RING ligases(CRLs),which degrade various immune regulatory *** recent study showed that while depletion of neddylation E2-E3 pair Ube2f-Sag in regulatory T(T_(reg))cells had no obvious phenotype,the same depletion of either Ube2m or Rbx1 caused inflammation disorders with different *** these E2s or E3s compensate each other in functional regulations of T_(reg)cells is,however,previously *** this report,we generated Foxp3^(Cre);Ube2m^(fl/fl);Ube2f^(fl/fl)or Foxp3^(Cre);Rbx1^(fl/fl);Sag^(fl/fl)double-null mice by simultaneous deletion of both neddylation E2s or E3s in T_(reg)cells,***,Ube2m&Ube2f double-null mice developed much severe autoimmune phenotypes than did Ube2m-null mice,indicating that Ube2m markedly compensates Ube2f in T_(reg)*** minor worsened autoimmune phenotypes seen at the very early stage in Rbx1&Sag double-null than Rbx1-null mice is likely due to already severe phenotypes of the later,indicating a minor compensation of Rbx1 for *** RNA profiling-based analyses revealed that up-and down-regulations of few signaling pathways in T_(reg)cells are associated with the severity of autoimmune ***,severer inflammation phenotypes seen in mice with double E3-null than with double E2-null T_(reg)cells indicate a neddylation-independent mechanism of 2 E3s,also known to serve as the RING component of CRLs in regulation of T_(reg)cell fitness.

关键词： Foxp3 inflammation markedly

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CSCO guidelines for colorectal cancer version 2024:Updates and discussions

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Chinese Journal of cancer Research 2024年第3期36卷 233-239页

作者： Liubo Chen Hanguang Hu Ying Yuan Shanshan Weng Department of Medical Oncology(key laboratory of cancer prevention and intervention China National Ministry of EducationKey Laboratory of Molecular Biology in Medical SciencesZhejiang ProvinceChina)the Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China Zhejiang Provincial Clinical Research Center for cancer Hangzhou 310009China cancer Center Zhejiang UniversityHangzhou 310058China

According to the latest global cancer statistics,colorectal cancer(CRC)is the most common malignancy of the digestive system and the second most lethal among all cancer types(1).In China,CRC is the second most prevalent cancer,following only after lung cancer(2).The first version of the Chinese Society of Clinical Oncology(CSCO)guideline was launched in 2017 and has been updated annually based on the latest findings of clinical research,drug accessibility and expert consensus(3-8).Here,we present the main updates of the 2024 version compared to the 2023 version.

关键词： CSCO colorectal cancer

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Ultratough Yet Dynamic Crystalline Poly(thiourethane)Network Directly from Low Viscosity Precursors

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CCS Chemistry 2024年第3期6卷 682-692页

作者： Haijun Feng Yi Sheng Guancong Chen Binjie Jin Zizheng Fang Bo Yang Xiaorui Zhou Wenxuan Wu Tao Xie Ning Zheng State key laboratory of Chemical Engineering College of Chemical and Biological EngineeringZhejiang UniversityHangzhou 310058 Department of Colorectal Surgery and Oncology Key Laboratory of Cancer Prevention and InterventionMinistry of EducationThe Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310027

Thermosets based on direct curing of multifunctional monomers offer processing flexibility that thermoplastics cannot ***,this type of thermoset is typically amorphous since it is difficult to meet the stringent requirement of long-range molecular regularity for ***,we report here a crystallizable poly(thiourethane)thermoset synthesized directly from the curing of low-viscosity liquid precursors that does not employ any *** crystalline nature results in superior toughness,comparable to commercial high-density polyethylene,in sharp contrast to the brittleness of the typical,rigid,glassy thermoset *** that,the network polymer exhibits shape-memory behavior in which the crystalline transition is utilized for temporary shape fixing/recovery whereas the dynamic thiourethane bonds can be activated for bond exchange as a mechanism for complex shape *** with these combined features represent attractive options for demanding engineering applications due to their high performance and multifunctinality.

关键词： thermosets crystalline polymer thiourethane thermadapt

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Graphene as adsorbent for highly efficient extraction of modified nucleosides in urine prior to liquid chromatography-tandem mass spectrometry analysis

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Chinese Chemical Letters 2024年第4期35卷 490-495页

作者： Cheng Guo Xiaoxiao Zhang Xiujuan Hong Yiqiu Hu Lingna Mao Kezhi Jiang cancer Institute(key laboratory of cancer prevention and intervention China National Ministry of Education)The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China cancer Center Zhejiang UniversityHangzhou 310058China key laboratory of Organosilicon Chemistry and Material Technology College of Material Chemistry and Chemical EngineeringHangzhou Normal UniversityHangzhou 311121China Department of General Practice The Second Affiliated HospitalZhejiang University School of MedicineHangzhou 310009China

RNA modifications have been involved in numerous biological processes, and aberrations of these modifications are tightly associated with various diseases including cancer. Herein, we developed graphenebased solid-phase extraction and robust ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) combined with stable isotope-dilution for simultaneous enrichment and accurate determination of 17 modified nucleosides in human urine. We found graphene could effectively adsorb various modified nucleosides in human urine samples. With this method, we identified and quantified these modified nucleosides in urine samples collected from lung cancer patients and healthy *** revealed that the levels of 12 modified nucleosides were all diminished in urine from lung cancer patients, compared with healthy controls. It is worth noting that we demonstrated, for the first time, the presence of 5,2-O-dimethyluridine(m~5U_m) in human urine. Together, we established a robust analytical method for simultaneous determinations of 17 modified nucleosides in human urine, and our results revealed a close correlation between the concentrations of urinary modified nucleosides and the occurrence of lung cancer, implying the potential applications of these modified nucleosides as noninvasive biomarkers for the early detection of lung cancer. Moreover, this study will stimulate future investigations on the regulatory roles of RNA modifications in the initiation and progression of lung cancer.

关键词： Mass spectrometry RNA modification Modified nucleosides Graphene Biomarker Urine

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Emerging role of lncRNAs as mechanical signaling molecules in mechanotransduction and their association with Hippo-YAP signaling:a review

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第4期25卷 280-292页

作者： Siyi LIN Xinyu HE Ying WANG Yu CHEN Aifu LIN College of Medicine Zhejiang UniversityHangzhou 310058China College of Life Sciences Zhejiang UniversityHangzhou 310058China cancer Center Zhejiang UniversityHangzhou 310058China key laboratory for Cell and Gene Engineering of Zhejiang Province Hangzhou 310058China International School of Medicine International Institutes of Medicinethe Fourth Affiliated Hospital of Zhejiang University School of MedicineYiwu 322000China key laboratory of cancer prevention and intervention China National Ministry of EducationHangzhou 310058China Future Health laboratory Innovation Center of Yangtze River DeltaZhejiang UniversityJiaxing 314100China

Cells within tissues are subject to various mechanical forces,including hydrostatic pressure,shear stress,compression,and *** mechanical stimuli can be converted into biochemical signals through mechanoreceptors or cytoskeleton-dependent response processes,shaping the microenvironment and maintaining cellular physiological *** studies have demonstrated the roles of Yes-associated protein(YAP)and its homolog transcriptional coactivator with PDZ-binding motif(TAZ)as mechanotransducers,exerting dynamic influence on cellular phenotypes including differentiation and disease *** regulatory function entails the involvement of the cytoskeleton,nucleoskeleton,integrin,focal adhesions(FAs),and the integration of multiple signaling pathways,including extracellular signal-regulated kinase(ERK),wingless/integrated(WNT),and Hippo ***,emerging evidence substantiates the implication of long non-coding RNAs(lncRNAs)as mechanosensitive molecules in cellular *** this review,we discuss the mechanisms through which YAP/TAZ and lncRNAs serve as effectors in responding to mechanical ***,we summarize and elaborate on the crucial signal molecules involved in mechanotransduction.

关键词： YAP/TAZ Long non-coding RNA(lncRNA) Mechanotransduction F-actin

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Tumor microenvironment of cancer stem cells:Perspectives on cancer stem cell targeting

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Genes & Diseases 2024年第3期11卷 275-302页

作者： Qianqian Guo Yi Zhou Tianyuan Xie Yin Yuan Huilong Li Wanjin Shi Lufeng Zheng Xiaoman Li Wenzhou Zhang Department of Pharmacy The Affiliated Cancer Hospital of Zhengzhou University&Henan Cancer HospitalZhengzhouHenan 450003China Jiangsu key laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica School of PharmacyNanjing University of Chinese MedicineNanjingJiangsu 210023China School of Life Science and Technology Jiangsu Key Laboratory of Carcinogenesis and InterventionChina Pharmaceutical UniversityNanjingJiangsu 211198China

There are few tumor cell subpopulations with stem cell characteristics in tumor tis-sue,defined as cancer stem cells(CSCs)or cancer stem-like cells(CSLCs),which can recon-struct neoplasms with malignant biological behaviors such as invasiveness via self-renewal and unlimited *** microenvironment that CsCs depend on consists of various cellular components and corresponding medium *** these factors existing at a variety of levels and forms,cytokine networks and numerous signal pathways play an important role in signaling *** factors promote or maintain cancer cell stem-ness,and participate in cancer recurrence,metastasis,and *** review aims to summarize the recent molecular data concerning the multilayered relationship between CsCs and CsC-favorable *** also discuss the therapeutic implications of target-ing this synergistic interplay,hoping to give an insight into targeting cancer cell stemness for tumortherapyandprognosis.

关键词： cancer stem cells cancerstem-like cells Cellular factors Non-cellularfactors Tumor microenvironment

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Decoupled deep hough voting for point cloud registration

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Frontiers of Computer Science 2024年第2期18卷 147-155页

作者： Mingzhi YUAN Kexue FU Zhihao LI Manning WANG Digital Medical Research Center School of Basic Medical SciencesFudan UniversityShanghai 200032China Shanghai key laboratory of Medical Image Computing and Computer Assisted intervention Shanghai 200032China

Estimating rigid transformation using noisy correspondences is critical to feature-based point cloud ***,a series of studies have attempted to combine traditional robust model fitting with deep *** them,DHVR proposed a hough voting-based method,achieving new state-of-the-art ***,we find voting on rotation and translation simultaneously hinders achieving better ***,we proposed a new hough voting-based method,which decouples rotation and translation ***,we first utilize hough voting and a neural network to estimate *** based on good initialization on rotation,we can easily obtain accurate rigid *** experiments on 3DMatch and 3DLoMatch datasets show that our method achieves comparable performances over the state-of-the-art *** further demonstrate the generalization of our method by experimenting on KITTI dataset.

关键词： point cloud registration robust model fitting deep learning hough voting

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Targeting lncRNA16 by GalNAc-siRNA conjugates facilitates chemotherapeutic sensibilization via the HBB/NDUFAF5/ROS pathway

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Science China(Life Sciences) 2024年第4期67卷 663-679页

作者： Yanfang Liu Yan Wang Bing Liu Wenzhong Liu Yuanyuan Ma Yiren Cao Shi Yan Panpan Zhang Lixin Zhou Qimin Zhan Nan Wu key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Thoracic Surgery IIPeking University Cancer Hospital and InstituteBeijing 100142China key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Laboratory of Molecular OncologyPeking University Cancer Hospital and InstituteBeijing 100142China key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Thoracic Oncology IIPeking University Cancer Hospital and InstituteBeijing 100142China key laboratory of Carcinogenesis and Translational Research(Ministry of Education) Department of PathologyPeking University Cancer Hospital and InstituteBeijing 100142China Peking University International cancer Institute Beijing 100191China Institute of cancer Research Shenzhen Bay LaboratoryShenzhen 518132China

Chemoresistance is a significant barrier to effective cancer *** mechanisms for chemoresistance include reactive oxygen species(ROS)accumulation and expression of chemoresistance-promoting ***,we report a novel function of lncRNA16 in the inhibition of ROS generation and the progression of *** analyzing the serum levels of lncRNA16 in a cohort of 35 patients with non-small cell lung cancer(NSCLC)and paired serum samples pre-and post-treatment from 10 NSCLC patients receiving neoadjuvant platinum-based chemotherapy,performing immunohistochemistry(IHC)assays on 188 NSCLC tumor samples,using comprehensive identification of RNA-binding proteins by mass spectrometry(ChIRP-MS)assays,as well as RNA immunoprecipitation(RIP)and RNA pull-down analyses,we discovered that patients with increased serum levels of lncRNA16 exhibited a poor response to platinum-based *** expression of hemoglobin subunit beta(HBB)and NDUFAF5 significantly increases with the development of ***16 binds to HBB and promotes HBB accumulation by inhibiting ***16 can also inhibit ROS generation via the HBB/NDUFAF5 axis and function as a scaffold to facilitate the colocalization of HBB and NDUFAF5 in the ***,preclinical studies in mouse models of chemo-resistant NSCLC have suggested that lncRNA16 targeting by trivalent N-acetylgalactosamine(GalNAc)-conjugated siRNA restores chemosensitivity and results in tumor growth inhibition with no detectable toxicity in ***,lncRNA16 is a promising therapeutic target for overcoming chemoresistance,and the combination of first-line platinum-based chemotherapy with lncRNA16 intervention can substantially enhance anti-tumor efficacy.

关键词： chemoresistance lncRNARNA interference ROs chemosensitizer

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Progression from ductal carcinoma in situ to invasive breast cancer:molecular features and clinical significance

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Signal Transduction and Targeted Therapy 2024年第5期9卷 1841-1868页

作者： Jing Wang Baizhou Li Meng Luo Jia Huang Kun Zhang Shu Zheng Suzhan Zhang Jiaojiao Zhou The key laboratory of cancer prevention and intervention China National Ministry of Educationthe Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina Department of Breast Surgery and Oncology the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina Zhejiang Provincial Clinical Research Center for cancer HangzhouChina Department of Pathology the Fourth Affiliated HospitalZhejiang University School of MedicineYiwuChina Department of Plastic Surgery the Second Affiliated HospitalZhejiang University School of MedicineHangzhouChina cancer Center Zhejiang UniversityHangzhouChina

Ductal carcinoma in situ(DCIS)represents pre-invasive breast *** untreated cases,25-60%DCIS progress to invasive ductal carcinoma(IDC).The challenge lies in distinguishing between non-progressive and progressive DCIS,often resulting in over-or under-treatment in many *** increasing screen-detected DCIS in these years,the nature of DCIS has aroused worldwide attention.A deeper understanding of the biological nature of DCIS and the molecular journey of the DCIS-IDC transition is crucial for more effective clinical ***,we reviewed the key signaling pathways in breast cancer that may contribute to DCIS initiation and *** also explored the molecular features of DCIS and IDC,shedding light on the progression of DCIS through both inherent changes within tumor cells and alterations in the tumor *** addition,valuable research tools utilized in studying DCIS including preclinical models and newer advanced technologies such as single-cell sequencing,spatial transcriptomics and artificial intelligence,have been systematically ***,we thoroughly discussed the clinical advancements in DCIS and IDC,including prognostic biomarkers and clinical managements,with the aim of facilitating more personalized treatment strategies in the *** on DCIS has already yielded significant insights into breast carcinogenesis and will continue to pave the way for practical clinical applications.

关键词： clinical breast alterations

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Eubacterium coprostanoligenes alleviates chemotherapy-induced intestinal mucositis by enhancing intestinal mucus barrier

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1677-1692页

作者： Dongsheng Bai Jiawei Zhao Runde Wang Jiaying Du Chen Zhou Chunyang Gu Yuxiang Wang Lulu Zhang Yue Zhao Na Lu State key laboratory of Natural Medicines Jiangsu Key Laboratory of Carcinogenesis and InterventionDepartment of PhysiologySchool of Basic Medicine and Clinical PharmacyChina Pharmaceutical UniversityNanjing 210009China Department of Clinical Pharmacology School of PharmacyNanjing Medical UniversityNanjing 211166China

Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment,significantly curtailing the efficacy of these treatments and,in some cases,resulting in fatal *** identifying intestinal epithelial cell damage as a key factor in chemotherapy-induced mucositis,the paucity of effective treatments for such damage is *** our study,we discovered that Eubacterium coprostanoligenes promotes mucin secretion by goblet cells,thereby fortifying the integrity of the intestinal mucus *** enhanced barrier function serves to resist microbial invasion and sub-sequently reduces the inflammatory ***,this effect remains unobtrusive to the anti-tumor efficacy of chemotherapy ***,*** up-regulates the expression of AUF1,leading to the stabilization of Muc2 mRNA and an increase in mucin synthesis in goblet *** espe-cially significant finding is that *** activates the AhR pathway,thereby promoting the expression of *** summary,our results strongly indicate that *** enhances the intestinal mucus barrier,effec-tively alleviating chemotherapy-induced intestinal mucositis by activating the AhR/AUFl pathway,consequently enhancing Muc2 mRNA stability.

关键词： Chemotherapy Mucositis Eubacterium coprostanoligenes MUC2 AUF1

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