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Multidisciplinary management of ulcerative colitis complicated by immune checkpoint inhibitor-associated colitis with life-threatening gastrointestinal hemorrhage:A case report

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World Journal of Gastrointestinal Surgery 2024年第7期16卷 2329-2336页

作者： Na Hong Bo Wang Hang-cheng Zhou Zheng-xiang Wu Hua-Ying Fang geng-Qing Song Yue Yu Department of Gastroenterology The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230001Anhui ProvinceChina Department of Pathology The First Affiliated Hospital of University of Science and Technology of ChinaDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230036Anhui ProvinceChina Intelligent Pathology Institute Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230036Anhui ProvinceChina Department of Gastroenterology and Hepatology Metro Health Medical CenterCase Western Reserve UniversityClevelandOH 44109United States

BACKGROUND Programmed cell death 1(PD-1)inhibitors are immune checkpoint inhibitors(ICI)that have demonstrated significant efficacy in treating various advanced malignant *** most patients tolerate treatment well,several adverse drug reactions,such as fatigue,myelosuppression,and ICI-associated colitis,have been *** SUMMARY This case involved a 57-year-old male patient with ulcerative colitis complicated by hepatocarcinoma who underwent treatment with tirelizumab(a PD-1 inhibitor)for six *** treatment led to repeated life-threatening lower gastrointestinal *** patient received infliximab,vedolizumab,and other salvage procedures but ultimately required subtotal colectomy due to uncontrollable massive lower gastrointestinal ***,postoperative gastrointestinal bleeding has stopped,the patient’s stool has turned yellow,and his full blood cell count has returned to *** This case highlights the necessity of early identification,timely and adequate treatment of ICI-related colitis,and rapid escalation to achieve the goal of improving prognosis.

关键词： Ulcerative colitis Hepatocarcinoma Immune checkpoint inhibitor-associated colitis Colectomy Case report

Cholangiocarcinoma combined with biliary obstruction:an exosomal circRNA signature for diagnosis and early recurrence monitoring

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2642-2654页

作者： Ningyuan Wen Dingzhong Peng xianze xiong geng Liu Guilin Nie Yaoqun Wang Jianrong xu Shaofeng Wang Sishu Yang Yuan Tian Bei Li Jiong Lu Nansheng cheng Division of Biliary Surgery Department of General SurgeryWest China HospitalSichuan UniversityChengduSichuanChina Research Center for Biliary Diseases West China HospitalSichuan UniversityChengduSichuanChina

Cholangiocarcinoma(CCA)is a highly malignant biliary tract cancer with currently suboptimal diagnostic and prognostic *** present a novel system to monitor CCA using exosomal circular RNA(circRNA)via serum and biliary liquid biopsies.A pilot cohort consisting of patients with CCA-induced biliary obstruction(CCA-BO,n=5)and benign biliary obstruction(BBO,n=5)was used to identify CCA-derived exosomal circRNAs through microarray *** was followed by a discovery cohort(n=20)to further reveal a CCA-specific circRNA complex(hsa-circ-0000367,hsa-circ-0021647,and hsa-circ-0000288)in both bile and serum *** vitro and in vivo studies revealed the three circRNAs as promoters of CCA *** and prognostic models were established and verified by two independent cohorts(training cohort,n=184;validation cohort,n=105).An interpreter-free diagnostic model disclosed the diagnostic power of biliary exosomal circRNA signature(Bile-DS,AUROC=0.947,RR=6.05)and serum exosomal circRNA signature(Serum-DS,AUROC=0.861,RR=4.04)compared with conventional CA19-9(AUROC=0.759,RR=2.08).A prognostic model of CCA undergoing curative-intent surgery was established by calculating early recurrence score,verified with bile samples(Bile-ERS,C-index=0.783)and serum samples(Serum-ERS,C-index=0.782).These models,combined with other prognostic factors revealed by COx-PH model,enabled the establishment of nomograms for recurrence monitoring of *** study demonstrates that the exosomal triple-circRNA panel identified in both bile and serum samples serves as a novel diagnostic and prognostic tool for the clinical management of CCA.

关键词： biliary diagnosis Serum

An engineered DNA aptamer-based PROTAC for precise therapy of p53-R175H hotspot mutant-driven cancer

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Science Bulletin 2024年第13期69卷 2122-2135页

作者： Lingping Kong Fanlu Meng Ping Zhou Ruixin Ge xiaoshan geng Zhihao Yang Guo Li Linlin Zhang Jing Wang Jinfeng Ma cheng Dong Jun Zhou Sijin Wu Diansheng Zhong Songbo xie Department of Medical Oncology Tianjin Medical University General HospitalTianjin 300052China Center for Cell Structure and Function Collaborative Innovation Center of Cell Biology in Universities of ShandongCollege of Life SciencesShandong Normal UniversityJinan 250014China The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics Key Laboratory of Immune Microenvironment and Disease(Ministry of Education)School of Basic Medical SciencesTianjin Medical UniversityTianjin 300070China Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment Lung Cancer InstituteTianjin Medical University General HospitalTianjin 300052China Haihe Laboratory of Cell Ecosystem State Key Laboratory of Medicinal Chemical BiologyCollege of Life SciencesNankai UniversityTianjin 300071China Wisdom Lake Academy of Pharmacy Xi’an Jiaotong-Liverpool UniversitySuzhou 215028China Department of Ophthalmology Tianjin Medical University General HospitalLaboratory of Molecular OphthalmologyTianjin Key Laboratory of Ocular TraumaTianjin Medical UniversityTianjin 300052China

Targeting oncogenic mutant p53 represents an attractive strategy for cancer treatment due to the high frequency of gain-of-function mutations and ectopic expression in various cancer *** extensive efforts,the absence of a druggable active site for small molecules has rendered these mutants therapeutically *** we develop a selective and effective proteolysis-targeting chimera(PROTAC)for p53-R175H,a common hotspot mutant with dominant-negative and oncogenic *** a novel iterative molecular docking-guided post-SELEx(systematic evolution of ligands by exponential enrichment)approach,we rationally engineer a high-performance DNA aptamer with improved affinity and specificity for *** this resulting aptamer as a binder for PROTACs,we successfully developed a selective p53-R175H degrader,named ***53m induces the ubiquitin–protea some-dependent degradation of p53-R175H while sparing wildtype ***,dp53m demonstrates significant antitumor efficacy in p53-R175H-driven cancer cells both in vitro and in vivo,without ***,dp53m significantly and synergistically improves the sensitivity of these cells to cisplatin,a commonly used chemotherapy *** findings provide evidence of the potential therapeutic value of dp53m in p53-R175H-driven cancers.

关键词： P53 Aptamer PROTAC Cancer Drug resistance

Fourier-domain-compressed optical time-stretch quantitative phase imaging flow cytometry

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Photonics Research 2024年第8期12卷 1627-1639页

作者： RUBING LI YUEYUN WENG SHUBIN WEI SIYUAN LIN JIN HUANG CONGKUAN SONG HUI SHEN JINxUAN HOU YU xU LIYE MEI DU WANG YUJIE ZOU TAILANG YIN FULING ZHOU QING geng SHENG LIU cheng LEI Institute of Technological Sciences Wuhan UniversityWuhan 430072China School of Power and Mechanical Engineering Wuhan UniversityWuhan 430072China Department of Thoracic Surgery Renmin HospitalWuhan UniversityWuhan 430060China Department of Hematology Zhongnan HospitalWuhan UniversityWuhan 430071China Department of Thyroid and Breast Surgery Zhongnan HospitalWuhan UniversityWuhan 430071China Department of Radiation and Medical Oncology Zhongnan HospitalWuhan UniversityWuhan 430071China School of Computer Science Hubei University of TechnologyWuhan 430068China Reproductive Medical Center Renmin HospitalWuhan UniversityWuhan 430060China Suzhou Institute of Wuhan University Suzhou 215000China Shenzhen Institute of Wuhan University Shenzhen 518057China

Optical time-stretch(OTS)imaging flow cytometry offers a promising solution for high-throughput and highprecision cell analysis due to its capabilities of high-speed,high-quality,and continuous *** sensing(CS)makes it practically applicable by significantly reducing the data volume while maintaining its highspeed and high-quality imaging *** enrich the information of the images acquired with CS-equipped OTS imaging flow cytometry,in this work we propose and experimentally demonstrate Fourier-domaincompressed OTS quantitative phase imaging flow *** is capable of acquiring intensity and quantitative phase images of cells simultaneously from the compressed *** evaluate the performance of our method,static microparticles and a corn root cross section are experimentally measured under various compression ***,to show how our method can be applied in practice,we utilize it in the drug response analysis of breast cancer *** results show that our method can acquire high-quality intensity and quantitative phase images of flowing cells at a flowing speed of 1 m/s and a compression ratio of 30%.Combined with machine-learning-based image analysis,it can distinguish drug-treated and drug-untreated cells with an accuracy of over 95%.We believe our method can facilitate cell analysis in both scientific research and clinical settings where both high-throughput and high-content cell analysis is required.

关键词： flow stretch phase

Human ESC-derived vascular cells promote vascular regeneration in a HIF-1α dependent manner

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Protein & Cell 2024年第1期15卷 36-51页

作者： Jinghui Lei xiaoyu Jiang Daoyuan Huang Ying Jing Shanshan Yang Lingling geng Yupeng Yan Fangshuo Zheng Fang cheng Weiqi Zhang Juan Carlos Izpisua Belmonte Guang-Hui Liu Si Wang Jing Qu Advanced Innovation Center for Human Brain Protection National Clinical Research Center for Geriatric DisordersXuanwu Hospital Capital Medical UniversityBeijing 100053China State Key Laboratory of Membrane Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China State Key Laboratory of Stem Cell and Reproductive Biology Institute of ZoologyChinese Academy of SciencesBeijing 100101China Aging Translational Medicine Center Intermational Center for Aging and CancerBeijing Municipal Geriatric Medical Research CenterXuanwu HospitalCapital Medical UniversityBeijing 100053China University of Chinese Academy of Sciences Beijing 100049China Institute for Stem Cell and Regeneration CASBeijing 100101China The Fifth People's Hospital of Chongqing Chongqing 400062China Beijing Institute for Stem Cell and Regenerative Medicine Beijing 100101China National Laboratory of Biomacromolecules CAs Center for Excellence in BiomacromoleculesInstitute of BiophysicsBeijing 100101China CAS Key Laboratory of Genomic and Precision Medicine Beijing Institute of GenomicsChinese Academy of SciencesBeijing 100101China China National Center for Bioinformation Beijing 100101China Sino-Danish College University of Chinese Academy of SciencesBeijing 101408China Sino-Danish Center for Education and Research Beijing 101408China Aging Biomarker Consortium China Altos Labs San DiegoCA 92121United State

Hypoxia-inducible factor(HIF-1α),a core transcription factor responding to changes in cellular oxygen levels,is closely associated with a wide range of physiological and pathological ***,its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely ***,we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-ia-deficient human vascular cells including vascular endothelial cells,vascular smooth muscle cells,and mesenchymal stem cells(MsCs),as a platform for discovering cell type-specific hypox-ia-induced response *** comparative molecular profiling across cell types under normoxic and hypoxic conditions,we provide insight into the indispensable role of HIF-1αin the promotion of ischemic vascular *** found human MSCs to be the vascular cell type most susceptible to HIF-1a deficiency,and that transcriptional inactivation of ANKZF1,an effector of HIF-1a,impaired pro-angiogenic ***,our findings deepen the understanding of HIF-ia in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.

关键词： HIF-1 human ESC vascular cell regeneration

IRE1α regulates the PTHrP-IHH feedback loop to orchestrate chondrocyte hypertrophy and cartilage mineralization

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Genes & Diseases 2024年第1期11卷 464-478页

作者： Mengtian Fan Nana geng xingyue Li Danyang Yin Yuyou Yang Rong Jiang cheng Chen Naibo Feng Li Liang xiaoli Li Fengtao Luo Huabing Qi Qiaoyan Tan Yangli xie Fengjin Guo Laboratory of Developmental Biology Department of Cell Biology and GeneticsSchool of Basic Medical ScienceChongqing Medical UniversityChongqing 400016China Laboratory of Stem Cells and Tissue Engineering School of Basic Medical ScienceChongqing Medical UniversityChongqing 400016China Department of Orthopedics The 1st Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Wound Repair and Rehabilitation Medicine State Key Laboratory of TraumaBurns and Combined InjuryTrauma CenterResearch Institute of SurgeryDaping HospitalArmy Medical UniversityChongqing 400042China

Cartilage development is controlled by the highly synergistic proliferation and differentiation of growth plate chondrocytes,in which the Indian hedgehog(IHH)and parathyroid hormone-related protein-parathyroid hormone-1 receptor(PTHrP-PTH1R)feedback loop is *** inositol-requiring enzyme 1a/x-box-binding protein-1 spliced(IRE1α/xBP1s)branch of the unfolded protein response(UPR)is essential for normal cartilage ***,the precise role of ER stress effector IRE1α,encoded by endoplasmic reticulum to nucleus signaling 1(ERN1),in skeletal development remains ***,we reported that loss of IRE1α accelerates chondrocyte hypertrophy and promotes endochondral bone ***1 acts as a negative regulator of chondrocyte proliferation and differentiation in postnatal growth *** deficiency interrupted PTHrP/PTH1R and IHH homeostasis leading to impaired chondrocyte hypertrophy and ***1s,produced by p-IRE1α-mediated splicing,binds and up-regulates PTH1R and IHH,which coordinate cartilage ***,ER stress cannot be activated normally in ERN1-deficient *** conclusion,ERN1 deficiency accelerates chondrocyte hypertrophy and cartilage mineralization by impairing the homeostasis of the IHH and PTHrP/PTH1R feedback loop and ER ***1 may have a potential role as a new target for cartilage growth and maturation.

关键词： Cartilage development ER stress ERN1 IHH PTHrP/PTH1R

Strength criterion for crystalline rocks considering grain size effect and tensile-compressive strength ratio

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Journal of Central South University 2024年第7期31卷 2365-2378页

作者： ZHANG cheng-han JI Hong-guang JIANG Peng YOU Shuang geng Qian-cheng JIAO Chen-jiang Beijing Key Laboratory of Urban Underground Space Engineering University of Science and Technology BeijingBeijing 100083China School of Civil and Resource Engineering University of Science and Technology BeijingBeijing 100083China

The macroscopic mechanical properties of rocks are significantly influenced by their *** a material bonded by mineral grains,the grain morphology of crystalline rock is the primary factor influencing the ***,most strength criteria neglect the strength variations caused by different grain characteristics in ***,the traditional linear criteria tend to overestimate tensile strength and exhibit apex *** address these shortcomings,a piecewise strength criterion that considers the grain size effect has been proposed.A part of an ellipse was employed to construct the envelope of the tensive-shear region on the meridian plane,to accurately reproduce the low tensile-compressive strength *** on the analysis of experimental data,both linear and exponential modification functions that account for grain size effects were integrated into the proposed *** corresponding finite element algorithm has been *** accuracy and applicability of the proposed criterion were validated by comparing with the experimental data.

关键词： crystalline rock grain size effect strength criterion tensile-compressive strength ratio finite element algorithm

MEIC-global-CO_(2):A new global CO_(2)emission inventory with highly-resolved source category and sub-country information

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Science China Earth Sciences 2024年第2期67卷 450-465页

作者： Ruochong xU Dan TONG Qingyang xIAO xinying QIN Cuihong CHEN Liu YAN Jing cheng Can CUI Hanwen HU Wenyu LIU xizhe YAN Huaxuan WANG xiaodong LIU Guannan geng Yu LEI Dabo GUAN Kebin HE Qiang ZHANG Department of Earth System Science Ministry of Education Key Laboratory for Earth System ModelingInstitute for Global Change StudiesTsinghua UniversityBeijing100084China State Key Joint Laboratory of Environment Simulation and Pollution Control School of EnvironmentTsinghua UniversityBeijing100084China Chinese Academy of Environmental Planning Beijing100041China Institute for Carbon Neutrality Tsinghua UniversityBeijing100084China

CO_(2)emission inventory provides fundamental data for climate research and emission ***,most global CO_(2)emission inventories were developed with energy statistics from International Energy Agency(IEA)and were available at country level with limited source ***,as the first step toward a high-resolution and dynamic updated global CO_(2)emission database,we developed a data-driven approach to construct seamless and highly-resolved energy consumption data cubes for 208 countries/territories,797 sub-country administrative divisions in 29 countries,42 fuel types,and 52 sectors,with the fusion of activity data from 24 international statistics and 65 regional/local *** CO_(2)emissions from fossil fuel combustion and cement production in 1970–2021 were then estimated with highly-resolved source category(1,484 of total)and sub-country information(797 of total).Specifically,73%of global CO_(2)emissions in 2021 were estimated with sub-country information,providing considerably improved spatial resolution for global CO_(2)emission *** the support of detailed information,the dynamics of global CO_(2)emissions across sectors and fuel types were presented,representing the evolution of global economy and progress of climate *** differences of sectoral contribution were found across sub-country administrative divisions within a given country,revealing the uneven distribution of energy and economic structure among different *** estimates were generally consistent with existing databases at aggregated level for global total or large emitters,while large discrepancies were observed for middle and small *** database,named the Multiresolution Emission Inventory model for Climate and air pollution research(MEIC)is publicly available through http://*** with highly-resolved information and timely update,which provides an independent carbon emission accounting data source for climate rese

关键词： CO_(2)emissions Data-driven approach Highly-resolved source category Sub-country information

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考虑海铁联运的集装箱码头泊位分配优化

重庆交通大学学报（自然科学版） 2024年第1期43卷 46-51,66页

作者：户佐安孙燕耿成西南交通大学交通运输与物流学院四川成都611756 西南交通大学综合交通大数据应用技术国家工程实验室四川成都611756 西南交通大学综合交通运输智能化国家地方联合工程实验室四川成都611756

在海铁联运背景下,协同考虑到港船舶及铁路班列特点,优化集装箱码头泊位分配,对于提高港口作业效率至关重要。在满足码头岸线、泊位水深、岸桥等资源约束前提下,综合考虑船舶服务优先级和偏好泊位、铁路集装箱班列到发时间等约束,以船... 详细信息

在海铁联运背景下,协同考虑到港船舶及铁路班列特点,优化集装箱码头泊位分配,对于提高港口作业效率至关重要。在满足码头岸线、泊位水深、岸桥等资源约束前提下,综合考虑船舶服务优先级和偏好泊位、铁路集装箱班列到发时间等约束,以船舶在港停留时间和泊位偏移惩罚时间最小为优化目标,建立海铁联运集装箱码头泊位分配优化模型;针对模型特点,设计自适应遗传算法进行求解,选取计划周期48 h内的到港船舶数据进行案例分析,通过MATLAB数值实验,得到符合船舶服务优先级和泊位偏好要求且契合铁路班列开行计划的海铁联运码头泊位分配方案。数值实验结果表明:在海铁联运协同优化条件下,船舶平均等泊时间为2.9 min,最大等泊时间为11.4 min,同时船舶的靠泊位置与偏好泊位之间的距离均不超过100 m,船舶在港的停留时间及偏好泊位差都得到了较好的控制。研究可进一步优化海铁联运集装箱码头泊位分配方案,有利于提高海铁联运集装箱在港转运效率。

关键词：交通运输工程海铁联运协同优化泊位分配自适应遗传算法铁路班列开行计划