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Chinese Journal of Natural Medicines 2024年第2期22卷 137-145页

作者： LIU Mingming GUO Jiatian ZHAO Jing LI Hongye FENG Xiaoxiao LIU Haojun ZHANG Hao JIA Xuejun WEI Rushuai LI Fang CHEN Chong HOU Mingzhuang LV Nanning XU Haiyan Department of human anatomy Xuzhou Medical UniversityXuzhou 221004China Department of Orthopedic Surgery The Affiliated Lianyungang Clinical College of Xuzhou Medical University(The Second People’s Hospital of Lianyungang)Lianyungang 222003China Department of Orthopaedics The First Afliated Hospital of Soochow UniversitySoochow UniversitySuzhou 215006China Institute of Hematology Xuzhou Medical UniversityXuzhou 221004China

Excessive oxidative stress impairs cartilage matrix metabolism balance,significantly contributing to osteoarthritis(OA)***(CSL),a drug derived from Tripterygium wilfordii,has recognized applications in the treatment of cancer and immune system disorders,yet its antioxidative stress mechanisms in OA remain *** study aimed to substantiate CSL’s chondroprotective effects and unravel its underlying *** investigated CSL’s impact on chondrocytes under both normal and inflammatory *** vitro,CSL mitigated interleukin(IL)-1β-induced activation of proteinases and promoted cartilage extracellular matrix(ECM)*** vivo,intra-articular injection of CSL ameliorated cartilage degeneration and mitigated subchondral bone lesions in OA ***,it was found that inhibiting nuclear factor erythroid 2-related factor 2(NRF2)abrogated CSL-mediated antioxidative functions and exacerbated the progression of *** study is the first to elucidate the role of CSL in the treatment of OA through the activation of NRF2,offering a novel therapeutic avenue for arthritis therapy.

关键词： Osteoarthritis Celastrol Articular cartilage Extracellular matrix NRF2

Antitumor activity and low gastrointestinal toxicity of a novel selective inhibitor of nuclear export,SZJK-0421,in multiple myeloma

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3281-3285页

作者： Jing Wang Hang Miao Xuxing Shen Lin Yang Yongqiang Zhu Lijuan Chen Department of Hematology Jiangsu Province Hospitalthe First Affiliated Hospital of Nanjing Medical UniversityNanjing 210029China College of Life science Nanjing Normal UniversityNanjing 210037China Multi-component of Traditional Chinese Medicine and Microecology Researh Center Jiangsu Probince Academy of Traditional Chinese MedicineNanjing 210028China

To the Editor:Multiple myeloma(MM)is a plasma cell disease that remains *** anti-MMtherapies are currently in clinical research,including CAR-T therapy,bispecific antibodies,and XPO1 ***1 is a nuclear export protein that helps leucine-rich proteins transport from the nucleus to the ***1 is highly expressed in patients with MM and XPO1 overexpression is associated with short PFS and OS^(2).These observations suggest that XPO1 has considerable value as a therapeutic target for patients with MM.

关键词： Multiple myeloma Selective inhibitor Nuclear export Cytotoxicity Gastrointestinal toxicity

An aqueous rechargeable Fe//LiMn_(2)O_()hybrid battery with superior electrochemical performance beyond mainstream Fe-based batteries

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Nano Research 2024年第6期17卷 5168-5178页

作者： Yu Liu Dehui Xie Yuxin Shi Rongguan Lv Yingna Chang Yuzhen Sun Zhiyuan Zhao Jindi Wang Kefan Song Huayu Wu Tuan K.A.Hoang Rong Xing Huan Pang Institute of New Energy on Chemical Storage and Power Sources School of Chemical and Environmental EngineeringYancheng Teachers UniversityYancheng 224000China School of Chemistry and Chemical Engineering Yangzhou UniversityYangzhou 225009China Department of Chemical Engineering University of Waterloo200 University Avenue WestWaterlooOntario N2L 3G1Canada

Aqueous rechargeable batteries(ARBs)are generally safer than non-aqueous analogues,they are also less-expensive,and more friendly to the ***,the inherent disadvantage of the narrow electrochemical window of H2O seriously restricts the energy density and output voltage of ARBs,especially aqueous rechargeable Fe-based ***,we introduce a new battery system:the anode contains C@Fe/Fe_(2)O_(3)composite,which is interfaced with an alkaline electrolyte;the cathode contains LiMn_(2)O_()in contact with a neutral electrolyte.A Li^(+)-conducting membrane is carefully selected to decouple the electrode-electrolyte,which effectively widens the electrochemical window to above 2.65 V,thereby enables an aqueous rechargeable iron *** average output voltage is 1.83 V and its energy density is 235.3 Wh/kg at 549 W/*** this work,we propose the energy storage mechanism with the aid of density functional theory(DFT).The calculated reduction potential of the anode agrees with the experimental ***,this battery system demonstrates long cycle lifespan of approximately 2500 cycles at 2 A/g,corresponding to a capacity retention of 82.1%.These results are very far superior than those of mainstream aqueous rechargeable Fe-based batteries,which guarantee future investigation for storing electricity energy.

关键词： aqueous battery high voltage high energy iron oxide theoretical calculation

Fabricating a smart clothing system based on strain-sensing yarn and novel stitching technology for health monitoring

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science China(Technological sciences) 2024年第2期67卷 587-596页

作者： TANG Jian WU YuTing MA ShiDong ZHANG YuMin XU RuoJie YAN Tao PAN ZhiJuan College of Textile and Clothing Engineering Soochow UniversitySuzhou 215123China National Engineering Laboratory for Modern Silk Suzhou 215123China

Various yarn-shaped flexible strain sensors have recently been ***,research is lacking on additive manufacturing for smart clothing for integrating yarn sensors with commercial ***,a strain-sensing yarn is sewn into a piece of fabric through a novel stitching technique,and the influence of the stitching method and needle pitch on the sensing performance is investigated using finite element analysis(FEA).The sensing performance could be improved when the sensing yarn is self-locked in the fabric at the needle eyes,and the needle pitch was reduced to 0.5 cm,which is attributed to the enhanced stress and strain ***,the composite sensing fabric featured outstanding performance,including a low detection limit(0.1%),rapid response(280 ms),excellent durability(10000 cycles),and high stability(negligible drift and frequency independence).In addition,the remarkable wear resistance,washability,and anti-interference to ambient humidity and perspiration were ***,the optimal stitch trace lengths of sensing yarn for detecting elbow motion,breathing,and heartbeats are ***,a smart clothing system composed of smart clothing,data acquisition unit,and mobile APP was developed to simultaneously detect human movement and physiological *** work provides a reference to produce intelligent garments based on yarn sensors for health monitoring.

关键词： strain-sensing yarn composite sensing fabric smart clothing system stitching technology health monitoring

Revolutionizing tumor immunotherapy:unleashing the power of progenitor exhausted T cells

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Cancer Biology & Medicine 2024年第6期21卷 499-512页

作者： Zhang Fang Xinyi Ding Hao Huang Hongwei Jiang Jingting Jiang Xiao Zheng Department of Tumor Biological Treatment The Third Affiliated Hospital of Soochow UniversityChangzhou 213003China jiangsu Engineering Research Center for Tumor Immunotherapy The Third Affiliated Hospital of Soochow UniversityChangzhou 213003China Institute for Cell Therapy of Soochow University The Third Affiliated Hospital of Soochow UniversityChangzhou 213003China

In exploring persistent infections and malignancies, a distinctive subgroup of CD8^(+) T cells, progenitor exhausted CD8^(+) T(Tpex) cells, has been identified. These Tpex cells are notable for their remarkable self-renewal and rapid proliferation abilities. Recent strides in immunotherapy have demonstrated that Tpex cells expand and differentiate into responsive exhausted CD8^(+) T cells, thus underscoring their critical role in the immunotherapeutic retort. Clinical examinations have further clarified a robust positive correlation between the proportional abundance of Tpex cells and enhanced clinical prognosis. Tpex cells have found noteworthy applications in the formulation of inventive immunotherapeutic approaches against tumors. This review describes the functions of Tpex cells in the tumor milieu, particularly their potential utility in tumor immunotherapy. Precisely directing Tpex cells may be essential to achieving successful outcomes in immunotherapy against tumors.

关键词： Progenitor exhausted CD8^(+)T cells TCF-1 immunotherapy tumor microenvironment cellular crosstalk

Clinical applications of metagenomics next-generation sequencing in infectious diseases

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Journal of Zhejiang University-science B(Biomedicine & Biotechnology) 2024年第6期25卷 471-484页

作者： Ying LIU Yongjun MA Department of Clinical Laboratory Affiliated Jinhua HospitalZhejiang University School of MedicineJinhua 321000China

Infectious diseases are a great threat to human *** and accurate detection of pathogens is important in the diagnosis and treatment of infectious *** next-generation sequencing(mNGS)is an unbiased and comprehensive approach for detecting all RNA and DNA in a *** the development of sequencing and bioinformatics technologies,mNGS is moving from research to clinical application,which opens a new avenue for pathogen *** studies have revealed good potential for the clinical application of mNGS in infectious diseases,especially in difficult-to-detect,rare,and novel ***,there are several hurdles in the clinical application of mNGS,such as:(1)lack of universal workflow validation and quality assurance;(2)insensitivity to high-host background and low-biomass samples;and(3)lack of standardized instructions for mass data analysis and report ***,a complete understanding of this new technology will help promote the clinical application of mNGS to infectious *** review briefly introduces the history of next-generation sequencing,mainstream sequencing platforms,and mNGS workflow,and discusses the clinical applications of mNGS to infectious diseases and its advantages and disadvantages.

关键词： Metagenomics next-generation sequencing(mNGS) Infectious disease Cerebrospinal fluid(CSF) Oxford Nanopore Technologies(ONT) Microbiome

Engineered extracellular vesicles for targeted reprogramming of cancer-associated fibroblasts to potentiate therapy of pancreatic cancer

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Signal Transduction and Targeted Therapy 2024年第7期9卷 3077-3096页

作者： Pengcheng Zhou Xuanlong Du Weilu Jia Kun Feng Yewei Zhang Department of General Surgery Affiliated Hospital of Nantong UniversityNantongChina School of Medicine Southeast UniversityNanjingChina Nanjing Medical University NanjingChina Hepatobiliary and Pancreatic Center The Second Affiliated Hospital of Nanjing Medical UniversityNanjingChina

Pancreatic cancer is one of the deadly malignancies with a significant mortality rate and there are currently few therapeutic options for *** tumor microenvironment(TME)in pancreatic cancer,distinguished by fibrosis and the existence of cancer-associated fibroblasts(CAFs),exerts a pivotal influence on both tumor advancement and resistance to *** advancements in the field of engineered extracellular vesicles(EVs)offer novel avenues for targeted therapy in pancreatic *** study aimed to develop engineered EVs for the targeted reprogramming of CAFs and modulating the TME in pancreatic *** obtained from bone marrow mesenchymal stem cells(BMSCs)were loaded with miR-138-5p and the anti-fibrotic agent pirfenidone(PFD)and subjected to surface modification with integrinα5-targeting peptides(named IEVs-PFD/138)to reprogram CAFs and suppress their pro-tumorigenic ***α5-targeting peptide modification enhanced the CAF-targeting ability of ***-138-5p directly inhibited the formation of the FERMT2-TGFBR1 complex,inhibiting TGF-βsignaling pathway *** addition,miR-138-5p inhibited proline-mediated collagen synthesis by directly targeting the FERMT2-PYCR1 *** combination of miR-138-5p and PFD in EVs synergistically promoted CAF reprogramming and suppressed the pro-cancer effects of *** experiments using the orthotopic stroma-rich and patient-derived xenograft mouse models yielded promising *** particular,IEVs-PFD/138 effectively reprogrammed CAFs and remodeled TME,which resulted in decreased tumor pressure,enhanced gemcitabine perfusion,tumor hypoxia amelioration,and greater sensitivity of cancer cells to ***,the strategy developed in this study can improve chemotherapy *** IEVs-PFD/138 as a targeted therapeutic agent to modulate CAFs and the TME represents a promising therapeutic approach for pancreatic cancer.

关键词： inhibited targeted chemotherapy

First-line camrelizumab(a PD-1 inhibitor)plus apatinib(an VEGFR-2 inhibitor)and chemotherapy for advanced gastric cancer(SPACE):a phase 1 study

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1760-1767页

作者： Xiaofeng Chen Hao Xu Xiaobing Chen Tongpeng Xu Yitong Tian Deqiang Wang Fen Guo Kangxin Wang Guangfu Jin Xiao Li Rong Wang Fengyuan Li Yongbin Ding Jie Tang Yueyu Fang Jing Zhao Liang Liu Ling Ma Lijuan Meng Zhiguo Hou Rongrong Zheng Yang Liu Ni Guan Bei Zhang Shuang Tong Shiqing Chen Xing Li Yongqian Shu Department of Oncology The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Gusu School Nanjing medical UniversitySuzhouChina jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer Personalized MedicineNanjing Medical UniversityNanjingChina Department of General surgery The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Department of Oncology Henan Cancer Hospital Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhouChina Henan Engineering Research Center of Precision Therapy of Gastrointestinal Cancer&Zhengzhou Key Laboratory for Precision Therapy of Gastrointestinal Cancer ZhengzhouChina Department of Oncology Digestive Disease Institute&Cancer Institute of Jiangsu UniversityAffiliated Hospital of Jiangsu UniversityZhenjiangChina Department of Oncology Suzhou Hospital of Nanjing Medical UniversitySuzhouChina Department of Oncology Nanjing PuKou People’s HospitalNanjingChina Department of Epidemiology School of Public HealthNanjing Medical UniversityNanjingChina Department of Pathology The First Affiliated Hospital with Nanjing Medical UniversityNanjingChina Department of general surgery Jurong Branch hospital of Jiangsu Province People HospitalJurongChina Department of Medical Oncology Liyang People’s HospitalLiyangChina Department of radiology Nanjing PuKou People’s HospitalNanjingChina jiangsu Hengrui Pharmaceuticals ShanghaiChina Department of Medical Affairs 3D Medicines Inc.ShanghaiChina Shanghai OrigiMed Co. Ltd.ShanghaiChina

Patients with advanced gastric cancer typically face a grim *** phase 1a(dose escalation)and phase 1b(dose expansion)study investigated safety and efficacy of first-line camrelizumab plus apatinib and chemotherapyfor advanced gastric or gastroesophageal junction *** primary endpoints included maximum tolerated dose(MTD)in phase 1a and objective response rate(ORR)across phase 1a and *** 1a tested three dose regimens of camrelizumab,apatinib,oxaliplatin,and *** regimen 1:camrelizumab 200 mg on day 1,apatinib 250 mg every other day,oxaliplatin 100 mg/m^(2) on day 1,and S-140 mg twice a day on days *** regimen 2:same as dose regimen 1,but oxaliplatin 130mg/*** regimen3:same as dose regimen 2,but apatinib 250 mg ***-four patients were included(9 in phase 1a,25 in phase 1b).No dose-limiting toxicities occurred so no MTD was *** 3 was set for the recommended phase 2 doses and administered in phase *** confrmed ORR was 76.5%(95%CI 58.8-89.3).The median progression-free survival was 8.4 months(95%CI 5.9-not evaluable[NE]),and the median overall survival(OS)was not mature(11.6-NE).Ten patients underwent surgery after treatment and the multidisciplinary team *** 24 patients without surgery,the median OS was 19.6 months(7.8-NE).Eighteen patients(52.9%)developed grade≥3 treatment-emergent adverse *** plus apatinib and chemotherapy showed favorable clinical outcomes and manageable safety for untreated advanced gastric cancer(ChiCTR2000034109).

关键词： regimen cancer doses

Federated Meta Reinforcement Learning for Personalized Tasks

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Tsinghua science and technology 2024年第3期29卷 911-926页

作者： Wentao Liu Xiaolong Xu Jintao Wu Jielin Jiang School of Computer science Nanjing University of Information Science and TechnologyNanjing 210044China School of Software Nanjing University of Information Science and TechnologyNanjing 210044China

As an emerging privacy-preservation machine learning framework,Federated Learning(FL)facilitates different clients to train a shared model collaboratively through exchanging and aggregating model parameters while raw data are kept local and *** this learning framework is applied to Deep Reinforcement Learning(DRL),the resultant Federated Reinforcement Learning(FRL)can circumvent the heavy data sampling required in conventional DRL and benefit from diversified training data,besides privacy preservation offered by *** FRL implementations presuppose that clients have compatible tasks which a single global model can *** practice,however,clients usually have incompatible(different but still similar)personalized tasks,which we called task *** may severely hinder the implementation of FRL for practical *** this paper,we propose a Federated Meta Reinforcement Learning(FMRL)framework by integrating Model-Agnostic Meta-Learning(MAML)and ***,we innovatively utilize Proximal Policy Optimization(PPO)to fulfil multi-step local training with a single round of ***,considering the sensitivity of learning rate selection in FRL,we reconstruct the aggregation optimizer with the Federated version of Adam(Fed-Adam)on the server *** experiments demonstrate that,in different environments,FMRL outperforms other FL methods with high training efficiency brought by Fed-Adam.

关键词： federated learning reinforcement learning meta-learning personalization

Magnetic resonance imaging-based lymph node radiomics for predicting the metastasis of evaluable lymph nodes in rectal cancer

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1849-1860页

作者： Yong-Xia Ye Liu Yang Zheng Kang Mei-Qin Wang Xiao-Dong Xie Ke-Xin Lou Jun Bao Mei Du Zhe-Xuan Li Department of Radiology The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210011Jiangsu ProvinceChina Department of Colorectal Surgery Jiangsu Cancer Hospital and Jiangsu Institute of Cancer Research and The Affiliated Cancer Hospital of Nanjing Medical UniversityNanjing 210000Jiangsu ProvinceChina1 Department of Pathology The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210011Jiangsu ProvinceChina Colorectal Center The Affiliated Cancer Hospital of Nanjing Medical University&Jiangsu Cancer Hospital&Jiangsu Institute of Cancer ResearchNanjing 210011Jiangsu ProvinceChina

BACKGROUND Lymph node(LN)staging in rectal cancer(RC)affects treatment decisions and patient *** radiologists,the traditional preoperative assessment of LN metastasis(LNM)using magnetic resonance imaging(MRI)poses a *** To explore the value of a nomogram model that combines Conventional MRI and radiomics features from the LNs of RC in assessing the preoperative metastasis of evaluable *** In this retrospective study,270 LNs(158 nonmetastatic,112 metastatic)were randomly split into training(n=189)and validation sets(n=81).LNs were classified based on pathology-MRI *** MRI features[size,shape,margin,T2-weighted imaging(T2WI)appearance,and CE-T1-weighted imaging(T1WI)enhancement]were *** radiomics models used 3D features from T1WI and T2WI ***,a nomogram model combining conventional MRI and radiomics features was *** model used univariate analysis and multivariable logistic *** employed the receiver operating characteristic curve,with DeLong test for comparing diagnostic *** performance was assessed using calibration and decision curve *** The nomogram model outperformed conventional MRI and single radiomics models in evaluating *** the training set,the nomogram model achieved an area under the curve(AUC)of 0.92,which was significantly higher than the AUCs of 0.82(P<0.001)and 0.89(P<0.001)of the conventional MRI and radiomics models,*** the validation set,the nomogram model achieved an AUC of 0.91,significantly surpassing 0.80(P<0.001)and 0.86(P<0.001),*** The nomogram model showed the best performance in predicting metastasis of evaluable LNs.

关键词： Radiomics Lymph node metastasis Rectal cancer Magnetic resonance imaging