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Anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab for first-line treatment in advanced natural killer T cell lymphoma

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1665-1674页

作者： Jie Xiong Shu cheng Xiao Gao Shan-He Yu Yu-Ting Dai Xin-Yun Huang Hui-Juan Zhong Chao-Fu Wang hong-Mei Yi Hao Zhang Wei-guo Cao Rong Li Wei Tang Yan zhao Peng-Peng Xu Li Wang Wei-Li zhao Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational Medicine at ShanghaiRuijin Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Nuclear Medicine Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Pathology Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Otolaryngology Shanghai Rujin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Radiation Shanghai Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghaiChina Department of Hematology Navy Medical Center of PLAShanghaiChina Pole de Recherches Sino-Francais en Science du Vivant et Genomique Laboratory of Molecular PathologyShanghaiChina

Natural killer T cell lymphoma(NKTCL)is highly aggressive,with advanced stage patients poorly responding to intensive *** explore effective and safe treatment for newly diagnosed advanced stage NKTCL,we conducted a phase ll study of anti-metabolic agent pegaspargase plus PD-1 antibody sintilimab(NCT04096690).Twenty-two patients with a median age of 51 years(range,24-74)were enrolled and treated with induction treatment of pegaspargase 2500 IU/m2 intramuscularly on day 1 and sintilimab 200 mg intravenously on day 2 for 6 cycles of 21 days,followed by maintenance treatment of sintilimab 200 mg for 28 cycles of 21 *** complete response and overall response rate after induction treatment were 59%(95%Cl,43-79%)and 68%(95%Cl,47-84%),*** a median follow-up of 30 months,the 2 year progression-free and overall survival rates were 68%(95%Cl,45-83%)and 86%(95%Cl,63-95%),*** most frequently grade 3/4 adverse events were neutropenia(32%,n=7)and hypofibrinogenemia(18%,n=4),which were manageable and led to no discontinuation of *** proportion score of PD-L1,peripheral blood high-density lipoprotein cholesterol,and apolipoprotein A-l correlated with good response,while PD-1 on tumor infiltrating lymphocytes and peripheral Treg cells with poor response to pegaspargase plus sintilimab *** conclusion,the chemo-free regimen pegaspargase plus sintilimab was effective and safe in newly diagnosed,advanced stage *** lipid profle and immunosuppressive signature contributed to treatment resistance,providing an alternative therapeutic approach dual targeting fatty acid metabolism and CTLA-4 in NKTCL.

关键词： killer metabolism lymphoma

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Improving RSW nugget diameter prediction method:unleashing the power of multi-fidelity neural networks and transfer learning

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Advances in Manufacturing 2024年第3期12卷 409-427页

作者： Zhong-Jie Yue Qiu-Ren Chen Zu-guo Bao Li Huang guo-Bi Tan Ze-hong Hou Mu-Shi Li Shi-Yao Huang Hai-Long zhao Jing-Yu Kong Jia Wang Qing Liu Key Laboratory for Light-weight Materials Nanjing Tech UniversityNanjing210009People’s Republic of China School of Advanced Technology Xi’an Jiaotong-Liverpool UniversitySuzhou215123JiangsuPeople’s Republic of China Material Academy JITRISuzhou215100JiangsuPeople’s Republic of China School of Mechanical Engineering Shanghai Jiao Tong UniversityShanghai200240People’s Republic of China

This research presents an innovative approach to accurately predict the nugget diameter in resistance spot welding(RSW)by leveraging machine learning and transfer learning ***,low-fidelity(LF)data were obtained through finite element numerical simulation and design of experiments(DOEs)to train the LF machine learning ***,high-fidelity(HF)data were collected from RSW process experiments and used to fine-tune the LF model by transfer learning *** accuracy and generalization performance of the models were thoroughly *** results demonstrated that combining different fidelity datasets and employing transfer learning could significantly improve the prediction accuracy while minimize the costs associated with experimental trials,and provide an effective and valuable method for predicting critical process parameters in RSW.

关键词： Resistance spot welding(RSW) Nugget diameter prediction Multi-fidelity neural networks Transfer learning

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An engineered Cas12i nuclease that is an efficient genome editing tool in animals and plants

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The Innovation 2024年第2期5卷 61-69页

作者： Zhiqiang Duan Yafeng Liang Jialei Sun hongjin Zheng Tong lin Pengyu Luo Mengge Wang Ruiheng Liu Ying Chen Shuhua guo Nannan Jia hongtao Xie Meili Zhou Minghui Xia Kaijun zhao Shuhui Wang Na Liu Yongling Jia Wei Si Qitong Chen Yechun hong Ruilin Tian Jian-Kang Zhu Institute of Advanced Biotechnology and School of Medicine Southern University of Science and TechnologyShenzhen 518055China Bellagen Biotechnology Jinan 250000China Department of Medical Neuroscience School of MedicineKey University Laboratory of Metabolism and Health of GuangdongSouthern University of Science and TechnologyShenzhenGuangdong Province 518055China

The type V-I CRISPR-Cas system is becoming increasingly more attractive for genome ***,natural nucleases of this system often exhibit low efficiency,limiting their ***,we used structure-guided rational design and protein engineering to optimize an uncharacterized Cas12i nuclease,*** a result,we developed Cas-SF01,a Cas12i3 variant that exhibits significantly improved gene editing activity in mammalian ***-SF01 shows comparable or superior editing performance compared to SpCas9 and other Cas12 *** to natural Cas12i3,Cas-SF01 has an expanded PAM range and effectively recognizes NTTN and noncanonical NATN and TTVN *** addition,we identified an amino acid substitution,D876R,that markedly reduced the off-target effect while maintaining high on-target activity,leading to the development of CasSF01^(HiFi)(high-fidelity Cas-SF01).Finally,we show that Cas-SF01 has high gene editing activities in mice and *** results suggest that CasSF01 can serve as a robust gene editing platform with high efficiency and specificity for genome editing applications in various organisms.

关键词： system attractive rational

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Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection:How to achieve a better outcome

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1833-1848页

作者： Fan Mu Liang-Shuo Hu Kun Xu Zhen zhao bai-Cai Yang Yi-Meng Wang Kun guo Jian-Hua Shi Yi Lv Bo Wang Department of Hepatobiliary Surgery First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Department of Anaesthesiology First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061Shaanxi ProvinceChina Department of Gynaecology Wenzhou Medical University Affiliated Jiaxing Women and Children HospitalJiaxing 314000Zhejiang ProvinceChina

BACKGROUND Although the benefits of antiviral therapy for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)have been proven,researchers have not con-firmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time(at least 24 wk)and patients who received remedial antiviral therapy just before radical resection for HBV-related *** To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related *** A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi’an Jiaotong University from January 2016 to June 2019 was *** the history of antiviral therapy,patients were assigned to remedial antiviral therapy and preoperative antiviral therapy *** Kaplan–Meier analysis revealed significant differences in overall survival(P<0.0001)and disease-free survival(P=0.035)between the two *** analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival(hazard ratio=0.27;95%confidence interval:0.08-0.88;P=0.030).CONCLUSION In patients with HBV-related HCC,it is ideal to receive preoperative long-term antiviral therapy,which helps patients tolerate more extensive hepatectomy;however,remedial antiviral therapy,which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL,can also result in improved outcomes.

关键词： Hepatectomy Hepatitis B virus Antiviral therapy Hepatocellular carcinoma Hepatitis B virus-DNA

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Insights into photocatalytic mechanism over a novel Cu_(2)WS_(4)/MoS_(2) S-scheme heterojunction

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Rare Metals 2024年第7期43卷 3118-3133页

作者： Wei zhao Ji-Hui Cao Jun-Jie Liao Yun Liu Xiao-Jun Zeng Jun-Yu Shen Xue-Kun hong Yang guo He-Hua Zeng Ya-Zi Liu School of Materials Engineering Jiangsu Key Laboratory of Advanced Functional MaterialsSchool of Electronic and Information EngineeringChangshu Institute of TechnologyChangshu215500China School of Chemistry and Chemical Engineering Changji UniversityChangji 831100China State Environmental Protection Key Laboratory of Soil Environmental Management and Pollution Control Ministry of Ecology and EnvironmentNanjing Institute of Environmental SciencesNanjing 210023China School of Environment Jiangsu Engineering Lab of Water and Soil Eco-RemediationNanjing Normal UniversityNanjing 210023China Department of Chemical Engineering Curtin UniversityPerthWA6845Australia

A novel efficient Cu_(2)WS_(4)/MoS_(2) step-scheme(S-scheme)heterojunction photocatalyst was constructed for the first time and applied in the removal of environmental *** the as-prepared photocatalysts,the Cu_(2)WS_(4)/MoS_(2)-8%heterojunc tion photoc atalyst demonstrates the optimal photocatalytic performance,with the catalytic oxidation efficiency of tetracycline(TC)and the catalytic reduction efficiency of Cr^(6+)reaching 93.3%and 82.1%,*** excellent catalytic properties of Cu_(2)WS_(4)/MoS_(2) heterojunction photocatalysts are attributed to the effective separation pathways of charges and the presence of S-scheme heterojunctions,together with stronger redox *** is speculated that the photogenerated carrier migration path of the Cu_(2)WS_(4)/MoS_(2) catalyst follows the typical S-scheme photocatalytic mechanism,which is verified by the in-depth experimental study and simulated calculations including the electron paramagnetic resonance(EPR)analysis,free radical quenching experiments,charge density distribution,and simulated built-in electric field formation at the interface,which acts as driving force to promote the separation of photoinduced electrons and ***,the photocatalytic mechanism of S-scheme photogenerated carrier migration for the Cu_(2)WS_(4)/MoS_(2) catalyst is revealed based on the systematic experimental techniques and simulated calculations,accounting for its superior photocatalytic oxidation and reduction *** study provides inspiring implications to develop high-efficient S-scheme photocatalytic systems for versatile applications in solarenergy conversion.

关键词： Cu_(2)WS_(4)/MoS_(2) S-scheme Heterojunction Photocatalysis

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Stepped-up development of accelerator mass spectrometry method for the detection of ^(60)Fe with the HI-13 tandem accelerator

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Nuclear Science and Techniques 2024年第4期35卷 136-143页

作者： Yang Zhang Sheng-Quan Yan Ming He Qing-Zhang zhao Wen-Hui Zhang Chao-Xin Kan Jian-Ming Zhou Kang-Ning Li Xiao-Fei Wang Jian-cheng Liu zhao-Hua Peng Zhuo Liang Ai-ling Li Jian Zheng Qi-Wen Fan Yun-Ju Li You-Bao Wang Zhi-hong Li Yang-Ping Shen Ding Nan Wei Nan Yu-Qiang Zhang Jia-Ying-Hao Li Jun-Wen Tian Jiang-lin Hou Chang-Xin guo Zhi-cheng Zhang Ming-Hao Zhu Yu-Wen Chen Yu-Chen Jiang Tao Tian Jin-Long Ma Yi-Hui Liu Jing-Yu Dong Run-Long Liu Mei-Yue-Nan Ma Yong-Shou Chen Wei-Ping Liu Bing guo China Institute of Atomic Energy P.O.Box 275(10)Beijing 102413China College of Science Southern University of Science and TechnologyShenzhen 518055China School of Physics Xi’an Jiaotong UniversityXi’an 710049China

The Moon provides a unique environment for investigating nearby astrophysical events such as *** samples retain valuable information from these events,via detectable long-lived“fingerprint”radionuclides such as^(60)*** this work,we stepped up the development of an accelerator mass spectrometry(AMS)method for detecting^(60)Fe using the HI-13tandem accelerator at the China Institute of Atomic Energy(CIAE).Since interferences could not be sufficiently removed solely with the existing magnetic systems of the tandem accelerator and the following Q3D magnetic spectrograph,a Wien filter with a maximum voltage of±60 kV and a maximum magnetic field of 0.3 T was installed after the accelerator magnetic systems to lower the detection background for the low abundance nuclide^(60)Fe.A 1μm thick Si_(3)N_(4) foil was installed in front of the Q3D as an energy *** particle detection,a multi-anode gas ionization chamber was mounted at the center of the focal plane of the ***,an^(60)Fe sample with an abundance of 1.125×10^(-10)was used to test the new AMS *** results indicate that^(60)Fe can be clearly distinguished from the isobar^(60)*** sensitivity was assessed to be better than 4.3×10^(-14)based on blank sample measurements lasting 5.8 h,and the sensitivity could,in principle,be expected to be approximately 2.5×10^(-15)when the data were accumulated for 100 h,which is feasible for future lunar sample measurements because the main contaminants were sufficiently separated.

关键词： Accelerator mass spectrometry Wien filter Isobar separation Supernovae Chang'e-5 lunar samples

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Trends in Incidence of HIV and Syphilis Among Men Who Have Sex with Men—Tianjin Municipality,China,2013-2022

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China CDC weekly 2024年第27期6卷 651-657页

作者： Yan guo Fangfang Chen Hui Gong Ziming Wu Xinying Zhang Tielin Ning Zhongquan Liu Jianyun bai Long Li Jie Yang Fangning zhao Jinyu Hou Maohe Yu Houlin Tang STD&AIDS Control and Prevention Section Tianjin Center for Disease Control and PreventionTianjinChina National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases National Center for AIDS/STD Control and PreventionChinese Center for Disease Control and PreventionBeijingChina STD&AIDS Control and Prevention department Tianjin Hongqiao District Center for Disease Control and PreventionTianjinChina Tianjin Shenlan Public Health Counseling Service Center TianjinChina Tianjin Key Laboratory of Pathogenic Microbiology of Infectious Disease Tianjin Centers for Disease Control and PreventionTianjinChina

Summary What is already known about this topic?Given the common modes of transmission,outbreaks of both human immunodeficiency virus(HIV)and syphilis are primarily observed in men who have sex with men(MSM).However,minimal research has been conducted to concurrently evaluate the rates and trends of HIV and syphilis incidence within this community in *** is added by this report?

关键词： Incidence primarily immunodeficiency

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Themechanism of resistance to CDK4/6 inhibition and novel combination therapy with RNR inhibition for chemo-resistant bladder cancer

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Cancer Communications 2024年第6期44卷 700-704页

作者： Zhichao Tong Yubo zhao Shiyu bai Benedikt Ebner Lou Lienhard Yuling zhao Ziqi Wang Qi Pan Pengyu guo Thilo Bracht Barbara Sitek Jürgen E.Gschwend Wanhai Xu Roman Nawroth Department of Urology Harbin Medical University Cancer HospitalHarbinHeilongjiangP.R.China NHC and CAMS Key Laboratory of Molecular Probe and Targeted Theranostics Harbin Medical UniversityHarbinHeilongjiangP.R.China Department of Urology Klinikum rechts der IsarTechnical university of MunichMunichGermany Department of Urology The Fourth Hospital of Harbin Medical UniversityHarbinHeilongjiangP.R.China Department of Urology Ludwig-Maximilians-University of MunichMunichGermany Department of Urology Shanghai General HospitalShanghai Jiao Tong UniversityShanghaiP.R.China Medizinisches Proteom-Center Ruhr-Universität BochumBochumGermany Clinic for Anesthesiology Intensive Care and Pain TherapyUniversity Medical Center Knappschaftskrankenhaus BochumBochumGermany

Bladder cancer(BCa)is the most prevalent urological cancer worldwide[1].A significant proportion of BCa(89%)exhibits molecular alterations in the cell cycle pathway,and targeting cyclin-dependent kinases 4 and 6(CDK4/6)is deemed as a promising therapeutic strategy[2].Selective inhibitors of CDK4/6(CDK4/6is)have been approved by the US Food and Drug Administration(FDA)[3].

关键词： bladder CDK4 alterations

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SETD3-mediated histidine methylation of MCM7 regulates DNA replication by facilitating chromatin loading of MCM

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Science China Life Sciences 2024年

作者： hong-guo Duan Shuang Wang Wen-Jie Shu Yong-Jia Tong Hai-Zhen Long guo-hong Li Hai-Ning Du Meng-Jie zhao Hubei Key Laboratory of Cell Homeostasis College of Life SciencesTaiKang Center for Life and Medical SciencesFrontier Science Center for Immunology and MetabolismEmergency CenterZhongnan Hospital of Wuhan UniversityRNA InstituteWuhan University The Institute for Advanced Studies Wuhan University Shenzhen Bay Laboratory Hubei Key Laboratory of Cell Homeostasis College of Life Sciences TaiKang Center for Life and Medical Sciences Frontier Science Center for Immunology and Metabolism Wuhan University

The minichromosome maintenance complex(MCM) DNA helicase is an important replicative factor during DNA replication. The proper chromatin loading of MCM is a key step to ensure replication initiation during S phase. Because replication initiation is regulated by multiple biological cues, additional changes to MCM may provide better understanding towards this event. Here, we report that histidine methyltransferase SETD3 promotes DNA replication in a manner dependent on enzymatic activity. Nascent-strand sequencing(NS-seq)shows that SETD3 regulates replication initiation, as depletion of SETD3 attenuates early replication origins firing. Biochemical studies reveal that SETD3 binds MCM mainly during S phase, which is required for the CDT1-mediated chromatin loading of MCM. This MCM loading relies on histidine-459 methylation(H459me) on MCM7 which is catalyzed by SETD3. Impairment of H459 methylation attenuates DNA synthesis and chromatin loading of MCM. Furthermore, we show that CDK2 phosphorylates SETD3 at Serine-21 during the G1/S phase,which is required for DNA replication and cell cycle progression. These findings demonstrate a novel mechanism by which SETD3 methylates MCM to regulate replication initiation.

关键词： histidine methylation SETD3 DNA replication MCM replication origin firing

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Malignant glaucoma treated by low-dose laser cycloplasty: a 1-year multicenter prospective noncomparative study

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1248-1254页

作者： Hai-Shuang lin Xiao-Ping Xu Xuan-Li Zheng Ji-Bing Wang Su-Jie Fan Zuo-hongWu Su-Mian cheng Li-Jun zhao Qin-Hua Cai Shao-Dan Zhang Shan-Shan Liu Ai-guo Lyu Ying Zhang hong Chen Dan-Ni Jiang Wu-Liang Li Nathan Congdon Clement C Tham Ming-Guang He Yuan-Bo Liang the Malignant Glaucoma TreatmentTrial Study(MGTT)Group Wenzhou Medical University Wenzhou 325027Zhejiang ProvinceChina Ningbo Eye Hospital Ningbo 315100Zhejiang ProvinceChina Weifang Eye Hospital Weifang 261000Shandong ProvinceChina Handan Eye Hospital Handan 056000Hebei ProvinceChina Aier Eye Hospital(Wuhan) Wuhan 430061Hubei ProvinceChina Hebei Eye Hospital Xingtai 054001Hebei ProvinceChina The Third People’s Hospital of Dalian Dalian 116033Liaoning ProvinceChina First Affiliated Hospital of Suzhou University Suzhou 215031Jiangsu ProvinceChina National Clinical Research Center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina Glaucoma Research Institute Wenzhou Medical UniversityWenzhou 325027Zhejiang ProvinceChina Centre for Public Health Queen’s University BelfastBelfast BT71NNUK Orbis International New YorkUSA Department of Ophthalmology and Visual Sciences the Chinese University of Hong KongHong Kong SAR 999077China Centre for Eye Research Australia University of MelbourneRoyal Victorian Eye and Ear HospitalEast Melbourne 3000VICAustralia 不详

AIM:To report a one-year clinical outcomes of low-dose laser cycloplasty(LCP)among malignant glaucoma ***:In this prospective,multicenter,noncomparative clinical study,participants with malignant glaucoma were recruited and underwent LCP at eight ophthalmic centers in *** were followed up at 1wk,1,3,6,and *** pressure(IOP),number of glaucoma medications,anterior chamber depth(ACD),and complications were *** success was defined as the reformation of the anterior chamber based on slit-lamp *** was defined by the presence of a shallow orﬂat anterior chamber after initial recovery from ***:A total of 34 eyes received *** IOP and medications decreased from 36.1±11.5 mm Hg with 3.3±1.5 glaucoma medications pre-treatment to 20.9±9.8 mm Hg(Pline to 1.7±1.0 mm and to 2.0±0.5 mm at 1d and 12mo,respectively.A total of 32(94.1%)eyes achieved initial anatomical *** follow-up,2(5.9%)eyes failed and 8(23.5%)eyes relapsed,yielding a 12-month anatomical success rate of 64.3%.Complications including anterior synechia(8.82%),choroidal/ciliary detachment(5.88%)and hypopyon(2.94%)were observed within ***:LCP is simple,safe,and effective in reforming the anterior chamber in malignant glaucoma.

关键词： anterior chamber reformation intraocular pressure low-dose laser cycloplasty malignant glaucoma anatomical success

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