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Advances in targeted therapy for human epidermal growth factor receptor 2 positive in advanced gastric cancer

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World Journal of Gastrointestinal Oncology 2024年第6期16卷 2318-2334页

作者： Ya-Kun Jiang wei li Ying-Yang Qiu Meng Yue Department of Gastroenterology Central Hospital Affiliated to Shandong First Medical UniversityJinan 250013Shandong ProvinceChina Health Management Center Central Hospital Affiliated to Shandong First Medical UniversityJinan 250013Shandong ProvinceChina Yong Loo lin School of Medicine National University of SingaporeSingapore 119077Singapore

Emerging therapeutic methods represented by targeted therapy are effective supplements to traditional first-line chemoradiotherapy *** epidermal growth factor receptor 2(HER2)is one of the most important targets in targeted therapy for gastric *** combined with chemotherapy has been used as the first-line treatment for advanced gastric *** safety and efficacy of pertuzumab and margetuximab in the treatment of gastric cancer have been ***,monoclonal antibodies,due to their large molecular weight,inability to penetrate the blood-brain barrier,and drug resistance,lead to decreased therapeutic efficacy,so it is necessary to explore the efficacy of other HER2-targeting therapies in gastric ***-molecule tyrosine kinase inhibitors,such as lapatinib and pyrrotinib,have the advantages of small molecular weight,penetrating the blood-brain barrier and high oral bioavailability,and are expected to become the drugs of choice for perioperative treatment and neoadjuvant therapy of gastric cancer after validation by large-scale clinical trials in the ***-drug conjugate,such as T-DM1 and T-DXd,can overcome the resistance of monoclonal antibodies despite their different mechanisms of tumor killing,and are a supplement for the treatment of patients who have failed the treatment of monoclonal antibodies such as ***,after more detailed stratification of gastric cancer patients,various gastric cancer drugs targeting HER2 are expected to play a more significant role.

关键词： Human epidermal growth factor receptor 2 Gastric cancer Targeted therapy Review

Styrax japonicus functional genomics:an efficient virus induced gene silencing(VIGS)system

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Horticultural Plant Journal 2024年第1期10卷 252-258页

作者： Gangyu Sun Yiqian Ju Cuiping Zhang Lulu li Xinqiang Jiang Xiaoman Xie Yizeng Lu Kuiling Wang wei li College of Landscape Architecture and Forestry Qingdao Agricultural UniversityQingdaoShandong 266109China Shandong Provincial Center of Forest and Grass Germplasm Resources JinanShandong 250102China

VIGS(Virus-induced gene silencing),a method for posttranscriptional gene silencing,is an effective technique for investigating the activities of genes in *** there is no report for available VIGS system in Styrax japonicus,the application of a VIGS approach that results in a gene knockdown to study gene function is *** this study,we compared the characteristics that could affect the viability of VIGS in ***,including the acetosyringone(AS)concentration,the Agrobacterium’s optical density and the inoculation *** stable reference genes of *** were selected to validate the gene’s knockdown by quantitative *** a result,we successfully constructed 2 VIGS systems based on TRV virus:vacuum with AS concentration of 200μmol·L^(-1)and OD600of 0.5,and friction-osmosis with AS concentration of 200μmol·L^(-1)and OD600of 1.0,which silencing efficiency was 83.33%and 74.19%,*** successfully applied VIGS method provides a rapid and effective reverse gene functional analysis approach in *** to identify unknown gene functions.

关键词： Styrax japonicus VIGS Reference gene

Structural Geology and Chronology of Shear Zones along the Shangdan Suture in Qinling Orogenic Belt,China:Implications for Late Mesozoic Intra-Continental Deformation of East Asia

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Journal of Earth Science 2024年第2期35卷 376-393页

作者： Falak Sheir wei li Le Zhang Basil Alabowsh liuqing Jiang li liang Sainan Gao Shair Baz Umar Ashraf State Key Laboratory of Continental Dynamics Department of GeologyNorthwest UniversityXi’an710069China Institute of Geology University of PunjabLahore45590Pakistan

The Shangdan suture zone(SDZ)in the Qinling orogenic belt(QOB)is a key to understanding the East Asia tectonic *** SDZ gives information about convergent processes between the North China Block(NCB)and South China Block(SCB).In the Late Mesozoic,several shear zones evolved along the SDZ boundary that helps us comprehend the collisional deformation between the NCB and SCB,which was neglected in previous *** shear zones play an essential role in the tectonic evolution of the East Asia *** study focuses on the deformation and geochronology of two shear zones distributed along the SDZ,identified in the Shaliangzi and Maanqiao *** shear sense indicators and kinematic vorticity numbers(0.54–0.90)suggest these shear zones have sinistral shear and sub-simple shear deformation *** quartz’s dynamic recrystallization and c-axis fabric analysis in the Maanqiao shear zone(MSZ)revealed that the MSZ experienced deformation under green-schist facies conditions at∼400–500℃.The Shaliangzi shear zone deformed under amphibolite facies at∼500–700℃.The^(40)Ar/^(39)Ar(muscovite-biotite)dating of samples provided a plateau age of 121–123 *** with previously published data,our results concluded that QOB was dominated by compressional tectonics during the Late Early ***,we suggested that the Siberian Block moved back to the south and Lhasa-Qiantang-Indochina Block to the north,which promoted intra-continental compressional tectonics.

关键词： Qinling orogenic belt Shangdan suture zone shear zone Late Mesozoic intra-continental deformation East Asia tectonics

Effect of inlet elbow on rotation stall in waterjet ppropulsionpump

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Fundamental Research 2024年第4期4卷 898-906页

作者： wei li Shuo li Leilei Ji Enda li weidong Shi Ramesh Agarwal Muhammad Awais National Research Center of Pumps Jiangsu UniversityZhenjiang 212013China Institute of Fluid Engineering Equipment Technology Jiangsu UniversityZhenjiang 212009China College of Mechanical Engineering Nantong UniversityNantong 226019China departmentof Mechanical Engineering&Materials Science Washington University in StLouisSt.LouisMO6330US.

To study the influence of an elbow inlet on the rotating stall characteristics of a waterjet propulsion pump(WJPP),a three-dimensional internal flow field in a WJPP under a straight-pipe inlet and elbow inlet is numerically *** comparing the hydraulic performance of WJPP under the two inlet conditions,the internal relationship between the inlet mode and the flow pattern in the pump is *** on unsteady pressure fluctuation characteristics and wavelet analysis,the influence of the inlet mode on the rotating stall is revealed,and the stall transient propagation characteristics under critical stall conditions are *** disturbance effects of the inlet channel geometry disappear under low flow rate conditions,the main disturbance is induced by the highspeed countercurrent,and the flow pattern under the elbow inlet is better than that under the straight-pipe *** the straight-pipe inlet,the single-stall nucleus in the WJPP temporarily experiences a low-frequency and high-amplitude disturbance,which subsequently transforms into a mode of multi-stall nuclei with high-frequency circumferential *** the elbow inlet,the rotating stall always maintains a mode of high-amplitude and low-frequency disturbance,which represents the transient characteristics of a single stall core propagating in the circumferential direction inside the *** results of this study have a reference value for structural design optimization in a WJPP.

关键词： Waterjet propulsion pump Inlet condition Rotation stall Flow structure Pressurefluctuation

Single droplet formation by controlling the viscoelasticity of polymer solutions during inkjet printing

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Chinese Chemical Letters 2024年第6期35卷 244-248页

作者： Dong Lv Xuelei liu wei li Qiang Zhang Xinhong Yu Yanchun Han State Key Laboratory of Polymer Physics and Chemistry Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China School of Applied Chemistry and Engineering University of Science and Technology of ChinaHefei 230026China

Inkjet printing has emerged as a potential solution processing method for large-area patterned *** inkjet printing,a single droplet without satellite droplet is required for high-quality ***,we propose a strategy for obtaining a single droplet by adjusting the reduced concentration(c/c^(*),where c^(*)is the critical overlap concentration)in the range of *** formation can be categorized into three distinct regimes:(1)c/c^(*)lite droplet;(2)c/c^(*)=1.0-1.5,single droplet;(3)c/c^(*)>2.0,no ***,an inertial-capillary balance led to the 2/3-power scaling of the minimum radius with time for the solutions of c/c^(*)ligament radius decreased exponentially with ***,the weissenberg number was higher than the critical value of 0.5,indicating that the polymer chains underwent coil-stretch *** viscoelastic-capillary balance dominated instead of the inertial-capillary *** resulting viscoelastic resistance reduced the length of the ligament and increased the velocity difference between the satellite and main ***,a single droplet was *** addition,the law can be successfully generalized to various molecular weights,molecular structures and solvents.

关键词： Inkjet printing Single droplet Satellite droplet Viscoelasticity Coil-stretch

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

Small molecule conjugates with selective estrogen receptor β agonism promote anti-aging benefits in metabolism and skin recovery

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2137-2152页

作者： Tarik Zahr Vijay K.Boda Jian Ge Lexiang Yu Zhongzhi Wu Jianwen Que wei li li Qiang Naomi Berrie Diabetes Center Columbia UniversityNew YorkNY 10032USA Department of Molecular Pharmacology and Therapeutics Columbia UniversityNew YorkNY 10032USA Department of Pharmaceutical Sciences College of PharmacyUniversity of Tennessee Health Science CenterMemphisTN 38163USA Drug Discovery Center College of PharmacyUniversity of Tennessee Health Science CenterMemphisTN 38163USA Division of Digestive and liver Diseases Columbia UniversityNew YorkNY 10032USA Center for Human Development Columbia UniversityNew YorkNY 10027USA Department of Pathology and Cell Biology Columbia UniversityNew YorkNY 10032USA Department of Medicine Columbia UniversityNew YorkNY 10032USA

Estrogen is imperative to mammalian reproductivity,metabolism,and ***,the hormone activating estrogen receptor(ERs)αcan cause major safety concerns due to the enrichment of ERαin female tissues and certain *** contrast,ERβis more broadly expressed in metabolic tissues and the ***,it is desirable to generate selective ERβagonist conjugates for maximizing the therapeutic effects of ERs while minimizing the risks of ERα***,we report the design and production of small molecule conjugates containing selective non-steroid ERβagonists Gtx878 or *** of aged mice with our synthesized conjugates improved aging-associated declines in insulin sensitivity,visceral adipose integrity,skeletal muscle function,and skin health,with validation in *** further uncovered the benefits of ERβconjugates in the skin using two inducible skin injury mouse models,showing increased skin basal cell proliferation,epidermal thickness,and wound ***,our ERβ-selective agonist conjugates offer novel therapeutic potential to improve aging-associated conditions and aid in rejuvenating skin health.

关键词： Estrogen receptorβ Aging Metabolism Skin injury Muscle metabolism Small molecule conjugates Regeneration Adiposity

Actively Reconfigurable Valley Topological Edge and Corner States in Photonic Crystals Based on Phase Change Material Ge2Sb2Te5

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激光与光电子学进展 2024年第5期61卷 557-571页

作者： li wei Peng Yuxiang Su Peihao li Jianbo Wang Kaijun liu Exian liu Jianqiang He Mengdong College of Science Hunan Province Key Laboratory of Materials Surface&Interface Science and TechnologyCentral South University of Forestry and TechnologyChangsha 410004HunanChina College of Science Jiujiang UniversityJiujiang 332005JiangxiChina

The immunity of topological states against backscattering and structural defects provides them with a unique advantage in the exploration and design of high-precision low-loss optical ***,the operating bandwidth of the topological states in certain photonic structures is difficult to actively tune and flexibly *** this study,we propose a valley topological photonic crystal(TPC)comprising two inverse honeycomb photonic crystals,consisting of hexagonal silicon and Ge2Sb2Te5(GST)*** GST transitions from the amorphous phase to the crystalline phase,the edge band of the TPC appears as a significant redshift and is inversed from a“∪”to an“∩”shape with topological phase transition,which enables active tuning of the operating bandwidth and propagation direction of topological edge *** the topological edge and corner states in a triangular structure constructed using TPCs can be simultaneously adjusted and reconfigured via GST phase transition,along with a change in the group number of corner *** the adjustability of topological edge states and electromagnetic coupling between two different topological bearded interfaces,we develop a multichannel optical router with a high tuning degree of freedom,where channels can be actively reconfigured and their on/off states can be freely *** study provides a strategy for the active regulation of topological states and may be beneficial for the development of reconfigurable topological optical devices.

关键词： topological edge states topological corner states phase change material active reconfiguration topological photonic crystal

JW-1-283 inhibits melanoma tumor growth via stabilization of the p53 pathway

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Genes & Diseases 2024年第3期11卷 18-21页

作者： Yang Xie Ruida Hou Kelli LHartman Jianxiong Jiang Zhongzhi Wu wei li Drug Discovery Center College of PharmacyUniversity of Tennessee Health Science CenterMemphisTN38163USA

Melanoma is a lethal skin malignancy and the fifth most diagnosed cancer in the United States.1 Currently,for unresectable melanoma,the recommended treatment options include checkpoint inhibitor immunotherapy targeting programmed cell death 1(PD-1),and inhibitors targeting the mitogen-activated protein kinase(MAPK)***,the response rate may vary among the patients,and therefore demanding the development of novel treatment *** suppressor TP53has been suggested as one of the critical regulators mediating the aggressiveness and progression of melanoma.

关键词： melanoma suppressor death