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Contactin-associated protein-like 2(CNTNAP2)mutations impair the essentialα-secretase cleavages,leading to autism-like phenotypes

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1625-1636页

作者： Qing Zhang Mengen xing Zhengkai Bao Lu Xu Yang Bai wanqi Chen wenhao Pan Fang Cai Qunxian w.ng Shipeng Guo Jing Zhang Zhe w.ng Yili wu Yun Zhang Jia-Da Li weihong Song Oujiang Laboratory(Zhejiang Lab for Regenerative Medicine Vision and Brain Health)Zhejiang Key Laboratory of Alzheimer's DiseaseZhejiang Provincial Clinical Research Center for Mental DisordersSchool of Mental Health and Wenzhou Kangning HospitalThe Second Affiliated Hospital and Yuying Children's HospitalInstitute of AgingWenzhou Medical UniversityWenzhouZhejiang 325035China Townsend Family Laboratories Department of PsychiatryBrain Research CenterThe University of British Columbia2255 Wesbrook MallVancouverBC V6T 1Z3Canada Chongqing Key Laboratory of Translational Medical Research in Cognitive Development and Learning and Memory Disorders Ministry of Education Key Laboratory of Child Development and DisordersChildren's Hospital of Chongqing Medical UniversityChongqing 400014China Center for Medical Genetics Hunan Key Laboratory of Animal Models for Human DiseasesHunan Key Laboratory of Medical GeneticsHunan International Scientific and Technological Cooperation Base of Animal Models for Human DiseasesSchool of Life SciencesCentral South UniversityChangsha 410078 HunanChina The National Clinical Research Center for Geriatric Disease Xuanwu HospitalCapital Medical UniversityBeijing 100053Chin

Mutations in the Contactin-associated protein-like 2(CNTNAP2)gene are associated with autism spectrum disorder(ASD),and ectodomain shedding of the CNTNAP2 protein plays a role in its ***,key enzymes involved in the C-terminal cleavage of CNTNAP2 remain largely unknown,and the effect of ASD-associated mutations on this process and its role in ASD pathogenesis remain *** this report we showed that CNTNAP2 undergoes sequential cleavages by furin,ADAM10/17-dependent a-secretase and presenilindependent *** identified that the cleavage sites of ADAM10 and ADAM17 in CNTNAP2 locate at its C-terminal residue I79 and L96,and the main a-cleavage product C79 by ADAM10 is required for the subsequent y-secretase cleavage to generate CNTNAP2 intracellular domain(CICD).ASD-associated CNTNAP2 mutations impair the a-cleavage to generate C79,and the inhibition leads to ASDIlike repetitive and social behavior abnormalties in the Cntnap2l1254T knock-in ***,exogenous expression of 79 improves autism-ike phenotypes in the Cntnap2^(11254T) knock-in and Cntnap2^(-/-)knockout *** data demonstrates that the a-secretase is essential for CNTNAP2 processing and its *** study indicates that inhibition of the cleavage by pathogenic mutations underlies ASD pathogenesis,and upregulation of its C-terminal fragments could have therapeutical potentials for ASD treatment.

关键词： NAP2 cleavage subsequent

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Taurine attenuates activation of hepatic stellate cells by inhibiting autophagy and inducing ferroptosis

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world Journal of Gastroenterology 2024年第15期30卷 2143-2154页

作者： Sen Li Qian-Jun Ren Can-Hao Xie Yang Cui Li-Tao Xu Yi-Dan w.ng Su Li xing-Qiu Liang Bin wen Ming-Kun Liang Xiao-Fang Zhao Department of Basic Science Guangxi University of Chinese MedicineNanning 541100Guangxi Zhuang Autonomous RegionChina Department of Science and Technology Ruikang Hospital Affiliated to Guangxi University of Chinese MedicineNanning 541100Guangxi Zhuang Autonomous RegionChina Traditional Chinese Medicine Specialty Office Ruikang Hospital Affiliated to Guangxi University of Chinese MedicineNanning 541100Guangxi Zhuang Autonomous RegionChina

BACKGROUND Liver fibrosis is a compensatory response during the tissue repair process in chronic liver injury,and finally leads to liver cirrhosis or even hepatocellular *** pathogenesis of hepatic fibrosis is associated with the progressive accumulation of activated hepatic stellate cells(HSCs),which can transdiffer-entiate into myofibroblasts to produce an excess of the extracellular matrix(ECM).Myofibroblasts are the main source of the excessive ECM responsible for hepatic ***,activated hepatic stellate cells(aHSCs),the principal ECM producing cells in the injured liver,are a promising therapeutic target for the treatment of hepatic *** To explore the effect of taurine on aHSC proliferation and the mechanisms *** Human HSCs(LX-2)were randomly divided into five groups:Normal control group,platelet-derived growth factor-BB(PDGF-BB)(20 ng/mL)treated group,mmol/L,respectively)with PDGF-BB(20 ng/mL)treated *** Counting Kit-8 method was performed to evaluate the effect of taurine on the viability of ***-linked immunosorbent assay was used to estimate the effect of taurine on the levels of reactive oxygen species(ROS),malondialdehyde,glutathione,and iron *** electron microscopy was applied to observe the effect of taurine on the autophagosomes and ferroptosis features in *** real-time polymerase chain reaction and western blot analysis were performed to detect the effect of taurine on the expression ofα-SMA,Collagen I,Fibronectin 1,LC3B,ATG5,Beclin 1,PTGS2,SLC7A11,and *** Taurine promoted the death of aHSCs and reduced the deposition of the *** with taurine could alleviate autophagy in HSCs to inhibit their activation,by decreasing autophagosome formation,downregulating LC3B and Beclin 1 protein expression,and upregulating p62 protein ***,treatment with taurine triggered ferroptosis and ferritinophagy to eliminate aHSCs characterized b

关键词： Hepatic stellate cells Autophagy Ferroptosis Molecular docking Taurine

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Multifactor roadmap for designing low-power-consumed micro thermoelectric thermostats in a closed-loop integrated 5G optical module

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Interdisciplinary Materials 2024年第2期3卷 326-337页

作者： Dongw.ng Yang Yubing xing Jiang w.ng Kai Hu Yani Xiao Kechen Tang Jianan Lyu Junhao Li Yutian Liu Peng Zhou Yuan Yu Yonggao Yan Xinfeng Tang State Key Laboratory of Advanced Technology for Materials Synthesis and Processing Wuhan University of TechnologyWuhanChina Nanostructure Research Center Wuhan University of TechnologyWuhanChina Research Center for Materials Genome Engineering Wuhan University of TechnologyWuhanChina Institute of Physics(IA) RWTH Aachen UniversityAachenGermany

As the core components of fifth-generation(5G)communication technology,optical modules should be consistently miniaturized in size while improving their level of *** inevitably leads to a dramatic spike in power consumption and a consequent increase in heat flow density when operating in a confined *** ensure a successful start-up and operation of 5G optical modules,active cooling and precise temperature control via the Peltier effect in confined space is essential yet *** this work,p-type Bi_(0.5)Sb_(1.5)Te_(3)and n-type Bi_(2)Te_(2.7)Se_(0.3)bulk thermoelectric(TE)materials are used,and a micro thermoelectric thermostat(micro-TET)(device size,2×9.3×1.1mm^(3);leg size,0.4×0.4×0.5mm^(3);number of legs,44)is successfully integrated into a 5G optical module with Quad Small Form Pluggable 28 *** a result,the internal temperature of this kind of optical module is always maintained at 45.7°C and the optical power is up to 7.4 ***,a multifactor design roadmap is created based on a 3D numerical model using the ANSYS finite element method,taking into account the number of legs(N),leg width(w),leg length(L),filling atmosphere,electric contact resistance(Rec),thermal contact resistance(Rtc),ambient temperature(Ta),and the heat generated by the laser source(QL).It facilitates the integrated fabrication of micro-TET,and shows the way to enhance packaging and performance under different operating *** to the roadmap,the micro-TET(2×9.3×1mm^(3),w=0.3 mm,L=0.4 mm,N=68 legs)is fabricated and consumes only 0.89w in cooling mode(Q_(L)=0.7w,T_(a)=80℃)and 0.36win heating mode(T_(a)=0℃)to maintain the laser temperature of 50℃.This research will hopefully be applied to other microprocessors for precise temperature control and integrated manufacturing.

关键词： 5G optical module finite element simulation micro thermoelectric thermostat Peltier effect

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Effects of typical karst tourist town on the Lijiang River water: from heavy metals to N-nitrosamines

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Journal of Earth Science 2024年

作者： Yuanyu Shan Yuru Su Xinli xing Bingquan Zhu Honghu Zeng Yuan Zhang Junyu Li Xiaoyu Yan wenwen Chen Benjian Li College of Environmental Science and Engineering， Guilin University of Technology School of Environmental Studies， China University of Geosciences State Key Laboratory of Biogeology and Environmental Geology， China University of Geosciences College of arts， Guilin University of Technology College of arts and communication， China University of Geosciences 430070 China

N-nitrosamines are nitrogenous organic pollutants with high carcinogenicity to human. Heavy metal pollution in aquatic system is currently a major environmental problem. Tourism in typical karst areas may influence the environment through wastewater discharge. However， it remains unclear whether these activities would cause water pollution. To evaluate the impact of tourism activities in typical tourist towns， this study investigated the occurrence and sources of 18 N-nitrosamines， eight heavy metals （HMs）， and dissolved inorganic nitrogen （DIN） in the Lijiang River and its tributaries. Seven N-nitrosamines were detected as the dominant compounds in N-nitroso-N-ethylaniline （NEA， average of 24.8 ng/L） and N-nitroso-l-proline （NPRO， 20.4 ng/L）， while especially low concentrations of HMs （Mn， Cu， As， Ni， Cr， Co， Pb， and Cd） and DIN (NH4+-N， NO2--N， and NO3--N) were observed. The most important influencing factors were seasonal factors， followed by land-use type and mainstem and tributary factors. Principal component analysis revealed that in the city with developed tourism and relatively less heavy industry， aquaculture and agricultural wastewater were identified as the primary sources of N-nitrosamines. Meanwhile， domestic sewage and agricultural wastewater were found to be the main sources of HMs and DIN， respectively. The ecological risk assessments for all pollutants are relatively low （ng River.

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Cross-section distortion and springback characteristics of double-cavity aluminum profile in force controlled stretch-bending

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Transactions of Nonferrous Metals Society of China 2024年第8期34卷 2476-2490页

作者： Zhi-wen LIU Zi-xuan DOng Cong-chang XU Jie YI Luo-xing LI School of Mechanical Engineering University of South ChinaHengyang 421001China State Key Laboratory of Advanced Design and Manufacturing Technology for Vehicle Hunan UniversityChangsha 410082China

3D elastic-plastic FE model for simulating the force controlled stretch-bending process of double-cavity aluminum profile was established using hybrid explicit−implicit solvent *** the computational accuracy and efficiency,the optimal choices of numerical parameters and algorithms in FE modelling were *** formation mechanisms of cross-section distortion and springback were *** effects of pre-stretching,post-stretching,friction,and the addition of internal fillers on forming quality were *** results show that the stress state of profile in stretch-bending is uniaxial with only a circumferential *** stress distribution along the length direction of profile is non-uniform and the maximum tensile stress is located at a certain distance away from the center of *** aluminum profile is gradually attached to bending die,the distribution characteristic of cross-section distortion along the length direction of profile changes from V-shape to *** unloading the forming tools,cross-section distortion decreases obviously due to the stress relaxation,with a maximum distortion difference of 13%before and after *** pre-stretching and post-stretching forces increase,cross-section distortion increases gradually,while springback first decreases and then remains *** increasing friction between bending die and profile,cross-section distortion slightly decreases,while springback ***-section distortion decreases by 83%with adding PVC fillers into the cavities of profile,while springback increases by 192.2%.

关键词： hollow aluminum profile force controlled stretch-bending numerical parameters springback analysis approach cross-section distortion springback process parameters

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Production and test of sPHENIX w/SciFiber electromagnetic calorimeter blocks in China

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Nuclear Science and Techniques 2024年第8期35卷 167-176页

作者： Xiao‑Zhou Yu Xi‑Yang w.ng wei‑Hu Ma Shi‑Hong Fu Peng‑Fei Sun Jin‑xing Song wan‑Bing He Yang Shen Long Ma Jin‑Hui Chen Huan‑Zhong Huang Si‑Guang w.ng Jing Zhou Xiao‑Mei Li Institute of Modern Physics Fudan UniversityShanghai 200433China Key Laboratory of Nuclear Physics and Ion‑Beam Application(MOE) Fudan UniversityShanghai 200433China Science and Technology on Nuclear Data Laboratory China Institute of Atomic EnergyBeijing 102413China Department of Physics and Astronomy University of CaliforniaLos AngelesCA 90095USA State Key Laboratory of Nuclear Physics and Technology School of PhysicsPeking UniversityBeijing 100871China

The sPHENIX experiment is a new generation of large acceptance detectors at the relativistic heavy ion collider at Brookhaven National Laboratory,with scientific goals focusing on probing the strongly interacting Quark–Gluon plasma with hard probes of jets,open heavy flavor particles,andγ*** EMCal detector,which covers the pseudo-rapidity region of|η|≤1.1,is an essential subsystem of *** this study,we focused on producing and testing EMCal blocks covering a pseudo-rapidity of|η|∈[0.8,1.1].These,in conjunction with the central pseudo-rapidity EMCal blocks,significantly enhance the sPHENIX physics capability of the jet andγparticle *** this paper,the detector module production and testing of sPHENIX w-powder/scintillating fiber(w/ScFi)electromagnetic calorimeter blocks are *** selection of the tungsten powder,mold fabrication,QA procedures,and cosmic ray test results are discussed.

关键词： sPHENIX Tungsten/scintillating fiber electromagnetic calorimeter Cosmic ray test

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Efficacy and safety of anlotinib combined with the STUPP regimen in patients with newly diagnosed glioblastoma: a multicenter, single-arm, phase Ⅱ trial

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Cancer Biology & Medicine 2024年第5期21卷 433-444页

作者： Shuzhen Lai Peijing Li Xiaohui Liu Guihong Liu Tieming Xie xing Zhang Xiaoxuan w.ng Jing Huang Yiqiang Tang Zhigang Liu Guoping Shen Chaoming Li Fangxiao Lu Lei w.ng Fagui Jiang Caixing Sun Yuanyuan Chen Ming Chen Department of Radiation Oncology The Second Affiliated Hospital of Soochow UniversitySuzhou 215000China Department of Radiation Oncology Yuebei People’s Hospital Affiliated to the Medical College of Shantou UniversityShaoguan 512026China Chinese Academy of SciencesHangzhou 310022China Department of Radiation Oncology The Second Clinical Medical College of Zhejiang Chinese Medical UniversityHangzhou 311403China Department of Radiation Oncology The Affiliated Hospital of Xuzhou Medical UniversityXuzhou 221004China Chinese Academy of SciencesHangzhou 310022China State Key Laboratory of Translational Medicine and Innovative Drug Development Jiangsu Simcere Diagnostics Co.LtdNanjing 210000China Department of Radiation Oncology The Affiliated Huai’an First People’s Hospital of Nanjing Medical UniversityHuai’an 223399China Department of Radiation Oncology Jiangxi Cancer Hospital of Nanchang UniversityNanchang 330029China Department of Radiotherapy Dongguan Institute of Clinical Cancer ResearchDongguan Key Laboratory of Precision Diagnosis and Treatment for TumorsAffiliated Dongguan HospitalSouthern Medical UniversityDongguan 523059China The Cancer Center The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai 519000China Department of Radiation Oncology The First Affiliated Hospital of Sun Yat-Sen UniversityGuangzhou 510080China Department of Oncology Maoming People’s HospitalMaoming 525000China Department of Radiation Oncology Kecheng District People’s HospitalQuzhou 324003China Chinese Academy of SciencesHangzhou 310022China Department of Radiation Oncology State Key Laboratory of Oncology in South ChinaSun Yat-sen University Cancer CenterGuangzhou 510060China United Laboratory of Frontier Radiotherapy Technology of Sun Yat-sen University&Chinese Academy of Sciences Ion Medical Technology Co. LtdGuangzhou 510060China

Objective:Glioblastomas are highly vascularized malignant *** determined the efficacy and safety of the anti-angiogenic multi-kinase inhibitor,anlotinib,for a newly diagnosed ***:This multicenter,single-arm trial(NCT04119674)enrolled 33 treatment-naïve patients with histologically proven glioblastomas between March 2019 and November *** underwent treatment with the standard STUPP regimen[fractionated focal irradiation in daily fractions of 1.8-2 Gy given 5 d/w×6 w(total=54-60 Gy)]or radiotherapy plus continuous daily temozolomide(TMZ)(75 mg/m^(2)of body surface area/d,7 d/w from the first to the last day of radiotherapy),followed by 6 cycles of adjuvant TMZ(150-200 mg/m^(2)×5 d during each 28-d cycle)plus anlotinib(8 mg/d on d 1-14 of each 3-w cycle for 2 cycles during concomitant chemoradiotherapy,8 maximal cycles as adjuvant therapy,followed by maintenance at 8 mg/*** primary endpoint was progression-free survival(PFS).Secondary endpoints included overall survival(OS)and adverse events(AEs).Results:Thirty-three patients received the planned *** median PFS was 10.9 months(95%CI,9.9-18.7 months)and the 12-month PFS rate was 48.5%.The median OS was 17.4 months(95%CI,14.5-21.1 months)and the 12-month OS rate was 81.8%.The most common AEs included hypertriglyceridemia[58%(n=19)],hypoalbuminemia[46%(n=15)],and hypercholesterolemia[46%(n=15)]during concurrent chemoradiotherapy and leukopenia[73%(n=24)],hypertriglyceridemia[67%(n=22)],and neutropenia[52%(n=17)]during adjuvant *** patients discontinued treatment due to ***1(HR,5.6;95%CI,1.3-23.7;P=0.021)and RP1L1 alterations(HR,11.1;95%CI,2.2-57.2;P=0.004)were associated with a significantly shorter ***:Anlotinib plus the STUPP regimen has promising anti-tumor activity against glioblastoma and manageable ***1 and RP1L1 alterations might be novel predictive biomarkers of the response to anlotinib.

关键词： Glioblastoma anti-angiogenesis multi-kinase inhibitor anlotinib temozolomide progression-free survival

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一类上临界状态的两性分支过程的Berry-Esseen界

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南开大学学报（自然科学版） 2024年第1期57卷 106-109,115页

作者：邢永胜山东工商学院数学学院山东烟台264005

考虑了一类一夫多妻制配对模式下两性分支过程,分析了其标准化过程的收敛速度,得到了它的Berry-Esseen界.

关键词：两性Galton-watson分支过程一夫多妻制 Berry-Esseen界

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Donor-acceptor modulation of coordination polymers for effective photothermal conversion

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Science China Chemistry 2024年

作者： Bo Zhang xing-w.ng Li Han Fang Chang-Tai Li Si-Jia Yu Mei-Hui Yu Ze Chang Xian-He Bu School of Materials Science and Engineering Nankai University State Key Laboratory of Elemento-Organic Chemistry Nankai University

The targeted construction of donor-acceptor（D-A） materials featuring efficient photothermal（PT） conversion properties has been an attractive but challenging goal. Herein, a new series of coordination polymers（CPs） featuring different PT performances were constructed with flexible linker 1,1′-Ferrocenedicarboxylic acid（FCA） and 2,4,6-tri（pyridin-4-yl）-1,3,5-triazine（TPT） as acceptor and donor molecules including coronene and tetrathiafulvalene（TTF）. Based on the flexible configurations of FCA ligand and the directing of donor dependent D-A interactions, the structures of TF-1 to TF-3 featuring distinctive dimension were obtained based on Cd（II） ions for investigating the PT property in configurational perspectives. A systematic investigation of the PT properties of the CPs was performed. Notably, TF-3 exhibits the finest PT conversion effect under the irradiation of 560 nm laser, while TF-2 shows optimal PT conversion under 808 nm laser irradiation required for biological PT therapy,illustrating the correlation between the structural and component features of the CPs and their PT performances. Furthermore,Zn（II） as bio-friendly ion was utilized to construct hypotoxic TF-4 that reveals similar structure to that of TF-2 for potential application. Polydimethylsiloxane（PDMS） patches doped with TF-4 exhibits considerable NIR PT conversion effect under808 nm, represented by the nearly 80 °C temperature increased in 120 s for TF-4@PDMS patch（1.2 wt%） under 0.9 w cm-2irradiation, the results of which herein indicate the potential of D-A CPs as versatile platform for the modulation of PT materials.

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Cryogenic springback of 2219-w aluminum alloy sheet through V-shaped bending

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Transactions of Nonferrous Metals Society of China 2024年第10期34卷 3185-3193页

作者： Xiao-bo FAN Qi-liang w.ng Fang-xing wU Xu-gang w.ng School of Mechanical Engineering Dalian University of TechnologyDalian 116081China School of Materials Science and Engineering Harbin Institute of TechnologyHarbin 150096China

A V-shaped bending device was established to evaluate the effects of temperature and bending fillet radius on springback behavior of 2219-w aluminum alloy at cryogenic *** cryogenic springback mechanism was elucidated through mechanical analyses and numerical *** results indicated that the springback angle at cryogenic temperatures was greater than that at room *** springback angle increased further as the temperature returned to ambient conditions,attributed to the combined effects of the “dual enhancement effect” and thermal ***,a critical fillet radius made the springback angle zero for 90° V-shaped *** critical fillet radius at cryogenic temperatures was smaller than that at room temperature,ow.ng to the influence of temperature variations on the bending moment ratio between the forward bending section at the fillet and the reverse bending section of the straight arm.

关键词： 2219-w aluminum alloy cryogenic forming V-shape bending springback critical fillet radius

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