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Als-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating bCl2–bECN1 interaction

Acta Pharmaceutica sinica b 2024年第5期14卷 2026-2038页

作者： shiqiang Xu Qilian Ma Junwen shen Ningning li shan sun Nana Wang Yang Chen Chunsheng dong kin Yip tam Jochen h.M.Prehn hongfeng Wang Zheng Ying Jiangsu Key laboratory of Neuropsychiatric diseases and College of Pharmaceutical sciences Soochow UniversitySuzhou 215123China MOE Key laboratory of Geriatric diseases and immunology College of Pharmaceutical SciencesSuzhou Medical College of Soochow UniversitySuzhou 215123China Jiangsu Province Engineering Research Center of Precision diagnostics and therapeutics development Soochow UniversitySuzhou 215123China dept.of Physiology&Medical Physics and FUtURE-NEURO Research Centre Royal College of Surgeons in IrelandDublin D02 YN77Ireland Faculty of health sciences University of MacaoTaipaMacao 999078China insititutes of biology and Medical science Soochow UniversitySuzhou 215123China

Growing evidences indicate that dysfunction of autophagy contributes to the disease pathogenesis of amyotrophic lateral sclerosis(Als)and frontotemporal dementia(Ftd),two neurodegenerative *** GGGGCC·GGCCCC repeat rnA expansion in chromosome 9 open reading frame 72(C9orf72)is the most genetic cause of both Als and *** to the previous studies,GGGGCC·GGCCCC repeat undergoes the unconventional repeat-associated non-AtG translation,which produces dipeptide repeat(dPR)*** there is a growing understanding that C9orf72 dPRs have a strong ability to harm neurons and induce C9orf72-linked Als/Ftd,whether these dPRs can affect autophagy remains *** the present study,we find that poly-GR and poly-PR,two arginine-containing dPRs which display the most cytotoxic properties according to the previous studies,strongly inhibit starvation-induced ***,our data indicate that arginine-rich dPRs enhance the interaction between bCl2 and bECN1/beclin 1 by inhibiting bCl2 phosphorylation,therefore they can impair autophagic clearance of neurodegenerative disease-associated protein aggregates under starvation condition in ***,our study not only highlights the role of C9orf72 dPR in autophagy dysfunction,but also provides novel insight that pharmacological intervention of autophagy using sW063058,a small molecule compound that can disrupt the interaction between bECN1 and bCl2,may reduce C9orf72 dPR-induced neurotoxicity.

关键词： Amyotrophic lateral sclerosis Frontotemporal dementia C9orf72 Autophagy bCl2 bECN1/beclin 1 dipeptide repeat Neurodegeneration

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small-molecule agents for cancer immunotherapy

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Acta Pharmaceutica sinica b 2024年第3期14卷 905-952页

作者： Fang Wang Kai Fu Yujue Wang Can Pan Xueping Wang Zeyu liu Chuan Yang Ying Zheng Xiaopeng li Yu lu Kenneth kin Wah to Chenglai Xia Jianye Zhang Zhi shi Zeping hu Min huang liwu Fu state Key laboratory of Oncology in south China Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China school of Pharmaceutical sciences Tsinghua-Peking Center for Life SciencesBeijing Frontier Research Center for Biological StructureTsinghua UniversityBeijing 100084China state Key laboratory of drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China department of Cell biology&institute of biomedicine National Engineering Research Center of Genetic MedicineMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Guangzhou Municipal and Guangdong Provincial Key laboratory of Molecular target&Clinical Pharmacology NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China school of Pharmacy The Chinese University of Hong KongHong Kong 999077China Affiliated Foshan Maternity and Child healthcare hospital Southern Medical UniversityFoshan 528000China

Cancer immunotherapy,exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor t-cell therapy,is revolutionizing cancer *** induce long-term tumor regression and overall survival benefit in many types of *** the advances in our knowledge about the tumor immune microenvironment,remarkable progress has been made in the development of small-molecule drugs for *** molecules targeting PRR-associated pathways,immune checkpoints,oncogenic signaling,metabolic pathways,cytokine/chemokine signaling,and immune-related kinases have been extensively *** of smallmolecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor ***,we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.

关键词： Cancer immunotherapy small-molecule agents immune checkpoints Oncogenic signaling Metabolic pathways Cytokine/chemokine signaling Antitumor immunity tumor immune microenvironment

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bcl-2转基因小鼠的视神经再生

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中华眼科杂志 2005年第9期41卷 832-836页

作者：杨柳 kin-sang Cho 北京大学第一医院眼科 100034 美国哈佛医学院schepens眼科研究所

目的探讨新生小鼠bcl2高表达是否足以使视神经损伤后再生,并探讨再生的神经轴突能否到达脑内正常的靶组织。方法对出生后3d的C57bl/6J野生小鼠和bcl2转基因小鼠进行视神经夹闭损伤,1～4d后处死小鼠,做视神经和脑组织切片,利用神经轴突... 详细信息

目的探讨新生小鼠bcl2高表达是否足以使视神经损伤后再生,并探讨再生的神经轴突能否到达脑内正常的靶组织。方法对出生后3d的C57bl/6J野生小鼠和bcl2转基因小鼠进行视神经夹闭损伤,1～4d后处死小鼠,做视神经和脑组织切片,利用神经轴突顺行性标记物—带有荧光的霍乱毒素b和GAP43免疫荧光染色检查并评估视神经的再生。结果C57bl/6J野生小鼠视神经损伤后不能再生,损伤的轴突在24h内退缩,而bcl2转基因小鼠的视神经活跃地再生了相当长的距离,并于4d后到达脑内的靶组织,但大部分再生的神经轴突沿着对侧眼的视路到达损伤同侧的脑内的靶组织,只有很少的神经轴突到达对侧。结论在出生后3d,bcl2高表达足以使小鼠视网膜神经节细胞损伤后再生,并且再生的神经轴突可以长距离生长至中脑的靶组织,但神经轴突沿着已存在的视路进入同侧的脑内。

关键词： bcl-2转基因小鼠神经再生视神经视网膜神经节

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Cloaking nanosecond events at any time

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Frontiers of Optoelectronics 2020年第2期13卷 188-189页

作者： bowen li Kenneth kin-Yip WONG department of Electrical Computerand Energy EngineeringUniversity of ColoradoBoulderColoradoUSA department of Electrical and Electronic Engineering The University of Hong KongHong KongChina

the concept of cloaking has never failed to fascinate scientific *** recent years,the idea has ignited a whole new trend of research effort when extended to temporal domain.A typical temporal cloak conceals events from probing light by creating a temporal intensity gap(cloaking time)that will later be closed back by manipulating the speed of light leveraging the chromatic dispersion in dielectric media.

关键词： domain. dielectric dispersion

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inhibition of angiogenesis and hCt-116 xenograft tumor growth in mice by kallistatin

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World Journal of Gastroenterology 2007年第34期13卷 4615-4619页

作者： Yong diao Jian Ma Wei-dong Xiao Jia luo Xin-Yan li kin-Wah Chu Peter WC Fung Nagy habib Farzin Farzaneh Rui-An Xu Molecular Medicine Engineering Research Center of the Ministry of Education Institute of Molecular Medicine Huaqiao University Quanzhou362021 Fujian Province China department of Medicine Hong Kong University Hong Kong China department of Pharmacy Chicago UniversityUnited States department of transplantation Imperial College London United Kingdom department of haematological & Molecular Medicine King's College London London SE5 9NUUnited Kingdom

AiM： tO investigate the inhibitory effect of kallistatin （KAl） on angiogenesis and hCt-116 xenograft tumor growth.MEthOds： heterotopic subcutaneous injection of 2 seven days later, 2 x 1011 injected intratumorally （n tumors were induced by x 106 hCt-11 cells in mice. rAAV-GFP or rAAV-KAl was = 5 for each group）. the mice were sacrificed at d 28, by which time the tumors in the rAAV-GFP group had grown to beyond 5% of the total body weight. tumor growth was measured by calipers in two dimensions. tumor angiogenesis was determined with tumor microvessel density （MVd） by immunohistology. tumor cell proliferation was assessed by Ki-67 staining.REsUlts： intratumor injection of rAAV-KAl inhibited tumor growth in the treatment group by 78% （171 ＋ 52 mm^3） at d 21 after virus infection compared to the control group （776 ＋ 241 mm^3）. Microvessel density was significantly inhibited in tumor tissues treated with rAAV-KAl, rAAV-KAl also decreased the proportion of proliferating cells （Ki-67 positive cells） in tumors compared with the control group.CONClUsiON： rAAV-mediated expression of KAl inhibits the growth of colon cancer by reducing angiogenesis and proliferation of tumor cells, and may provide a promising anti-angiogenesis-based approach to the treatment of metastatic colorectal cancer.

关键词： Kallistatin Adeno-associated virus Angiogenesis inhibitors Colon Neoplasm

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Methods for a blind analysis of isobar data collected by the stAR collaboration

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Nuclear science and techniques 2021年第5期32卷 43-50页

作者： J.Adam l.Adamczyk J.R.Adams J.K.Adkins G.Agakishiev M.M.Aggarwal Z.Ahammed i.Alekseev d.M.Anderson A.Aparin E.C.Aschenauer M.U.Ashraf F.G.Atetalla A.Attri G.s.Averichev V.bairathi K.barish A.behera R.bellwied A.bhasin J.bielcik J.bielcikova l.C.bland i.G.bordyuzhin J.d.brandenburg A.V.brandin J.butterworth h.Caines M.Calderon de la barca sanchez d.Cebra i.Chakaberia P.Chaloupka b.K.Chan F-h.Chang Z.Chang N.Chankova-bunzarova A.Chatterjee d.Chen J.Chen J.h.Chen X.Chen Z.Chen J.Cheng M.Cherney M.Chevalier s.Choudhury W.Christie X.Chu h.J.Crawford M.Csanad M.daugherity t.G.dedovich i.M.deppner A.A.derevschikov l.didenko X.dong J.l.drachenberg J.C.dunlop t.Edmonds N.Elsey J.Engelage G.Eppley s.Esumi O.Evdokimov A.Ewigleben O.Eyser R.Fatemi s.Fazio P.Federic J.Fedorisin C.J.Feng Y.Feng P.Filip E.Finch Y.Fisyak A.Francisco l.Fulek C.A.Gagliardi t.Galatyuk F.Geurts A.Gibson K.Gopal X.Gou d.Grosnick W.Guryn A.i.hamad A.hamed s.harabasz J.W.harris s.he W.he X.h.he Y.he s.heppelmann s.heppelmann N.herrmann E.hoffman l.holub Y.hong s.horvat Y.hu h.Z.huang s.l.huang t.huang X.huang t.J.humanic P.huo G.igo d.isenhower W.W.Jacobs C.Jena A.Jentsch Y.Ji J.Jia K.Jiang s.Jowzaee X.Ju E.G.Judd s.Kabana M.l.Kabir s.Kagamaster d.Kalinkin K.Kang d.Kapukchyan K.Kauder h.W.Ke d.Keane A.Kechechyan M.Kelsey Y.V.Khyzhniak d.P.Kikoła C.Kim b.kimelman.d.kin.s.s.t.a.kin.h.rn.i.kis.l A.kiselev M.Kocan l.Kochenda l.K.Kosarzewski l.Kramarik P.Kravtsov K.Krueger N.Kulathunga Mudiyanselage l.Kumar s.Kumar R.Kunnawalkam Elayavalli J.h.Kwasizur R.lacey s.lan J.M.landgraf J.lauret A.lebedev R.lednicky J.h.lee Y.h.leung C.li C.li W.li W.li X.li Y.li Y.liang R.licenik t.lin Y.lin M.A.lisa F.liu h.liu P.liu P.liu t.liu X.liu Y.liu Z.liu t.ljubicic W.J.llope R.s.longacre N.s.lukow s.luo X.luo G.l.Ma l.Ma R.Ma Y.G.Ma N.Magdy R.Majka d.Mallick s.Margetis C.Markert h.s.Matis J.A.Mazer N.G.Minaev s.Mioduszewski b.Mohanty i.Mooney Z.Moravcova d.A.Morozov M.Nagy J.d.Nam Md.Nasim K.Nayak d.Neff J.M.Nelson d.b.Nemes M.Nie G.Nigmatkulov t.Niida l.V.Nogach t.Nonak Christian University AbileneTX 796992 AGh University of science and technology FPACSCracow 30-059Poland Alikhanov institute for theoretical and Experimental Physics NRC"Kurchatov institute" MoscowRussia 117218 Argonne National laboratory ArgonneIL 60439 American University of Cairo New CairoNew Cairo 11835Egypt brookhaven National laboratory UptonNY 11973 University of California BerkeleyCA 94720 University of California DavisCA 95616 University of California Los AngelesCA 90095 University of California RiversideCA 92521 Central China Normal University Wuhan 430079 University of illinois at Chicago ChicagoIL 60607 Creighton University OmahaNE 68178 Czech technical University in Prague FNSPEPrague 11519Czech Republic technische Universitat darmstadt Darmstadt 64289Germany EltE Eotvos lorand University Budapest 1117Hungary Frankfurt institute for Advanced studies FiAs Frankfurt 60438Germany Fudan University Shanghai 200433 University of heidelberg 69120 HeidelbergGermany University of houston HoustonTX 77204 huzhou University Huzhou 313000 indian institute of science Education and Research(iisER) Berhampur 760010India indian institute of science Education and Research(iisER)tirupati Tirupati 517507India indian institute technology PatnaBihar 801106India indiana University BloomingtonIN 47408 institute of Modern Physics Chinese Academy of SciencesLanzhou 730000 University of Jammu Jammu 180001India Joint institute for Nuclear Research DubnaRussia 141980 Kent state University KentOH 44242 University of Kentucky LexingtonKY 40506-0055 lawrence berkeley National laboratory BerkeleyCA 94720 lehigh University BethlehemPA 18015 Max-Planck-institut fur Physik 80805 MunichGermany Michigan state University East LansingMI 48824 National Research Nuclear University MEPhi MoscowRussia 115409 National institute of science Education and Research HBNIJatni 752050India National Cheng Kung University Tainan 70101 Nuclear Physics institute of the CAs Rez 25068Czech Republic Ohio state University

in 2018,the stAR collaboration collected data from^(96)_(44)Ru+^(96)_(44)Ru and^(96)_(40)Zr+^(96)_(40)Zr at√^(s)NN=200 Ge V to search for the presence of the chiral magnetic effect in collisions of *** isobar collision species alternated frequently between 9644 Ru+^(96)_(44)Ru and^(96)_(40)Zr+^(96)_(40)*** order to conduct blind analyses of studies related to the chiral magnetic effect in these isobar data,stAR developed a three-step blind analysis *** are initially provided a"reference sample"of data,comprised of a mix of events from the two species,the order of which respects time-dependent changes in run *** tuning analysis codes and performing time-dependent quality assurance on the reference sample,analysts are provided a species-blind sample suitable for calculating efficiencies and corrections for individual≈30-min data-taking *** this sample,species-specific information is disguised,but individual output files contain data from a single isobar *** run-by-run corrections and code alteration subsequent to these corrections are allowed at this *** these modifications,the"frozen"code is passed over the fully un-blind data,completing the blind *** a check of the feasibility of the blind analysis procedure,analysts completed a"mock data challenge,"analyzing data from Au+Au collisions at√^(s)NN=27 Ge V,collected in *** Au+Au data were prepared in the same manner intended for the isobar blind *** details of the blind analysis procedure and results from the mock data challenge are presented.

关键词： blind analysis Chiral magnetic effect heavy-ion collisions

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核禁试监控:加拿大法律地震学之近期研究

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地球物理学进展 1993年第4期8卷 1-38页

作者： kin-YipChun 邹其嘉

本报告叙述了:(a)核查及其合理性;(b)地震核查的基本任务;(c)辨别地震源和/或爆炸源的物理基础和爆炸当量的测定;(d)和地下核试验的地震监测有关的技术问题;(e)解决多伦多大学法律地震学研究组所发展的战略的基本问题;(f)该组研究工作... 详细信息

本报告叙述了:(a)核查及其合理性;(b)地震核查的基本任务;(c)辨别地震源和/或爆炸源的物理基础和爆炸当量的测定;(d)和地下核试验的地震监测有关的技术问题;(e)解决多伦多大学法律地震学研究组所发展的战略的基本问题;(f)该组研究工作的科学意义。地震学为监测地下核爆炸提供了首要方法。改进的地震仪硬件、加拿大的研究专长和广袤试验场地(加拿大地域辽阔,与有核禁试侦察意义的其它地区极其相似)的可资利用,这些都有助于使加拿大对法律地震学这个高度专业化的分支日益变成引人注意的贡献者。1985年12月以来,多伦多大学完成的研究工作有两部分:(a)利用老的新近重新更新过的黄刀地震台阵(YKA)记录的P 波进行远震核查和(b)利用加拿大东部的遥测台网(一组记录地震的台站)记录的高频l_(?)和P_n 进行区域性(近距离)核查。对YKA 的600多条爆炸远震记录分析表明,在这个固定的侦察站和世界上7个流动的核试验区相连接的路径中,P 波衰减有很大差别。利用YKA 所取得的大量归档保存的核爆资料和最新可资利用的信号分析技术,我们已经能够对以前发表的这些相同路径上的P 波衰减结果做出重要的修正。为鉴别这些修正的震级,我们曾指出,利用以前的衰减值和我们修正后的衰减值,从YKA 的资料推断出的爆炸当量估计值之间相差2倍之大,这依赖于核试验场地的位置。为了从另一种观点来理解修正的重要意义,我们还使用自己的新衰减值进行爆炸资料的分析。该研究得出的结果是,震源深度的标志器(称为震相pP)可从地下核爆的信号中成功地揭示出来。为改善远震快速定位精度,我们还对利用台阵定位和全球地震台网定位之间深度上的系统偏差进行了研究。根据7000多个地震的记录分析,该研究导致以系统位置校正项来描述。利用这些修正项将有助于可靠地、快速地(从20分钟到1小时)对那些发生在YKA1000km 半径范围内的任何记录较好的地震事件进行震中测定。上述资料的深入研究是用新发展的信号识别和处理的方法完成的。“定向能量法”(Oriented energy approach)植根于数学工程的最新进展,多伦多大学研究组利用最近重新更新的YKA 的三分向宽频带记录,把该方法引进到地震波场分析中。初步的研究已表明,这种新方法易于有效地识别出淹没于噪声中的信号。利用在监测区范围内外地震台网的各个台站,上述远震核查研究和以监测低当量核爆为目标的区域性(近距离)核查研究双管齐下。我们所作的区域性研究着重于核禁试侦察中最重要的两种区域性地震波——l_(?)和P_n 的传播、衰减和地质学畸变(场地效应)。测量l_(?)波的能量随距离而减小(即衰减)的新技术已获发展,并在低衰减的加拿大地盾中得到成功的检验。我们已指出,在有与场地明显有关的差别的情况下,在加拿大地盾中即使100km 那么短的路径上,这种方法也能够侦测出l_(?)波经受的微小衰减量。这种尺度的空间分辨率,在监测低阈值的核禁试条约中是个重要的优点。发展测量P_n 衰减的一种有效方法肯定是有前途的。不像其它震相,P_n 的传播模式以及其能量的几何扩散(和衰减无关的现象)方式, 所知甚少。众所周知,关于P_n 几何扩散率的不确定性是测定P_n 衰减的主要误差源。最近,我们在加拿大地盾中已完成改善和检验联合测定P_n 衰减及其几何扩散率的方法。为了保持到达的l_(?)波和P_n 波的“地震状”和“爆炸状”的图像特征以及为可靠的当量估值“标准化”台基的放大因子,我们已努力解决了由于台站附近构造复杂性引起的近台信号失真问题。对于l_(?)波和P_n波已制定了标定方案。为了示范,我们使用了l_(?)场地效应的标定方案以构成台网校正的新方法。为有效地把台网的各个台站(仪器加上台站地质场地效应)变成近于同一的“克隆”(clones),对于正源识别和可靠的当量估计,每个地震事件只需要有很少几个记录台站。事实上,我们完全有能力获得一个折合源(reduced source)识别阈值。

关键词：地震学地震波核爆炸地震监测

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Measurement of away-side broadening with self-subtraction of flow in Au+Au collisions at √sNN=200 GeV

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Chinese Physics C 2020年第10期44卷 59-67页

作者： l.Adamczyk J.R.Adams J.K.Adkins G.Agakishiev M.M.Aggarwal Z.Ahammed i.Alekseev d.M.Anderson A.Aparin E.C.Aschenauer M.U.Ashraf F.G.Atetalla A.Attri G.s.Averichev V.bairathi K.barish A.behera R.bellwied A.bhasin J.bielcik J.bielcikova l.C.bland i.G.bordyuzhin J.d.brandenburg A.V.brandin J.butterworth h.Caines M.Calderón de la barca sánchez d.Cebra i.Chakaberia P.Chaloupka b.K.Chan F-h.Chang Z.Chang N.Chankova-bunzarova A.Chatterjee d.Chen J.h.Chen X.Chen Z.Chen J.Cheng M.Cherney M.Chevalier s.Choudhury W.Christie X.Chu h.J.Crawford M.Csanád M.daugherity t.G.dedovich i.M.deppner A.A.derevschikov l.didenko X.dong J.l.drachenberg J.C.dunlop t.Edmonds N.Elsey J.Engelage G.Eppley s.Esumi O.Evdokimov A.Ewigleben O.Eyser R.Fatemi s.Fazio P.Federic J.Fedorisin C.J.Feng Y.Feng P.Filip E.Finch Y.Fisyak A.Francisco l.Fulek C.A.Gagliardi t.Galatyuk F.Geurts A.Gibson K.Gopal d.Grosnick W.Guryn A.i.hamad A.hamed s.harabasz J.W.harris s.he W.he X.h.he s.heppelmann s.heppelmann N.herrmann E.hoffman l.holub Y.hong s.horvat Y.hu h.Z.huang s.l.huang t.huang X.huang t.J.humanic P.huo G.igo d.isenhower W.W.Jacobs C.Jena A.Jentsch Y.Ji J.Jia K.Jiang s.Jowzaee X.Ju E.G.Judd s.Kabana M.l.Kabir s.Kagamaster d.Kalinkin K.Kang d.Kapukchyan K.Kauder h.W.Ke d.Keane A.Kechechyan M.Kelsey Y.V.Khyzhniak d.P.Kikoła C.Kim b.kimelman.d.kin.s.s.t.a.kin.h.rn.i.kis.l A.kiselev M.Kocan l.Kochenda l.K.Kosarzewski l.Kramarik P.Kravtsov K.Krueger N.Kulathunga Mudiyanselage l.Kumar s.Kumar R.Kunnawalkam Elayavalli J.h.Kwasizur R.lacey s.lan J.M.landgraf J.lauret A.lebedev R.lednicky J.h.lee Y.h.leung C.li W.li W.li X.li Y.li Y.liang R.licenik t.lin Y.lin M.A.lisa F.liu h.liu P.liu P.liu t.liu X.liu Y.liu Z.liu t.ljubicic W.J.llope R.s.longacre N.s.lukow s.luo X.luo G.l.Ma l.Ma R.Ma Y.G.Ma N.Magdy R.Majka d.Mallick s.Margetis C.Markert h.s.Matis J.A.Mazer N.G.Minaev s.Mioduszewski b.Mohanty i.Mooney Z.Moravcova d.A.Morozov M.Nagy J.d.Nam Nasim Md K.Nayak d.Neff J.M.Nelson d.b.Nemes M.Nie G.Nigmatkulov t.Niida l.V.Nogach t.Nonaka A.s.Nunes G.Odyniec A.Ogawa Abilene Christian University AbileneTexas 79699 AGh University of science and technology FPACSCracow 30-059Poland Alikhanov institute for theoretical and Experimental Physics NRC"Kurchatov institute" Moscow 117218Russia Argonne National laboratory ArgonneIllinois 60439 American University of Cairo New Cairo 11835New CairoEgypt brookhaven National laboratory UptonNew York 11973 University of California BerkeleyCalifornia 94720 University of California DavisCalifornia 95616 University of California Los AngelesCalifornia 90095 University of California RiversideCalifornia 92521 Central China Normal University WuhanHubei 430079 University of illinois at Chicago ChicagoIllinois 60607 Creighton University OmahaNebraska 68178 Czech technical University in Prague FNSPEPrague 11519Czech Republic technische Universität darmstadt Darmstadt 64289Germany EltE Eötvös loránd University BudapestHungary H-1117 Frankfurt institute for Advanced studies FiAs Frankfurt 60438Germany Fudan University Shanghai 200433 University of heidelberg Heidelberg 69120Germany University of houston HoustonTexas 77204 huzhou University HuzhouZhejiang 313000 indian institute of science Education and Research(iisER) Berhampur 760010India indian institute of science Education and Research(iisER)tirupati Tirupati 517507India indian institute technology PatnaBihar 801106India indiana University BloomingtonIndiana 47408 institute of Modern Physics Chinese Academy of SciencesLanzhouGansu 730000 University of Jammu Jammu 180001India Joint institute for Nuclear Research Dubna 141980Russia Kent state University KentOhio 44242 University of Kentucky LexingtonKentucky 40506-0055 lawrence berkeley National laboratory BerkeleyCalifornia 94720 lehigh University BethlehemPennsylvania 18015 Max-Planck-institut für Physik Munich 80805Germany Michigan state University East LansingMichigan 48824 National Research Nuclear University MEPhi Moscow 115409Russia National institute of science Education and Research HBNIJatni 752050Indi

high transverse momentum(pt)particle production is suppressed owing to the parton(jet)energy loss in the hot dense medium created in relativistic heavy-ion *** of energy at low-to-modest pt has been difficult to measure,owing to large anisotropic *** report a data-driven method for background evaluation and subtraction,exploiting the away-side pseudorapidity gaps,to measure the jetlike correlation shape in Au+Au collisions at √sNN=200 GeV in the stAR *** correlation shapes,for trigger particles pt>3GeV/c and various associated particle pt ranges within 0.5tsistent with Gaussians,and their widths increase with *** results indicate jet broadening in the medium created in central heavy-ion collisions.

关键词： di-hadron correlations jet heavy-ion

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determinants for asthma control, quality of life and use of complementary and alternative medicine in asthmatic pediatric patients in four cities

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World Journal of Pediatrics 2018年第5期14卷 482-491页

作者： Kam lun hon Yan Min bao Kate C.Chan kin Wai Chau Rong-shan Chen Kun tat Gary Cheok Wa Keung Chiu li deng Chun-hui he kin Mui ieong Jeng sum C.Kung Ping lam shu Yan david lam Qun Ui lee so lun lee ting Fan leung theresa N.h.leung lei shi Ka Ka siu Wei-Ping tan Maggie haitian Wang tak Wai Wong bao-Jing Wu Ada Y.F.Yip Yue-Jie Zheng daniel K.Ng department of Pediatrics The Chinese University of Hong Kong 6/F Prince of Wales HospitalRoom 84042ShatinN.THong Kong SARChina department ofR espiratory diseases Shenzhen Children’s HospitalShenzhen 518026China hong Kong society of P ediatric Respirology and Aller gy Hong K ong S ARChina Pediatric Respiratory andsleep disorders Center Room 1315DArgyle Centre Phase 1688 Nathan RoadMongkokKowloonHong K ong S ARChina department of R espiration Guangzhou Women and Children’s Medical CenterGuangzhou 510623China department of P ediatrics Kiang Wu HospitalMacaoChina department of P ediatrics and A dolescent Medicine United Christian Hospital130Hip Wo StreetKwun TongHong K ong S ARChina department of P ediatrics Central Hospital Conde S.JanuarioMacaoChina department of P ediatrics and A dolescent Medicine Caritas Medical Center111Wing Hong StreetSham Shui PoHong K ong S ARChina department of P ediatrics and A dolescent Medicine Tuen Mun Hospital23 Tsing Chung Koon RoadTuen MunNewT erritoriesHongK ongS ARChina department of P ediatrics and A dolescent Medicine Princess Margaret Hospital2-10 Princess Margaret Hospital RoadLai Chi KokKowloonHong K ong S ARChina department of P ediatrics and A dolescent Medicine Queen Mary Hospital102Pokfulam RoadHong K ong S ARChina department of P ediatrics and A dolescent Medicine The University of Hong KongHong K ong S ARChina department of P ediatrics and A dolescent Medicine Pamela Youde Nethersole Eastern Hospital3Lok Man RoadChaiwanHong K ong S ARChina department of P ediatrics The University of Hong Kong-Shenzhen Hospital1Haiyuan 1st RoadFutianShenzhenChina department of P ediatrics and A dolescent Medicine Kwong Wah Hospital25 Waterloo RoadKLN Hong K ong S ARChina department of P ediatrics Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China JC school of Public health and Primary Care Faculty of MedicineThe Chinese University of Hong KongHong K ong S ARChina department of P ediatrics and A dolescen

background Asthma is a significant chronic health problem worldwide. Management aims at disease control by reducing functional impairment and exacerbations and improving quality of life (Qol). We report a multi-center study to survey asthma control and Qol in four cities in the Pearl River delta. Methods the conjoint survey involved ten hong Kong pediatric hospitals/units, two shenzhen hospitals, two Macao hos-pitals, and two Guangzhou hospitals on asthma control (using Asthma Control test) and Qol (Pediatric Allergic disease Quality of life Questionnaire, PAdQlQ). Acceptability of a treatment is graded as very good/good/fair/poor. Results Good asthma control was only reported in 80% subjects in hong Kong, but higher in sister cities (85–94%, Pllergic rhinitis, 'incense burning', and 'smoker in family' were prevalent among the four cities. logistic regres-sion showed better control of asthma was associated with better PAdQlQ (b=?0.029, P better acceptability of bronchodilator (b=?1.488, P = 0.025), negatively with 'smoker in family' (b=?0.83, P = 0.015) and various PAdQlQ domains. Conversely, worse PAdQlQ was associated with allergic rhinitis severity (b=4.77, P trol of asthma (b=7.56, P increased frequency of traditional Chinese medicine use (b=1.7, P increased fre-quency of bronchodilator usage (b=1.05, P smoker in family' (b=4.05, P d incense burning at home (b=3.9, P lusions there are some clinical and cultural differences among the four southern Chinese cities within the Guangdong province. this study identifies potentially modifiable environmental and treatment factors associated with poor asthma control and Qol for health-care interventions. having a smoker in the family is independently associated with poor asthma control and Qol.

关键词： Asthma Complementary and alternative medicine Control inhaled bronchodilator inhaled corticosteroid Pediatric Allergic disease Quality of life Questionnaire smoking traditional Chinese medicine

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Counteracting lineage-specific transcription factor network finely tunes lung adeno-to-squamous transdifferentiation through remodeling tumor immune microenvironment

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National science Review 2023年第4期10卷 37-55页

作者： shijie tang Yun Xue Zhen Qin Zhaoyuan Fang Yihua sun Chongzhe Yuan Yunjian Pan Yue Zhao Xinyuan tong Jian Zhang hsinyi huang Yuting Chen liang hu dasong huang Ruiqi Wang Weiguo Zou Yuan li Roman K.thomas Andrea Ventura Kwok-kin Wong haiquan Chen luonan Chen hongbin Ji state Key laboratory of Cell biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of Sciences College of life sciences University of Chinese Academy of Sciences Zhejiang University-University of Edinburgh institute Zhejiang University School of Medicine the second Affiliated hospital Zhejiang University School of Medicine department of thoracic surgery Fudan University Shanghai Cancer Center department of Oncology Shanghai Medical CollegeFudan University school of life science and technology Shanghai Tech University department of Mathematics Shanghai University department of translational Genomics Center of Integrated Oncology Cologne-BonnMedical FacultyUniversity of Cologne department of Pathology University Hospital Cologne Cancer biology and Genetics Program Memorial Sloan Kettering Cancer Center laura and isaac Perlmutter Cancer Center New York University Langone Medical Center Key laboratory of systems biology Shanghai Institutes for Biological SciencesChinese Academy of Sciences school of life science Hangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesChinese Academy of Sciences

human lung adenosquamous cell carcinoma(lUAs), containing both adenomatous and squamous pathologies, harbors strong plasticity and is significantly associated with poor prognosis. We established an up-to-date comprehensive genomic and transcriptomic landscape of lUAs in 109 Chinese specimens and demonstrated lUAs development via adeno-to-squamous transdifferentiation. Unsupervised transcriptomic clustering and dynamic network biomarker analysis identified an inflammatory subtype as the critical transition stage during lUAs development. dynamic dysregulation of the counteracting lineage-specific transcription factors(tFs), containing adenomatous tFs NKX2-1 and FOXA2, and squamous tFs tP63 and sOX2, finely tuned the lineage transition via promoting CXCl3/5-mediated neutrophil infiltration. Genomic clustering identified the most malignant subtype featured with stK11-inactivation, and targeting lsd1 through genetic deletion or pharmacological inhibition almost eradicated stK11-deficient lung tumors. these data collectively uncover the comprehensive molecular landscape, oncogenic driver spectrum and therapeutic vulnerability of Chinese lUAs.

关键词： lUAs AlK fusion counteracting tF regulatory network CXCl3/CXCl5 lsd1

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