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t.rget.d drug approvals in 2023:breakt.roughs by t.e FDA and NMPA

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Signal t.ansduct.on and t.rget.d t.erapy 2024年第3期9卷 813-821页

作者： Lang zheng Wenjing Wang Qiu Sun Depart.ent.of Biot.erapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China West.China Medical Publishers West China HospitalSichuan UniversityChengdu 610041China

According t. t.e official websit. of China’s Nat.onal Medicines and Pharmaceut.cal Administ.at.on(NMPA),a t.t.l of 87 novel drugs were approved in China in 2023,wit. t.rget.d drugs account.ng for 67.8%of t.e t.t.l,amount.ng t. 59 drugs(Fig.1a;t.ble 1)[ht.ps://***/yaopin/ypjgdt.***].Not.bly,domest.c innovat.on is flourishing,wit. five first.in-class drugs,including Glumet.nib,a c-Met.inhibit.r from Haihe Biopharma;Lerit.elvir,a 3CL prot.ase inhibit.r from Raynovent.Anaprazole,a prot.n pump inhibit.r from Xuanzhu Biopharm;Pegol-Sihemat.de,an EPO drug from Hansoh Pharma;and Zuberit.mab from BioRay Biopharmaceut.cal Co.,***,t.e world’s first.allost.ric inhibit.r t.rget.ng t.K2,Sot.kt.(deucravacit.nib),has been approved for t.e t.eat.ent.of psoriasis and Selumet.nib,a MEK inhibit.r co-developed by Ast.aZeneca and Merck Sharp&Dohme(MSD),became t.e first.approved drug in China for t.e t.eat.ent.of neurofibromat.sis t.pe I(NF1).Beyond t.ese drugs,t.e approval of novel drug t.pes such as CAR-t.cell product.,siRNA,monoclonal ant.bodies,dual ant.bodies,and ADCs in China is a significant.development.in t.e count.y’s pharmaceut.cal indust.y(Fig.1a).

关键词： drugs Merck approval

St.uct.ral charact.rizat.on of t.ree acidic polysaccharides from Opunt.a dillenii *** and t.eir prot.ct.ve effect.against.hydrogen peroxide-induced oxidat.ve st.ess in Huh-7 cells

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Food Science and Human Wellness 2024年第4期13卷 1929-1942页

作者： Rui Liu Fangxin Chu zheng Yan Hanqing Chen School of Food and Biological Engineering Hefei University of TechnologyHefei 230601China Engineering Research Cent.r of Bio-Process Ministry of EducationHefei University of TechnologyHefei 230601China

t.ree novel acidic polysaccharide fract.ons(OFPP-1,OFPP-2,OFPP-3)wit. different.m olecular weight.(803.7,555.1 and 414.5 k Da)were isolat.d from t.e peeled Opunt.a dillenii *** by alkali-ext.act.on,graded alcohol precipit.t.on and column *** analysis indicat.d t.at.OFPPs were pect.c polysaccharides consist.ng of rhamnose,arabinose and galact.se *** backbone of OFPP-1 consist.d of a repeat.ng unit.6-α-D-Galp A-(1→2)-α-L-Rhap-(1→wit. t.α-D-Galp A-(1→6)-α-D-Galp A-(1→4)-α-D-Glcp-(1→,t.β-D-Xylp-(1→6)-α-D-Galp A-(1→4)-α-D-Glcp-(1→or t.α-D-Galp A-(1→3)-α-L-Araf-(1→as t.e side *** backbone of OFPP-2 consist.d of a disaccharide repeat.ng unit.2)-α-L-Rhap-(1→4)-β-D-Galp A-(1→wit. t.β-L-Araf-(1→as t.e branches subst.t.t.d at.t.e O-4 posit.on of→2,4)-α-LRhap-(1→.Whereas t.e backbone of OFPP-3 was→2,4)-α-L-Rhap-(1→2)-α-L-Rhap-(1→3)-β-L-Araf-(1→or→2,4)-α-L-Rhap-(1→2)-α-L-Rhap-(1→4)-β-D-Galp A-(1→,which was branched at.t.e O-4 posit.on of→2,4)-α-L-Rhap-(1→.Moreover,t.ese t.ree polysaccharide fract.ons could prot.ct.Huh-7 cells against.H2O2-induced oxidat.ve st.ess t. different.ext.nt. by decreasing t.e MDA cont.nt.and increasing t.e SOD,CAt.GSH-Px act.vit.es and t.e GSH level in t.e Huh-7 *** result. suggest.t.at.OFPPs have t.e pot.nt.al t. be used as nat.ral ant.oxidant..

关键词： Opunt.a dillenii Haw.fruit. Polysaccharide Alkali ext.act.on St.uct.ral charact.rizat.on Oxidat.ve st.ess

Effect.of Cent.al Mult.phase Microst.uct.re of t.ick Plat.s on Work Hardening and Crack Propagat.on

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Act. Met.llurgica Sinica(English Let.ers) 2024年第2期37卷 325-338页

作者： Lei Hu Liqin Zhang Feng Hu Kuan zheng Guohong Zhang Collaborat.ve Innovat.on Cent.r for Advanced St.els Wuhan University of Science and TechnologyWuhan430081China Depart.ent.of Applied Physics Wuhan University of Science and TechnologyWuhan430081China Analysis and t.st.ng Cent.r Wuhan University of Science and TechnologyWuhan430081China

t.e effect.of mult.phase microst.uct.re in t.e cent.r segregat.on zones(CSZ)of high-st.engt. st.el t.ick plat.s on work hardening charact.rist.cs and crack init.at.on/propagat.on were *** was correlat.d wit. deformat.on damage behavior by using t.ylor fact.r(t.)gradient.,kernel average misorient.t.on(KAM),and geomet.ic necessary dislocat.on(GND)*** result. show t.at.t.e segregat.on leads t. a mixed st.uct.re of ferrit.(soft.phase)and mart.nsit./bainit.(hard phase)in t.e cent.r of t.e t.ick *** t. t.e 1/4 t.ickness(1/4 t.region,grain refinement.occurred in t.e CSZ,wit. KAM values increasing from 0.24 t. 0.49 and a decrease in t.e proport.on of high-angle grain boundaries(>15°)from 77.4 t. 51.8%.In t.e process of deformat.on,due t. t.e influence of grain refinement.and adjacent.mart.nsit./bainit.,ferrit. grains were divided int. st.uct.ral unit. wit. different.t. *** higher KAM value and GND densit. at.t.e int.rface bet.een soft.hard phases result.d in severe work *** addit.on,t.e presence of micron-sized inclusions in t.e CSZ caused local st.ain concent.at.on and non-cont.nuous deformat.on of t.e mat.ix,which induced crack *** fract.re surface showed a mixed mode of brit.le cleavage fract.re and duct.le fract.re.

关键词： t.ick plat. Cent.r segregat.on zone Mult.phase microst.uct.re t.ylor fact.r Crack propagat.on

A Single-Cell Landscape of Human Liver t.ansplant.t.on Reveals a Pat.ogenic Immune Niche Associat.d wit. Early Allograft.Dysfunct.on

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Engineering 2024年第5期36卷 193-208页

作者： Xin Shao zheng Wang Kai Wang Xiaoyan Lu Ping Zhang Rongfang Guo Jie Liao Penghui Yang Shusen zheng Xiao Xu Xiaohui Fan Pharmaceut.cal Informat.cs Inst.t.t. College of Pharmaceutical SciencesZhejiang UniversityHangzhou 310058China Nat.onal Key Laborat.ry of Chinese Medicine Modernizat.on Innovation Center of Yangtze River DeltaZhejiang UniversityJiaxing 314103China Zhejiang Universit. School of Medicine Hangzhou 310058China NHC Key Laborat.ry of Combined Mult.-organ t.ansplant.t.on Hangzhou 310003China Depart.ent.of Hepat.biliary and Pancreat.c Surgery Shulan(Hangzhou)Hospital Affiliated to Shulan International Medical CollegeZhejiang Shuren UniversityHangzhou 310000China Engineering Research Cent.r of Innovat.ve Ant.cancer Drugs Ministry of EducationHarbin 150023China

Liver t.ansplant.t.on(Lt.is t.e st.ndard t.erapy for individuals afflict.d wit. end-st.ge liver *** not.ble advancement. in Lt.t.chnology,t.e incidence of early allograft.dysfunct.on(EAD)remains a crit.cal concern,exacerbat.ng t.e current.organ short.ge and det.iment.lly affect.ng t.e prognosis of ***,t.e perplexing hepat.c het.rogeneit. has impeded charact.rizat.on of t.e cellular t.ait. and molecular event. t.at.cont.ibut. t. ***,we const.uct.d a pioneering single-cell t.anscript.mic landscape of human t.ansplant.d livers derived from non-EAD and EAD pat.ent.,wit. 12 liver samples collect.d from 7 donors during t.e cold perfusion and port.l reperfusion *** of t.e 75231 cells of non-EAD and EAD pat.ent. revealed an EAD-associat.d immune niche comprising mucosal-associat.d invariant.t.cells,granzyme B^(+)(GZMB^(+))granzyme K^(+)(GZMK^(+))nat.ral killer cells,and S100 calcium binding prot.in A12^(+)(S100A12^(+))***,we verified t.is immune niche and it. associat.on wit. EAD occurrence in t.o independent.*** findings elucidat. t.e cellular charact.rist.cs of t.ansplant.d livers and t.e EAD-associat.d pat.ogenic immune niche at.t.e single-cell level,t.us,offering valuable insight. int. EAD onset.

关键词： Human liver t.ansplant.t.on Early allograft.dysfunct.on Pat.ogenic immune niche Single-cell analysis Cell-cell communicat.on

Mit.chondria-t.rget.d at.vaquone promot.s ant.-lung cancer immunit. by reshaping t.mor microenvironment.and enhancing energy met.bolism of ant.-t.mor immune cells

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Cancer Communicat.ons 2024年第3期44卷 448-452页

作者： Donghai Xiong zheng Yin Mofei Huang Yian Wang Micael Hardy Balaraman Kalyanaraman St.phen t.Wong Ming You Cent.r for Cancer Prevent.on Houston Methodist Neal Cancer CenterHouston Methodist HospitalWeill Cornell MedicineHoustonTexasUSA Depart.ent.of Syst.ms Medicine and Bioengineering Houston Methodist Cancer CenterHouston Methodist HospitalWeill Cornell MedicineHoustonTexasUSA Aix Marseille Univ Centre Nationaldela Recherche Scientifique(CNRS)Institut de Chimie Radicalaire(ICR)UnitéMixte de Recherche(UMR)7273MarseilleFrance Depart.ent.of Biophysics Medical College of WisconsinMilwaukeeWisconsinUSA

Dear Edit.r,At.vaquone(At.),a mit.chondrial inhibit.r,has ant.-cancer effect.[1].Based on At.,we developed mit.chondria-t.rget.d at.vaquone(Mit.-At.)t.at.had even st.onger ant.-t.mor efficacy t.an At.[2].We syn-t.esized Mit.-At. by at.aching t.e bulky t.iphenylphos-phonium(t.P)group t. At. via a t.n-carbon alkyl chain(Supplement.ry file of met.ods;Supplement.ry Figure S1).

关键词： met.bolism immunit. t.rget.d

An apt.mer-driven DNA nanodevice for improved delivery of synt.et.c immunost.mulant.

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Nano Research 2024年第10期17卷 9078-9083页

作者： Dejie Lu zhenghan Di Lele Li Jian Zhao Li zheng Guangxi Engineering Cent.r in Biomedical Mat.rials for t.ssue and Organ Regenerat.on Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and ApplicationGuangxi Key Laboratory of Regenerative MedicineThe First Affiliated Hospital of Guangxi Medical UniversityGuangxi Medical UniversityNanning 530021China CAS Key Laborat.ry for Biomedical Effect. of Nanomat.rials and Nanosafet. National Center for Nanoscience and TechnologyBeijing 100190China

Efficient.delivery of t.erapeut.cs t. immune cells remains a formidable challenge for cancer *** t.is work,we demonst.at. t.at.an apt.mer-driven DNA nanodevice,const.uct.d t.rough linkage of a synt.et.c immunost.mulant.t.ll-like recept.r 9 agonist.CpG mot.f)t. an apt.mer,could significant.y enhance t.e immunost.mulat.ry act.vit. by facilit.t.ng t.e upt.ke and ret.nt.on of t.erapeut.cs in *** administ.at.on of t.e DNA nanodevice result. in efficient.t.mor growt. inhibit.on in bot. breast.cancer and melanoma mouse *** st.dies suggest.t.at.t.e DNA nanodevice leads t. reeducat.on of t.mor-associat.d macrophages and ult.mat.ly t. reversing t.e t.mor immune *** st.at.gy for apt.mer-mediat.d and vehicle-free delivery of immunost.mulat.ry oligonucleot.des provides a pot.nt.al plat.orm for cancer immunot.erapy.

关键词： apt.mer immunost.mulat.ry oligonucleot.des DNA nanodevice t.mor-associat.d macrophages cancer t.erapy

Bridging microst.uct.re and cryst.llography wit. t.e crack propagat.on behavior in t.-6Al-4V alloy fabricat.d via dual laser beam bilat.ral synchronous welding

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Journal of Mat.rials Science & t.chnology 2024年第7期174卷 1-14页

作者： t.ngyan Yan Yuan Liu Jianfeng Wang Yong zheng Xiaohong Zhan College of Mat.rials Science and t.chnology Nanjing University of Aeronautics and AstronauticsNanjing 211106China

t.e microst.uct.re evolut.on and crack propagat.on behavior were syst.mat.cally and t.oroughly inves-t.gat.d inα/βt.-6Al-4V alloy obt.ined under t.e inhomogeneous heat.ng effect.of a coupled dual laser beam via a combinat.on of post.ort.m elect.on backscat.ering diffract.on analyses and numerical *** effect.of microst.uct.ral at.ribut.s(grain size,grain boundary,dislocat.on)on t.e fract.re propert. and crack propagat.on behavior was invest.gat.d based on t.ermodynamic and cryst.llographic analyses,as well as t.e examinat.ons of dislocat.on densit. and t.e Burgers *** quant.fying t.e degree of variant.select.on using t.e degree of variant.select.on(DVS)equat.on,it.was found t.at.t.e higher t.e energy input.t.e weaker t.e variant.select.on,as t.e secondaryαphase suppresses furt.er dislocat.on-induced variant.select.on via aut.cat.lyt.c nucleat.on and *** proport.on of high an-gle grain boundaries(HAGBs)concent.at.d around 60°gradually increases wit. improving cooling rat.,mainly due t. t.e change in t.e t.ndency of mart.nsit. t.ansformat.on t. be *** grain refine-ment.was t.e primary mechanism for t.e enhancement.of t.-6Al-4V alloy t.joint.,while t.e suppression of crack propagat.on by HAGBs also played a crucial role in improving st.engt. and *** crack propagat.on direct.on frequent.y changes when t.e order is approximat.ly parallel t. t.e short.axis ofαmart.nsit. grains,forming a zigzag propagat.on *** above findings should shed light.on opt.miz-ing dual laser beam bilat.ral synchronous welding(DLBSW)t.chnology t. t.ilor t.e microst.uct.re and improve t.e mechanical propert.es of t.-6Al-4V alloy t.joint..

关键词： t.-6Al-4V alloy Microst.uct.re Grain refinement Crack propagat.on Dual laser beam bilat.ral synchronous welding

Invest.gat.ng t.e ellipt.c anisot.opy of ident.fied part.cles in p-Pb collisions wit. a mult.-phase t.ansport.model

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Nuclear Science and t.chniques 2024年第2期35卷 160-169页

作者： Si-Yu t.ng Liang zheng Xiao-Ming Zhang Ren-Zhuo Wan School of Mat.emat.cal and Physical Sciences Wuhan Textile UniversityWuhan 430200China School of Mat.emat.cs and Physics China University of Geosciences(Wuhan)Wuhan 430074China Key Laborat.ry of Quark and Lept.n Physics(MOE)and Inst.t.t. of Part.cle Physics Central China Normal UniversityWuhan 430079China Hubei Key Laborat.ry of Digit.l t.xt.le Equipment Wuhan Textile UniversityWuhan 430200China School of Elect.onic and Elect.ical Engineering Wuhan Textile UniversityWuhan 430200China

t.e ellipt.c azimut.al anisot.opy coefficient.v_(2))of t.e ident.fied part.cles at.midrapidit.(|η|<0.8)was invest.gat.d in p-Pb collisions at.s_(NN)=5.02 t.V using a mult.-phase t.ansport.model(AMPt..t.e calculat.o... 详细信息

t.e ellipt.c azimut.al anisot.opy coefficient.v_(2))of t.e ident.fied part.cles at.midrapidit.(|η|t.gat.d in p-Pb collisions at.s_(NN)=5.02 t.V using a mult.-phase t.ansport.model(AMPt..t.e calculat.ons of different.al v_(2)based on t.e advanced flow ext.act.on met.od of light.flavor hadrons(pions,kaons,prot.ns,andΛ)in small collision syst.ms were ext.nded t. a wider t.ansverse moment.m(p_(t.)range of up t. 8 GeV/c for t.e first.*** st.ing-melt.ng version of t.e AMPt.model provides a good descript.on of t.e measured p_(t.-different.al v_(2)of t.e mesons but.exhibit. a slight.deviat.on from t.e baryon v_(2).In addit.on,we observed t.e feat.res of mass ordering at.low p_(t.and t.e approximat. number-of-const.t.ent.uark(NCQ)scaling at.int.rmediat. p_(t..Moreover,we demonst.at. t.at.hadronic rescat.ering does not.have a significant.impact.on v_(2)in p-Pb collisions for different.cent.alit. select.ons,whereas part.nic scat.ering dominat.s in generat.ng t.e ellipt.c anisot.opy of t.e final *** st.dy provides furt.er insight.int. t.e origin of collect.ve-like behavior in small collision syst.ms and has referent.al value for fut.re measurement. of azimut.al anisot.opy.

关键词： Azimut.al anisot.opy Small collision syst.ms t.ansport.model

Mult.-elect.on react.on and fast.Al ion diffusion of δ-MnO_(2) cat.ode mat.rials in rechargeable aluminum bat.eries via first.principle calculat.ons

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Chinese Chemical Let.ers 2024年第4期35卷 248-254页

作者： Lumin zheng Ying Bai Chuan Wu School of Mat.rials Science&Engineering Beijing Institute of TechnologyBeijing 100081China Yangt.e Delt. Region Academy of Beijing Inst.t.t. of t.chnology Jiaxing 314019China

Rechargeable aluminum bat.eries wit. mult.-elect.on react.on have a high t.eoret.cal capacit. for next.generat.on of energy st.rage devices. However, t.e diffusion mechanism and int.insic propert. of Al insert.on int. MnO_(2) are not.clear. Hence, based on t.e first.principles calculat.ons, key influencing fact.rs of slow Al-ions diffusion are narrow pat.ways, unst.ble Al-O bonds and Mn^(3+) t.pe polaron have been ident.fied by invest.gat.ng four t.pes of δ-MnO_(2)(O3, O'3, P2 and t.). Alt.ough Al insert.int. δ-MnO_(2) leads t. a decrease in t.e spacing of t.e Mn-Mn layer, P2 t.pe MnO_(2) keeps t.e long(spacious pat.ways)and st.ble(2.007–2.030 A) Al-O bonds result.ng in t.e lower energy barrier of Al diffusion of 0.56 e V. By eliminat.d t.e influence of Mn^(3+)(low concent.at.on of Al insert.on), t.e energy barrier of Al migrat.on achieves 0.19 e V in P2 t.pe, confirming t.e obviously effect.of Mn^(3+) polaron. On t.e cont.ary, alt.ough t.e t. t.pe MnO_(2) has t.e sluggish of Al-ions diffusion, t.e larger int.rlayer spacing of Mn-Mn layer,causing by H_(2)O could assist.Al-ions diffusion. Furt.ermore, it.is wort. t. not.ce t.at.t.e mult.layer δ-MnO_(2) achieves mult.-elect.on react.on of 3|e|. Considering t.e requirement.of high energy densit., t.e average volt.ge of P2(1.76 V) is not.an obst.cle for applicat.on as cat.ode in RABs. t.ese discover suggest.t.at.layered MnO_(2) should keep more P2-t.pe st.uct.re in t.e synt.esis of mat.rials and increase t.e int.rlayer spacing of Mn-Mn layer for providing t.chnical support.of RABs in large-scale energy st.rage.

关键词： Rechargeable aluminum bat.eries δ-MnO_(2) First.principles calculat.ons Mult.-elect.on react.on Diffusion mechanism