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Inducing neuronal regeneration and differentiation via the BDNF/ TrkB signaling pathway: a key target against neurodegenerative diseases?

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Neural Regeneration Research 2024年第3期19卷 495-496页

作者： Mirjana Antonijevic Patrick Dallemagne christophe Rochais Normandie University UNICAENCERMNCaenFrance

Brain-derived neurotrophic factor(BDNF)is one of the neurotrophins,a specific polypeptide growth factor,which plays a crucial role in the proliferation,differentiation,survival,and death of neurons and non-neuronal *** is not only essential to maintain the balance between death on one side and survival of neurons on the other,but also it mediates additional higher-order activities such as learning,memory,and *** is initially synthesized as a precursor protein,proBDNF,that can be secreted as it is or it can be cleaved intracellularly by furin and proconvertases,or extracellularly by extracellular proteases such as matrix metalloprotease-9 and matrix metalloprotease-2,or plasmin to give mature BDNF.

关键词： death diseases degenerative

Immunobiodiversity:Conserved and specific immunity across land plants and beyond

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Molecular Plant 2024年第1期17卷 92-111页

作者： Baptiste Castel Karima El Mahboubi christophe Jacquet Pierre-Marc Delaux Laboratoire de Recherche en Sciences Végétales(LRSV) Universitéde ToulouseCNRSUPSToulouse INPCastanet-TolosanFrance

Angiosperms represent most plants that humans cultivate,grow,and ***,angiosperms are only one of five major land plant *** a whole lineage,plants also include algal *** these clades represent a tremendous genetic diversity that can be investigated to reveal the evolutionary history of any given *** this review,we describe the current model of the plant immune system,discuss its evolution based on the recent literature,and propose future directions for the *** angiosperms,plant–microbe interactions have been intensively studied,revealing essential cell surface and intracellular immune receptors,as well as metabolic and hormonal defense *** diversity at the genomic and functional levels demonstrates the conservation of these pathways across land plants,some of which are beyond *** basis of the conserved mechanisms,lineage-specific variations have occurred,leading to diversified reservoirs of immune *** rare cases,this diversity has been harnessed and successfully transferred to other species by integration of wild immune receptors or engineering of novel forms of receptors for improved resistance to *** propose that exploring further the diversity of immune mechanisms in the whole plant lineage will reveal completely novel sources of resistance to be deployed in crops.

关键词： evolution MPMI immunity plant evoMPMI symbiosis

Lateral ring compression test applied to a small caliber steel jacket:Identification of a constitutive model

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Defence Technology（防务技术） 2024年第6期36卷 133-148页

作者： Yann Coget Yael Demarty christophe Czarnota Anthony Bracq Jean-Sebastien Brest Alexis Rusinek French-German Research Institute of Saint-Louis 5 Rue Du General Cassagnou68300 Saint-LouisFrance Laboratoire d'Etude des Microstructures et de Mecanique des Materiaux(LEM3) CNRSUniversite de LorraineArts&Metiers ParisTechF-57000 MetzFrance

The evolution of threats and scenarios requires continuous performance improvements of ballistic protections for armed *** a modeling point of view,it is necessary to use sufficiently precise material behavior models to accurately describe the phenomena observed during the impact of a projectile on a protective *** this context,the goal of this paper is to characterize the behavior of a small caliber steel jacket by combining experimental and numerical *** experimental method is based on the lateral compression of ring specimens directly machined from the thin and small *** speeds and temperatures are considered in a quasi-static regime in order to reveal the strain rate and temperature dependencies of the tested *** Finite Element Updating Method(FEMU)is *** results are coupled with an inverse optimization method and a finite element numerical model in order to determine the parameters of a constitutive model representative of the jacket *** of the present model are verified against experimental results and a parametric study as well as a discussion on the identified material parameters are *** results indicate that the strain hardening parameter can be neglected and the behavior of the thin steel jacket can be described by a modeling without strain hardening sensitivity.

关键词： Full metal jacket ammunition Lateral ring compression Inverse identification Numerical simulation

Psychiatric outcomes in outpatients affected by long COVID:A link between mental health and persistence of olfactory complaint

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World Journal of Psychiatry 2024年第4期14卷 507-512页

作者： Victoria Metelkina-Fernandez Louise-Emilie dumas Clair Vandersteen David Chirio Auriane Gros Arnaud Fernandez Florence Askenazy Valeria Manera Department of Psychiatry Nice University HospitalNice 06000France Department of Child and Adolescent Psychiatry UniversitéCôte d’AzurNice 06200France ENT Head and Neck InstituteNice 06100France Department of Infectiology Nice University HospitalNice 06200France Department of Orthophony UniversitéCôte d’AzurNice 06100France Cobtek UniversitéCôte d’AzurNice 06100France

BACKGROUND Anosmia was one of the main symptoms of coronavirus disease 2019(COVID-19).A psychiatric history(i.e.,depression)may be an independent contributor to the risk of COVID-19 diagnosis,and COVID-19 survivors appear to have an increased risk of neuropsychiatric sequelae(bidirectional association).AIM To compare the rate of psychiatric disorder among post-COVID patients without anosmia vs patients with persistent olfactory *** We conducted a prospective case control study from March 2020 to May *** recruited at the ENT department of Nice University Hospital had a subjective olfactory complaint(visual analogue scale)for over 6 wk and a molecular or CT-proven severe acute respiratory syndrome coronavirus 2 diagnosis confirmed by ***-COVID patients without persistent olfactory disorders were recruited at the university hospital infectiology *** medical histories were collected by a psychiatrist during the *** Thirty-four patients with post-COVID-19 olfactory complaints were included in the first group of the *** percent of the patients were female(n=17).The group’s mean age was 40.5±12.9 *** control group included 32 participants,of which 34.4%were female(n=11),and had a mean age of 61.2±12.2 *** rate of psychiatric disorder among post-COVID patients with olfactory complaints was significatively higher(41.7%)than among patients without(18.8%)(χ2=5.9,P=0.015).CONCLUSION The presence of a psychiatric history may constitute a potential risk factor for the development of long COVID due to persistent *** therefore seems important to establish reinforced health monitoring after a COVID 19 infection in at-risk *** prospective,translational,and collaborative studies are needed to extrapolate these results to the general population.

关键词： COVID-19 Anosmia Psychiatry Stress Neuroplasticity Psychiatric history

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The Knight Of Change

ChinAfrica 2024年第10期16卷 40-41页

作者： christophe ALEXANDRE 不详

A Nigerian chess player transforms the lives of children through his *** Onakoya is a Nigerian chess player and social activist whose influence extends far beyond the 64 squares of the *** the founder of the Chess in Slums initiative,he uses chess as a powerful tool to educate,motivate,and transform the lives of young people in Nigeria’s underprivileged *** work,which began in the slums of Lagos,has garnered international admiration.

关键词： player lives beyond

Structure-based design and optimization lead to the identification of novel dihydrothiopyrano[3,2-d]pyrimidine derivatives as potent HIV-1 inhibitors against drug-resistant variants

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1257-1282页

作者： Zhao Wang Heng Zhang Zhen Gao Zihao Sang Erik De Clercq christophe Pannecouque Dongwei Kang Peng Zhan Xinyong Liu Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJinan 250012China Rega Institute for Medical Research Laboratory of Virology and ChemotherapyK.U.LeuvenLeuven B-3000Belgium China-Belgium Collaborative Research Center for Innovative Antiviral Drugs of Shandong Province Jinan 250012China Suzhou Research Institute Shandong UniversitySuzhou 215123China

With our continuous endeavors in seeking potent anti-HIV-1 agents,we reported here the discovery,biological characterization,and druggability evaluation of a class of nonnucleoside reverse transcriptase *** fully explore the chemical space of the NNRTI-binding pocket,novel series of dihydrothiopyrano[3,2-d]pyrimidines were developed by employing the structure-based design *** of the derivatives were endowed with prominent antiviral activities against HIV-1 wild-type and resistant strains at nanomolar *** them,compound 23h featuring the aminopiperidine moiety was identified as the most potent inhibitor,with EC50values ranging from 3.43 to 21.4 nmol/***,for the challenging double-mutants F227L+V106A and K103N+Y181C,23h exhibited 2.3-to 14.5-fold more potent activity than the first-line drugs efavirenz and ***,the resistance profiles of 23h achieved remarkable improvement compared to efavirenz and *** binding target of 23h was further confirmed to be HIV-1 reverse *** modeling studies were also performed to elucidate the biological evaluation results and give guidance for the optimization ***,no apparent inhibition of the major CYP450 enzymes and hERG channel was observed for *** importantly,23h was characterized by good pharmacokinetic properties and excellent safety in ***,23h holds great promise as a potential candidate for its effective antiviral efficacy and favorable drug-like profiles.

关键词： HIV-1 Reverse transcriptase Dihydrothiopyrano[3,2-d]pyrimidine Antiviral agent

Bridging Continents,Shaping Futures

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China Today 2024年第10期73卷 20-21页

作者： JEAN-christophe DESLARZES Board of the Adecco Group

The combined strengths of China and Europe can build a workforce that is well-prepared for the future and capable of driving economic *** highly anticipated China-Europe Talent Forum 2024 provides us with an invaluable platform to discuss and enhance the strong ties between China and Europe,focusing on the future of talent *** relationship between China and Europe has long been marked by mutual respect and a deep commitment to collaboration in various sectors,including trade,technology,education,and culture.

关键词： mutual driving education

Design and optimization of piperidinesubstituted thiophene[3,2-d]pyrimidine-based HIV-1 NNRTIs with improved drug resistance and pharmacokinetic profiles

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3110-3124页

作者： Yanying Sun Zhenzhen Zhou Zhongling Shi Fabao Zhao Minghui Xie Zongji Zhuo Erik De Clercq christophe Pannecouqueb Dongwei Kang Peng Zhan Xinyong Liu Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesShandong UniversityJinan 250012China Rega Institute for Medical Research Laboratory of Virology and ChemotherapyK.U.LeuvenLeuven B-3000Belgium China-Belgium Collaborative Research Center for Innovative Antiviral Drugs of Shandong Province Jinan 250012China

HIV-1 reverse transcriptase(RT)has received great attention as an attractive therapeutic target for acquired immune deficiency syndrome(AIDS),but the inevitable drug resistance and side effects have always been major challenges faced by non-nucleoside reverse transcriptase inhibitors(NNRTIs).This work aimed to identify novel chemotypes of anti-HIV-1 agents with improved drugresistance profiles,reduced toxicity,and excellent druggability.A series of diarylpyrimidine(DAPY)derivatives were prepared via structural modifications of the leads K-5a2 and *** them,15a with dimethylphosphine oxide moiety showed the most prominent antiviral potency against all of the tested viral panel,being 1.6-fold(WT,EC_(50) Z 1.75 nmol/L),3.0-fold(L100I,EC_(50) Z 2.84 nmol/L),2.4-fold(K103N,EC_(50) Z 1.27 nmol/L),3.3-fold(Y181C,EC50 Z 5.38 nmol/L),2.9-fold(Y188L,EC_(50) Z 7.96 nmol/L),2.5-fold(E138K,EC_(50) Z 4.28 nmol/L),4.8-fold(F227L/V106A,EC_(50) Z 3.76 nmol/L)and 5.3-fold(RES056,EC_(50) Z 15.8 nmol/L)more effective than that of the marketed drug *** docking results illustrated the detailed interactions formed by compound 15a and WT,F227L/V106A,and RES056 ***,15a-HCl carried outstanding pharmacokinetic(t1/2 Z 1.32 h,F Z 40.8%)and safety profiles(LD_(50)>2000 mg/kg),which demonstrated that 15a HCl is a potential anti-HIV-1 drug candidate.

关键词： HIV-1 NNRTIs NNIBP Structural alert Anti-HIV-1 drug candidate

Design,synthesis,and biological evaluation of benzo[4,5]thieno[2,3-d]pyrimidine derivatives as novel HIV-1 NNRTIs

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Chinese Chemical Letters 2024年第6期35卷 344-348页

作者： Bairu Meng Zongji Zhuo Han Yu Sining Tao Zixuan Chen Erik De Clercq christophe Pannecouque Dongwei Kang Peng Zhan Xinyong Liu Department of Medicinal Chemistry Key Laboratory of Chemical Biology(Ministry of Education)School of Pharmaceutical SciencesCheeloo College of MedicineShandong UniversityJi’nan 250012China Laboratory of Virology and Chemotherapy Rega Institute for Medical ResearchK.U.LeuvenLeuven B-3000Belgium China-Belgium Collaborative Research Center for Innovative Antiviral Drugs of Shandong Province Ji’nan 250012China

Inspired by our previous studies to discover novel human immunodeficiency virus-1(HIV-1)nonnucleoside reverse transcriptase inhibitors(NNRTIs)by targeting the tolerant region II of the NNRTIs binding pocket(NNIBP),a series of novel benzo[4,5]thieno[2,3-d]pyrimidine derivatives were designed through structure-based drug design as novel potent HIV-1 *** results showed that compound16b was the most active inhibitor,exhibiting 50% effective concentration(EC50)values from 0.021μmol/L to 0.298μmol/L against wild-type(WT)and a panel of NNRTIs-resistant HIV-1 ***,16b was demonstrated with a significantly low 50% cytotoxicity concentration(CC_(50))value(>200μmol/L)and high selectivity index(SI)*** addition,16b yielded moderate reverse transcriptase(RT)enzyme inhibition with a 50% inhibition concentration(IC_(50))value of 0.183μmol/L,which demonstrated that it acted as HIV-1 *** binding mode of 16b with RT was also illustrated via molecular ***,this work provided a novel lead compound for developing potent HIV-1 NNRTIs.

关键词： HIV-1 NNRTIs DAPYs Tolerant regionⅡ Drug design