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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

Programming nonlinear propagation for efficient optical learning machines

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Advanced Photonics 2024年第1期6卷 73-83页

作者： Ilker Oguz Jih-Liang Hsieh Niyazi Ulas Dinc Ugur Tegin Mustafa Yildirim Carlo Gigli christophe Moser Demetri Psaltis École Polytechnique Fédérale de Lausanne Institute of Electrical and Micro EngineeringEcublensSwitzerland Koc University Department of Electrical and Electronics EngineeringIstanbulTurkey

The ever-increasing demand for training and inferring with larger machine-learning models requires more efficient hardware solutions due to limitations such as power dissipation and *** is a promising contender for providing lower power computation,since light propagation through a nonabsorbing medium is a lossless ***,to carry out useful and efficient computations with light,generating and controlling nonlinearity optically is a necessity that is still *** fibers(MMFs)have been shown that they can provide nonlinear effects with microwatts of average power while maintaining parallelism and low *** propose an optical neural network architecture that performs nonlinear optical computation by controlling the propagation of ultrashort pulses in MMF by wavefront *** a surrogate model,optimal sets of parameters are found to program this optical computer for different tasks with minimal utilization of an electronic *** show a remarkable decrease of 97%in the number of model parameters,which leads to an overall 99%digital operation reduction compared to an equivalently performing digital neural *** further demonstrate that a fully optical implementation can also be performed with competitive accuracies.

关键词： neural networks nonlinear optics fiber optics surrogate optimization neuromorphic computing wavefront shaping

Late-onset Very long-chain acyl-CoA dehydrogenase deficiency diagnosis complicated by fulminant myocarditis in adult patient

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Journal of Intensive Medicine 2024年第3期4卷 400-402页

作者： Martin Gérard Clair Douillard Julien Poissy Mehdi Marzouk christophe Vinsonneau Intensive Care Unit Centre Hospitalier de Bethune-BeuvryBethuneFrance Endocrinology diabetologymetabolism departmentLille reference centre of inborn errors of metabolismLille University HospitalLilleFrance Inserm U1285 CHU LillePôle de réanimationCNRSUMR 8576-UGSF-Unitéde Glycobiologie Structurale et FonctionnelleUniv.LilleLilleFrance

Introduction A 21-year-old woman presented to the emergency department with fatigue,abdominal pain and *** physical activity in school was strictly *** had no family medical history and no personal history but reported frequent episodes of nausea and vomiting lasting 2 to 7 days during the past two years,as well as a weight loss of 9 kg due to reactive anorexia(Body Mass Index 17.5),without triggering factors or *** gastrointestinal symptoms led to the detection of isolated elevated transaminases(aspartate aminotransferase[AST]190 U/L and alanine aminotransferase[ALT]170 U/L);however,the patient did not pursue the proposed etiological *** has been using cannabis once a day for several years,with an increase in consumption over the past year,but no *** reported no other recent change in her habits.

关键词： diagnosis patient elevated

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

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

The Substructure of Elementary Particles Demonstrated by the I-Theory

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Journal of High Energy Physics, Gravitation and Cosmology 2024年第2期10卷 469-514页

作者： H. H. Swami Isa christophe Dumas Global Energy Parliament Trivandrum Kerala India

Present studies in physics assume that elementary particles are the building blocks of all matter, and that they are zero-dimensional objects which do not occupy space. The new I-Theory predicts that elementary particles do indeed have a substructure, three dimensions, and occupy space, being composed of fundamental particles called I-particles. In this article we identify the substructural pattern of elementary particles and define the quanta of energy that form each elementary particle. We demonstrate that the substructure comprises two classes of quanta which we call “attraction quanta” and “repulsion quanta”. We create a model that defines the rest-mass energy of each elementary particle and can predict new particles. Lastly, in order to incorporate this knowledge into the contemporary models of science, a revised periodic table is proposed.

关键词： I-Theory I-Particle Causal Subtle Gross Quanta Attraction Quanta Repulsion Quanta Elementary Particles Leptons Bosons Hadron Periodic Table Black Matter White Matter Red Matter Gravitation Strong Force Weak Force Quantum Theory Heat Quantum Photon Neutrino