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Linker optimization of HEPT derivatives as potent non-nucleoside HIV-1 reverse transcriptase inhibitors: From S=O to CHOR

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Chinese Chemical Letters 2023年第4期34卷 188-192页

作者： Qingqing Hao Xu Ling christophe Pannecouque Erik De Clercq Fener Chen Sichuan Research Center for Drug Precision Industrial Technology West China School of PharmacySichuan UniversityChengdu 610041China Department of Chemistry Engineering Center of Catalysis and Synthesis for Chiral MoleculesFudan UniversityShanghai 200433China Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs Shanghai 200433China Rega Institute for Medical Research KU LeuvenHerestraat 49Leuven B-3000Belgium

A novel series of CHOR-HEPT non-nucleoside HIV-1 reverse transcriptase inhibitors were developed by means of structure-based design strategy based on compound 6 reported previously by our group. Most of these compounds showed moderate to good activity toward wild-type HIV-1 strain with EC50values in the range of 0.18–51.88 μmol/L and SI values in the range of 4–907. The compound 14aj with a CHOH linker and compound 13i with a CHOTMS linker in this series exhibited improved anti-HIV-1 activity(EC50= 0.18 μmol/L, and 0.20 μmol/L) with higher selectivity(SI = 907, and 665) as comparison with the lead compound 6(EC50= 0.59 μmol/L, SI = 9). These two compounds 14aj and 13i were more sensitive than 6 toward clinically relevant mutant L100I, K103N and E138K viruses, which were further evaluated for their activity against wild-type reverse transcriptase and displayed a good correlation with the cell-based activity. Preliminary molecular modeling investigations provided insight for further structural optimization of HEPT.

关键词： HIV NNRTIs HEPTs RT Optimization

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Gate length dependent transport properties of in-plane core-shell nanowires with raised contacts

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Nano Research 2020年第1期13卷 61-66页

作者： Alexandre Bucamp christophe Coinon David Troadec Sylvie Lepilliet Gilles Patriarche Xavier Wallart Ludovic Desplanque Univ.Lille CNRSCentrale LilleYncréa ISENUniv.Polytechnique Hauts-de-FranceUMR 8520-IEMNF-59000LilleFrance C2N-UMR 9001 CNRS UniversitéParis-Sud-UniversitéParis-Saclay91120PalaiseauFrance

Three-dimensional(3D)nanoscale crystal shaping has become essential for the precise design of advanced electronic and quantum devices based on electrically gated *** this context,Ⅲ-Ⅴ semiconductor-based nanowires with low electron effective mass and strong spin-orbit coupling are particularly investigated because of their exceptional quantum transport properties and the good electrostatic control they *** the main challenges involved in the processing of these nanodevices are(i)the management of the gate stack which requires ex-situ passivation treatment to reduce the density of traps at the oxide/semiconductor interface,(ii)the ability to get good ohmic contacts for source and drain electrodes and(iii)the scalability and reliability of the process for the fabrication of complex architectures based on nanowire *** this paper,we show that selective area molecular beam epitaxy of in-plane InGaAs/InP core-shell nanowires with raised heavily doped source and drain contacts can address these different *** characterization of the devices down to 4 K reveals the positive impact of the InP shell on the gate electrostatic control and effective electron *** comparable to the best reported values for In(Ga)As nanostructures grown on InP,this latter is severely reduced for sub-100 nm channel highlighting remaining issue to reach the ballistic regime.

关键词： molecular beam epitaxy core-shell nanowire selective area growth effective electron mobility

Deciphering the role of monosaccharides during phage infection of Staphylococcus aureus

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Nano Research 2022年第10期15卷 9234-9242页

作者： Baptiste Arbez Marion Gardette christophe Gantzer Neus Vilà Isabelle Bertrand Sofiane El-Kirat-Chatel Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement(LCPME) CNRSUniversité de Lorraine405 rue de Vandoeuvre54602 Villers-lès-NancyFrance

As phages are extensively investigated as novel therapy tools but also as transfer agents for antibiotic resistance genes,thorough understanding of phage–host interactions becomes *** for phage infection is its adhesion to the host ***,we used atomic force microscopy-based single-particle force spectroscopy with phage-decorated tips to decipher the adhesion of phage 187 on living Staphylococcus aureus *** found that addition of free N-acetyl-Dglucosamine was able to decrease phage adhesion,suggesting that this monosaccharide plays major role in phage 187 infection of ***,phage 187 adhesion on monosaccharide-coated model surfaces combined with plaque forming unit counts suggested that a direct link can be established between the propensity to bind to a saccharide and the capability of the latter to inhibit phage *** a nanoscale level,single-particle force spectroscopy was successfully used to identify a major receptor required for phage 187 infection of *** but also evidenced that this receptor was responsible for phage adhesion on *** work demonstrates that single-particle force spectroscopy is a powerful platform to screen and predict the molecular target of phages on their host surfaces.

关键词： atomic force microscopy single-particle force spectroscopy phage 187 Staphylococcus aureus phage-bacteria interactions

Narrow bandwidth fiber-optic spectral combs for renewable hydrogen detection

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Science China(Information Sciences) 2020年第12期63卷 221-229页

作者： Shunshuo CAI Fu LIU Runlin WANG Yongguang XIAO Kaiwei LI christophe CAUCHETEUR Tuan GUO Institute of Photonics Technology Jinan University Department of Electronics Carleton University Electromagnetism and Telecommunications Department University of Mons

Hydrogen sensors are of great importance to detect leakage in time because the hydrogen-air mixture is highly flammable. Based on optical fiber-based configurations reported so far, using palladium coating only does not meet stringent performance targets, such as fast response time and limited deactivation caused by poisoning. Here, a palladium-gold alloy-coated optical fiber hydrogen sensor, i.e., highly tilted fiber Bragg grating(TFBG), was proposed by using its narrow bandwidth cladding modes whose effective refractive index(ERI) extends to 1.0 where the gas measurement is possible, which led to faster specific hydrogen measurement response time(a shorter stabilization time during the association and dissociation phases less than 20s and 30s, respectively) and improved deactivation resistance(higher than 99% per test cycle). Meanwhile, the temperature cross-sensitivity can be eliminated via referencing the "target" spectral combs to the core mode. We are sure that this promising configuration extends research directions for rapid,repeatable and high deactivation-resistance in hydrogen gas detection.

关键词： fiber-optic sensing probe tilted fiber Bragg grating hydrogen measurement palladium-gold alloy nanocoating

An Alternative to the Marshall-Olkin Family of Distributions:Bootstrap,Regression and Applications

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Communications on Applied Mathematics and Computation 2022年第4期4卷 1229-1257页

作者： christophe Chesneau Kadir Karakaya Hassan S.Bakouch Coskun Kus LMNO Université de CaenCampus ⅡScience 314032 CaenFrance Department of Statistics Faculty of ScienceSelcuk University42250 KonyaTurkey Department of Mathematics Faculty of ScienceTanta UniversityTantaEgypt

This paper introduces a new rich family of distributions based on mixtures and the so-called Marshall-Olkin family of *** includes a wide variety of well-established mixture distributions,ensuring a high ability for data *** distributional properties are derived for the general *** Weibull distribution is then considered as the base-line,exhibiting a pliant four-parameter lifetime *** estimation methods for the related parameters are *** confidence intervals are also considered for these *** distribution is reparametrized with location-scale parameters and it is used for a lifetime regression *** extensive simulation is carried out on the esti-mation methods for distribution parameters and regression model *** are given to two practical data sets to illustrate the applicability of the new family.

关键词： Marshall-Olkin family of distributions Estimation Confidence intervals Bootstrap Data analysis

Selection of appropriate organic additives for enhancing Zn and Cd phytoextraction by hyperaccumulators

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Journal of Environmental Sciences 2006年第6期18卷 1113-1118页

作者： WU Qi-tang DENG Jin-chuan LONG Xin-xian MOREL Jean-louis SCHWARTZ christophe College of Natural Resource and Environment South China Agricultural University Guangzhou 510642 China Laboratoire Sol et Environnement ENSAIA-INRA 54505 Vandoeuvre-les-Nancy France

Chelant-enhanced phytoextraction is one of the most promising technologies to remove heavy metals from soil. The key of the technology is to choose suitable additives in combination with a suitable plant. In the present study, laboratory batch experiment of metal solubilization, cress seeds germination were undertaken to investigate the metal-mobilizing capability and the phytotoxicity of organic additives, including ethylene diamine triacetic acid （EDTA）, citric acid, acetic acid, oxalic acid, glutamine and monosodium glutamate waste liquid （MGWL） from food industry. Experiments in pots were carried out to study the effects of the additives on Zn and Cd phytoextraction. Furthermore, a leaching experiment with lysimeter was performed to evaluate the environmental risks of additive-induced leaching to underground water. The results showed that EDTA had a strong mobilizing ability for Zn and Cd, followed by mixed reagent （MR） and MGWL. MGWL and acetic acid at 5 mmol equivalent per liter resulted in seed germination index less than 2%. Experiments in pots verified the phytotoxicity of acetic acid and MGWL. Addition of the mixed reagent at 6--10 mmol/kg significantly increased Zn phytoextraction by Thlaspi caerulescens. The same for EDTA and the mixed reagent at 10 mmol/kg by Sedum dfredii. But only mixed reagents could significantly increase Cd phytoextraction by the studied hyperaccumulators. This suggested that the strong chelant was not always the good agent to enhance phytoextraction. S. alfredii combined with 2--10 mmol/kg soil MR was preferred for phytoremediation of Cd/Zn contaminated soils in southern China, this could result in high phytoextraction of Cd/Zn and reduce the leaching risk to underground water than EDTA assisted phytoextration.

关键词： enhanced phytoextraction heavy metals Thlaspi caerulescens Sedum alfredii EDTA organic acids mixed reagent leaching risk

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Reactive Oxygen Species during Plant-microorganism Early Interactions

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Journal of Integrative Plant Biology 2010年第2期52卷 195-204页

作者： Amrit K.Nanda Emilie Andrio Daniel Marino Nicolas Pauly christophe Dunand SCSV-UMR5546 CNRS/UPS 24 Chemin de BorderougeBP 42617 Auzeville31326 Castanet-TolosanFrance Interactions Biotiques et Santé Végétale UMR INRA 1301-Université de Nice-Sophia Antipolis-CNRS 6243400 Route des ChappesBP167F-06903 Sophia Antipolis CedexFrance

Reactive Oxygen Species （ROS） are continuously produced as a result of aerobic metabolism or in response to biotic and abiotic stresses. ROS are not only toxic by-products of aerobic metabolism, but are also signalling molecules involved in several developmental processes in all organisms. Previous studies have clearly shown that an oxidative burst often takes place at the site of attempted invasion during the early stages of most plant-pathogen interac- tions. Moreover, a second ROS production can be observed during certain types of plant-pathogen interactions, which triggers hyper- sensitive cell death （HR）. This second ROS wave seems absent during symbiotic interactions. This difference between these two responses is thought to play an important signalling role leading to the establishment of plant defense. In order to cope with the deleterious effects of ROS, plants are fitted with a large panel of enzymatic and non-enzymatic antioxidant mechanisms. Thus,increasing numbers of publications report the characterisation of ROS producing and scavenging systems from plants and from microorganisms during interactions. In this review, we present the current knowledge on the ROS signals and their role during plant-microorganism interactions.

关键词： ROS Reactive Oxygen Species during Plant-microorganism Early Interactions

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Differences in egg hatching time between cyclical and obligate parthenogenetic lineages of aphids

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Insect Science 2019年第1期26卷 135-141页

作者： Charles-Antoine Dedryver Joel Bonhomme Jean-Francois Le Gallic Jean-christophe Simon Unite Mixte de Recherche IGEPP 1349 INRAIAgrocampus OuestlUniversite Rennes 1Le Rheu cedexFrance

Many aphid species exhibit a variation in reproductive mode which is influenced by winter climate regimes,with cyclical parthenogenetic (CP)lines dominating in cold winter areas (because they produce cold-resistant eggs)and obligate parthenogenetic (OP) ones in mild winter regions (because of their parthenogenetic overwintering).Genetic studies on several aphid species have shown that the OP trait can be transmitted during sexual events involving the 2 types of *** genetic system could be considered as a local safeguarding mechanism for OP alleles in case severe frost would have killed all parthenogenetically overwintering ***,this strategy would only be efficient in restoring local polymorphism in breeding systems if the newly hatched OP recombinants remain competitive over their CP *** this study we compared egg hatching sequences of CP and OP F1 clones from several crosses obtained for 2 cereal aphid species,Sitobion avenae (constant 5℃,8 h of light)and Rhopalosiphum padi (winter outdoor conditions).For ***,we obtained F1 offspring from 6 crosses, involving 4 clones while in *** F1 were obtained from 11 crosses involving 14 clones. We showed that in both species proportions of OP clones were higher in the first half of the progeny relative to the second *** addition,F1 OP clones hatched in the mean about a week earlier than their CP sibs,which gives them a demographic advantage at the start of the growth *** then discussed the consequences of this fitness advantage for the maintenance and spread of the OP trait in aphid populations.

关键词： asexuality diapauses genetic variation insects overwintering strategies reproductive mode

Dihydrosphingosine-lnduced Programmed Cell Death in Tobacco BY-2 Cells Is Independent of H2O2 Production

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Molecular Plant 2011年第2期4卷 310-318页

作者： christophe Lachaud Universite de Toulouse UPS UMR 5546 Surfaces Cellulaires et Signalisation chez les Vegetaux BP 42617 F-31326 Castanet-Tolosan France CNRS UMR 5546 BP 42617 F-31326 Castanet-Tolosan France

Sphinganine or dihydrosphingosine （d18：0, DHS）, one of the most abundant free sphingoid Long Chain Base （LCB） in plants, has been recently shown to induce both cytosolic and nuclear calcium transient increases and a correlated Programmed Cell Death （PCD） in tobacco BY-2 cells. In this study, in order to get deeper insight into the LCB signaling pathway leading to cell death, the putative role of Reactive Oxygen Species （ROS） has been investigated. We show that DHS triggers a rapid dose-dependent production of H2O2 that is blocked by diphenyleniodonium （DPI）, indicating the involvement of NADPH oxidase（s） in the process. In addition, while DPI does not block DHS-induced calcium increases, the ROS production is inhibited by the broad spectrum calcium channel blocker lanthanum （La^3＋）. Therefore, ROS production occurs downstream of DHS-induced Ca^2＋ transients. Interestingly, DHS activates expression of defense-related genes that is inhibited by both La^3＋ and DPI. Since DPI does not prevent DHS-induced cell death, these results strongly indicate that DHS-induced H2O2 production is not implicated in PCD mechanisms but rather would be associated to basal cell defense mechanisms.

关键词： Tobacco BY-2 cells calcium signaling cytosolic calcium aequorin sphingolipids LCBs dihydrosphingosine sphinganine apoptosis Programmed Cell Death (PCD) Reactive Oxygen Species (ROS) H2O2 oxidative burst.