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Evidence for using pimavanserin for the treatment of Parkinson’s disease psychosis

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World journal of Psychiatry 2019年第3期9卷 47-54页

作者： Rajesh R Tampi Deena j Tampi juan j young Silpa Balachandran Rakin A Hoq Geetha Manikkara Department of Psychiatry and Behavioral Sciences Cleveland Clinic Akron GeneralOhioNH 44106United States Cleveland Clinic Lerner College of Medicine of Case Western Reserve University OhioCleveland 44195United States Diamond Healthcare RichmondVA 23219United States Case Western Reserve University School of Medicine Department of PsychiatryClevelandOH 44109United States Department of Psychiatry Summa Health SystemAkronOH 44304United States Department of Psychiatry Texas Tech University Health Science CenterMidlandTX 79701United States

The aim of this editorial is to evaluate the evidence for using pimavanserin for the treatment of Parkinson's disease psychosis(PDP)from randomized controlled trials(RCTs).We only identified two published trials that evaluated the use of pimavanserin among individuals with *** studies found that pimavanserin improved psychotic symptoms among individuals with PDP when compared to *** was fairly well tolerated in both studies and did not appear to cause significant sedation or worsen motor symptoms among individuals with ***,given the limited data,additional confirmatory studies are required before pimavanserin can be considered as a first line agent for the treatment of psychotic symptoms among individuals with PD.

关键词： Pimavanserin Parkinson’s disease Parkinson’s disease psychosis Psychosis Antipsychotic

Phosphorus fractionation and release characteristics of sediment in the Saemangeum Reservoir for seasonal change

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International journal of Sediment Research 2018年第3期33卷 250-261页

作者： Dong-Heui Kwak young-Tae jeon young Duck Hur jeongeup Industry-Academic Cooperation Support Center Chonbuk National University jeollabuk-do Provincial Covernment Department of Environmental Engineering Chonbuk National University

Periodical algal blooms result in deposition and release of phosphorus(P) from the sediment into the water. Therefore, during seasonal changes when algal particles begin to settle to the bottom, understanding the behavior and distribution characteristics of the P in sediment is the most important key to manage the water quality of the Saemangeum Reservoir. In this study, the variation of water quality and sediment composition including chlorophyll-a(Chl-a) and P was investigated to determine the interaction between water and sediment. The study focused primarily on algal particle sedimentation that affects the P release and mineralization of sediment. The Chl-a concentration in water showed a sharp decline in October when the algae began to die in the fall, and afterward the concentration of chemical oxygen demand(COD) and total P(TP) in the sediment increased due to the sedimentation of decaying algal particles in *** the same period of time, the readily bio-available P(RAP) in the sediment showed a drastic increase in the upper region where the Chl-a concentration of water was high. In sequence, the high RAP zone shifted from the upper region to the lower region in the early winter. The RAP shift was considered to be derived from the physical flow of the overlying water from which the decomposing algae settled on the surface of the sediment. The Saemangeum Reservoir was constructed recently; therefore, all the types of inorganic P fractions except soluble reactive phosphorus(SRP) that exist on the bottom surface of the lake and the marsh’s sediment layer were not sufficient to significantly influence the overlying water. On the other hand, the released P from the algae was distinct and sensitive to the seasonal change. In conclusion,the algal particle sedimentation was important to control eutrophication rather than P release from the mineralized inorganic P of the sediment surface layer in the Seamangeum Reservoir.

关键词： Algal bloom Fractionation Phosphorus Water management Release Sediment

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

Investigation of factors influencing roof stability at a Western *** coal mine

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International journal of Mining Science and Technology 2019年第1期29卷 139-143页

作者： Meriel young Gabriel Walton Elizabeth Holley Department.Geology&Geol.Engineering Colorado School of Mines Department Mining Engineering Colorado School of Mines

The coal mine roof rating(CMRR) was developed to bridge the gap between geological variation in underground coal mines and engineering design. The CMRR accounts for the compressive strength of the immediate roof, the shear strength and intensity of any discontinuities present, and the moisture sensitivity of the immediate roof. The CMRR has been widely used and validated in Eastern US coal mines, but it has seen limited application in the Western US. This study focuses on roof behavior at a Western coal mine(Mine A). Mine A shows significant lateral geological variation, along with localized faulting and a laterally extensive sandstone channel network. The CMRR is not used to predict roof instability at the mine. It is, therefore, hypothesized that there are other factors that are correlated with roof instability in underground coal mines that could potentially also be considered in conjunction with the *** hypothesis was tested by collecting 30 CMRR measurements at Mine A. At each measurement location, a binary record of the roof condition(stable or unstable) was made, and other parameters such as depth of cover, presence of faulting, and sandstone channels were also recorded. ANOVA tests showed that the CMRR values and the roof conditions were not strongly correlated, indicating that the CMRR input criteria are not fully predictive of roof stability at this mine. The CMRR values showed statistically significant correlations(p less than 0.05) with faulting as well as with location at an intersection. For areas that had previously experienced roof fall but were currently stable, faulting was correlated with roof condition(p less than 0.05) only when the condition was classified as unstable.

关键词： Coal mine roof stability CMRR Western U.S.coal Case study

Local HY5 Activity Mediates Hypocotyl Growth and Shoot-to-Root Communication

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Plant Communications 2020年第5期1卷 64-72页

作者： Yogev Burko christophe.Gaillochet Adam Seluzicki joanne Chory Wolfgang Busch Howard Hughes Medical Institute Salk Institute for Biological StudiesLa JollaCA 92037USA Plant Biology Laboratory Salk Institute for Biological Studies10010 North Torrey Pines RoadLa JollaCA 92037USA Integrative Biology Laboratory Salk Institute for Biological Studies10010 North Torrey Pines RoadLa JollaCA 92037USA

Plants optimize their growth in fluctuating environments using information acquired by different *** information is then transmitted through the rest of the plant using both short-and long-distance signals,including hormones and mobile *** a few of these signals have been characterized,long-distance signaling is not well understood in ***,the light-regulated transcription factor HY5 was reported to move from the shoot to the root to regulate root *** generated a cell-type specifically expressed HY5 fusion protein that could not be detected outside the tissue in which it was *** expressing this DOF-HY5 protein in specific cell types of the hypocotyl,we showed that its local activity was sufficient to regulate hypocotyl *** also found that,although DOF-HY5 was expressed specifically in the shoot and not detected in the roots,it could rescue hy5 growth defects in primary roots but not in lateral *** therefore conclude that HY5 protein mobility is not required in the hypocotyl or for shoot-to-root *** results indicate that a signal downstream of,or in parallel with,HY5 in the shoot is mobile and links shoot and root growth.

关键词： HY5 shoot-to-root communication hypocotyl root lateral root Arabidopsis

Ultrafiltration for environmental safety in shellfish production: A case of bloom emergence

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Water Science and Engineering 2021年第1期14卷 46-53页

作者： Clemence Cordier Alexandra Voulgaris christophe.Stavrakakis Patrick Sauvade Franz Coelho Philippe Moulin Aix-Marseille Universite M2P2 UMR 7340Equipe Procedes MembranairesLaboratoire de Mecanique Modelisation et Procedes PropresAix en Provence 13545France Plateforme Experimentale Mollusques Marins Station Ifremer de BouinPolder des ChampsBouin 85230France Suez-Aquasource Toulouse 31029France

The process of ultrafiltration(UF)of natural seawater often encounters the problems of variation in water quality and coastal *** validate the feasibility of UF in shellfish farms,this study compared the hydraulic performance and pollutant removal efficiency of the UF process with those of the commonly used treatments that combine several filtration steps with ultraviolet(UV)*** comparison was conducted in the cases of natural seawater and a coastal *** that the UF process encountered the specific type of pollution,this study evaluated the filtration performance of the UF process and the retention of total suspended solids(TSS),bacteria,phytoplankton,and zooplankton.A real coastal bloom was considered in the case study of an experimental shellfish hatchery/nursery in *** results show that both treatments were able to eliminate approximately 50%of ***,in contrast with UV treatment combined with filtration,the UF process retained total amounts of phytoplankton,zooplankton,and bacteria in the *** the hydraulic performance of the UF process was impacted by the coastal bloom,the fouling was eliminated through chemical cleaning conducted at a frequency less than once per 12 *** the severe pollution,this study confirmed the pollution resistance and treatment performance of the UF process,indicating that UF has the potential to enhance the biosecurity level.

关键词： Ultrafiltration Environmental safety Aquaculture Shellfish culture Coastal bloom

Structure-directed expansion of biphenyl-pyridone derivatives as potent non-nucleoside reverse transcriptase inhibitors with significantly improved potency and safety

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Chinese Chemical Letters 2023年第12期34卷 126-131页

作者： Li-Min Zhao christophe.Pannecouque Erik De Clercq Shuai Wang Fen-Er Chen Engineering Center of Catalysis and Synthesis for Chiral Molecules Department of ChemistryFudan UniversityShanghai 200433China Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs Shanghai 200433China Key Laboratory of Natural Resources of Changbai Mountain&Functional Molecules Ministry of EducationYanbian University College of PharmacyYanbian UniversityYanji 133002China Rega Institute for Medical Research KU LeuvenHerestraat 49Leuven B-3000Belgium

Following our previous work on human immunodeficiency virus-1(HIV-1)non-nucleoside reverse transcriptase inhibitors(NNRTIs),a series of novel biphenyl-pyridone derivatives were synthesized and evaluated for their anti-HiV-1 activity to expand their structure-activity *** of them exhibited low nanomolar activity toward wild-type HiV-1 and clinically relevant single/double mutant *** most active compound B1 was 231-fold more potent(EC_(50)=17nmol/L)than the lead compound 2(EC_(50)=3.93μmol/L)against wild-type(WT)*** compound was approximately 3.5-fold less cytotoxic(CC_(50)=100.58μmol/L)than compound 2(CC_(50)=28.24μmol/L),presenting a higher selectivity index(SI)value of *** with 2,the antiviral potency of B1 was significantly increased against five single mutant strains(L1001,K103N,E138K,Y181C and Y188L)and two double mutant strains(F227L+V106A and K103N+Y181C).Especially,K103N,Y181C and K103N+Y181C were more sensitive to B1 than both 2 and ***,the enzymatic inhibitory activity of B1 against wild-type HIV-1 reverse transcriptase was approximately 32-fold higher(IC_(50)=100nmol/L)than 2(IC_(50)=3.21μmol/L).Molecular docking studies and dynamic simulations were conducted to explain their potent *** together,this research represents an important step toward the discovery of novel biphenylpyridone drug candidates for HIV therapy.

关键词： HIV-1 NNRTI Doravirine Biphenyl-pyridone Safety

Picomolar inhibitor of reverse transcriptase featuring significantly improved metabolic stability

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Acta Pharmaceutica Sinica B 2023年第7期13卷 3054-3066页

作者： Ya-Li Sang christophe.Pannecouque Erik De Clercq Shuai Wang Fen-Er Chen 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 School of Science Harbin Institute of Technology(Shenzhen)Shenzhen 518055China Rega Institute for Medical Research KU LeuvenLeuven B-3000Belgium

Considering the undesirable metabolic stability of our recently identified NNRTI 5(t1/2=96 min)in human liver microsomes,we directed our efforts to improve its metabolic stability by introducing a new favorable hydroxymethyl side chain to the C-5 position of *** strategy provided a series of novel methylol-biphenyl-diarylpyrimidines with excellent anti-HIV-1 *** best compound 9g was endowed with remarkably improved metabolic stability in human liver microsomes(t1/2=2754 min),which was about 29-fold longer than that of 5(t1/2=96 min).This compound conferred picomolar inhibition of WT HIV-1(EC50=0.9 nmol/L)and low nanomolar activity against five clinically drug-resistant mutant *** maintained particularly low cytotoxicity(CC50=264μmol/L)and good selectivity(SI=256,438).Molecular docking studies revealed that compound 9g exhibited a more stable conformation than 5 due to the newly constructed hydrogen bond of the hydroxymethyl group with ***,compound 9g was characterized by good safety *** displayed no apparent inhibition of CYP enzymes and h *** acute toxicity assay did not cause death and pathological damage in mice at a single dose of 2 g/*** findings paved the way for the discovery and development of new-generation anti-HIV-1 drugs.

关键词： NNRTI HIV-1 DAPYs Picomolar Metabolic stability

Suppression of gold nanoparticle agglomeration and its separation via nylon membranes

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Chinese journal of Chemical Engineering 2017年第7期25卷 931-937页

作者： Ayyavoo jayalakshmi In-Chul Kim young-Nam Kwon School of Urban and Environmental Engineering Ulsan National Institute of Sdence and TechnologyUlsan 689-798Korea KIST-UNIST UIsan Center for Convergent Materials UNIST(Ulsan National Institute of Science and Technology)Korea Environment and Resources Research Center Korea Research Institute Chemical TechnologyDaejeon 305-606Korea

Use of ultraporous nylon membrane is one of the most widely employed techniques for removal of hard and soft nanoparticles in the semiconductor industry, and the accurate determination of membrane pore size is necessary in order to avoid manufacturing defects caused by contamination. The gold nanoparticle has several benefits for the evaluation of polymeric membranes; however, the nanoparticles agglomerate easily on the nylon membrane and make it difficult to evaluate the membrane precisely. The properties of 2-amino-2-hydroxymethyl-1,3-propanediol(ADP) ligand in gold nanoparticle solution were systematically investigated, and ADP was utilized for improved evaluation of the nylon membranes. Nylon membrane used in this study was prepared by phase inversion techniques. Ultrathin dense layer on top of the membrane surface and Darcy structures in the microporous membrane support were observed. The gold particle rejection was carried out at various p H values from 4 to14 and higher rejection was observed at p H 4 and 8. The suppression of gold colloid agglomeration using ADP and monodispersity of gold colloids was also analyzed by confocal laser scanning microscopy(CLSM), transmission electron microscopy(TEM), and scanning electron microscopy(SEM). van der Waals interaction energy of the particles was reduced in the addition of ADP. The presence of ADP ligand in the gold solutions prevented the agglomeration of gold nanoparticles and reduced the adsorption of the particles on the nylon membrane surface,leading to precise evaluation of membrane pore sizes.

关键词： Particle size Electron microscopy Gold colloid flock Semiconductor