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Dual PPAR delta/gamma agonist offer therapeutic potential for Alzheimer's disease

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Neural Regeneration research 2024年第6期19卷 1175-1176页

作者： Ian Steinke Meenakshi Singh Rajesh Amin department of Drug discovery and Development Auburn UniversityAuburn AlabamaALUSA

The increasing incidence of Alzheimer's disease(AD)in the aging population,indicates the critical need for the development of novel targeted molecular therapies for ameliorating AD ***,clinical and preclinical evidence demonstrates that peroxisomal proliferator activating receptors(PPAR)agonists regulate energy and lipid homeostasis in models of diabetes,as well as improve spatial memory in animal models of AD(Khan et al.,2019).

关键词： Alzheimer clinical homeostasis

CFD-DEM analysis of particle polydispersity on the performance of fluidised bed reactor during silane pyrolysis Author links open overlay panel

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Particuology 2024年第8期91卷 72-87页

作者： Akshayveer Vijay M.Shinde MS2discovery Interdisciplinary research Institute Wilfrid Laurier UniversityWaterlooOntarioN2L3C5Canada department of Chemical Engineering Indian Institute of Technology(BHU)Varanasi221005India

A CFD-DEM model is developed for chemical vapour deposition of silane in a fluidized bed reactor to investigate the effect of polydispersity on local phase dynamics,mass and heat transport,as well as the rate of Si *** gas-phase fines formation and heterogeneous deposition on the seed particle,as well as the scavenging effect for Si particle growth,are *** method is first validated against the experimentally measured Si deposition rate,percentage of fine production and minimum fluidisation ***,the properties,primarily particle intermixing,fluidisation behaviour and bubble dynamics along with the deposition process,are analyzed for several polydisperse beds under various operating *** effect of polydispersity of the bed on a fraction of the bubble size,dense phase expansion and interchange coefficient between various phases is thoroughly investigated to establish a correlation with reactor *** results show that broad-Gaussian particle size distribution(PSD)exhibits excellent improvement in fluidisation behaviour,resulting in a high deposition rate,and minimum formation of Si fines.

关键词： CFD-DEM method Chemical vapour deposition(CVD) Particle size distribution Silicon Gas-solid fluidized bed

Total Synthesis of Laurane and Guaiane Sesquiterpenoids via Oxidative Nazarov Reaction

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Chinese Journal of Chemistry 2024年第11期42卷 1267-1274页

作者： Yuye Chen Wenqing Chen Zhiting Zhang Jing Xu Shenzhen Grubbs Institute and department of Chemistry and Guangming Advanced research Institute and Guangdong Provincial Key Laboratory of Catalysis and Shenzhen Key Laboratory of Small Molecule Drug discovery and Synthesis Southern University of Science and TechnologyShenzhenGuangdong518055 China

As one of the most common structural motifs in natural products,cyclopentenones usually can be fabricated by Nazarov cyclization using divinyl ketones or functionalized tertiary divinyl carbinols(TDCs)as ***,straightforward method for transforming unfunctionalized TDCs to their corresponding cyclopentenones is currently ***,we wish to report the total syntheses of four structurally distinct terpenoids,namely laurane-type marine sesquiterpenoids isolaurene,debromoaplysin and aplysin,and guaiane sesquiterpenoid guaiadienone A,all using a novel synthetic method,named oxidative Nazarov cyclization,as the key *** work demonstrated our robust method is suitable for synthesizing various highly substituted cyclopentenones.

关键词： Total synthesis Synthetic methods Sesquiterpenoids Oxidative Nazarov reaction Electrocyclization Oxoammonium salt Pericyclic reaction Annulation

Development of SV2A Ligands for Epilepsy Treatment:A Review of Levetiracetam,Brivaracetam,and Padsevonil

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Neuroscience Bulletin 2024年第5期40卷 594-608页

作者： Peng-Peng Wu Bi-Rong Cao Fu-Yun Tian Zhao-Bing Gao Center for Neurological and Psychiatric research and Drug discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China University of Chinese Academy of Sciences Beijing100049China Zhongshan Institute for Drug discovery Shanghai Institute of Materia MedicaChinese Academy of SciencesZhongshan528400China

Epilepsy is a common neurological disorder that is primarily treated with antiseizure medications(ASMs).Although dozens of ASMs are available in the clinic,approximately 30%of epileptic patients have medically refractory seizures;other limitations in most traditional ASMs include poor tolerability and drug-drug ***,there is an urgent need to develop alternative ***(LEV)is a first-line ASM that is well tolerated,has promising efficacy,and has little drug-drug *** it is widely accepted that LEV acts through a unique therapeutic target synaptic vesicle protein(SV)2A,the molecular basis of its action remains *** so,the next-generation SV2A ligands against epilepsy based on the structure of LEV have achieved clinical *** review highlights the research and development(R&D)process of LEV and its analogs,brivaracetam and padsevonil,to provide ideas and experience for the R&D of novel ASMs.

关键词： Levetiracetam Epilepsy Antiseizure medications Synaptic vesicle protein 2A Brivaracetam Padsevonil

A sphingolipid message promotes neuronal health across generations

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Neural Regeneration research 2024年第11期19卷 2325-2326页

作者： Wenyue Wang Roger Pocock Development and Stem Cells Program Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental BiologyMonash UniversityMelbourneVICAustralia

Maternal nutrition can affect brain function of offspring in later life(Fitzgerald et al.,2020).Emerging studies have also shown that the maternal environment can modify susceptibility to neurodegenerative disease(Boots et al.,2023).Transmission of environmental information from mother to offspring depends on maternal nutrient *** the nematode Caenorhabditis elegans,maternal yolk,which is synthesized in the intestine and transferred to nourish oocytes and early embryos,can provide extranuclear inheritance factors to mediate phenotypic plasticity across ***,the molecular mechanisms of regulating such intergenerational effects remain largely unknown.

关键词： mother intestine transferred

CA IX-targeted Ag_(2)S quantum dots bioprobe for NIR-II imaging-guided hypoxia tumor chemo-photothermal therapy

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Journal of Pharmaceutical Analysis 2024年第6期14卷 878-888页

作者： Xinyue Cui Zhuang Hu Ruihan Li Peng Jiang Yongchang Wei Zilin Chen department of Radiation and Medical Oncology Zhongnan Hospital of Wuhan University and School of Pharmaceutical SciencesWuhan UniversityWuhan430071China Key Laboratory of Combinatorial Biosynthesis and Drug discovery Ministry of EducationHubei Province Engineering and Technology Research Center for Fluorinated PharmaceuticalsWuhan430071China

Hypoxia is the common characteristic of almost all solid tumors,which prevents therapeutic drugs from reaching the ***,the development of new targeted agents for the accurate diagnosis of hypoxia tumors is widely *** carbonic anhydrase IX(CA IX)is abundantly distributed on the hypoxia tumor cells,it is considered as a potential tumor biomarker.4-(2-Aminoethyl)benzenesulfonamide(ABS)as a CA IX inhibitor has inherent inhibitory activity and good targeting *** this study,Ag_(2)S quantum dots(QDs)were used as the carrier to prepare a novel diagnostic and therapeutic bioprobe(Ag_(2)S@polyethylene glycol(PEG)-ABS)through ligand exchange and amide condensation ***_(2)S@PEG-ABS can selectively target tumors by surface-modified ABS and achieve accurate tumor imaging by the near infrared-II(NIR-II)fluorescence characteristics of Ag_(2)S *** modification of Ag_(2)S QDs greatly improves its water solubility and stability,and therefore achieves high photothermal stability and high photothermal conversion efficiency(PCE)of 45.17%.Under laser irradiation,Ag_(2)S@PEG-ABS has powerful photothermal and inherent antitumor combinations on colon cancer cells(CT-26)in *** also has been proved that Ag_(2)S@PEG-ABS can realize the effective treatment of hypoxia tumors in vivo and show good ***,it is a new efficient integrated platform for the diagnosis and treatment of hypoxia tumors.

关键词： CA IX-targeted Hypoxia tumor combination therapy NIR-II imaging Photothermal effect

Multiplexed fluorescence and scatter detection with single cell resolution using on-chip fiber optics for droplet microfluidic applications

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Microsystems & Nanoengineering 2024年第2期10卷 207-218页

作者： Preksha Gupta Ambili Mohan Apurv Mishra Atindra Nair Neeladri Chowdhury Dhanush Balekai Kavyashree Rai Anil Prabhakar Taslimarif Saiyed discovery Innovation Accelerator Centre for Cellular and Molecular PlatformsBellary RoadBengaluru560065KarnatakaIndia department of Electrical Engineering Indian Institute of Technology MadrasChennai600036Tamil NaduIndia

Droplet microfluidics has emerged as a critical component of several high-throughput single-cell analysis techniques in biomedical research and *** significant progress in the development of individual assays,multiparametric optical sensing of droplets and their encapsulated contents has been *** current approaches,most commonly involving microscopy-based high-speed imaging of droplets,are technically complex and require expensive instrumentation,limiting their widespread *** address these limitations,we developed the OptiDrop platform;this platform is a novel optofluidic setup that leverages the principles of flow *** platform enables on-chip detection of the scatter and multiple fluorescence signals from the microfluidic droplets and their contents using optical *** highly customizable on-chip optical fiber-based signal detection system enables simplified,miniaturized,low-cost,multiparametric sensing of optical signals with high sensitivity and single-cell resolution within each *** demonstrate the ability of the OptiDrop platform,we conducted a differential expression analysis of the major histocompatibility complex(MHC)protein in response to IFNγ*** results showed the platform’s ability to sensitively detect cell surface biomarkers using fluorescently labeled ***,the OptiDrop platform combines the versatility of flow cytometry with the power of droplet microfluidics to provide wide-ranging,scalable optical sensing solutions for research and diagnostics.

关键词： scatter enable resolution

Assembly of functional carboxymethyl cellulose/polyethylene oxide/anatase TiO_(2) nanocomposites and tuning the dielectric relaxation, optical, and photoluminescence performances

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Journal of Semiconductors 2024年第7期45卷 26-38页

作者： Asmaa M.Ismail Abeer A.Reffaee Fawzy G.El Desouky Spectroscopy department Physics Research InstituteNational Research CentreGizaCairo 12622Egypt Microwave Physics and Dielectrics department National Research CentreDokkiCairoEgypt Solid State Physics department Physics Research InstituteNational Research CentreGizaCairo 12622Egypt

Nanocomposite films consisting of carboxymethyl cellulose,polyethylene oxide(CMC/PEO),and anatase titanium diox-ide(TO)were produced by the use of sol-gel and solution casting ***2 nanocrystals were effectively incorporated into CMC/PEO polymers,as shown by X-ray diffraction(XRD)and attenuated total reflectance fourier transform infrared(ATR-FTIR)*** roughness growth is at high levels of TO nanocrystals(TO NCs),which means increasing active sites and defects in CMC/*** differential scanning calorimetry(DSC)thermograms,the change in glass transition temperature(Tg)val-ues verifies that the polymer blend interacts with TO *** increment proportions of TO NCs have a notable impact on the dielectric performances of the nanocomposites,as *** electrical properties of the CMC/PEO/TO nanocomposite undergo significant *** nanocomposite films exhibit a red alteration in the absorption edge as the concentration of TO NCs increases in the polymer *** decline in the energy gap is readily apparent as the weight percentage of TO NCs *** photoluminescence(PL)emission spectra indicate that the sites of the luminescence peak maximums show slight variation;peaks get wider,while their intensities decrease dramatically as the concentration of TO *** nanocomposite materials show potential for multifunctional applications including optoelectronics,antireflection coatings,pho-tocatalysis,light emitting diodes,and solid polymer electrolytes.

关键词： anatase TiO_(2) CMC/PEO nanocomposites optical photoluminescent electrical optoelectronics

SRY-Box transcription factor 9 triggers YAP nuclear entry via direct interaction in tumors

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2285-2297页

作者： Hui Qian Chen-Hong Ding Fang Liu Shi-Jie Chen Chen-Kai Huang Meng-Chao Xiao Xia-Lu Hong Ming-Chen Wang Fang-Zhi Yan Kai Ding Ya-Lu Cui Bai-Nan Zheng Jin Ding Cheng Luo Xin Zhang Wei-Fen Xie department of Gastroenterology Changzheng HospitalNaval Medical UniversityShanghaiChina department of Gastroenterology Shanghai East HospitalSchool of MedicineTongji UniversityShanghaiChina Drug discovery and Design Center CAS Key Laboratory of Receptor ResearchState Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of SciencesShanghaiChina department of Gastroenterology First Affiliated Hospital of Nanchang UniversityNanchangChina Clinical Cancer Institute Center for Translational MedicineNaval Medical UniversityShanghaiChina

The translocation of YAP from the cytoplasm to the nucleus is critical for its activation and plays a key role in tumor ***,the precise molecular mechanisms governing the nuclear import of YAP are not fully *** this study,we have uncovered a crucial role of SOX9 in the activation of ***9 promotes the nuclear translocation of YAP by direct ***,we have identified that the binding between Asp-125 of SOX9 and Arg-124 of YAP is essential for SOX9-YAP interaction and subsequent nuclear entry of ***,we have discovered a novel asymmetrical dimethylation of YAP at Arg-124(YAP-R124me2a)catalyzed by ***-R124me2a enhances the interaction between YAP and SOX9 and is associated with poor prognosis in multiple ***,we disrupted the interaction between SOX9 and YAP using a competitive peptide,S-A1,which mimics anα-helix of SOX9 containing Asp-125.S-A1 significantly inhibits YAP nuclear translocation and effectively suppresses tumor *** study provides the first evidence of SOX9 as a pivotal regulator driving YAP nuclear translocation and presents a potential therapeutic strategy for YAP-driven human cancers by targeting SOX9-YAP interaction.

关键词： interaction interaction precise