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High-throughput discovery of highly selective reversible hMAO-B inhibitors based on at-line nanofractionation

Acta Pharmaceutica Sinica B 2024年第4期14卷 1772-1786页

作者： Yu Fan Jincai wang Jingyi Jian Yalei Wen Jiahao li Hao Tian Jacques Crommen Wei Bi Tingting Zhang Zhengjin Jiang Institute of Pharmaceutical Analysis/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education(MOE)of China/College of Pharmacy Jinan UniversityGuangzhou 510632China KU Leuven-University of Leuven Pharmaceutical AnalysisDepartment of Pharmaceutical and Pharmacological SciencesLeuven 3000Belgium Laboratory of Analytical Pharmaceutical Chemistry Department of Pharmaceutical SciencesCIRMUniversity of LiegeLiege B-4000Belgium Department of Neurology the First Affiliated Hospital of Jinan University/Clinical Neuroscience Institutethe First Affiliated Hospital of Jinan UniversityGuangzhou 510630China

Human monoamine oxidase B(hMAO-B)has emerged as a pivotal therapeutic target for Parkinson's *** to adverse effects and shortage of commercial drugs,there is a need for novel,highly selective,and reversible hMAO-B inhibitors with good blood-brain barrier *** this study,a high-throughput at-line nanofractionation screening platform was established with extracts from Chuanxiong Rhizoma,which resulted in the discovery of 75 active compounds,including phenolic acids,volatile oils,and phthalides,two of which were highly selective novel natural phthalide hMAO-B inhibitors that were potent,selective,reversible and had good blood‒brain *** docking and molecular dynamics simulations elucidated the inhibition ***(IC_(50)=103 nmol/L;SI=645)and neocnidilide(IC_(50)=131 nmol/L;SI=207)demonstrated their excellent potential as hMAO-B *** offset the limitations of deactivating enzymes associated with irreversible hMAO-B inhibitors such as *** SH-SY5Y cell assays,sedanolide(EC_(50)=0.962μmol/L)and neocnidilide(EC_(50)=1.161μmol/L)exhibited significant neuroprotective effects,comparable to the positive drugs rasagiline(EC_(50)=0.896μmol/L)and safinamide(EC_(50)=1.079μmol/L).These findings underscore the potential of sedanolide as a novel natural hMAO-B inhibitor that warrants further development as a promising drug candidate.

关键词： Human monoamine oxidase B inhibitors High-throughput screening At-linenanofractionation Parkinson's disease Cellular neuroprotection Traditional Chinese medicines(TCMs)

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Preliminary assessment of the data appropriateness of electronic health records for real-world studies:A survey of hospitals in a developing region in China

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Chinese Medical Journal 2024年第9期137卷 1130-1131页

作者： Yuelin Yu lin Zhuo Ruogu Meng Wanqian guo Yuanyuan Chen Yunjing Zhang Ying Chen Hongjing Shi Zhi lin Siyan Zhan Shengfeng wang Department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijing 100191China Research Center of Clinical Epidemiology Peking University Third HospitalBeijing 100191China National Institute of Health Data Science Peking UniversityBeijing 100191China Health Science Center Peking UniversityBeijing 100191China

To the Editor:Assessment of data appropriateness is a process to answer whether electronic health records(EHRs)from routine healthcare practices couldt intended study purposes,for example,available to be proceeded,with enough individual records,with relevant information able to be extracted from records,etc.[1-3]This has been increasingly underscored as a prerequisite when using EHRs(one important type of real-world data[RWD])for scientic purposes.[4-6]Although controversies remain on the denitions,types and assessment methods of the dimensions of RWD appropriateness,the latest ofcial guidelines(i.e.,from the *** and Drug Administration[FDA][4]and China National Medical Products Administration[NMPA][6])suggest that the assessment start from a preliminary stage on variable existence,and subsequently deepen into the issue of data value(such as missing value,outliers,etc.),as the preliminary assessment is the foundation of the overall RWD appropriateness.[7]little is known about the appropriateness of EHRs in developing regions,which feature high visit volumes and a great number of ***,this study aimed to preliminarily investigate RWD appropriateness from hospitals in developing regions from the perspective of core variables’comparison.

关键词： electronic dimensions records

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Experimental study on photodegradation and leaching of typical pesticides in greenhouse soil from Shouguang, Shandong Province, East China

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Ecological Processes 2024年第2期 32-47页

作者： li-Ting Hua Rui-lin Wu Cun-Lu li Chao-Nan wang Yi-Long li Fu-liu Xu MOE Laboratory for Earth Surface Processes College of Urban and Envi-ronmental Sciences Peking University Department of Ecology and Environment of Shanxi Province

Background Pesticide use contributes to national food security. The dissipation pathways and degradation mecha-nisms of pesticides have been widely studied and pesticide residues have remained a focus of public concern. How-ever, studies on the migration and transformation behaviors of pesticide residues in real-world greenhouse soils are insufficient. Therefore, in this study, we collected greenhouse soil from Shouguang, Shandong Province, and investi-gated the photodegradation and leaching of 17 common pesticides, which leave residues in the soil and are the most frequently used pesticides in Shouguang. The environmental behavior of pesticides in greenhouse soils will provide new information on pesticide residues in the real environment and provide a scientific basis for the prevention and control of pesticide pollution in greenhouse *** The photodegradation of trifloxystrobin followed a first-order kinetic equation, whereas those of emamec-tin benzoate, chlorantraniliprole, buprofezin, difenoconazole, pyraclostrobin, boscalid, tebuconazole, isoprothiolane, metalaxyl, and oxadixyl followed second-order kinetics. The half-lives of 17 pesticides under light and dark conditions ranged from 2.5–104(mean: 36.2) and 2.6–110(mean: 31.4) days, respectively. The half-lives of emamectin benzoate, pyraclostrobin, and metalaxyl in the light were 86.6%, 68.5%, and 94.5% of their half-lives in the dark, respectively. Chlorantraniliprole, metalaxyl, nitenpyram, diethofencarb, acetamiprid, carbendazim, and oxadixyl were leached to ≥ 90% in aqueous solution. Six pesticides, avermectin B1A, emamectin benzoate, trifloxystrobin, difenoconazole, pyraclostrobin, and buprofezin, were difficult to leach from aqueous *** The degradation rate of some pesticides was higher in the light environment than in the dark. The leaching potential of the leachable pesticides was nitenpyram ? metalaxyl > acetamiprid > carbendazim > diethofen-carb ≈ chlorantraniliprole > iso

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Reynosin protects neuronal cells from microglial neuroinflammation by suppressing NLRP3 inflammasome activation mediated by NADPH oxidase

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Chinese Journal of Natural Medicines 2024年第6期22卷 486-500页

作者： YANG Yanqiu CHE Yue FANG Mingxia YAO Xiaohu ZHOU Di wang Feng CHEN Gang liANG Dong li Ning HOU Yue Key Laboratory of Bioresource Research and Development of liaoning Province College of Life and Health SciencesNorth-eastern UniversityShenyang 110000China National Frontiers Science Center for Industrial Intelligence and Systems Optimization Key Laboratory of Data Analytics and Optimization for Smart IndustryMinistry of EducationNortheastern UniversityShenyang 110000China School of Traditional Chinese Materia Medica Key Laboratory of Innovative Traditional Chinese Medicine for Major Chronic Diseases of Liaoning provinceKey Laboratory for TCM Material Basis Study and Innovative Drug Development of Shenyang CityShenyang Pharmaceutical UniversityShenyang 110000China State Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources School of Chemistry and Pharmaceutical SciencesGuangxi Normal UniversityGuilin 541000China

Neuroinflammation,mediated by the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing-3(NLRP3)inflammasome,is a significant contributor to the pathogenesis of neurodegenerative diseases(NDDs).Reynos-in,a natural sesquiterpene lactone(SL),exhibits a broad spectrum of pharmacological effects,suggesting its potential therapeutic ***,the effects and mechanism of reynosin on neuroinflammation remain *** current study explores the effects and mechanisms of reynosin on neuroinflammation using mice and BV-2 microglial cells treated with lipopolysaccharide(LPS).Our findings reveal that reynosin effectively reduces microglial inflammation in vitro,as demonstrated by decreased CD11b expression and lowered interleukin-1 beta(IL-1β)and interleukin-18(IL-18)mRNA and protein ***,in vivo,results showed a re-duction in the number of Iba-1 positive cells and alleviation of morphological alterations,alongside decreased expressions of IL-1βand *** analysis indicates that reynosin inhibits NLRP3 inflammasome activation,evidenced by reduced transcription of NLRP3 and caspase-1,diminished NLRP3 protein expression,inhibited apoptosis-associated speck-like protein containing a CARD(ASC)oli-gomerization,and decreased caspase-1 ***,reynosin curtailed the activation of nicotinamide adenine dinuc-leotide phosphate(NADPH)oxidase,demonstrated by reduced NADP^(+)and NADPH levels,downregulation of gp91^(phox) mRNA,pro-tein expression,suppression of p47^(phox) expression and translocation to the ***,reynosin exhibited a neuroprotective effect against microglial inflammation in vivo and in *** collective findings underscore reynosin’s capacity to mitigate mi-croglial inflammation by inhibiting the NLRP3 inflammasome,thus highlighting its potential as a therapeutic agent for managing neuroinflammation.

关键词： Microglia NLRP3 inflammasome Reactive oxygen species NADPH oxidase Neuron Reynosin

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Establishment of an indirect immunofluorescence assay for the detection of African swine fever virus antibodies

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Journal of Integrative Agriculture 2024年第1期23卷 228-238页

作者： Wan wang Zhenjiang Zhang Weldu Tesfagaber Jiwen Zhang Fang li Encheng Sun lijie Tang Zhigao Bu Yuanmao Zhu Dongming Zhao State Key Laboratory for Animal Disease Control and Prevention National African Swine Fever Para-reference LaboratoryNational High Containment Facilities for Animal Diseases Control and PreventionHarbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China College of Veterinary Medicine Northeast Agricultural UniversityHarbin 150069China

African swine fever(ASF)continues to cause enormous economic loss to the global pig *** there is no safe and effective vaccine,accurate and timely diagnosis of ASF is essential to implement control *** immunofluorescence assay(IFA)is a gold standard serological method recommended by the World Organization for Animal Health(WOAH).In this study,we used primary fetal kidney cells to establish a wild boar cell line(BK2258)that supported the efficient replication of ASF virus(ASFV)SD/DY-I/21 and showed visible cytopathic effect(CPE).Moreover,using BK2258,we established a sensitive and specific IFA for ASFV antibody *** standardize and evaluate the performance of this assay,we used serum samples from pigs infected with the low virulent genotype I SD/DY-I/21 and genotype II HLJ/HRB1/20,and immunized with the vaccine candidate HLJ/18-7GD,field samples,and negative serum *** IFA reacted with the ASFV-positive sera and displayed bright fluorescence *** was no non-specific green fluorescence due to cellular senescence or other cell damage-causing *** to a commercial indirect enzyme-linked immunosorbent assay(iEliSA),ASFV antibodies were detected 1–4 days earlier using our *** detection limits of the IFA and iEliSA for the same ASFV-antibody positive serum samples were 1:25,600 and 1:6,400,respectively,indicating that the IFA is more sensitive than *** newly established IFA was highly specific and did not cross-react with sera positive for six other important porcine pathogens(i.e.,Classical swine fever virus(CSFV),Porcine reproductive and respiratory syndrome virus(PRRSV),Porcme circovirus type 2(PCV2),Pseudorabies virus(PRV),Foot-and-Mouth disease virus type O(FMDV/O),and Porcine epidemic diarrhea virus(PEDV)).This study thus provides a sensitive,specific,and reliable detection method that is suitable for the serological diagnosis of ASF.

关键词： African swine fever antibody IFA serological method

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Targeted G-to-T base editing for generation of novel herbicide-resistance gene alleles in rice

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Journal of Integrative Plant Biology 2024年第6期66卷 1048-1051页

作者： Yifu Tian Xinbo li Jiyong Xie Zai Zheng Rundong Shen Xuesong Cao Mugui wang Chao Dong Jian-Kang Zhu Ministry of Agriculture and Rural Affairs Key Laboratory of Gene Editing Technologies(Hainan) Institute of Crop Sciences and National Nanfan Research InstituteChinese Academy of Agricultural SciencesSanya 572024China Hainan Seed Industry Laboratory Sanya 572024China Shanghai Center for Plant Stress Biology CAS Center for Excellence in Molecular Plant SciencesThe Chinese Academy of SciencesShanghai 201602China University of Chinese Academy of Sciences Beijing 100049China Institute of Advanced Biotechnology and School of MedicineSouthern University of Science and TechnologyShenzhen 518055China

Deaminase-based cytosine base editors(CBEs)and adenine base editors(ABEs)induce C-to-T and A-to-G transitions,respectively,enabling single-nucleotide variants(SNVs)in plants for research and crop enhancement(li et al.,2023a).The C-to-G base editors(CGBEs)and A-to-Y base editors(AYBEs),developed by incorporating glycosylases with CBEs and ABEs,expand the repertoire of base editing products,allowing C-to-T/G and A-to-T/G transversions in plants(li et al.,2023b,2023c;Sretenovic et a.,2021).

关键词： base alleles CBE

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Wave nature of Rosensweig instability

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Chinese Physics B 2024年第3期33卷 471-479页

作者：李柳李德才戚志强王璐张志力 School of Mechanical Electronicand Control EngineeringBeijing Jiaotong UniversityBeijing 100044China Beijing Key Laboratory of Flow and Heat Transfer of Phase Changing in Micro and Small Scale Beijing 100044China State Key Laboratory of Tribology Tsinghua UniversityBeijing 100084China

The explicit analytical solution of Rosensweig instability spikes'shapes obtained by Navier-Stokes(NS)equation in diverse magnetic field H vertical to the flat free surface of ferrofluids are systematically studied experimentally and *** carefully analyzing and solving the NS equation in elliptic form,the force balanced surface equations of spikes in Rosensweig instability are expressed as cosine wave in perturbated magnetic field and hyperbolic tangent in large magnetic field,whose results both reveal the wave-like nature of Rosensweig *** results of hyperbolic tangent form are perfectly fitted to the experimental results in this paper,which indicates that the analytical solution is basically *** the forementioned theoretical results,the total energy of the spike distribution pattern is *** analyzing the energy components under different magnetic field intensities H,the hexagon-square transition of Rosensweig instability is systematically discussed and explained in an explicit way.

关键词： ferrofluids Rosensweig instability hexagon-square transition

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Comprehensive transcriptional atlas of human adenomyosis deciphered by the integration of single-cell RNA-sequencing and spatial transcriptomics

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Protein & Cell 2024年第7期15卷 530-546页

作者： Tao Chen Yiliang Xu Xiaocui Xu Jianzhang wang Zhiruo Qiu Yayuan Yu Xiaohong Jiang Wanqi Shao Dandan Bai Mingzhu wang Shuyan Mei Tao Cheng li Wu Shaorong Gao Xuan Che Department of Obstetrics and Gynecology Affiliated Women and Children Hospital of Jiaxing UniversityJiaxing 314000China Shanghai Key Laboratory of Maternal Fetal Medicine Clinical and Translational Research Center of Shanghai First Maternity and Infant HospitalFrontier Science Center for Stem Cell ResearchSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China Key Laboratory of Animal Bioengineering and Disease Prevention of Shandong Province College of Animal Science and TechnologyShandong Agricultural UniversityTaian 271018China Women’s Hospital School of MedicineZhejiang UniversityHangzhou 310013China Postgraduate training base Alliance of Wenzhou Medical University Wenzhou Medical UniversityWenzhou 325035China Jiaxing University Master Degree Cultivation Base Zhejiang Chinese Medical UniversityHangzhou 310053China Shanghai Key Laboratory of Maternal Fetal Medicine Shanghai Institute of Maternal-Fetal Medicine and Gynecologic OncologyClinical and Translational Research CenterShanghai First Maternity and Infant HospitalSchool of Life Sciences and TechnologyTongji UniversityShanghai 200092China

Adenomyosis is a poorly understood gynecological disorder lacking effective *** persists regarding“invagination”and“metaplasia”*** endometrial-myometrial junction(EMJ)connects the endometrium and myometrium and is important for diagnosing and classifying adenomyosis,but its in-depth study is just *** single-cell RNA sequencing and spatial profiling,we mapped transcriptional alterations across eutopic endometrium,lesions,and *** lesions,we identified unique epithelial(LGR5+)and invasive stromal(PKIB+)subpopulations,along with WFDC1+progenitor cells,supporting a complex interplay between“invagination”and“metaplasia”theories of ***,we observed endothelial cell heterogeneity and abnormal angiogenic signaling involving vascular endothelial growth factor and angiopoietin ***-cell communication differed markedly between ectopic and eutopic endometrium,with aberrant signaling in lesions involving pleiotrophin,TWEAK,and WNT *** study reveals unique stem cell-like and invasive cell subpopulations within adenomyosis lesions identified,dysfunctional signaling,and EMJ abnormalities critical to developing precise diagnostic and therapeutic strategies.

关键词： adenomyosis single-cell RNA sequencing spatial transcriptomics endometrial-myometrial junction progenitor cells

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Roles of THEM4 in the Akt pathway:a double-edged sword

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第7期25卷 541-556页

作者： Wen XIE Weidong liU Lei wang Bin ZHU Cong ZHAO Ziling liAO Yihan li Xingjun JIANG Jie liU Caiping REN NHC Key Laboratory of Carcinogenesis Department of NeurosurgeryXiangya HospitalCentral South UniversityChangsha 410008China National Clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangsha 410008China The Key Laboratory of Carcinogenesis and Cancer Invasion of the Ministry of Education Cancer Research InstituteSchool of Basic Medical ScienceCentral South UniversityChangsha 410078China Department of Critical Care Medicine Hainan Hospital of Chinese PLA General HospitalHainan Province Clinical Medical CenterSanya 572013China

The protein kinase B(Akt)pathway can regulate the growth,proliferation,and metabolism of tumor cells and stem cells through the activation of multiple downstream target genes,thus affecting the development and treatment of a range of *** superfamily member 4(THEM4),a member of the thioesterase superfamily,is one of the Akt kinase-binding *** studies on the mechanism of cancers and other diseases have shown that THEM4 binds to Akt to regulate its ***,THEM4 was considered an endogenous inhibitor of Akt,which can inhibit the phosphorylation of Akt in diseases such as lung cancer,pancreatic cancer,and liver cancer,but subsequently,THEM4 was shown to promote the proliferation of tumor cells by positively regulating Akt activity in breast cancer and nasopharyngeal carcinoma,which contradicts previous *** these two distinct views,this review summarizes the important roles of THEM4 in the Akt pathway,focusing on THEM4 as an Akt-binding protein and its regulatory relationship with Akt phosphorylation in various diseases,especially *** work provides a better understanding of the roles of THEM4 combined with Akt in the treatment of diseases.

关键词： Protein kinase B(Akt) Thioesterase superfamily member 4(THEM4) Tumor proliferation Tumor metastasis

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Ultrathin polyimide-based composites with efficient low-reflectivity electromagnetic shielding and infrared stealth performance

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Nano Research 2024年第7期17卷 6700-6712页

作者： Xu Zhao Xinwei Tang Yunlong Qiao Shuangshuang li Zihang Zhang Yezi Lu Mingyang Zhu Zaiyin Hu lijuan Long Zicheng wang Tianxi liu The Key Laboratory of Synthetic and Biological Colloids Ministry of EducationSchool of Chemical and Material EngineeringInternational Joint Research Laboratory for Nano Energy CompositesJiangnan UniversityWuxi 214122China Guizhou Aerospace Wujiang Electro-mechanical Equipment Co. Ltd.No.20-5Dalian Road Aerospace Industrial ParkHuichuan DistrictZunyi 563000China School of Materials and Architectural Engineering Guizhou Normal UniversityGuiyang 550025China

Researching and manufacturing materials that possess both electromagnetic interference(EMI)shielding and infrared stealth capabilities is of great ***,an ultrathin polyimide-based nonwoven fabric with low-reflection EMI shielding/infrared stealth performance is successfully fabricated by in-situ loading of Fe_(3)O_(4)/Ag nanoparticles on the surface of polyimide(PI)fiber(PFA),and followed by bonding with a commercial Cu/Ni *** synergistic assembly of PFA and Cu/Ni promotes the rational construction of hierarchical impedance matching,inducing electromagnetic waves(EMW)to enter the composite and be dissipated as much as ***,the existence of Cu/Ni mesh on back of PFA facilitates the formation of electromagnetic resonance and destructive interference of EMW reflected from composite,leading to a lowerreflectivity(0.26)EMI shielding performance of 58 dB within 24–40 GHz at a thinner thickness(430μm).More importantly,the fluffy PFA nonwoven fabric and metal Cu/Ni mesh endow composite with good thermal insulation and low infrared emissivity,resulting in excellent infrared stealth performance in various *** a result,such excellent compatibility makes it possible to become a promising defense material to be applied in military tent for preventing electromagnetic and infrared radiation.

关键词： polyimide electromagnetic interference shielding low reflection infrared stealth

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