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NPC1-regulated dynamic of clathrin-coated pits is essential for viral entry

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Science China(Life Sciences) 2022年第2期65卷 341-361页

作者： Guoli Li Bingqian Su Pengfei Fu Yilin Bai Guangxu Ding Dahua Li Jiang Wang Guoyu Yang beibei chu College of Veterinary Medicine Henan Agricultural UniversityZhengzhou 450046China Key Laboratory of Animal Biochemistry and Nutrition Ministry of Agriculture and Rural Affairs of the People’s Republic of ChinaZhengzhou 450046China International Joint Research Center of National Animal Immunology Henan Agricultural UniversityZhengzhou 450046China College of Veterinary Medicine Northwest A&F UniversityYangling 712100China

Viruses utilize cellular lipids and manipulate host lipid metabolism to ensure their replication and spread.Therefore,the identification of lipids and metabolic pathways that are suitable targets for antiviral development is crucial.Using a library of compounds targeting host lipid metabolic factors and testing them for their ability to block pseudorabies virus(PRV)and vesicular stomatitis virus(VSV)infection,we found that U18666A,a specific inhibitor of Niemann-Pick C1(NPC1),is highly potent in suppressing the entry of diverse viruses including pseudotyped severe acute respiratory syndrome coronavirus 2(SARS-CoV-2).NPC1 deficiency markedly attenuates viral growth by decreasing cholesterol abundance in the plasma mem-brane,thereby inhibiting the dynamics of clathrin-coated pits(CCPs),which are indispensable for clathrin-mediated endocytosis.Significantly,exogenous cholesterol can complement the dynamics of CCPs,leading to efficient viral entry and infectivity.Administration of U18666A improves the survival and pathology of PRV-and influenza A virus-infected mice.Thus,our studies demonstrate a unique mechanism by which NPC1 inhibition achieves broad antiviral activity,indicating a potential new therapeutic strategy against SARS-CoV-2,as well as other emerging viruses.

关键词： broad-spectrum antiviral NPC inhibition CCP dynamics viral entry

Motor cortical circuit adaptations in parkinsonism

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Neural Regeneration Research 2024年第10期19卷 2107-2108页

作者： Hong-Yuan chu Department of Neurodegenerative Science Van Andel Research InstituteGrand RapidsMIUSA Aligning Science Across Parkinson’s(ASAP)Collaborative Research Network

Parkinson's disease is a chronic and progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta,which leads to the featured motor impairment of parki... 详细信息

关键词： parkin impairment rigidity

Ball milling pretreatment of corn straw and Pediococcus acidilactici fermentation for non‑ruminant diet

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Systems Microbiology and Biomanufacturing 2022年第2期2卷 355-360页

作者： Dianhui Wu Wenzhe Li beibei chu Lulu Wang Xiaomin Li Guolin Cai Jian Lu The Key Laboratory of Industrial Biotechnology Ministry of EducationJiangnan University1800 Lihu RoadWuxi 214122People’s Republic of China National Engineering Laboratory for Cereal Fermentation Technology Jiangnan UniversityNo.1800 Lihu RoadWuxi 214122JiangsuPeople’s Republic of China Jiangsu Provincial Research Center for Bioactive Product Processing Technology Jiangnan University1800 Lihu RoadWuxi 214122People’s Republic of China School of Biotechnology Jiangnan University1800 Lihu RoadWuxi 214122People’s Republic of China Charoen Pokphan Food Research and Development Co. LtdModern Agricultural ParkCixi 315300People’s Republic of China

A new strategy was proposed to improve the utilization rate of corn straw by making non-ruminant feed products.The corn straw was ball milled,and the crushed straw was subjected to solid-state fermentation.After ball milling,the particle size of corn straw decreased signifcantly from 4.85±0.07 cm to 10–100μm,the content of neutral detergent fber and acid detergent fber decreased by 1.3%and 3.5%,respectively,and the total soluble sugar content increased by 16.2 mg/g.At the same time,the straw treated by ball milling as substrate could promote the rapid growth of Pediococcus acidilactici R30,the increase of organic acid production and further improvement of other nutrients during solid-state fermentation.In conclusion,the fermented straw products after ball milling could signifcantly improve the performance of pig feed in terms of digestibility and nutritional value,and better meet the feed needs of non-ruminant animals while saving resources.

关键词： Corn straw Ball milling Solid-state fermentation Non-ruminant diet Probiotics

Aberrant protamination in sperm correlates to anomalous nuclear and cytoplasmic architectures in infertile males with sperm dysmorphology

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Asian Journal of Andrology 2024年第2期26卷 183-188页

作者： Huan Jiang chu-Jie Huang Department of Reproductive Endocrinology Longgang District Maternity&Child Healthcare Hospital of Shenzhen City(Longgang Maternity and Child Institute of Shantou University Medical College)Shenzhen 518172China Institute of Reproductive Immunology College of Life Science and TechnologyJinan UniversityGuangzhou 510632China

Aberrant sperm protamination is linked to sperm dysmorphology and nuclear chromatin condensation.Yet,its effects on sperm cytoplasmic maturation remain largely unexplored.The relationships of protamines,sperm morphology,DNA damage,and cytoplasmic remodeling were illustrated in this study to provide fresh perspectives on the mechanisms of male infertility.A total of 205 infertile males were allocated into 5 groups according to the percentage of spermatozoa exhibiting abnormal morphology within their samples.Sperm concentration,motility,abnormal sperm morphology,cytoplasmic droplets(CDs),and excess residual cytoplasm(ERC)were analyzed according to the World Health Organization manual(2010).Sperm nuclear vacuoles(NVs)were determined by propidium iodide(PI)staining.Sperm protamine expressions(P1 and P2)were detected by western blot.DNA damage was measured by acridine orange test(AOT)to calculate the proportion of sperm with single-strand DNA breaks(SSBs).Our data showed that sperm concentration and motility in infertile males significantly decreased with the severity of abnormal sperm morphology(both P<0.01).P1 level,P1/P2 ratio,and SSB rate increased with the severity of sperm dysmorphology,whilst the P2 level decreased(all P

关键词： abnormal sperm morphology excess residual cytoplasm male infertility protamines sperm DNA damage sperm nuclear vacuoles

Lysosomal cholesterol accumulation is commonly found in most peroxisomal disorders and reversed by 2-hydroxypropyl-β-cyclodextrin

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Science China(Life Sciences) 2023年第8期66卷 1786-1799页

作者： Lewei Dong Jian Xiao Shuai Liu Gang Deng Yacheng Liao beibei chu Xiaolu Zhao Bao-Liang Song Jie Luo College of Life Sciences Taikang Center for Life and Medical SciencesHubei Key Laboratory of Cell HomeostasisWuhan UniversityWuhan 430072China College of Veterinary Medicine Henan Agricultural UniversityZhengzhou 450046China

Peroxisomal disorders(PDs)are a heterogenous group of diseases caused by defects in peroxisome biogenesis or functions.Xlinked adrenoleukodystrophy is the most prevalent form of PDs and results from mutations in the ABCD1 gene,which encodes a transporter mediating the uptake of very long-chain fatty acids(VLCFAs).The curative approaches for PDs are very limited.Here,we investigated whether cholesterol accumulation in the lysosomes is a biochemical feature shared by a broad spectrum of PDs.We individually knocked down fifteen PD-associated genes in cultured cells and found ten induced cholesterol accumulation in the lysosome.2-Hydroxypropyl-β-cyclodextrin(HPCD)effectively alleviated the cholesterol accumulation phenotype in PD-mimicking cells through reducing intracellular cholesterol content as well as promoting cholesterol redistribution to other cellular membranes.In ABCD1 knockdown cells,HPCD treatment lowered reactive oxygen species and VLCFA to normal levels.In Abcd1 knockout mice,HPCD injections reduced cholesterol and VLCFA sequestration in the brain and adrenal cortex.The plasma levels of adrenocortical hormones were increased and the behavioral abnormalities were greatly ameliorated upon HPCD administration.Together,our results suggest that defective cholesterol transport underlies most,if not all,PDs,and that HPCD can serve as a novel and effective strategy for the treatment of PDs.

关键词： cholesterol peroxisome lysosome peroxisomal disorders X-ALD cyclodextrin ABCD1 VLCFA

A Fully-Integrated Memristor Chip for Edge Learning

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Nano-Micro Letters 2024年第9期16卷 123-127页

作者： Yanhong Zhang Liang chu Wenjun Li School of Elecronics and Information Hangzhou Dianzi UniversityHangzhou 310018People’s Republic of China

It is still challenging to fully integrate computing in memory chip as edge learning devices.In recent work published on Science,a fully-integrated chip based on neuromorphic memristors was developed for edge learning as artificial neural networks with functionality of synapses,dendrites,and somas.A crossbar-array memristor chip facilitated edge learning including hardware realization,learning algorithm,and cycle-parallel sign-and threshold-based learning(STELLAR)scheme.The motion control and demonstration platforms were executed to improve the edge learning ability for adapting to new scenarios.

关键词： Computing in memory Edge learning Fully-integrated chip

Demixing microwave signals using system-on-chip photonic processor

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Light(Science & Applications) 2024年第3期13卷 399-401页

作者： Sheng Gao chu Wu Xing Lin Department of Electronic Engineering Tsinghua University100084 BeijingChina Beijing National Research Center for Information Science and Technology Tsinghua University100084 BeijingChina

The integrated photonic processor,co-packaged with electronic peripherals,is proposed for blind source separation of microwave signals,which separates signal-of-interest from dynamic interference with real-time adapta... 详细信息

关键词： processor microwave mixing

Strigolactone regulates nitrogen-phosphorus balance in rice

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Science China(Life Sciences) 2024年第2期67卷 428-430页

作者： Huwei Sun Hanyun Wang Chengcai chu Guangdong Provincial Key Laboratory of Plant Molecular Breeding College of AgricultureSouth China Agricultural UniversityGuangzhou 510642China Key Laboratory for Enhancing Resource Use Efficiency of Crops in South China Ministry of Agriculture and Rural AffairsSouth China Agricultural UniversityGuangzhou 510642China Guangdong Laboratory for Lingnan Modern Agriculture Guangzhou 510642

Phosphorus(P) is one of the essential elements for growth and development of crops.Modern agriculture depends heavily on the application of large amounts of fertilizers,including P fertilizers.Excessive application of P fertilizers causes severe environmental pollution.Additionally,phosphate(Pi) mining is a non-renewable resource(Raghothama,1999).

关键词： pollution phosphorus fertilizers

Process metallurgy and data-driven prediction and feedback of blast furnace heat indicators

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International Journal of Minerals,Metallurgy and Materials 2024年第6期31卷 1228-1240页

作者： Quan Shi Jue Tang Mansheng chu School of Metallurgy Northeastern UniversityShenyang 110819China Institute for Frontier Technologies of Low-carbon Steelmaking Northeastern UniversityShenyang 110819China Engineering Research Center of Frontier Technologies for Low-carbon Steelmaking(Ministry of Education) Shenyang 110819China

The prediction and control of furnace heat indicators are of great importance for improving the heat levels and conditions of the complex and difficult-to-operate hour-class delay blast furnace(BF)system.In this work,a prediction and feedback model of furnace heat indicators based on the fusion of data-driven and BF ironmaking processes was proposed.The data on raw and fuel materials,process op-eration,smelting state,and slag and iron discharge during the whole BF process comprised 171 variables with 9223 groups of data and were comprehensively analyzed.A novel method for the delay analysis of furnace heat indicators was established.The extracted delay variables were found to play an important role in modeling.The method that combined the genetic algorithm and stacking efficiently im-proved performance compared with the traditional machine learning algorithm in improving the hit ratio of the furnace heat prediction model.The hit ratio for predicting the temperature of hot metal in the error range of±10℃ was 92.4%,and that for the chemical heat of hot metal in the error range of±0.1wt%was 93.3%.On the basis of the furnace heat prediction model and expert experience,a feedback model of furnace heat operation was established to obtain quantitative operation suggestions for stabilizing BF heat levels.These sugges-tions were highly accepted by BF operators.Finally,the comprehensive and dynamic model proposed in this work was successfully ap-plied in a practical BF system.It improved the BF temperature level remarkably,increasing the furnace temperature stability rate from 54.9%to 84.9%.This improvement achieved considerable economic benefits.

关键词： blast furnace furnace heat genetic algorithm stacking prediction and feedback