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Drosophila models used to simulate human ATP1A1 gene mutations that cause Charcot-Marie-Tooth type 2 disease and refractory seizures

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Neural Regeneration research 2025年第1期20卷 265-276页

作者： Yao Yuan Lingqi Yu Xudong Zhuang Dongjing Wen Jin He Jingmei Hong Jiayu Xie Shengan Ling Xiaoyue Du Wenfeng Chen Xinrui Wang Institute of Life Sciences College of Biological Science and EngineeringFuzhou UniversityFuzhouFujian ProvinceChina NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate(Fujian Maternity and child health Hospital) FuzhouFujian ProvinceChina Medical research center Fujian Maternity and Child Health HospitalCollege of Clinical Medicine for Obstetrics&Gynecology and PediatricsFujian Medical UniversityFuzhouFujian ProvinceChina Department of Neurology and Institute of Neurology of The First Affiliated Hospital Institute of Neuroscienceand Fujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian ProvinceChina

Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory *** develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause *** located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)*** addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive *** these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut *** found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in *** heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal *** Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.

关键词： ATP1A1 Atpα bang-sensitive paralysis Charcot-Marie-Tooth disease type 2 CRISPR/Cas9 homology-directed repair Na^(+)/K^(+)-ATPase point mutation seizures sodium pump

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Longitudinal investigation of mineral composition in human milk and its correlation with infant anthropometric outcomes among Tibetan mother-infant dyads during the first 6 months postpartum

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Food Science and Human Wellness 2024年第5期13卷 2857-2865页

作者： Xiaomei Zhang Yaling Wang Junying Zhao Weicang Qiao Yanpin Liu Lijun Chen national engineering research center of dairy health for maternal and child Beijing Sanyuan Foods Co.Ltd.Beijing 100163China Beijing engineering research center of dairy Beijing Technical Innovation Center of Human Milk ResearchBeijing Sanyuan Foods Co.Ltd.Beijing 100163China

Nutrients in human milk,including minerals,relate growth and development of breast-fed *** mother-infant dyads possess unique characteristics on early nutrition due to their featured long-lasting *** study longitudinally investigated the relationship between the mineral composition in human milk and the Z-scores of infants among Tibetan mother-infant dyads during their first 6 months postpartum through a prospective cohort *** results show that the minerals of Na,Mg,K,Ca,Cu,Zn,and Se were of higher levels in colostrum than other lactation *** minerals were below the recommended values for infants according to Chinese dietary ***,a large proportion of infant Z-scores were below-2 as lactation period *** statistical analysis revealed that classifications and correlations in varying degrees were observed between minerals in human milk and infant *** findings will be advantageous for research upon Chinese early nutrition and progress of tailor-made infant formula.

关键词： Tibetan mother-infant dyads Minerals Z-scores Classification and correlation Breastfeeding

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Calcium-fortified fresh milk ameliorates postmenopausal osteoporosis via regulation of bone metabolism and gut microbiota in ovariectomized rats

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Food Science and Human Wellness 2024年第3期13卷 1258-1270页

作者： Qishan Wang Bin Liu Xianping Li Junying Zhao Zongshen Zhang Weicang Qiao Xinyue Wei Lijun Chen School of Bioengineering Dalian Polytechnic UniversityDalian 116034China national engineering research center of dairy health for maternal and child Beijing Sanyuan Foods Co.Ltd.Beijing 100163China Beijing engineering research center of dairy Beijing Sanyuan Foods Co.Ltd.Beijing 100163China

The aging of the global population has made postmenopausal osteoporosis prevention essential;however,pharmacological treatments are ***,we evaluate the effect of calcium-fortified fresh milk(FM)in ameliorating postmenopausal osteoporosis in a rat model established using bilateral *** 3 months of FM(containing vitamin D,and casein phosphopeptides,1000 mg Ca/100 g)or control milk(110 mg Ca/100 g milk)supplementation,bone changes were assessed using dual-energy X-ray absorptiometry,microcomputed tomography,and bone biomechanical *** results revealed that FM can regulate bone metabolism and gut microbiota composition,which act on bone metabolism through pathways associated with steroid hormone biosynthesis,relaxin signaling,serotonergic synapse,and unsaturated fatty acid ***,FM administration significantly increased bone mineral content and density in the lumbar spine and femur,as well as femoral compressive strength,while improving femoral trabecular bone parameters and ***,we found that the effects may be due to increased levels of estrogen,bone formation marker osteocalcin,and procollagen typeⅠN-propeptide,and decreased expression of the bone resorption marker C-telopiptide and tartrate-resistant acid phosphatase ***,the findings suggest that FM is a potential alternative therapeutic option for ameliorating postmenopausal osteoporosis.

关键词： dairy products Calcium Vitamin D Bone turnover markers Gut microbiota Postmenopausal osteoporosis

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Spatial transcriptomics combined with single-nucleus RNA sequencing reveals glial cell heterogeneity in the human spinal cord

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Neural Regeneration research 2025年第11期20卷 3302-3316页

作者： Yali Chen Yiyong Wei Jin Liu Tao Zhu Cheng Zhou Donghang Zhang Department of Anesthesiology West China HospitalSichuan UniversityChengduSichuan ProvinceChina Laboratory of Anesthesia and Critical Care Medicine National-Local Joint Engineering Research Center of Translational Medicine of AnesthesiologyWest China HospitalSichuan UniversityChengduSichuan ProvinceChina Department of Anesthesiology Longgang District Maternity&Child Healthcare Hospital of Shenzhen City(Longgang Maternity and Child Institute of Shantou University Medical College)ShenzhenGuangdong ProvinceChina Department of Anesthesiology Affiliated Hospital of Zunyi Medical UniversityZunyiGuizhou ProvinceChina

Glial cells play crucial roles in regulating physiological and pathological functions,including sensation,the response to infection and acute injury,and chronic neurodegenerative *** cells include astrocytes,microglia,and oligodendrocytes in the central nervous system,and satellite glial cells and Schwann cells in the peripheral nervous *** the greater understanding of glial cell types and functional heterogeneity achieved through single-cell and single-nucleus RNA sequencing in animal models,few studies have investigated the transcriptomic profiles of glial cells in the human spinal ***,we used high-throughput single-nucleus RNA sequencing and spatial transcriptomics to map the cellular and molecular heterogeneity of astrocytes,microglia,and oligodendrocytes in the human spinal *** explore the conservation and divergence across species,we compared these findings with those from *** the human spinal cord,astrocytes,microglia,and oligodendrocytes were each divided into six distinct transcriptomic *** the mouse spinal cord,astrocytes,microglia,and oligodendrocytes were divided into five,four,and five distinct transcriptomic subclusters,*** comparative results revealed substantial heterogeneity in all glial cell types between humans and ***,we detected sex differences in gene expression in human spinal cord glial ***,in all astrocyte subtypes,the levels of NEAT1 and CHI3L1 were higher in males than in females,whereas the levels of CST3 were lower in males than in *** all microglial subtypes,all differentially expressed genes were located on the sex *** addition to sex-specific gene differences,the levels of MT-ND4,MT2A,MT-ATP6,MT-CO3,MT-ND2,MT-ND3,and MT-CO_(2) in all spinal cord oligodendrocyte subtypes were higher in females than in ***,the present dataset extensively characterizes glial cell heterogeneity and offers a valuable resource for explo

关键词： astrocyte glial cell human microglia oligodendrocyte sex differentiation single-nucleus RNA sequencing spatial transcriptomics species variation spinal cord

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A multicenter prospective study of next-generation sequencing-based newborn screening for monogenic genetic diseases in China

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World Journal of Pediatrics 2023年第7期19卷 663-673页

作者： Ru-Lai Yang Gu-Ling Qian Ding-Wen Wu Jing-Kun Miao Xue Yang Ben-Qing Wu Ya-Qiong Yan Hai-Bo Li Xin-Mei Mao Jun He Huan Shen Hui Zou Shu-Yuan Xue Xiao-Ze Li Ting-Ting Niu Rui Xiao Zheng-Yan Zhao national Clinical research center for child health Children's HospitalZhejiang University School of MedicineHangzhouChina Chongqing health center for Women and children Neonatal Screening CenterChongqingChina Guiyang maternal and child health Hospital GuiyangChina University of the Chinese Academy of Science Shenzhen HospitalShenzhen 518000GuangdongChina Shanxi children's Hospital Shanxi maternal and child health Hospital TaiyuanShanxiChina The Central Laboratory of Birth Defects Prevention and Control Ningbo Women and Children's HospitalNingbo 315012ZhejiangChina maternal and child health Hospital of Ningxia Hui Autonomous Region YinchuanChina Changsha maternal and child health Hospital ChangshaHunanChina Yunnan maternal and child health Hospital KunmingYunanChina Jinan Maternity and child Care Hospital Affiliated to Shandong First Medical University JinanShandongChina Urumqi maternal and child health Care Hospital Xinjiang Uygur Autonomous RegionUrumqi CityChina Medical Genetic center Changzhi Maternal and Child Health Care HospitalChangzhiShanxiChina maternal and child health Care Hospital of Shandong Province JinanShandongChina national engineering Laboratory for Key Technology of Birth Defect Control and Prevention Screening and Diagnostic R and D CenterHangzhouChina

Background Newborn screening(NBS)is an important and successful public health program that helps improve the long-term clinical outcomes of newborns by providing early diagnosis and treatment of certain inborn *** develop-ment of next-generation sequencing(NGS)technology provides new opportunities to expand current newborn screening *** We designed a a newborn genetic screening(NBGS)panel targeting 135 genes associated with 75 inborn disorders by multiplex PCR combined with *** this panel,a large-scale,multicenter,prospective multidisease analysis was conducted on dried blood spot(DBS)profiles from 21,442 neonates *** We presented the positive detection rate and carrier frequency of diseases and related variants in different regions;and 168(0.78%)positive cases were ***-6-Phosphate Dehydrogenase deficiency(G6PDD)and phenylketonuria(PKU)had higher prevalence rates,which were significantly different in different *** positive detection of G6PD variants was quite common in south China,whereas PAH variants were most commonly identified in north *** addi-tion,NBGS identified 3 cases with DUOX2 variants and one with SLC25A13 variants,which were normal in conventional NBS,but were confirmed later as abnormal in repeated biochemical testing after *** percent of high-frequency gene carriers and 60%of high-frequency variant carriers had obvious regional *** the premise that there was no significant difference in birth weight and gestational age,the biochemical indicators of SLC22A5 c.1400C>G and ACADSB c.1165A>G carriers were significantly different from those of *** We demonstrated that NBGS is an effective strategy to identify neonates affected with treatable diseases as a supplement to current NBS *** data also showed that the prevalence of diseases has significant regional charac-teristics,which provides a theoretical basis for screening diseases in di

关键词： Monogenic genetic diseases Newborn screening Next-generation sequencing Monogenic genetic diseases Regional features

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Effects of excessive body fat on colostrum lipid patterns: overweight/obese vs. normal weight mothers

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Food Science and Human Wellness 2024年第6期13卷 3708-3717页

作者： Qian Liu Yan Liu Di Yang Yanpin Liu Yan Liu Weicang Qiao Juncai Hou Yaling Wang Minghui Zhang Kai Yang Xiaofei Fan Ziqi Li Junying Zhao Lijun Chen Key Laboratory of dairy Science Ministry of EducationFood Science CollegeNortheast Agricultural UniversityHarbin 150030China national engineering research center of dairy health for maternal and child Beijing Sanyuan Foods Co.Ltd.Beijing 100163China Beijing engineering research center of dairy Beijing Technical Innovation Center of Human Milk ResearchBeijing Sanyuan Foods Co.Ltd.Beijing 100163China

Prenatal overweight/obesity(OW/OB)can alter colostrum lipid patterns,thereby affecting the lipid metabolism and even the cognitive and healthy development of ***,studies on changes in colostrum lipids in the context of OW/OB are limited,particularly for glycerides and polar ***,this study investigated the infl uence of maternal prenatal weight on colostrum in lipid subclasses and molecular *** concentration of triacylglycerols(TAGs)in the colostrum of the OW/OB group(35894.43 mg/L)was higher than that of the normal weight(NW)group(26639.20 mg/L),suggesting that colostrum from OW/OB mothers could provide more energy to their *** analysis of the fatty acid composition of TAGs revealed that elevated maternal body weight enhanced the concentration of TAGs containing saturated or n-6 fatty acids and shortened the carbon number of *** acid(DHA)/arachidonic acid(AA)/choline-containing lipids,such as DHA-containing TAGs,AA/DHA-containing phosphatidylethanolamine,and choline-containing phospholipids,were present in higher levels in the colostrum of OW/OB mothers than NW ***,the concentrations of palmitic acid-containing TAGs,linoleic acid-containing TAGs,dihomo-γ-linolenic acid-containing TAGs,and polar lipids and the ratio of TAGs containing n-6 fatty acid/n-3 fatty acid were signifi cantly higher in the colostrum of OW/OB mothers than in that of NW *** fatty acid composition and sphingoid bases of sphingolipids were also altered due to elevated body *** conclusion,OW/OB affects colostrum lipids with respect to composition,concentration,and *** the colostrum of healthy OW/OB mothers can provide suffi cient DHA/AA/choline-containing lipids to their infants,normalization of body weight and fat reserves should be considered as a strategy for highquality human milk lipids.

关键词： Overweight/obesity Colostrum maternal diet Fat reserves Glycerides Phospholipids Sphingolipids

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Ag/AgX nanostructures serving as antibacterial agents:achievements and challenges

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Rare Metals 2022年第2期41卷 519-539页

作者： Pei-Pei Li Hai-Xia Wu Alideertu Dong College of Chemistry and Chemical engineering Engineering Research Center of Dairy Quality and Safety Control TechnologyMinistry of EducationInner Mongolia UniversityHohhot 010021China

Bacterial infections,especially the frequently emerging "superbugs",seriously affect the quality of human life and even threaten human *** the emerging antimicrobial agents that effectively eradicate pathogens,nanomaterials have been widely explored due to their effectiveness against wide-spectrum bacteria and“superbugs”.Of them,Ag/AgX nanostructures(X representing Cl,Br or I)have emerged as an excellent antibacterial agent because of their excellent photocatalytic performance in inactivating pathogens under light irradiation,which provides a new opportunity for the development of high-efficient visible-light driven photocatalytic *** date,Ag/AgX nanostructures have been widely employed in antibacterial associated fields because they are efficient in producing reactive oxygen species(ROS)and reactive chlorine species(RCS)under visible light *** this review,we summarized the recent progress of Ag/AgX nanostructures as plasmonic photocatalysts in the antibacterial field,focusing on the antibacterial effects and mechanisms of Ag/AgX nanostructures,as well as their potent ***,the challenges and prospects of Ag/AgX nanostructures acting as active antibacterial agents were discussed.

关键词： Ag/AgX Photocatalytic Antibacterial Nanostructure Nanoengineering

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Potential of A Yogurt Enriched with Synbiotics for Influenza Prevention and Treatment

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Food Science and Human Wellness 2024年

作者： Liqiong Song Bin Liu Yuangming Huang Junying Zhao Xianping Li Weicang Qiao Siqin He Hanyu Ma Yanpin Liu Weicheng Nie Lijun Chen Zhihing Ren national Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases， national Institute for Communicable Disease Control and Prevention， Chinese center for Disease Control and Prevention national engineering research center of dairy health for maternal and child， Beijing Sanyuan Foods Co.Ltd. Beijing engineering research center of dairy， Beijing Technical Innovation center of Human Milk research， Beijing Sanyuan Foods Co.Ltd. Institute of Basic Theory for Chinese Medicine， China Academy of Chinese Medical Sciences Beijing University of Chinese Medicine Third Affiliated Hospital

Probiotics show anti-influenza activity， offering a potential variant-resistant alternative for infection prevention and control. In this study， we evaluated whether a specially formulated yogurt enriched with synbiotics (named yogurt 1 in this study) with seven probiotics and six prebiotics， has anti-influenza effects and its underlying mechanisms using a mouse model challenged with influenza virus H1N1 PR8 strain. The mice were treated with phosphate-buffered saline (negative control)， yogurt matrix， yogurt 1， and oseltamivir (positive control)， respectively. yogurt 1 treatment improved the survival of infected mice (from 0% to 30%)， alleviated pathological injuries in the lungs and colon， and reduced the viral load of influenza virus on days 3 and 7 post-infection. yogurt 1 also downregulated some inflammation-related signaling pathways and reduced the levels of proinflammatory cytokines or chemokines in the lungs or serum， including interleukin (IL)-1β， IL-6， tumor necrosis factor-α (TNF-α) and keratinocyte chemoattractant (KC). The levels of short-chain fatty acids in the cecal content were increased， the diversity of the intestinal flora was partially restored， and influenza-specific IgG and interferon-secreting lymphocytes were enhanced following yogurt 1 administration. Thus， yogurt 1， as a commercial and easily accessible dairy product， demonstrated a notable anti-influenza effect in mice by inhibiting viral proliferation， suppressing excessive inflammatory responses， and promoting influenza virus-specific adaptive humoral and cellular immune responses， demonstrating its potential for influenza epidemic prevention and control.

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Effect of chlorogenic acid on lipid metabolism in 3T3-L1 cells induced by oxidative stress

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Food Bioscience 2023年第1期51卷 1170-1179页

作者： Libo Liu Chenyi Zhang Min Zhai Tianshu Yu Mengqi Pei Peng Du Aili Li Jiayi Yan Chun Li Guofang Zhang Key Laboratory of dairy Science College of Food ScienceNortheast Agricultural UniversityHarbin150030China national dairy engineering Technology research center Harbin150028China Heilongjiang Green Food Science research Institute Harbin150028China

Chlorogenic acid(CGA),a phenolic acid compound found in a variety of natural plants,has strong antioxidant *** this study,we aimed to investigate the effects of CGA on differentiation and lipid metabolism of 3T3-L1 cells,as well as its protective effect against cellular oxidative stress induced by H_(2)O_(2).We found that CGA can reduce the accumulation of intracellular ROS and attenuate the production of inflammatory cytokines TNF-αunder oxidative *** treatment significantly inhibited preadipocytes differentiation and lipid accumulation in 3T3-L1 *** results suggest that CGA may regulate lipid metabolism by reducing the expression of differentiation-related genes and inhibiting triacylglyceride *** findings of this study support CGA as a potential therapeutic agent for *** effects of CGA and its metabolites in vivo should be investigated to further support its application in functional foods.

关键词： Antioxidants Cell differentiation Chlorogenic acid Lipid metabolism Oxidative stress

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Functional nucleic acid-based cell imaging and manipulation

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Science China Chemistry 2021年第11期64卷 1817-1825页

作者： Yan Zhou Yuting Zhuo Ruizi Peng Yutong Zhang Yulin Du Qiang Zhang Yue Sun Liping Qiu Molecular Science and Biomedicine Laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringCollege of BiologyAptamer Engineering Center of Hunan ProvinceHunan UniversityChangsha410082China NHC Key Laboratory of Birth Defect for research and Prevention Hunan Provincial Maternal and Child Health Care HospitalChangsha410000China

Cells are the basic structural and functional units of *** analysis and manipulation of specific components in living cells would provide valuable information for the study of related biological *** in fluorescence microscopy have allowed real-time monitoring of biological events at the molecular ***,the development of highperformance fluorescence probes has become a critical *** nucleic acids(FNAs)are oligonucleotides with special chemical and biological functions,and aptamers with excellent molecular recognition capability are one of the most important *** have attracted extensive attention in the field of live-cell study,owing to intrinsic advantages of simple synthesis,convenient modification,low immunogenicity and high *** review focuses on recent research progress in fluorescence imaging and manipulation of cells using FNAs,particularly aptamers,as the molecular ***,a summary is provided and the related challenges are discussed.

关键词： functional nucleic acid aptamer fluorescence cell imaging biological manipulation

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