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Lipidome Atlas of the Developing Heart Uncovers Dynamic Membrane Lipid Attributes Underlying Cardiac Structural and Metabolic Maturation

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Research 2023年第3期2022卷 263-280页

作者： Huan Miao Bowen Li Zehua Wang Jinming Mu Yanlin Tian Binhua Jiang Shaohua Zhang Xia Gong Guanghou Shui sin Man Lam State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China LipidALL Technologies Company Limited Changzhou 213022Jiangsu ProvinceChina

Precise metabolic rewiring during heart organogenesis underlies normal cardiac ***,we utilized high-coverage,quantitative lipidomic approaches to construct lipidomic atlases of whole hearts(861 lipids;31 classes)and mitochondria(587 lipids;27 classes)across prenatal and postnatal developmental stages in *** uncovered the progressive formation of docosahexaenoyl-phospholipids and enhanced remodeling of C18:2,C20:3,and C20:4 fatty acyl moieties into cardiolipins as cardiac development progresses.A preferential flow of ceramides toward sphingomyelin biosynthesis over complex glycosphingolipid formation was also *** maSigPro and GPclust algorithms,we identified a repertoire of 448 developmentally dynamic lipids and mapped their expression patterns to a library of 550 biologically relevant developmentally dynamic *** combinatorial transcriptomics and lipidomics approaches identified Hadha,Lclat1,and Lpcat3 as candidate molecular drivers governing the dynamic remodeling of cardiolipins and phospholipids,respectively,in heart *** analyses revealed that postnatal cardiolipin remodeling in the heart constitutes a biphasic process,which first accumulates polyunsaturated C78-cardiolipins prior to tetralinoleoyl cardiolipin forming the predominant *** analyses supplemented with transmission electron microscopy imaging uncovered enhanced mitochondria–lipid droplet contacts mediated by *** combinatorial analyses of multiomics data uncovered an association between mitochondrial-resident,docosahexaenoic acid-phospholipids and messenger RNA levels of proton-transporting adenosine triphosphate synthases on inner mitochondrial membranes,which adds credence to the membrane pacemaker theory of *** current findings offer lipid-centric biological insights potentially important to understanding the molecular basis of cardiac metabolic flexibility and disease pathology.

关键词： Lipid Atlas lying

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營養衛教對血液透析患者高血磷的影響

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镜湖医学 2024年第1期24卷 34-36页

作者：周惠碧冼詠萱黃懿茵張振榮澳門鏡湖醫院家庭醫學科中国

目的觀察營養衛教對高血磷的血液透析(hemodialysis,HD)患者飲食行為以及血磷水平的影響。方法選取經充分HD治療以及口服降磷藥物治療3個月後平均血磷值仍大於1.78mmol/L的患者,隨機分為研究組和對照組,營養師分别於第2和第4個月對研究... 详细信息

目的觀察營養衛教對高血磷的血液透析(hemodialysis,HD)患者飲食行為以及血磷水平的影響。方法選取經充分HD治療以及口服降磷藥物治療3個月後平均血磷值仍大於1.78mmol/L的患者,隨機分為研究組和對照組,營養師分别於第2和第4個月對研究組患者實施2次一對一個别式高磷血症飲食指導。分析比較衛教前後的知識、態度、行為問卷分數、血磷水平和血磷達標率。結果40例患者資料完整並完成研究,平均年齡64.6±12.1歲,平均每人每週外出用餐6次;75%的患者經常飲用咖啡、奶茶或茶。經衛教干預,研究組患者對加工食品是高磷食物的認知比例由66.7%顯著提升至90.5%(P<0.05);干預後對低磷飲食的知識(P=0.014)評分較干預前明顯提高,行為評分亦見有提高,但未達統計學差異。研究組患者干預後血磷值有下降趨勢,血磷達標率有上升趨勢,但未達統計學差異。結論營養衛教對改善患者對高磷食物的認知以及低磷飲食的知識和行為有一定幫助,但未能改善血磷水平。

关键词：血磷血液透析營養教育飲食行為

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Sanger Sequencing for Molecular Diagnosis of SARS-CoV-2 Omicron Subvariants and Its Challenges

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Journal of Biosciences and Medicines 2022年第9期10卷 182-223页

作者： sin Hang Lee Milford Molecular Diagnostics Laboratory Milford USA

Large population passages of the SARS-CoV-2 in the past two and a half years have allowed the circulating virus to accumulate an increasing number of mutations in its genome. The most recently emerging Omicron subvariants have the highest number of mutations in the Spike (S) protein gene and these mutations mainly occur in the receptor-binding domain (RBD) and the N-terminal domain (NTD) of the S gene. The European Centre for Disease Prevention and Control (eCDC) and the World Health Organization (WHO) recommend partial Sanger sequencing of the SARS-CoV-2 S gene RBD and NTD on the polymerase chain reaction (PCR)-positive samples in diagnostic laboratories as a practical means of determining the variants of concern to monitor possible increased transmissibility, increased virulence, or reduced effectiveness of vaccines against them. The author’s diagnostic laboratory has implemented the eCDC/WHO recommendation by sequencing a 398-base segment of the N gene for the definitive detection of SARS-CoV-2 in clinical samples, and sequencing a 445-base segment of the RBD and a 490 - 509-base segment of the NTD for variant determination. This paper presents 5 selective cases to illustrate the challenges of using Sanger sequencing to diagnose Omicron subvariants when the samples harbor a high level of co-existing minor subvariant sequences with multi-allelic single nucleotide polymorphisms (SNPs) or possible recombinant Omicron subvariants containing a BA.2 RBD and an atypical BA.1 NTD, which can only be detected by using specially designed PCR primers. In addition, Sanger sequencing may reveal unclassified subvariants, such as BA.4/BA.5 with L84I mutation in the S gene NTD. The current large-scale surveillance programs using next-generation sequencing (NGS) do not face similar problems because NGS focuses on deriving consensus sequence.

关键词： eCDC WHO Sanger Sequencing Omicron Variant Minor Subvariants BA.4/BA.5 L84I BA.2 Multi-Allelic Recombinant

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GM130 regulates pulmonary surfactant protein secretion in alveolar typeⅡcells

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Science China(Life Sciences) 2022年第1期65卷 193-205页

作者： Qianqian Pang Chunyi Liu Yulong Qiao Jian Zhao sin Man Lam Mei Mei Guanghou Shui Shilai Bao Qiuling Li State Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental BiologyThe Innovative Academy of Seed DesignChinese Academy of SciencesBeijing 100101China School of Life Sciences University of Chinese Academy of SciencesBeijing 100049China Institute of Forensic Medicine and Laboratory Medicine Jining Medical UniversityJining 272067China Department of Health Sciences Institute of Physical Science and Information TechnologyAnhui UniversityHefei 230601China

Pulmonary surfactant is a lipid-protein complex secreted by alveolar typeⅡepithelial cells and is essential for the maintenance of the delicate structure of mammalian alveoli to promote efficient gas exchange across the air-liquid *** Golgi apparatus plays an important role in pulmonary surfactant modification and secretory ***,the physiological function of the Golgi apparatus in the transport of pulmonary surfactants is *** the present study,deletion of GM130,which encodes for a matrix protein of the cis-Golgi cisternae,was shown to induce the disruption of the Golgi structure leading to impaired secretion of lung surfactant proteins and ***,the results of in vitro and in vivo analysis indicated that the loss of GM130 resulted in trapping of Sftpa in the endoplasmic reticulum,Sftpb and Sftpc accumulation in the Golgi apparatus,and an increase in the compensatory secretion of ***,global and epithelial-specific GM130 knockout in mice resulted in an enlargement of alveolar airspace and an increase in alveolar epithelial autophagy;however,surfactant repletion partially rescued the enlarged airspace defects in GM130-deficient ***,our results demonstrate that GM130 and the mammalian Golgi apparatus play a critical role in the control of surfactant protein secretion in pulmonary epithelial cells.

关键词： GM130 Golgi apparatus surfactant protein Alveolar typeⅡcells

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Endosonographic surveillance of 1-3 cm gastric submucosal tumors originating from muscularis propria

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World Journal of Gastroenterology 2017年第12期23卷 2194-2200页

作者： ming-luen hu keng-liang wu chi-sin changchien seng-kee chuah yi-chun chiu division of hepato-gastroenterology department of internal medicine kaohsiung chang gung memorial hospital and chang gung university college of medicine

AIM To observe the natural course of 1-3 cm gastric submucosal tumors originating from the muscularis propria(SMTMPs).METHODS By reviewing the computerized medical records over a period of 14 years(2000-2013), patients with 1-3 cm gastric SMTMPs who underwent at least two endoscopic ultrasound(EUS) examinations were enrolled. Tumor progression was defined as a ≥ 1.2 times enlargement in tumor diameter observed during EUS surveillance. All patients were divided into stationary and progressive subgroups and further analyzed. We also reviewed the patients in the progressive subgroup again in *** A total of 88 patients were studied, including 25 in the progressive subgroup. The mean time of EUS surveillance was 24.6 mo in the stationary subgroup and 30.7 mo in the progressive subgroup. Risk factors for tumor progression included larger tumor size and irregular border. Initial tumor size > 14.0 mm may be considered a cut-off size for predicting tumor progression. Seventeen patients underwent surgery, of whom 13 had gastrointestinal stromal tumors(GISTs) and 4 had leiomyomas. Tumor progression was found only in patients with GISTs. All of the tumors exhibited benign behaviors without metastasis until *** Most 1-3 cm gastric SMTMPs(71.6%) are indolent. Tumor progression was found only in GISTs, and it is a good predictor for differentiating GISTs from leiomyomas. Predictors of tumor progression include larger tumor size(> 14.0 mm) and irregular border.

关键词： Gastrointestinal stromal tumor Submucosal tumors originating from the muscularis propria Stomach Endosonographic surveillance

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New insights in the pathogenesis of alcohol-related liver disease:The metabolic,immunologic,and neurologic pathways

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Liver Research 2023年第1期7卷 1-8页

作者： Tom Ryu Kyurae Kim Sung Eun Choi Katherine Po sin Chung Won-Il Jeong Laboratory of Liver Research Graduate School of Medical Science and EngineeringKAISTDaejeonRepublic of Korea

Alcohol-related liver disease(ALD)became an important health issue *** chronic alcohol consumption,the development of ALD might be caused by metabolic and immunologic factors,such as reactive oxygen species(ROS)and pro-inflammatory *** example,hepatic cytochrome P4502E1 enzyme increases ROS production and stimulates de novo lipogenesis after alcohol *** addition,damage-and pathogen-associated molecular patterns stimulate their specific receptors in nonparenchymal cells,including Kupffer cells,hepatic stellate cells(HSCs),and lymphocytes,which result in hepatocyte death and infiltration of pro-inflammatory cells(e.g.,neutrophils and macrophages)in the ***,our studies have suggested the novel involvement of neurologic signaling pathways(e.g.,endocannabinoid and glutamate)through the metabolic synapse between hepatocytes and HSCs in the development of alcohol-related hepatic ***,agouti-related protein and beta2-adrenergic receptors aggravate hepatic ***,organ-crosstalk has emerged as a critical issue in *** alcohol consumption induces dysbiosis and barrier disruption in the gut,leading to endotoxin leakage into the portal circulation,or lipolysis-mediated transport of triglycerides from the adipose tissue to the *** summary,this review addresses multiple pathogeneses of ALD,provides novel neurologic signaling pathways,and emphasizes the importance of organ-crosstalk in the development of ALD.

关键词： Alcohol-related liver disease(ALD) Cannabinoid receptor Steatohepatitis Lipopolysaccharide(LPS) Metabotropic glutamate receptor(mGluR) Toll-like receptor 4(TLR4)

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Impact of Gender,Family Factors and Exploratory Activities on Students’Career and Educational Search Competencies in Shanghai and Hong Kong

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ECNU Review of Education 2018年第3期1卷 96-115页

作者： Esther Sui-Chu Ho Kwok Wing Sum Raymond sin Kwok Wong The Chinese University of Hong Kong University of California Santa Barbara

Purpose-This study examines the career and educational search competencies(CESC),a capability which may be necessary for a successful transition from high school to work or postsecondary education,of students from Shanghai and Hong ***/Approach/Methods-The data for this study was taken from the Main Study of PISA 2012 in Shanghai and Hong *** analysis was used to examine the relative impact of different forms of career and educational exploratory activities on students’***-Results showed a consistent pattern of socio-economic inequality in student’s self-reported CESC in the two Chinese cities,which was largely mediated by the family capital or ***,career and educational exploratory activities initiated by schools,enterprises or the students themselves were found to have significant positive associations with CESC regardless of socioeconomic ***/Value-The paper provides empirical evidence for enhancing students’career search capacity through engaging in career exploration in the face of structural *** light of this,the roles of schools,business sectors,and governments in students’capacity building are discussed.

关键词： Educational and career search educational inequality family capital PISA Shanghai Hong Kong

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Topological conformational changes of human papillomavirus(HPV)DNA bound to an insoluble aluminum salt—A study by low temperature PCR

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Advances in Biological Chemistry 2013年第1期3卷 76-85页

作者： sin Hang Lee Milford Hospital and Milford Molecular Laboratory MilfordConnecticutUSA

A low temperature (LoTemp?) polymerase chain reaction (PCR), conducted at cycling temperatures not to exceed 85℃and catalyzed by a novel highly processive HiFi? DNA polymerase with proofreading function, was used to study the topological conformational changes of the human papillomavirus (HPV) L1 gene DNA fragments bound to the insoluble amorphous aluminum hydroxyphosphate sulfate (AAHS) adjuvant in the quadrivalent HPV vaccine, Gardasil?. L1 gene DNA fragments of HPV-11, HPV-18 and HPV-16 were detected in the AAHS particles by nested PCR, but all were lacking a region that was amplifiable by an MY09 degenerate primer. In addition, a pair of degenerate consensus GP6/MY11 primers was able to amplify a target segment of the HPV-11 L1 gene DNA and the HPV-18 L1 gene DNA bound to the AAHS particles as expected for any HPV DNA in the B-conformation. However, there was no co-amplification of the HPV-16 L1 gene DNA known to coexist in the same samples. The lack of co-amplification was verified by direct DNA sequencing of the PCR amplicons. The companion HPV-16 L1 gene DNA in the same sample required repeated PCRs with a pair of modified non-degenerate GP6/ MY11 primers for detection. This melting profile of the HPV-16 L1 gene DNA was similar to that of the HPV-16 L1 gene DNA recently discovered in the postmortem blood of a young woman who suffered a sudden unexpected death 6 months after Gardasil? vaccination. The findings suggest that the topological conformational changes in the HPV L1 gene DNA residues bound to the AAHS adjuvant may be genotype-related. The special non-B-conformation may prevent the HPV-16 L1 gene DNA from being degraded in the body of the vaccine recipients after in- tramuscular injection.

关键词： Low Temperature PCR HPV DNA Conformation Gardasil^■ Postmortem AAHS Adjuvant Aluminum

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Intracellular calcium ions facilitate dengue virus entry into endothelial cells and compromise endothelial barrier integrity

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Asian Pacific Journal of Tropical Medicine 2021年第11期14卷 505-516页

作者： Meng-Hooi Shu Pooi-Fong Wong sing-sin Sam Shih-Keng Loong Boon-Teong Teoh Sazaly AbuBakar Tropical Infectious Diseases Research and Education Centre(TIDREC) Universiti Malaya50603 Kuala LumpurMalaysia Department of Pharmacology Faculty of MedicineUniversiti Malaya50603 Kuala LumpurMalaysia World Health Organization Collaborating Centre for Arbovirus Reference and Research(Dengue and Severe Dengue)MAA-12 Universiti Malaya50603 Kuala LumpurMalaysia

Objective:To investigate the involvement of Ca^(2+)in dengue virus(DENV)-infected human umbilical vein endothelial cells(HUVECs)and the disruption of endothelial ***:HUVECs were infected with DENV-2 in the presence of intracellular Ca^(2+)or endoplasmic reticulum Ca^(2+)*** infectivity was measured by focus-forming assay and quantitative *** Ca^(2+)was measured using Fluo-4-AM ***-cadherin and focal adhesion kinase(FAK)expressions were investigated by immunofluorescence and immunoblotting assays,***:DENV infection increased intracellular cytosolic Ca^(2+)levels and caused disassembly of the adherens junction protein,VEcadherin as evidenced by decreased VE-cadherin expression at the periphery of DENV-2 infected *** of intracellular Ca^(2+)stores,particularly those of the endoplasmic reticulum Ca^(2+),significantly decreased DENV yield in *** virus yield following the depletion of intracellular Ca^(2+)was caused by the inhibition of viral entry into HUVECs and not the inhibition of viral binding or ***-2 infection also resulted in Ca^(2+)-dependent activation of ***:Intracellular Ca^(2+)is required for the early phases of DENV infection in endothelial *** cytosolic Ca^(2+)levels in endothelial cells during DENV infection activated FAK,disrupted adherens junctions and compromised barrier ***,Ca^(2+)plays an important role in DENV infection in endothelial cells.

关键词： Endothelial cells Calcium signalling Dengue virus Endothelium permeability Intracellular calcium

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Detection of human papillomavirus L1 gene DNA fragments in postmortem blood and spleen after Gardasil^(■) vaccination—A case report

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Advances in Bioscience and Biotechnology 2012年第8期3卷 1214-1224页

作者： sin Hang Lee Milford Hospital and Milford Molecular Laboratory MilfordConnecticutUSA

A same-nested PCR was used to re-amplify the amplicon of a hypervariable region of the HPV-16 L1 gene DNA in the postmortem blood and splenic tissue obtained at autopsy of a formerly healthy teenage girl who suffered a sudden unexpected death in sleep 6 months after 3 intramuscular injections of a quadrivalent HPV vaccine, Gardasil?. A full autopsy analysis revealed no cause of death. The HPV-16 gene DNA detected in the postmortem materials was similar to the HPV-16 gene DNA fragments in Gardasil? in that both were in non-B-conformation, requiring nondegenerate GP6 and MY11 primers to re-amplify the PCR amplicon for detection and to generate a template useful for direct DNA sequencing. A sequence excised from the base-calling DNA sequencing electropherogram was analyzed by Basic Local Alignment Search Tool (BLAST) alignment and a 45 - 60 base sequence fully matched with a standard hypervariable region of the HPV-16 L1 gene retrieved from the National Center for Biotechnology Information database validated the correct genotyping for HPV- 16 L1 gene DNA. These naked non-proliferating HPV- 16 L1 gene DNA fragments appeared to be in the macrophages of the postmortem blood and spleen, and were protected from degradation by binding firmly to the particulate aluminum adjuvant used in vaccine formulation. The significance of these HPV DNA fragments of a vaccine origin found in post-mortem materials is not clear and warrants further investigation.

关键词： Gardasil^(■) Postmortem HPV DNA Aluminum Vaccine

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