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Neither Fluorocarbons nor Silicones:Hydrocarbon-Based Water-Borne Healable Supramolecular Elastomer with Unprecedent Dual Resistance to Water and Organic Solvents

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CCS Chemistry 2022年第12期4卷 3724-3734页

作者： Shuitao Gao Shasha Jiang Jinwan Qi Tongyue Wu Wenkai Wang Zhijie Liu Bin Zhang Jianbin Huang Yun Yan College of Chemistry and Molecular Engineering Peking UniversityBeijing 100871 Beijing National Laboratory for Molecular Sciences(BNLMS) Beijing 100190

Except for fluorocarbons and silicones,few artificial materials display both water and organic solvent resistance.Herein,we report an artificial hydrocarbonbased supramolecular elastomer that displays unprecedented dual resistance to both water and organic solvents.This elastomer is formed in water with two water soluble components,folic acid(FA)and branched poly(ethylene imine)(b-PEI).The hydrogen bonding between the two components occurs immediately,which further promotes the hydrogen bonding between the FA,yielding folate quartets and theirπ-πstacking.These multiple noncovalent interactions work synergistically,leading to a hydrophobic,transparent,stretchable,healable,notchinsensitive,and recyclable elastomer that resists both water and organic solvents.The elastomer remains intact after storage in high humidity and organic solvents for months.Films generated by stretching the elastomer are very hydrophobic,and the contact angle of water on the elastomer is up to 112.3°.The damaged elastomers also exhibit water-assisted healable behavior.This work discloses a new paradigm of material synthesis that can inspire the fabrication of robust nonfluorocarbon and silicone-based materials with green strategies.

关键词： folic acid elastomer quartets π-πstacking hydrogen bonding

Correlation Between Birth Defects and Dietary Nutrition Status in a High Incidence Area of China

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Biomedical and Environmental Sciences 2008年第1期21卷 37-44页

作者： BAO-YUAN ZHANG TING ZHANG LIANG-MING LIN FANG WANG RUO-LEI XIN XUE GU YU-NA HE DONG-MEI YU PEI-ZHEN LI QING-SHAN ZHANG JIN ZHAO Yu-Fu QIN XIU-FENG YANG GONG CHEN JU-FEN LIU XIN-MING SONG XIAO-YING ZHENG Capital Institute of Pediatrics Beijing 100020 China Chinese Center for Disease Control and Prevention Beijing 100050 China Department of Epidemiology Shanxi Medical University Taiyuan 030001 Shanxi China Center for Disease Control and Prevention of Shanxi Province Taiyuan 030012 Shanxi China Xinzhou Center for Disease Control and Prevention Xinzhou 034000 Shanxi China WHO Collaborating Center for Research in Reproductive Health and Population Science Institute of Population Research Peking University Beijing 100871 China

Objective To investigate the association between birth defects and dietary nutrient intake in a high risk area of China. Methods A dietary survey was performed and serum folic acid was measured in women whose pregnancy was affected by neural tube defects （NTDs） or unaffected by any birth defects （BDs） in Zhongyang and Jiaokou Counties in Shanxi Province of China. ResuIts The local average consumption of foods including dark green vegetables, fruits, fat and meat, and nutrient intake （e.g. energy, protein, retinol, riboflavin, vitamin E, and selenium） were lower than the national average level. In women of childbearing age, these regions, the intake of nutrients was much lower than the recommended nutrient intake （9%-77%）. The case-control dietary nutrition study of women whose pregnancy was affected by BDs （including NTDs and congenital heart defects） demonstrated that, in early pregnancy, adequate nutrition （i.e. eating meat, fresh vegetables, fruit more than once a week） was a protective factor, while eating germinated potatoes was a risk factor. The geometrical mean （pS- p95） of serum folic acid in women with NTD birth defects was 9.6 nmol/L （3.6, 23.03）, which was significantly lower than that in normal women （14.03 nmol/L）. Conclusion Women of childbearing age in the two counties of Shanxi Province, China, have a marked insufficient intake of some nutrients, especially folic acid, zinc, vitamins A and B12. This nutrient deficiency may be an important risk factor for the high prevalence of birth defects in these regions. Therefore, adequate dietary nutrition in early pregnancy can prevent BDs.

关键词： Birth defects Dietary survey folic acid Nutrition status

Effect of dihydrofolate reductase gene knock-down on the expression of heart and neural crest derivatives expressed transcript 2 in zebrafish cardiac development

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Chinese Medical Journal 2007年第13期120卷 1166-1171页

作者： SUN Shu-na GUI Yong-hao WANG Yue-xiang QIAN Lin-xi JIANG Qiu LIU Dong SONG Hou-yan Children＇s Hospital Fudan University Shanghai 200032 China Department of Molecular Genetics Shanghai Medical College and Key Laboratory of Molecular Medicine Ministry of Education Fudan University Shanghai 200032 China

Background folic acid is very important for embryonic development and dihydrofolate reductase is one of the key enzymes in the process of fotic acid performing its biological function. Therefore, the dysfunction of dihydrofolate reductase can inhibit the function of folic acid and finally cause the developmental malformations. In this study, we observed the abnormal cardiac phenotypes in dihydrofolate reductase （DHFR） gene knock-down zebrafish embryos, investigated the effect of DHFR on the expression of heart and neural crest derivatives expressed transcript 2 （HAND2） and explored the possible mechanism of DHFR knock-down inducing zebrafish cardiac malformations. Methods Morpholino oligonucleotides were microinjected into fertilized eggs to knock down the functions of DHFR or HAND2. Full length of HAND2 mRNA which was transcribed in vitro was microinjected into fertilized eggs to overexpress HAND2. The cardiac morphologies, the heart rates and the ventricular shortening fraction were observed and recorded under the microscope at 48 hours post fertilization. Whole-mount in situ hybridization and real-time PCR were performed to detect HAND2 expression. Results DHFR or HAND2 knock-down caused the cardiac malformation in zebrafish. The expression of HAND2 was obviously reduced in DHFR knock-down embryos （P〈0.05）. Microinjecting HAND2 mRNA into fertilized eggs can induce HAND2 overexpression. HAND2 overexpression rescued the cardiac malformation phenotypes of DHFR knock-down embryos. Conclusions DHFR plays a crucial role in cardiac development. The down-regulation of HAND2 caused by DHFR knock-down is the possible mechanism of DHFR knock-down inducing the cardiac malformation.

关键词： folic acid heart and neural crest derivatives expressed transcript 2 protein heart development zebrafish

MHC class Ⅱ in renal tubules plays an essential role in renal fibrosis

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Cellular & Molecular Immunology 2021年第11期18卷 2530-2540页

作者： Yunfeng Zhou Zhaokang Luo Chenghui Liao Rong Cao Zain Hussain Jie Wang Yeting Zhou Tie Chen Jie Sun Zhong Huang Baohua Liu Xiaoyan Zhang Youfei Guan Tuo Deng Department of Physiology Medical Research CenterShenzhen UniversityShenzhenChina Biological Therapy Institute Guangdong Provincial Key Laboratory of Regional Immunity and DiseasesDepartment of ImmunologyShenzhen UniversityShenzhenChina Department of Nephrology the First Affiliated Hospital of Shenzhen UniversityShenzhenChina Paul L.Foster School of Medicine Texas Tech University Health Sciences CenterEl PasoTXUSA Department of Internal Medicine Shenzhen Guangming Maternity and Child Healthcare HospitalShenzhenChina School of Pharmaceutical Sciences Shenzhen UniversityShenzhenChina Department of Biochemistry and Molecular Biology Medical Research CenterShenzhen UniversityShenzhenChina Shenzhen Key Laboratory for Systemic Aging and Intervention National Engineering Research Center for Biotechnology(Shenzhen)Medical Research CenterShenzhen UniversityShenzhenChina Department of Physiology and Pathophysiology School of Basic Medical SciencesAdvanced Institute of Medical SciencesDalian Medical UniversityDalianChina National Clinical Research Center for Metabolic Diseases Department of Metabolism and EndocrinologyThe Second Xiangya Hospital of Central South UniversityChangshaChina Key Laboratory of Diabetes Immunology Ministry of EducationChangshaChina Metabolic Syndrome Research Center Clinical Immunology CenterCentral South UniversityChangshaChina

Immunomodulation has been considered a potential therapeutic approach for chronic kidney disease(CKD).Although it has been previously reported that CD4+T cells contribute to the development of renal fibrosis after UUO,the role of MHC class Ⅱ(MHCII)in UUO-induced renal fibrosis remains largely uncharacterized.The present study reports that the expressions of MHCII molecules in renal cortical tubules are upregulated in a mouse unilateral ureter obstruction(UUO)model.Global or renal tubule-specific ablation of MHCII significantly alleviates renal fibrosis following UUO.Additionally,renal expression of profibrotic genes showcased consistent reduction in both MHCII gene deficient mouse lines.These results demonstrate that renal tubular MHCII plays an important role in pathogenesis of renal fibrosis.

关键词： Chronic kidney disease Renal fibrosis MHCII Unilateral ureteral obstruction folic acid

The common MTHFR C677T and A1298C variants are not associated with the risk of non-syndromic cleft lip/palate in northern Venezuela

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Journal of Genetics and Genomics 2009年第5期36卷 283-288页

作者： Mehmet A.Szen Marie M.Tolarova Richard A.Spritz Department of Medical Biology School of MedicineAfyon Kocatepe UniversityAfyonkarahisar03200 Turkey Human Medical Genetics Program University of Colorado DenverAnschutz Medical CampusAuroraCO 80045USA Department of Orthodontics University of the PacificSan FranciscoCA 94115USA

Non-syndromic cleft lip with or without cleft palate （nsCL/P） is among the most common major birth defects, with complex inheritance involving multiple genes and environmental factors. Numerous studies of MTHFR, encoding methylenetetrahydrofolate reductase, which catalyzes the rate-limiting step of folic acid biosynthesis, have shown inconsistent association of two common hypomorphic allelic variants, C677T and A1298C, in nsCL/P patients and, in some cases, their mothers. We have studied the MTHFR C677T and A1298C polymorphisms in nsCL/P patients, their mothers, and population-matched controls from northern Venezuela. We found no evidence for contribution of the MTHFR C677T and A1298C variants to the risk of nsCL/P in northern Venezuela. Overall, our findings fail to support a causal role of either the MTHFR C677T or A 1298C variants in the pathogenesis of nsCL/P in northern Venezuela.

关键词： cleft lip cleft palate methylenetetrahydrofolate reductase folic acid MTHFR polymorphisms

Machine Learning Models for Genetic Risk Assessment of Infants with Non-syndromic Orofacial Cleft

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Genomics, Proteomics & Bioinformatics 2018年第5期16卷 354-364页

作者： Shi-Jian Zhang Peiqi Meng Jieni Zhang Peizeng Jia Jiuxiang Lin Xiangfeng Wang Feng Chen Xiaoxing Wei Beijing Advanced Innovation Center for Food Nutrition and Human Health College of Agronomy and Biotechnology China Agricultural University Department of Orthodontics & Central Laboratory Peking University School and Hospital of Stomatology State Key Laboratory of Plateau Ecology and Agriculture Medical College of Qinghai University

The isolated type of orofacial cleft, termed non-syndromic cleft lip with or without cleft palate(NSCL/P), is the second most common birth defect in China, with Asians having the highest incidence in the world. NSCL/P involves multiple genes and complex interactions between genetic and environmental factors, imposing difficulty for the genetic assessment of the unborn fetus carrying multiple NSCL/P-susceptible variants. Although genome-wide association studies(GWAS)have uncovered dozens of single nucleotide polymorphism(SNP) loci in different ethnic populations, the genetic diagnostic effectiveness of these SNPs requires further experimental validation in Chinese populations before a diagnostic panel or a predictive model covering multiple SNPs can be built. In this study, we collected blood samples from control and NSCL/P infants inHan and Uyghur Chinese populations to validate the diagnostic effectiveness of 43 candidate SNPs previously detected using GWAS. We then built predictive models with the validated SNPs using different machine learning algorithms and evaluated their prediction performance. Our results showed that logistic regression had the best performance for risk assessment according to the area under curve. Notably, defective variants in MTHFR and RBP4, two genes involved in folic acid and vitamin A biosynthesis, were found to have high contributions to NSCL/P incidence based on feature importance evaluation with logistic regression. This is consistent with the notion that folic acid and vitamin A are both essential nutritional supplements for pregnant women to reduce the risk of conceiving an NSCL/P baby. Moreover, we observed a lower predictive power in Uyghur than in Han cases, likely due to differences in genetic background between these two ethnic populations.Thus, our study highlights the urgency to generate the HapMap for Uyghur population and perform resequencing-based screening of Uyghur-specific NSCL/P markers.

关键词： Orofacial cleft Genetic risk folic acid Vitamin A Nutritional intervention

Chemokine RANTES is upregulated in monocytes from patients with hyperhomocysteinemia

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Acta Pharmacologica Sinica 2005年第11期26卷 1317-1321页

作者： Wei SUN~(2,5), Guang WANG~(3,5), Zhen-min ZHANG~4, Xiao-kun ZENG~2, Xian WANG~(2,4,6) ~2 Institute of Vascular Medicine ~3 Department of Gerontology, Peking University Third Hospital ~4 Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Basic Medical College, Peking University, Beijing 100083, China Institute of Vascular Medicine Peking University Third Hospital Beijing China Department of Gerontology Peking University Third Hospital Beijing China Department of Physiology and Pathophysiology Key Laboratory of Molecular Cardiovascular Science Ministry of Education Basic Medical College Peking University Beijing China

Aim: To investigate the changes in plasma level of the chemokine RANTES (regulated upon activation, normal T cells expressed and secreted) and the responsiveness of lipopolysaccharide (LPS)-induced RANTES secretion from monocytes in patients with hyperhomocysteinemia (HHcy). Methods: The plasma levels of homocysteine (Hcy), folate, and RANTES were measured in 38 control patients with normal Hcy levels and 40 patients with HHcy and the mRNA synthesis of RANTES in isolated human monocytes was determined by RNase protection assays. Results: The plasma level of RANTES was elevated in HHcy patients compared with controls (median 5.3 vs 3.5 ng/mL, P<0.01). LPS-induced RANTES production from monocytes of HHcy patients was also increased significantly. In addition, Hcy directly increased the mRNA level of RANTES in isolated normal human monocytes in a time- and dose-dependent manner. Conclusion: Upregulated RANTES from monocytes in HHcy patients may be involved in the atherogenesis of HHcy-induced atherosclerosis.

关键词： homocysteine monocytes RANTES folic acid atherosclerosis humans

A new potential risk factor in patients with erectile dysfunction and premature ejaculation： folate deficiency

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Asian Journal of Andrology 2014年第6期16卷 902-906页

作者： Wen-Jie Yan Nan Yu Tai-Lang Yin Yu-]ie Zou Jing Yang Reproductive Medical Center Renmin Hospital of Wuhan University Wuhan China.

We investigated serum folic acid （FA） levels in patients with erectile dysfunction （ED） and/or premature ejaculation （PE）. Fasting serum samples were obtained from 42 patients with ED, 36 with PE, 25 ED patients with PE, and 30 healthy men; the mean intravaginal ejaculation latency time （IELT） was measured during a 4 weeks baseline period. Levels of sex hormones （follicle-stimulating hormone, luteinizing hormone, total testosterone）, homocysteine （Hcys）, and FA were measured using chemiluminescent immunoassays. The sexual functions of PE patients and normal control men were evaluated using the Chinese Index of Premature Ejaculation （CIPE）. The abridged Intemational Index of Erectile Function-5 （IIEF-5） questionnaire was used to gauge erectile quality for ED patients and for normal controls. Serum FA concentrations were lower in ED （7.61 ~ 3.97 ng ml-1）, PE （9.37 ＋ 3.40 ng ml-1）, and ED/PE （8.84 ＋ 4.28 ng m1-1） patients than in healthy men （12.23 ~ 5.76 ng ml-z, P〈 0.05）. No significant differences in sex hormone levels were found between patients with sexual dysfunction and healthy controls （P 〉 0.05）. There were positive correlations between serum FA concentrations and ClPE scores （r= 0.530, P〈 0.01）, IIEF-5 scores （r= 0.589, P〈 0.01）, and IELT （r= 0.445, P〈 0.01）; negative correlations with Hcys concentrations （r= -0.487, P〈 0.01） were found in all participants. These findings showed a strong relationship between serum FA levels and sexual dysfunction, possibly due to an effect of FA on the metabolism of nitric oxide, Hcys, and 5-hydroxytryptamine.

关键词： 5-hydroxytryptamine erectile dysfunction folic acid homocysteine nitric oxide premature ejaculation

Co-and N-doped carbon nanotubes with hierarchical pores derived from metal-organic nanotubes for oxygen reduction reaction

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Journal of Energy Chemistry 2021年第2期30卷 49-55,I0002页

作者： Xuewan Wang Xiuan Xi Ge Huo Chenyu Xu Pengfei Sui Renfei Feng Xian-Zhu Fu Jing-Li Luo College of Materials Science and Engineering Shenzhen UniversityShenzhen 518060GuangdongChina Department of Chemical and Materials Engineering University of AlbertaEdmonton T6G 1H9AlbertaCanada Canadian Light Source Saskatoon S7N 2V3SaskatchewanCanada

Biomolecules with a broad range of structure and heteroatom-containing groups offer a great opportunity for rational design of promising electrocatalysts via versatile chemistry.In this study,uniform folic acid-Co nanotubes(FA-Co NTs) were hydrothermally prepared as sacrificial templates for highly porous Co and N co-doped carbon nanotubes(Co-N/CNTs) with well-controlled size and morphology.The formation mechanism of FA-Co NTs was investigated and FA-Co-hydrazine coordination interaction together with the H-bond interaction between FA molecules was characterized to be the driving force for growth of one-dimensional nanotubes.Such distinct metal-ligand interaction afforded the resultant CNTs rich Co-N_x sites,hierarchically porous structure and Co nanoparticle-embedded conductive network,thus an overall good electrocatalytic activity for oxygen reduction.Electrochemical tests showed that Co-N/CNTs-900 promoted an efficient 4 e ORR process with an onset potential of 0.908 V vs.RHE,a limiting current density of 5.66 mA cm^(-2) at 0.6 V and a H_2 O_2 yield lower than 5%,comparable to that of 20%Pt/C catalyst.Moreover,the catalyst revealed very high stability upon continuous operation and remarkable tolerance to methanol.

关键词： folic acid Metal–organic nanotube Carbon nanotube In situ doping Oxygen reduction