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zinc finger protein ZPR1:promising survival motor neuron protein-dependent modifier for the rescue of spinal muscular atrophy

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Neural Regeneration Research 2022年第10期17卷 2225-2227页

作者： Juliana Cuartas Laxman Gangwani Center of Emphasis in Neurosciences Department of Molecular and Translational MedicinePaul L.Foster School of MedicineTexas Tech University Health Sciences Center El PasoEl PasoTXUSA

neuromuscular disease caused by the homozygous mutation or deletion of the survival motor neuron 1(SMN1)gene.A second copy,SMN2,is similar to SMN1,but produces only~10%SMN protein because of a single-point mutation(C>T)in coding exon 7 causing a splicing defect which leads to the exclusion of exon 7,resulting in a majority(~90%)of transcripts lacking exon 7 that translate into mutant SMN(SMNΔ7)protein.SMA is caused by chronic low levels of SMN and is characterized by the degeneration of the spinal cord motor neurons leading to symmetrical skeletal muscle atrophy,respiratory failure,and death(Ahmad et al.,2012).Chronic low levels of SMN cause the accumulation of pathogenic R-loops and double-stranded breaks(DSBs)in DNA,leading to genomic instability and neurodegeneration in SMA(Kannan et al.,2018).The severity of SMA disease correlates inversely with SMN levels.

关键词： atrophy degeneration zinc

zinc-doped Prussian blue nanoparticles for mutp53-carrying tumor ion interference and photothermal therapy

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Asian Journal of Pharmaceutical Sciences 2022年第5期17卷 767-777页

作者： Quanyi Jin Wenbao Zuo Qian Lin Ting Wu Cong Liu Nian Liu Jinxue Liu Xuan Zhu Fujian Provincial Key Laboratory of Innovative Drug Target Research School of Pharmaceutical SciencesXiamen UniversityXiamen 361005China Cancer Research Center School of MedicineXiamen UniversityXiamen 361000China

Quite a great proportion of known tumor cells carry mutation in TP53 gene,expressing mutant p53 proteins(mutp53)missing not only original genome protective activities but also acquiring gain-of-functions that favor tumor progression and impede treatment of cancers.zinc ions were reported as agents cytocidal to mutp53-carrying cells by recovering p53 normal functions and abrogating mutp53.Meanwhile in a hyperthermia scenario,the function of wild type p53 is required to ablate tumors upon heat treatment hence the effects might be hindered in a mutp53 background.We herein synthesized zinc-doped Prussian blue(ZP)nanoparticles(NPs)to combine Zn 2+based and photothermal therapeutic effects.An efficient release of Zn 2+in a glutathione-enriched tumor intracellular microenvironment and a prominent photothermal conversion manifested ZP NPs as zinc ion carriers and photothermal agents.Apoptotic death and autophagic mutp53 elimination were found to be induced by ZP NPs in R280K mutp53-containing MDA-MB-231 cells and hyperthermia was rendered to ameliorate the treatment in vitro through further mutp53 elimination and increased cell death.The combinatorial therapeutic effect was also confirmed in vivo in a mouse model.This study might expand zinc delivery carriers and shed a light on potential interplay of hyperthermia and mutp53 degradation in cancer treatment.

关键词： zinc Mutant p53 Prussian blue Photothermal therapy Ion interference therapy

Dietary intake and serum levels of copper and zinc and risk of hepatocellular carcinoma:A matched case-control study

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Chinese Medical Journal 2024年第5期137卷 596-603页

作者： Xiaozhan Liu Yaojun Zhang Dinuerguli Yishake Yan Luo Zhaoyan Liu Yuming Chen Huilian Zhu Aiping Fang Guangdong Provincial Key Laboratory of Food Nutrition and HealthSchool of Public HealthSun Yat-sen UniversityGuangzhouGuangdong 510080China State Key Laboratory of Oncology in South China Sun Yat-sen University Cancer CenterGuangzhouGuangdong 510060China

Background:Copper and zinc are involved in the development of multiple malignancies;yet,epidemiological evidence on hepatocellular carcinoma(HCC)is limited.This study aimed to investigate the association between dietary intake and serum levels of copper and zinc with the risk of HCC.Methods:A total of 434 case-control pairs matched for sex and age(±1 year)were included in this study.Cases with newly diagnosed HCC were from the Guangdong Liver Cancer Cohort(GLCC)study,and healthy controls were from the Guangzhou Nutrition and Health Study(GNHS).A semi-quantitative 79-item food frequency questionnaire(FFQ)was used to assess habitual dietary intakes of copper and zinc.Serum levels of copper and zinc were measured by using inductively coupled plasma mass spectrometry.The copper(Cu)/zinc(Zn)ratio was computed by dividing copper levels by zinc levels.Conditional logistic regression models were performed to calculate the odds ratio(OR)and 95%confidence intervals(CI)for per 1 standard deviation increase(per-SD increase)in copper and zinc levels.Results:Higher dietary intake(OR_(per-SD increase)=0.65,95%CI:0.44,0.96,P_(trend)=0.029)and serum levels of zinc(OR_(per-SD increase)=0.11,95%CI:0.04,0.30,P_(trend)zinc intake and 0.010 for serum zinc levels).Serum copper levels(OR_(per-SD increase)=2.05,95%CI:1.39,3.03,P_(trend)=0.020)and serum Cu/Zn ratio(OR_(per-SD increase)=6.53,95%CI:2.52,16.92,P_(trend)zinc may be a protective factor for HCC,especially among men,but the effects of copper on HCC risk are not clear.

关键词： Copper zinc Hepatocellular carcinoma risk Case-control studies Dietary intake Serum

MZF1(Myeloid zinc Finger 1)activates transcriptional activity of p53 and suppresses breast cancer cell proliferation via acetyltransferase PCAF(P300/CBP associated factor)

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Genes & Diseases 2023年第5期10卷 1775-1778页

作者： Bowen Li Shujing Li Xiaoxia Shi Yini Zhang Zhiqiang Xin Yuxi Yang Binggong Zhao Ping Ren Huijian Wu School of Bioengineering&Key Laboratory of Protein Modification and Disease Liaoning ProvinceDalian University of TechnologyDalianLiaoning 116024China The Second Hospital of Dalian Medical University DalianLiaoning 116024China

p53 is an important tumor suppressor gene.The p53 pathway is activated in response to cellular stress stimulation.However,in more than 50%of breast cancers,p53 is mutated or inactivated,which permits cancer growth.1 Although a large number of co-regulators of p53 have been identified,the integrated molecular network of p53 and the key co-factors that could transactivate p53 remain unclear.2 Myeloid zinc Finger 1(MZF1),a member of the SCAN-ZFP(SCAN-zinc finger protein)family,has been involved in the occurrence and development of various types of malignant tumors,including breast cancer.3 However,the exact mechanism of action remains unclear.Our study aims to investigate the cross-regulatory loop between MZF1 and p53 in breast cancer cells.

关键词： SCAN zinc p53

Effects of serum proteins on corrosion rates and product bioabsorbability of biodegradable metals

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Regenerative Biomaterials 2024年第1期3卷 132-148页

作者： Hongjie Zhang Xin Li Zehua Qu Wanqian Zhang Qunsong Wang Dinglingge Cao Yaoben Wang Xin Wang Yang Wang Lin Yu Jiandong Ding State Key Laboratory of Molecular Engineering of Polymers Department of Macromolecular ScienceFudan UniversityShanghai 200438China

Corrodible metals are the newest kind of biodegradable materials and raise a new problem of the corrosion products.However,the removal of the precipitated products has been unclear and even largely ignored in publications.Herein,we find that albumin,an abundant macromolecule in serum,enhances the solubility of corrosion products of iron in blood mimetic Hank’s solution significantly.This is universal for other main biodegradable metals such as magnesium,zinc and polyester-coated iron.Albumin also influences corrosion rates in diverse trends in Hank’s solution and normal saline.Based on quantitative study theoretically and experimentally,both the effects on corrosion rates and soluble fractions are interpreted by a unified mechanism,and the key factor leading to different corrosion behaviors in corrosion media is the interference of albumin to the Ca/P passivation layer on the metal surface.This work has illustrated that the interactions between metals and media macromolecules should be taken into consideration in the design of the next-generation metal-based biodegradable medical devices in the formulism of precision medicine.The improved Hank’s solution in the presence of albumin and with a higher content of initial calcium salt is suggested to access biodegradable metals potentially for cardiovascular medical devices,where the content of calcium salt is calculated after consideration of chelating of calcium ions by albumin,resulting in the physiological concentration of free calcium ions.

关键词： biodegradable metal macromolecule albumin corrosion bioabsorbability iron polylactide magnesium zinc

Recent Developments in Metallic Degradable Micromotors for Biomedical and Environmental Remediation Applications

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Nano-Micro Letters 2024年第3期16卷 1-35页

作者： Sourav Dutta Seungmin Noh Roger Sanchis Gual Xiangzhong Chen Salvador Pané Bradley J.Nelson Hongsoo Choi Department of Robotics and Mechatronics Engineering Daegu Gyeongbuk Institute of Science and Technology(DGIST)Daegu 42988Republic of Korea DGIST‑ETH Microrobotics Research Center DGISTDaegu 42988Republic of Korea Multi‑Scale Robotics Lab Institute of Robotics and Intelligent SystemsETH Zurich8092 ZurichSwitzerland Institute of Optoelectronics State Key Laboratory of Photovoltaic Science and TechnologyShanghai Frontiers Science Research Base of Intelligent Optoelectronics and PerceptionFudan UniversityShanghai 200433People’s Republic of China

Synthetic micromotor has gained substantial attention in biomedicine and environmental remediation.Metal-based degradable micromotor composed of magnesium(Mg),zinc(Zn),and iron(Fe)have promise due to their nontoxic fuel-free propulsion,favorable biocompatibility,and safe excretion of degradation products Recent advances in degradable metallic micromotor have shown their fast movement in complex biological media,efficient cargo delivery and favorable biocompatibility.A noteworthy number of degradable metal-based micromotors employ bubble propulsion,utilizing water as fuel to generate hydrogen bubbles.This novel feature has projected degradable metallic micromotors for active in vivo drug delivery applications.In addition,understanding the degradation mechanism of these micromotors is also a key parameter for their design and performance.Its propulsion efficiency and life span govern the overall performance of a degradable metallic micromotor.Here we review the design and recent advancements of metallic degradable micromotors.Furthermore,we describe the controlled degradation,efficient in vivo drug delivery,and built-in acid neutralization capabilities of degradable micromotors with versatile biomedical applications.Moreover,we discuss micromotors’efficacy in detecting and destroying environmental pollutants.Finally,we address the limitations and future research directions of degradable metallic micromotors.

关键词： Magnesium zinc Iron Biodegradable microrobot Biomedical Environmental

Synthesis of zinc-based metal-organic framework as highly efficient photocatalyst for decomposition of organic dyes in aqueous solution

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Rare Metals 2023年第4期42卷 1205-1213页

作者： Geng Tan Yu-Qiong Guo Lu-Yang Zuo Ka Zhang Yi-Ming Zhang Li-Lei Zhang Jing-Jing Yu Xun Feng Bo Li Li-Ya Wang College of Chemistry and Pharmaceutical Engineering Nanyang Normal UniversityNanyang473061China College of Chemistry and Chemical Engineering Luoyang Normal UniversityLuoyang471934China

In the present work,a zinc-based metal-organic framework{[Zn(ddpd)_(0.5)(bipy)_(0.5)]·H_(2)O]}_(n)(1-Zn)(where ddpd=2,5-di(2',4'-dic arboxylphenyl)-1,4-difluorobenzene,bipy=4,4-bipyridine)was synthesized by a solvothermal method.Complex 1-Zn features a threedimensional(2,4,6)-connected network with{4^2.6^2.8^2}_(2){4^4.6^6.8^5}{6}topology.Meanwhile,without the assistance of other reagents,complex 1-Zn not only exhibited an exceeded 95%photodegradation efficiency for rhodamine B(Rh B),methyl blue(MB)and methyl orange(MO)within 40 min,but also showed high stability and recyclability.In addition,free radical quenching experiments and electron spin resonance(ESR)spectroscopy verified that the main active species in the photodegradation process were·O_(2)^(-)and OH,and a more indepth degradation mechanism was further elucidated by density functional theory(DFT)calculations.

关键词： zinc Metal-organic frameworks(MOFs) ·O_(2)^(-) ·OH Photodegradation

zinc alleviates the heat stress of primary cultured hepatocytes of broiler embryos via enhancing the antioxidant ability and attenuating the heat shock responses

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Animal Nutrition 2021年第3期7卷 621-630页

作者： Tingting Li Wengang He Xiudong Liao Xi Lin Liyang Zhang Lin Lu Yanli Guo Zongping Liu Xugang Luo Poultry Mineral Nutrition Laboratory College of Animal Science and TechnologyYangzhou UniversityYangzhou 225009China Mineral Nutrition Research Division Institute of Animal ScienceChinese Academy of Agricultural SciencesBeijing 100193China College of Animal Science and Technology Gansu Agricultural UniversityLanzhou 730070China Department of Animal Science North Carolina State UniversityRaleighNC 27695USA College of Veterinary Medicine Yangzhou UniversityYangzhou 225009China

zinc(Zn)has been shown to attenuate the adverse effects of heat stress on broilers,but the mechanisms involving this process remain unclear.We aimed to investigate possible protective mechanisms of Zn on primary cultured hepatocytes of broiler embryos subjected to heat stress.Three experiments were conducted.In Exp.1,hepatocytes were treated with 0,50,100,200,or 400μmol/L added Zn as inorganic Zn sulfate(iZn)for 12,24 or 48 h.In Exp.2,cells were exposed to 40℃(a normal temperature[NT])and 44℃(a high temperature[HT])for 1,2,4,6,or 8 h.In Exp.3,cells were preincubated with 0 or 50μmol/L Zn as iZn or organic Zn lysine chelate(oZn)for 8 h under NT,and then incubated with the same Zn treatments under NT or HT for 4 or 6 h.The biomarkers of antioxidative status and heat stress in cells were measured.The results in Exp.1 indicated that 50μmol/L Zn and 12 h incubation were the optimal conditions for increasing antioxidant ability of hepatocytes.In Exp.2,the 4 or 6 h incubation under HT was effective in inducing heat shock responses of hepatocytes.In Exp.3,HT elevated(Pzinc superoxide dismutase(CuZnSOD)activity and metallothionein mRNA expression,and effectively decreased(P<0.05)the ex-pressions of HSP70 mRNA and protein,as well as HSP90 mRNA.Furthermore,oZn was more effective(P<0.05)than iZn in enhancing CuZnSOD activity of hepatocytes under HT.It was concluded that Zn(especially oZn)could alleviate heat stress of broiler hepatocytes via enhancing their antioxidant ability and attenuating heat shock responses.

关键词： Broiler hepatocyte zinc Heat stress Antioxidant ability Heat shock response

The relationship between zinc deficiency and infectious complications in patients with hepatitis B virus-related acute-on-chronic liver failure

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Gastroenterology Report 2022年第1期10卷 552-558页

作者： Xinhua Li Lu Wang Na He Yeqiong Zhang Jiahui Pang Heping Wang Meng Yu Yongyu Mei Liang Peng Wenxiong Xu Department of Infectious Diseases The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Guangdong Key Laboratory of Liver Disease Research The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Key Laboratory of Tropical Disease Control(Sun Yat-sen University) Ministry of EducationGuangzhouGuangdongP.R.China Department of Diagnostics Second School of Clinical MedicineBinzhou Medical UniversityYantaiShandongP.R.China

Background The prevalence of zinc deficiency is high in patients with chronic liver disease,but few studies have hitherto explored the relationship between the serum zinc level and hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).This study aimed to assess the association between zinc deficiency and infectious complications,and model for end-stage liver disease(MELD)score in patients with HBV-related ACLF.Methods Patients with HBV-related ACLF from the Department of Infectious Diseases of the Third Affiliated Hospital of Sun Yat-sen University(Guangzhou,China)between January 2019 and December 2019 were retrospectively analysed in this study.Their demographic,clinical,and laboratory data were retrieved from the hospital information system and analysed.The Student’s t-test was used for normally distributed continuous variables between two groups and the Chi-square test was used for categorical data.Univariate and multivariate logistic regression analyses were applied to identify independent parameters.Results A total of 284 patients were included in this study,including 205 liver cirrhosis and 79 non-cirrhosis patients.The proportion of patients with zinc deficiency was the highest(84.5%),followed by subclinical zinc deficiency(14.1%)and normal zinc level(1.4%).Patients in the zinc deficiency group had a higher MELD score than the subclinical zinc deficiency or normal zinc group(P=0.021).Age,total bilirubin,and serum zinc level were independent factors for infection(P_(s)zinc level in patients without complications at admission was significantly higher than that in patients with complications(P=0.004).Moreover,the serum zinc level in patients with prothrombin time activity(PTA)ofzinc deficiency is common in patients with HBV-related ACLF.zinc deficiency is closely associated with infectious complications and MELD score in patients with HBV-related

关键词： hepatitis B virus acute-on-chronic liver failure mortality zinc complications