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DNA polymerase delta interacting protein 3 facilitates the activation and maintenance of DNA damage checkpoint in response to replication stress

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Animal Models and Experimental Medicine 2022年第5期5卷 461-469页

作者： Sufang Zhang ernest Y.C.Lee Marietta Y.w.T.Lee Dong Zhang Department of Biochemistry and Molecular Biology New York Medical CollegeNew YorkUSA Department of Biomedical Sciences College of Osteopathic MedicineNew York Institute of TechnologyNew YorkUSA

Background:Replication stress response is crucial for the maintenance of a stable ***3(DNA polymerase delta interacting protein 3)was initially identified as one of the DNA polymeraseδ(Polδ)interacting proteins almost 20 years *** a variety of in vitro biochemical assays,we previously established that POLDIP3 is a key regulator of the enzymatic activity of Polδ.However,the in vivo function of POLDIP3 in DNA replication and DNA damage response has been ***:we first generated POLDIP3 knockout(KO)cells using the CRISPR/Cas9 *** then investigated its biological functions in vivo using a variety of biochemical and cell biology ***:we showed that although the POLDIP3-KO cells manifest no pronounced defect in global DNA synthesis under nonstress conditions,they are sensitive to a va-riety of replication fork ***,we found that POLDIP3 plays a crucial role in the activation and maintenance of the DNA damage checkpoint in response to exogenous as well as endogenous replication ***:Our results indicate that when the DNA replication fork is blocked,POLDIP3 can be recruited to the stalled replication fork and functions to bridge the early DNA damage checkpoint response and the later replication fork repair/restart.

关键词： DNA damage checkpoint DNA polymerase delta POLDIP3 replication stress

Effects of Medicines and Supplements on Spontaneous Pregnancy and Semen Parameters in Male Infertility:A Systematic Review Update and Network Meta-Analysis

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Engineering 2022年第9期16卷 198-209页

作者： Jian Li Qi wu ernest Hung Yu ng Ben willem J.Mol Xiao Ke wu Chi Chiu wang Department of Obstetrics and Gynecology First Affiliated HospitalHeilongjiang University of Chinese MedicineHarbin 150040China Department of Obstetrics and Gynecology The Affiliated Hospital of Gui Zhou Medical UniversityGuiyang 550004China Department of Obstetrics and Gynaecology Prince of Wales HospitalThe Chinese University of Hong KongHong Kong 999077China Department of Obstetrics and Gynecology Obstetrics and Gynecology HospitalFudan UniversityShanghai 30009China Department of Obstetrics and Gynaecology Queen Mary HospitalThe University of Hong KongHong Kong 999077China Department of Obstetrics and Gynaecology Monash UniversityClaytonVIC 3168Australia Heilongjiang Provincial Hospital Harbin Institute of TechnologyHarbin 150036China Reproduction and Development Laboratory Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong Kong 999077China i School of Biomedical SciencesThe Chinese University of Hong KongHong Kong 999077China The Chinese University of Hong Kong–Sichuan University Joint Laboratory of Reproductive Medicine Hong Kong 999077China

In this study,we used a network meta-analysis(NMA)to compare the effectiveness of medicines and supplements for idiopathic male infertility and to identify the best ***,Excerpta Medica Database(EMBASE),Ovid,and China National Knowledge Infrastructure(CNKI),were searched for the period from January 1990 to June 2021 using the keywords"male infertility,""medical therapy,""supplement/nutrient therapy,"and related *** controlled trials(RCTs)investigating medicines(mainly follicle-stimulating hormone(FSH),androgen,and clomiphene/tamoxifen)or supplements(mainly zinc,selenium,vitamin C or E,carnitine,coenzyme Q10(CoQ10),or combined treatment)for idiopathic infertile men were selected for *** reporting items for systematic reviews and meta-analysis(PRISMA)was used for data extraction,and a risk-of-bias tool and grades of recommendation,assessment,development,and evaluation(GRADE)system adapted to the NMA were employed to assess the quality of the *** primary outcomes were live birth and spontaneous pregnancy rate(SPR).The secondary outcomes were sperm parameters(including concentration,progressive motility,and morphology)and side *** total,65 RCTs involving 7541 men with sperm abnormalities but normal hormone levels were included.A total of 36 studies reported SPR but only three reported live birth *** quality of the included studies was found to be moderate to *** with a placebo or being untreated,carnitine plus vitamins significantly improved SPR(relative risk(RR)=3.7,95%confidence interval(95%CI),1.6-8.5);fatty acids significantly increased sperm concentrations(mean difference(MD)=12.5×10^(6)mL-1,95%CI,3.1×10^(6)-22.0×10^(6));and selective estrogen receptor modulator(SERM)plus CoQ10 significantly improved sperm progressive motility(MD=11.0%,95%CI,0.1%-21.9%)and normal sperm morphology(MD=11.0%,95%CI,4.6%-17.4%).The most optimal intervention was carnitine plus vitamins and fatty acids for SPR a

关键词： Male infertility Medicine Supplement Spontaneous pregnancy rate Sperm parameters

wnt signaling in midbrain dopaminerglc neuron development and regenerative medicine for Parkinson＇s disease

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Journal of Molecular Cell Biology 2014年第1期8卷 42-53页

作者： ernest Arenas Laboratory of Molecular Neurobiology Department of Medical Biochemistry and Biophysics Center of Developmental Biology for Regenerative MedicineKarolinska Institute Scheelevag 2 17 117 Stockholm Sweden

wnts are a highly conserved family of Upid-modified glycoproteins that work as morphogens to activate several signaling pathways, leading to remodeling of the cytoskeleton and the regulation of gene transcription. wnt signaling regulates multiple cellular functions and cell systems, including the development and maintenance of midbrain dopaminergic （m DA） neurons. These neurons are of consid- erable interest for regenerative medicine because their degeneration results in Parkinson＇s disease （PD）. This review focuses on new advances in understanding key functions of wnts in mDA neuron development and using novel tools to regulate wnt signaling in re- generative medicine for PD. Particularly, recent reports indicate that appropriate levels of wnt signaling are essential to improve the quantity and quality of stem ceil- or reprogrammed ceU-derived mDA neurons to be used in drug discovery and cell replacement therapy for PD.

关键词： wntl wnt5a sFRP stem cells transplantation reprogramming small molecules

The novel male meiosis recombination regulator coordinates the progression of meiosis prophase Ⅰ

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Journal of Genetics and Genomics 2020年第8期47卷 449-464页

作者： Miao Li Haiwei Feng Zexiong Lin Jiahuan Zheng Dongteng Liu Rui Guo Junshi Li Raymond H.w.Li ernest H.Y.ng Michael S.Y.Huen P.Jeremy wang william S.B.Yeung Kui Liu Shenzhen Key Laboratory of Fertility Regulation Center of Assisted Reproduction and EmbryologyThe University of Hong Kong-Shenzhen HospitalShenzhen518000China Department of Obstetrics and Gynecology Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong999077China Department of Biomedical Sciences University of Pennsylvania School of Veterinary MedicinePhiladelphiaPA19104USA School of Biomedical Sciences Li Ka Shing Faculty of MedicineThe University of Hong KongHong Kong999077China

Meiosis is a specialized cell division for producing haploid gametes in sexually reproducing *** this study,we have independently identified a novel meiosis protein male meiosis recombination regulator(MAMERR)/4930432 K21 Rik and showed that it is indispensable for meiosis prophase I progression in male *** super-resolution structured illumination microscopy,we found that MAMERR functions at the same double-strand breaks as the replication protein A and meiosis-specific with OB domains/spermatogenesis associated 22 *** generated a Mamerr-deficient mouse model by deleting exons 3 e6 and found that most of Mamerrà/àspermatocytes were arrested at pachynema and failed to progress to diplonema,although they exhibited almost intact synapsis and progression to the pachytene stage along with XY body *** mechanistic studies revealed that the recruitment of DMC1/RAD51 and heat shock factor 2 ebinding protein in Mamerrà/àspermatocytes was only mildly impaired with a partial reduction in double-strand break repair,whereas a substantial reduction in ubiquitination on the autosomal axes and on the XY body appeared as a major phenotype in Mamerrà/à*** propose that MAMERR may participate in meiotic prophase I progression by regulating the ubiquitination of key meiotic proteins on autosomes and XY chromosomes,and in the absence of MAMERR,the repressed ubiquitination of key meiotic proteins leads to pachytene arrest and cell death.

关键词： Meiosis 4930432K21Rik Recombination Ubiquitination

Evidence-based interventions of threatened miscarriage

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world Journal of Traditional Chinese Medicine 2017年第1期3卷 32-34页

作者： Juan Li Jing-shu Gao Chi Chiu wang ernest HY ng Xiao-ke wu Department of Traditional Chinese Medicine The First Affiliated Hospital of Guangzhou Medical University Department of Obstetrics & Gynaecology National Key Discipline and Clinical Base Heilongjiang University of Chinese Medicine Department of Obstetrics & Gynaecology The Chinese University of Hong Kong Hong Kong Special Administrative Region Department of Obstetrics & Gynaecology The University of Hong Kong Hong Kong Special Administrative Region

Threatened miscarriage is the commonest complication of early pregnancy and affects about 20% of pregnancies. It presents with vaginal bleeding with or without abdominal cramps. Increasing age of women, smoking, obesity or polycystic ovary syndrome(PCOS) and a previous history of miscarriage are risk factors for threatened miscarriage. The pathophysiology has been associated with changes in levels of cytokines or maternal immune dysfunction. Clinical history and examination, maternal serum biochemistry and ultrasound findings are important to determine the treatment options and provide valuable information for the prognosis. Bed rest is the commonest advice, but there is little evidence of its value. Other options include progesterone, human chorionic gonadotropin(HCG) and muscle relaxants. The complementary and alternative medicine(CAM) therapies such as acupuncture and Chinese herbs have also been tried. There is some evidence from clinical studies indicating that CAM therapies may reduce the rate of miscarriage, but the quality of studies is poor. Thus, further double-blind,randomized-controlled trials are necessary to confirm its effectiveness, especially acupuncture and Chinese herbs.

关键词： Threatened miscarriage Evidence-based Intervention Complementary and alternative medicine

Non-conventional humanitarian interventions on Ebola outbreak crisis in west Africa: health, ethics and legal implications

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Infectious Diseases of Poverty 2014年第1期3卷 386-396,385页

作者： ernest Tambo Sydney Brenner Institute for Molecular Bioscience Wits 21st Century InstituteFaculty of Health SciencesUniversity of the WitwatersrandJohannesburgSouth Africa Center for Sustainable Malaria Control Department of BiochemistryFaculty of Natural and Agricultural SciencesUniversity of PretoriaPretoriaSouth Africa National Institute of Parasitic Diseases Chinese Centre for Disease Control and Preventionand the WHO Collaborating Centre on MalariaSchistosomiasis and FilariasisShanghai 200025People’s Republic of China Facultédes Sciences Biomédicales et Pharmaceutiques Universitédes MontagnesBangangtéRépublique du Cameroun

Due to the lack of Ebola outbreak early warning alert,preparedness,surveillance and response systems,the most deadly,complex and largest ever seen Ebola war has been devastating west African *** unparalleled Ebola tsunami has prompted interrogations into,and uncertainties about,the effectiveness and efficiency of national,regional and international community’s illed-responses using conventional humanitarian control and containment approaches and *** late humanitarian and local non-government organisations emergency responses and challenges to curb transmission dynamics and stop the ongoing spread in the Ebola outbreak in west Africa have led to an unprecedented toll of 14,413 reported Ebola cases in eight countries since the outbreak began,with 5,177 reported deaths including 571 health-care workers and 325 died as 14 November *** indications the need of further evaluation of monitoring as substantial proportion of infections outside the context of Ebola epicentres,Ebola health centres treatment and care,infection prevention and control quality assurance checks in these *** the same time,exhaustive efforts should target ensuring an sufficient supply of optimal personal protective equipment(PPE)to all Ebola treatment facilities,along with the provision of training and relevant guidelines to limit to the minimum possible level of *** continent hosts a big proportion of the world’s wealth,yet its people live in abject poverty,with governments unable to feed and govern them effectively,and who are condemned to endure even darker moments with the Ebola outbreak in west *** of practical and operational non-conventional emergency response models efficient health systems,and tailored programmes can clearly support to prevent,control and eventually stamp out Ebola geo-distribution in addition to population mental health services that are requisite to address the massive range of the health,socio-psychological a

关键词： Non-conventional Response Ethics Legal Ebola Humanitarian crisis Africa

The impact of dielectrics on the electrical capacity, concentration, efficiency ozone generation for the plasma reactor with mesh electrodes

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Plasma Science and Technology 2018年第8期20卷 89-95页

作者： ernest GNAPOwSKI Sebastian GNAPOwSKI Jaroslaw PYTKA University College of Enterprise and Administration in Lublin Bursaki 12 20-150 Lublin Poland Fundamentals of Technology Faculty Lublin University of Technology ul. Nadbystrzycka 38 20-618 Lublin Poland Faculty of Mechanical Engineering Lublin University of Technology ul. Nadbystrzycka 36 20-618 Lublin Poland

This paper presents experimental results concerning the effect of dielectric type on ozone concentration and the efficiency of its generation in plasma reactor with two mesh *** types of dielectric solid were used in the study; glass, micanite and Kapton insulating foil. The experiments were conducted for voltage ranges from 2.3 to 13 k V. A plasma reactor equipped with two 0.3×0.3 mm^2 mesh electrodes made of acid resistant AISI 304 mesh was used in the experiments. The influence of the dielectric type on the concentration and efficiency of ozone generation was described. The resulting maximum concentration of the ozone was about 2.70–9.30 g O3 m^-3, depending on the dielectrics used. The difference between the maximum and the minimum ozone concentration depends on the dielectric used,this accounts for 70% at the variance. The reactor capacity has also been described in the paper; total Ct and dielectric capacitance Cd depending on the dielectric used and its thickness.

关键词： ozone generation efficiency dielectric mesh electrode ozone generator electrical capacity

Effect of Letrozole,Berberine,or Their Combination for Infertility in women with Polycystic Ovary Syndrome:Statistical Analysis Plan for a Multicenter Randomized Controlled Trial

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world Journal of Traditional Chinese Medicine 2016年第3期2卷 36-42页

作者： Hong-Li Ma Jing-Shu Gao Feng Tian ernest HY ng Xiao-Ke wu Jian-Ping Liu Centre for Evidence-Based Chinese Medicine Beijing University of Chinese Medicine Department of Obstetrics and Gynecology First Affiliated HospitalHeilongjiang University of Chinese Medicine Institute of Basic Research in Clinical Medicine China Academy of Chinese Medical Sciences Department of Obstetrics and Gynaecology The University of Hong KongQueen Mary Hospital

Introduction:Letrozole showed higher ovulation and live birth rates than clomiphene in infertile women with polycystic ovary syndrome(PCOS).Berberine,a major active component of Chinese herbal medicine rhizomacoptidis,has been used to improve insulin resistance to facilitate ovulation induction in women with PCOS,but there is no study reporting the live birth or its potential as a complementary treatment to *** aim to determine the efficacy of letrozole with or without berberine in achieving live births among 644 infertile women with PCOS in China's *** and analysis:This is a prospective,randomized,multicentre,double-blinded,controlled *** women with PCOS were randomized into three-arm,letrozole and berberine,letrozole and berberine placebo,letrozole placebo and *** and blood were collected at baseline,the third month and sixth month after treatment,or immediately were collected if subject was *** and clinical investigators were blinded to treatment allocation and treatment related study results until the central database was locked for final data extraction and analysis *** statistical analysis plan described basic analysis principles,methods commonly encountered in data analysis issues,and the specific statistical procedures for analyzing the primary,secondary,and safety *** and dissemination:The study was approved by the ethics committee of the First Affiliated Hospital,Heilongjiang University of Chinese *** study findings will be disseminated through peer-reviewed publications and conference *** registration:Chinese Clinical Trial Registry:Chi *** *** identifier:NCT01116167.

关键词： Polycystic ovary syndrome Statistical analysis plan Randomized controlled trial Letrozole Berberine

Building-Back-Better in Post-Disaster Recovery: Lessons Learnt from Cyclone Idai-Induced Floods in Zimbabwe

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International Journal of Disaster Risk Science 2021年第5期12卷 700-712页

作者： ernest Dube Gayan wedawatta Kanchana Ginige Department of Development Sciences Faculty of Agribusiness and EntrepreneurshipMarondera University of Agricultural Sciences and Technology(MUAST)Marondera.Zimbabwe Department of Civil Engineering School of Infrastructure and Sustainable EngineeringAston UniversityBirmingham B47ET.UK Department of Architecture and Built Environment Faculty of Engineering and EnvironmentNorthumbria UniversityNewcastle upon Tyne NE48STUK

This study evaluated the build-back-better considerations in post-disaster recovery,following the devastation of Chipinge and Chimanimani communities by Cyclone Idai-induced floods in *** in 2020,the study assessed the impact of Cyclone Idai-induced floods on communities in Chipinge and Chimanimani Districts of Zimbabwe;evaluated the build-back-better considerations;and analyzed the lessons *** on a qualitative approach and case study design,the study depended on focus group discussions,interviews,and researcher observations to gather data from 85 *** findings indicate that Cyclone Idai-induced floods seriously impacted human lives,infrastructure,and livelihoods of communities that had been living with flood risk and ***-back-better considerations were absent in much of the post-disaster recovery effort to address the cyclone disaster *** are important early lessons for both practitioners and community members to learn from the Cyclone Idai *** lessons still can inform policy and disaster risk reduction practice in the medium and long ***-back-better should be a mandatory objective in the recovery from any disaster *** training is also recommended to improve the disaster knowledge of stakeholders and increase local ability to cope with future disaster events.

关键词： Build-back-better Cyclone Idai Flood hazard Post-disaster recovery Zimbabwe