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Potentials of ribosomopathy gene as pharmaceutical targets for cancer treatment

Journal of Pharmaceutical Analysis 2024年第3期14卷 308-320页

作者： Mengxin Wang Stephen Vulcano Changlu Xu Renjian Xie Weijie Peng Jie Wang Qiaojun liu Lee Jia Zhi li yumei li Key Laboratory of Biomaterials and Biofabrication in Tissue Engineering of Jiangxi Province Gannan Medical UniversityGanzhouJiangxi341000China School of Rehabilitation Medicine Gannan Medical UniversityGanzhouJiangxi341000China Autoimmunity and Inflammation Program HSS Research InstituteHospital for Special Surgery New YorkNew YorkNY10021USA Division of Oral and Systemic Health Sciences School of DentistryUniversity of CaliforniaLos AngelesCA90095USA School of Medical Information Engineering Gannan Medical UniversityGanzhouJiangxi341000China Inflammation and Immune Mediated Diseases Laboratory of Anhui Province Anhui Institute of Innovative DrugsInstitute for Liver Diseases of Anhui Medical UniversitySchool of PharmacyAnhui Medical UniversityHefei230032China School of Basic Medicine Gannan Medical UniversityGanzhouJiangxi341000China Institute of Oceanography Minjiang UniversityFuzhou350108China

Ribosomopathies encompass a spectrum of disorders arising from impaired ribosome biogenesis and reduced functionality.Mutation or dysexpression of the genes that disturb any finely regulated steps of ribosome biogenesis can result in different types of ribosomopathies in clinic,collectively known as ribosomopathy genes.Emerging data suggest that ribosomopathy patients exhibit a significantly heightened susceptibility to cancer.Abnormal ribosome biogenesis and dysregulation of some ribosomopathy genes have also been found to be intimately associated with cancer development.The correlation between ribosome biogenesis or ribosomopathy and the development of malignancies has been well established.This work aims to review the recent advances in the research of ribosomopathy genes among human cancers and meanwhile,to excavate the potential role of these genes,which have not or rarely been reported in cancer,in the disease development across cancers.We plan to establish a theoretical framework between the ribosomopathy gene and cancer development,to further facilitate the potential of these genes as diagnostic biomarker as well as pharmaceutical targets for cancer treatment.

关键词： Ribosome biogenesis Ribosomopathy gene Cancer treatment target Pharmaceutical target

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Straw mulching alters the composition and loss of dissolved organic matter in farmland surface runoff by inhibiting the fragmentation of soil small macroaggregates

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Journal of Integrative Agriculture 2024年第5期23卷 1703-1717页

作者： Shanshan Cai Lei Sun Wei Wang Yan li Jianli Ding liang Jin yumei li Jiuming Zhang Jingkuan Wang Dan Wei College of Land and Environment Shenyang Agricultural UniversityShenyang 110866China Heilongjiang Academy of Black Soil Conservation and Utilization Harbin 150086China Institute of Plant Nutrition Resources and EnvironmentBeijing Academy of Agricultural and Forestry SciencesBeijing 100097China

Straw mulching is a widespread practice for reducing the soil carbon loss caused by erosion.However,the effects of straw mulching on dissolved organic matter(DOM)runoff loss from black soil are not well studied.How straw mulching affects the composition and loss of runoff DOM by changing soil aggregates remains largely unclear.Here,a straw mulching treatment was compared to a no mulching treatment(as a control)on sloping farmland with black soil erosion in Northeast China.We divided the soil into large macroaggregates(>2 mm),small macroaggregates(0.25-2 mm),and microaggregates(like acid and protein-like components.With straw mulching treatment,the protein-like components in small macroaggregates accumulated and the protein-like components in runoff declined with rain events.Fluorescence spectroscopy technology may help in understanding the hydrological paths of rain events by capturing the dynamic changes of runoff and soil DOM characteristics.A variation partitioning analysis(VPA)indicated that the DOM concentration and composition of microaggregates explained 68.2%of the change in runoff DOM from no mulching plots,while the change in runoff DOM from straw mulching plots was dominated by small macroaggregates at a rate of 55.1%.Taken together,our results demonstrated that straw mulching reduces the fragmentation of small macroaggregates and the loss of microaggregates,thus effecting DOM compositions in soil and reducing the DOM loss in runoff.These results provide a theoretical basis for reducing carbon loss

关键词： dissolved organic matter black soil surface runoff aggregates fluorescence spectrum

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Combined effects of climate and land-use changes on the alpha and beta functional diversities of terrestrial mammals in China

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Science China life Sciences 2024年

作者： Chao Zhang yumei li Wei Wang Zexuan Gao Hanqing liu Yonggang Nie Key Laboratory of Animal Ecology and Conservation Biology Institute of Zoology Chinese Academy of Sciences College of life Sciences Hebei University University of Chinese Academy of Sciences

Climate and land-use changes are predicted to impact biodiversity,threatening ecosystem services and functions.However,their combined effects on the functional diversity of mammals at the regional scale remain unclear,especially at the beta level.Here,we use projected climate and land-use changes in China to investigate their potential effects on the alpha and beta functional diversities of terrestrial mammals under low-and high-emission scenarios.In the current projection,we showed strong positive spatial correlations between functional richness and species richness.Functional evenness (FEve),functional specialization (FSpe),and functional originality (FOri)decreased with species richness,and functional divergence (FDiv) increased first and then plateaued.Functional beta diversity was dominated by its nestedness component,in contrast to the taxonomic facet.Potential changes in species richness are more strongly influenced by land-use change under the low-emission scenario,while under the high-emission scenario,they are more strongly influenced by climate change.Changes in functional richness (FRic) were inconsistent with those in species richness,with a magnitude of decreases greater than predicted from species richness.Moreover,mammal assemblages showed potential functional differentiation (FD) across the country,and the trends exceeded those towards taxonomic differentiation (TD).Our findings help us understand the processes underlying biodiversity responses to global changes on multiple facets and provide new insight for conservation plans.

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Efficacy and safety of CM310 in moderate-to-severe atopic dermatitis:A multicenter,randomized,double-blind,placebo-controlled phase 2b trial

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Chinese Medical Journal 2024年第2期137卷 200-208页

作者： Yan Zhao Jianzhong Zhang Bin Yang Jingyi li Yangfeng Ding liming Wu litao Zhang Jinyan Wang Xiaohong Zhu Furen Zhang Xiaohua Tao yumei li Chunlei Zhang linfeng li Jianyun Lu Qingchun Diao Qianjin Lu Xiaoyong Man Fuqiu li Xiujuan Xia Hao Cheng Yingmin Jia Guoqing Zhao Jinchun Yan Bo Chen Department of Dermatology Peking University People’s HospitalBeijing 100044China Department of Dermatology Dermatology HospitalSouthern Medical UniversityGuangzhouGuangdong 510091China Department of Dermatology West China HospitalSichuan UniversityChengduSichuan 610041China Department of Dermatology Shanghai Skin Disease HospitalInstitute of PsoriasisTongji University School of MedicineShanghai 200443China Department of Dermatology Affiliated Hangzhou First People’s HospitalZhejiang University School of MedicineHangzhouZhejiang 310006China Department of Dermatology Tianjin Academy of Traditional Chinese Medicine Affiliated HospitalTianjin 300120China Department of Dermatology Ningbo No.2 HospitalNingboZhejiang 315010China Department of Dermatology The Wuxi Second Affiliated Hospital of Nanjing Medical UniversityWuxiJiangsu 214002China Shandong Provincial Hospital for Skin Diseases&Shandong Provincial Institute of Dermatology and Veneorology Shandong First Medical University&Shandong Academy of Medical SciencesJinanShandong 250022China Center for Plastic&Reconstructive Surgery Department of DermatologyZhejiang Provincial People’s Hospital(Affiliated People’s HospitalHangzhou Medical College)HangzhouZhejiang 310014China Department of Dermatology Affiliated Hospital of Jiangsu UniversityZhenjiangJiangsu 212001China Department of Dermatology Peking University Third HospitalBeijing 100191China Department of Dermatology Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China Department of Dermatology The Third Xiangya Hospital of Central South UniversityChangshaHunan 410013China Department of Dermatology Chongqing Traditional Chinese Medicine HospitalChongqing 400011China Hunan Key Laboratory of Medical Epigenomics Department of DermatologyThe Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China Department of Dermatology The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310009China Departme

Background:Atopic dermatitis(AD)affects approximately 10%of adults worldwide.CM310 is a humanized monoclonal antibody targeting interleukin-4 receptor alpha that blocks interleukin-4 and interleukin-13 signaling.This trial aimed to evaluate the efficacy and safety of CM310 in Chinese adults with moderate-to-severe AD.Methods:This multicenter,randomized,double-blind,placebo-controlled,phase 2b trial was conducted in 21 medical institutions in China from February to November 2021.Totally 120 eligible patients were enrolled and randomized(1:1:1)to receive subcutaneous injections of 300 mg CM310,150 mg CM310,or placebo every 2 weeks for 16 weeks,followed by an 8-week follow-up period.The primary endpoint was the proportion of patients achieving≥75%improvement in the Eczema Area and Severity Index(EASI-75)score from baseline at week 16.Safety and pharmacodynamics were also studied.Results:At week 16,the proportion of EASI-75 responders from baseline was significantly higher in the CM310 groups(70%[28/40]for high-dose and 65%[26/40]for low-dose)than that in the placebo group(20%[8/40]).The differences in EASI-75 response rate were 50%(high vs.placebo,95%CI 31%-69%)and 45%(low vs.placebo,95%CI 26%-64%),with both P valueslife Quality Index compared with placebo.CM310 treatment reduced levels of thymus and activation-regulated chemokine,total immunoglobulin E,lactate dehydrogenase,and blood eosinophils.The incidence of treatment-emergent adverse events(TEAEs)was similar among all three groups,with the most common TEAEs reported being upper respiratory tract infection,atopic dermatitis,hyperlipidemia,and hyperuricemia.No severe adverse events were deemed to be attributed to CM310.Conclusion:CM310 at 150 mg and 300 mg every 2 weeks demonstrated significant efficacy and was well-tolerated in adults with moderate-to-severe AD.Tria

关键词： CM310 Moderate-to-severe atopic dermatitis Interleukin-4 receptor alpha Adults

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Degradation of organics using LaFeO_(3)as a persulfate activator under low-intensity ultra-violet-light irradiation:Catalytic performance and mechanism

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Journal of Rare Earths 2022年第7期40卷 1043-1052页

作者： yumei li Jian Fan Xiaonan Feng Tao Tao School of Environment Huazhong University of Science and TechnologyWuhan 430074China School of Energy and Environment Inner Mongolia University of Science and TechnologyBaotou 014010China

ABO_(3)-type perovskite oxides with abounding defect structures and diverse physical chemistry attributes have been extensively studied in heterogeneous catalysis.Semiconductor LaFeO_(3)perovskites fabricated via the sol-gel method were used as peroxydisulfate(PDS)activators for methylene blue(MB)degradation under low-intensity ultra-violet(UV)-light to evaluate the degradation efficiency of organic pollutants and mechanism.The results indicate that under low-intensity UV irradiation,the developed UV/LaFeO_(3)/PDS system shows excellent degradation ability of organic pollutants in a wide pH range.Electron spin resonance and radical quenching experiments verify that SO_(4)^(·-),·OH,h^(+)and ^(1)O_(2)are generated during the activation process,and ^(1)O_(2)plays a dominant role in MB degradation.Reduction of low oxidation state Fe(Ⅱ)and O_(2)^(2-)/O^(-)on the LaFeO_(3)surface shows that oxygen vacancy,as the electron transfer mediator,enhances the redox cycle efficiency of Fe(Ⅱ)/Fe(Ⅲ).Photogenerated electrons of LaFeO_(3)involved in the cyclic transformation of Fe(Ⅱ)/Fe(Ⅲ)and PDS activation further increase the number of active radicals and thus promote the synergistic effect of photocatalytic coupled with sulfate radicalbased advanced oxidation processes.

关键词： LaFeO_(3) Peroxydisulfate Singlet oxygen Low-intensity UV-light Rare earths

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Population-scale genetic control of alternative polyadenylation and its association with human diseases

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Quantitative Biology 2022年第1期10卷 44-54页

作者： Lei li yumei li Xudong Zou Fuduan Peng Ya Cui Eric J.Wagner Wei li Institute of Systems and Physical Biology Shenzhen Bay LaboratoryShenzhen 518055China Division of Computational Biomedicine Department of Biological ChemistrySchool of MedicineUniversity of CaliforniaIrvineCA 92697USA Department of Biochemistry&Molecular Biology University of Texas Medical BranchGalvestonTX 77555USA

Background:Genome-wide association studies(GWAS)have identified thousands of genomic non-coding variants statistically associated with many human traits and diseases,including cancer.However,the functional interpretation of these non-coding variants remains a significant challenge in the post-GWAS era.Alternative polyadenylation(APA)plays an essential role in post-transcriptional regulation for most human genes.By employing different poly(A)sites,genes can either shorten or extend the 3'-UTRs that contain cu-regulatory elements such as miRNAs or RNA-binding protein binding sites.Therefore,APA can affect the mRNA stability,translation,and cellular localization of proteins.Population-scale studies have revealed many inherited genetic variants that potentially impact APA to further influence disease susceptibility and phenotypic diversity,but systematic computational investigations to delineate the connections are in their earliest states.Results:Here,we discuss the evolving definitions of the genetic basis of APA and the modern genomics tools to identify,characterize,and validate the genetic influences of APA events in human populations.We also explore the emerging and surprisingly complex molecular mechanisms that regulate APA and summarize the genetic control of APA that is associated with complex human diseases and traits.Conclusion:APA is an intermediate molecular phenotype that can translate human common non-coding variants to individual phenotypic variability and disease susceptibility.

关键词： GWAS eQTL disease alternative polyadenylation

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The application of the entropy-based statistic for genomic association study of QTL

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Journal of Genetics and Genomics 2008年第3期35卷 183-188页

作者： Yang Xiang yumei li Zaiming liu Zhenqiu Sun College of Mathematics Central South University Changsha 410081 China School of Public Health Central South University Changsha 410078 China Mathematics Department of Huaihua College Huaihua 418000 China

An entropy-based statistic TpE has been proposed for genomic association study for disease-susceptibility locus. The statistic TpE may be directly adopted and/or extended to quantitative-trait locus （QTL）mapping for quantitative traits. In this article, the statistic TpE was extended and applied to quantitative trait for association analysis of QTL by means of selective genotyping. The statistical properties （the type I error rate and the power） were examined under a range of parameters and population-sampling strategies （e.g., various genetic models, various heritabilities, and various sample-selection threshold values） by simulation studies. The results indicated that the statistic TpE is robust and powerful for genomic association study of QTL. A simulation study based on the haplotype frequencies of 10 single nucleotide polymorphisms （SNPs） of angiotensin-I converting enzyme genes was conducted to evaluate the performance of the statistic TPE for genetic association study.

关键词： entropy quantitative-trait locus association analysis extreme sample

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E3 ligase MG53 suppresses tumor growth by degrading cyclin D1

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Signal Transduction and Targeted Therapy 2023年第8期8卷 3768-3779页

作者： Meng Fang Hong-Kun Wu Yumeng Pei Yan Zhang Xiangyu Gao Yanyun He Gengjia Chen Fengxiang Lv Peng Jiang yumei li Wenwen li Peng Jiang lin Wang Jiafu Ji Xinli Hu Rui-Ping Xiao State Key Laboratory of Membrane Biology Institute of Molecular MedicineCollege of Future TechnologyPeking University100871 BeijingChina Peking-Tsinghua Center for life Sciences 100871 BeijingChina Department of Hepatobiliary and Pancreatic Surgery the First Affiliated HospitalZhejiang University School of Medicine310003 HangzhouChina Zhejiang Provincial Key Laboratory of Pancreatic Disease 310003 HangzhouChina Beijing City Key Laboratory of Cardiometabolic Molecular Medicine Peking University100871 BeijingChina Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Gastrointestinal Tumor CenterPeking University Cancer Hospital&Institute100142 BeijingChina School of life Sciences Tsinghua University100084 BeijingChina Research Center for Tissue Engineering and Regenerative Medicine Union HospitalTongji Medical CollegeHuazhong University of Science and Technology430022 WuhanChina

Due to the essential role of cyclin D1 in regulating transition from G1 to S phase in cell cycle,aberrant cyclin D1 expression is a major oncogenic event in many types of cancers.In particular,the dysregulation of ubiquitination-dependent degradation of cyclin D1 contributes to not only the pathogenesis of malignancies but also the refractory to cancer treatment regiments with CDK4/6 inhibitors.Here we show that in colorectal and gastric cancer patients,MG53 is downregulated in more than 80%of tumors compared to the normal gastrointestinal tissues from the same patient,and the reduced MG53 expression is correlated with increased cyclin D1 abundance and inferior survival.Mechanistically,MG53 catalyzes the K48-linked ubiquitination and subsequent degradation of cyclin D1.Thus,increased expression of MG53 leads to cell cycle arrest at G1,and thereby markedly suppresses cancer cell proliferation in vitro as well as tumor growth in mice with xenograft tumors or AOM/DSS induced-colorectal cancer.Consistently,MG53 deficiency results in accumulation of cyclin D1 protein and accelerates cancer cell growth both in culture and in animal models.These findings define MG53 as a tumor suppressor via facilitating cyclin D1 degradation,highlighting the therapeutic potential of targeting MG53 in treating cancers with dysregulated cyclin D1 turnover.

关键词： MG53 markedly thereby

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Cancer metastasis chemoprevention prevents circulating tumour cells from germination

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Signal Transduction and Targeted Therapy 2022年第11期7卷 4053-4068页

作者： Xiaodong Xie yumei li Shu lian Yusheng Lu Lee Jia College of Materials and Chemical Engineering Minjiang UniversityFuzhouFujian350108China School of Basic Medicine Gannan Medical UniversityGanzhouJiangxi341000China Cancer Metastasis Alert and Prevention Center College of ChemistryFujian Provincial Key Laboratory of Cancer Metastasis Chemoprevention and ChemotherapyFuzhou UniversityFuzhouFujian350116China

The war against cancer traces back to the signature event half-a-century ago when the US National Cancer Act was signed into law.The cancer crusade costs trillions with disappointing returns,teasing the possibility of a new breakthrough.Cure for cancer post-metastases still seems tantalisingly out of reach.Once metastasized,cancer-related death is extremely difficult,if not impossible,to be reversed.Here we present cancer pre-metastasis chemoprevention strategy that can prevent circulating tumour cells(CTCs)from initiating metastases safely and effectively,and is disparate from the traditional cancer chemotherapy and cancer chemoprevention.Deep learning of the biology of CTCs and their disseminating organotropism,complexity of their adhesion to endothelial niche reveals that if the adhesion of CTCs to their metastasis niche(the first and the most important part in cancer metastatic cascade)can be pharmaceutically interrupted,the lethal metastatic cascade could be prevented from getting initiated.We analyse the key inflammatory and adhesive factors contributing to CTC adhesion/germination,provide pharmacological fundamentals for abortifacients to intervene CTC adhesion to the distant metastasis sites.The adhesion/inhibition ratio(AIR)is defined for selecting the best cancer metastasis chemopreventive candidates.The successful development of such new therapeutic modalities for cancer metastasis chemoprevention has great potential to revolutionise the current ineffective post-metastasis treatments.

关键词： metastasis prevention reversed

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Lymphoepithelial cyst of the pancreas: a case report

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Hepatobiliary & Pancreatic Diseases International 2004年第1期3卷 155-157页

作者： XiaoPing Zou yumei li ZhaoShen li GuoMing Xu Department of Internal Medicine Changhai Hospital Second Military Medical University Shanghai 200433 China. zxpfcp@***

BACKGROUND:Lymphoepithelial cyst of the pancreas is a rare lesion of undetermined pathogenesis that had been documented almost exclusively in males. The literature on this entity is limited to reports of single or a small number of cases.;METHODS:The case we described herein was compared with a total of 36 cases reported elsewhere.;RESULTS:The 37 cases of lymphoepithelial cyst of the pancreas including our case were reviewed. Lymphoepithelial cysts have uniform and distinctive clinicopathologic features. Approximately 46% of the reported cases were asymptomatic with the lesions found incidentally, and their symptoms were non-specific.;CONCLUSIONS:Lymphoepithelial cyst is a rare benign lesion of the pancreas. Fine-needle aspiration biopsy (FNAB) is a rapid and reliable technique that can be used as the first diagnostic step in cases of cystic lesions of the pancreas.

关键词： lymphoepithelial cyst pancreas

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