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ReishiMax inhibits mTORC1/2 by activating AMPK and inhibiting IGFR/PI3K/Rheb in tumor cells

Signal Transduction and Targeted Therapy 2019年第1期4卷 496-503页

作者： Didem Sohretoglu Chao Zhang Jun Luo Shile Huang Department of Pharmacognosy Faculty of PharmacyHacettepe UniversityTR 06100 AnkaraTurkey Department of Biochemistry and Molecular Biology Louisiana State University Health Sciences Center1501 Kings HighwayShreveportLA 71130-3932USA Key Laboratory of National health and family Planning Commission on Parasitic Disease Control and Prevention Jiangsu Provincial Key Laboratory on Parasite and Vector Control TechnologyJiangsu Institute of Parasitic Diseases214064 WuxiJiangsu ProvinceChina College of Veterinary Medicine South China Agricultural University510642 GuangzhouChina Feist-Weiller Cancer Center Louisiana State University Health Sciences Center1501 Kings HighwayShreveportLA 71130-3932USA

Ganoderma lucidum(***)extracts,as dietary supplements,have been found to exert potent anticancer activity,which is attributed to the presence of polysaccharides and ***,the molecular mechanism underlying the anticancer action of *** extracts remains to be ***,we show that ReishiMax GLp,containing *** polysaccharides and triterpenes(GLPT),inhibited cell proliferation and induced cell death in human lung cancer cells(A549 and A427)and simultaneously suppressed the signaling pathways of mammalian target of rapamycin complexes 1 and 2(mTORC1 and mTORC2),***,GLPT downregulated the phosphorylation and protein levels of insulin-like growth factor 1 receptor(IGFR)and phosphoinositide 3-kinase(PI3K)as well as the protein level of RAS homolog enriched in brain(Rheb).In addition,GLPT also activated the AMP-activated protein kinase(AMPK)*** was evidenced by observations that GLPT increased the phosphorylation of AMPKα(T172)and its substrates tuberous sclerosis complex 2(TSC2,S1387)and regulatory-associated protein of mTOR(raptor,S792).Ectopic expression of dominant-negative AMPKαpartially mitigated the inhibitory effect of GLPT on mTORC1,indicating that GLPT inhibits mTORC1 partly by activating *** results suggest that *** extracts exert anticancer action at least partly by suppressing mTORC1/2 signaling via activation of AMPK and inhibition of IGFR/PI3K/Rheb in tumor cells.

关键词： inhibited inhibiting mTORC1

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Correlation between genotypes of Orientia tsutsugamushi and clinical characteristics of patients with scrub typhus in Guangzhou,China

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Asian Pacific Journal of Tropical Medicine 2024年第7期17卷 299-309,I0008,I0009页

作者： Jiali Long Ziyi Zeng Haiyan Chen Xia Tao Xinwei Wu Shouyi Chen Liqun Fang Xiuqing Zhang Jianxiong Xu Lin Zhang Yuehong Wei Guangzhou Center for Disease Control and Prevention GuangzhouChina institute of Public health Guangzhou Medical UniversityGuangzhouChina Outpatient department of Baogang the First Affiliated Hospital of Guangdong Pharmaceutical UniversityGuangzhouChina state Key Laboratory of Pathogen and Biosecurity Beijing Institute of Microbiology and EpidemiologyBeijingChina Guangzhou institute of Biomedicine and health Chinese Academy of SciencesGuangzhouChina

Objective:To explore the correlation between genotypes of Orientia(O.)tsutsugamushi and clinical characteristics of scrub typhus ***:Clinical data of patients with scrub typhus admitted to different types of medical institutions in Guangzhou from September 2012 to December 2016 were collected using medical *** data,clinical manifestations,as well as hematological and biochemical indicators of patients infected with different genotypes were analyzed and ***:A total of 192 patients were included in this study,including 121 patients with Karp genotype of *** infection(63.0%),36 patients with Gilliam genotype(19.0%),23 patients with Kato genotype(12.0%),and 12 patients with TA763 genotype(6.0%)*** median value of albumin in patients with Karp genotype infection was significantly lower than that of Gilliam-infected patients(P=0.032).Patients with Karp genotype infection had a significantly longer hospital stay(9 days)than those with Gilliam genotype(7 days)(P=0.009)and Kato genotype infection(6 days)(P=0.005).Karp-infected patients also represented for the largest number of patients with complicated organ involvement(88/133,66.2%).Furthermore,Karp-infected patients had higher risk of developing multiple organ dysfunction syndrome(18.2%)and requiring intensive care unit treatment(15.9%).Besides,patients with Gilliam genotype(8 days)and TA763 genotype infection(7.5 days)had shorter fever duration than those with Karp genotype(9 days)and Kato genotype(9 days)infection,***:Genotypes of Orientia tsutsugamushi were associated with varying clinical manifestations,organ involvement,and treatment outcomes,suggesting that genotypes ranged in virulence.

关键词： Scrub typhus Orientia tsutsugamushi Genotype Clinical characteristics

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Identification of a novel germline missense mutation of the androgen receptor in African American men with familial prostate cancer

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Asian Journal of Andrology 2010年第3期12卷 336-343,I0008,I0009页

作者： Si-Yi Hu Tao Liu Zhen-Zhen Liu Elisa Ledet Cruz Velasco-Gonzalez Diptasri M Mandal Shahriar Koochekpour Stanley S Scott Cancer Center Louisiana State University Health Sciences Center New Orleans LA 70112 USA Department of Genetics Louisiana State University Health Sciences Center New Orleans LA 70112 USA School of Public health Louisiana State University Health Sciences Center New Orleans LA 70112 USA 4Department of Microbiology and Immunology Department of Urology Department of Biochemistry and Molecular Biology Louisiana State University Healt Sciences Center New Orleans LA 70112 USA

Race, family history and age are the unequivocally accepted risk factors for prostate cancer （PCa）. Androgen receptor （AR）-dependent signaling is an important element in prostate carcinogenesis and its progression to metastatic disease. We examined the possibility of genomic changes in the AR in association with familial PCa in African Americans who have a higher incidence and mortality rate and a clinically more aggressive disease presentation than Caucasians. Genomic DNAs of 60 patients from 30 high-risk African American and Caucasian families participating in the Louisiana state University health Sciences Center genetic linkage study of PCa were studied. Exon-specific polymerase-chain reaction, bi-directional automated sequencing and restriction enzyme genotyping were used to analyze for mutations in the coding region of the AR gene. We identified a germline AR （A1675T）（T559S） substitution mutation in the DNA-binding domain in three PCa-affected members of an African- American family with a history of early-onset disease. The present study describes the first AR germline mutation in an African-American family with a history of familial PCa. The AR （T559S） mutation may contribute to the disease by altering AR DNA-binding affinity and/or its response to androgens, non-androgenic steroids or anti-androgens. Additional studies will be required to define the frequency and contribution of the AR （A 1675T） allele to early-onset and/or familial PCa in African Americans.

关键词： African Americans androgen receptor familial prostate cancer germline mutation

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Multi-Stage-Based Siamese Neural Network for Seal Image Recognition

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Computer Modeling in Engineering & Sciences 2025年第1期142卷 405-423页

作者： Jianfeng Lu Xiangye Huang Caijin Li Renlin Xin Shanqing Zhang Mahmoud Emam School of Computer Science and Technology Hangzhou Dianzi UniversityHangzhou310018China Shangyu institute of Science and Engineering Hangzhou Dianzi UniversityShaoxing312300China Faculty of Artificial Intelligence Menoufia UniversityShebin El-Koom32511Egypt

Seal authentication is an important task for verifying the authenticity of stamped seals used in various domains to protect legal documents from tampering and *** seal inspection is commonly audited manually to ensure document ***,manual assessment of seal images is tedious and laborintensive due to human errors,inconsistent placement,and completeness of the *** image recognition systems are inadequate enough to identify seal types accurately,necessitating a neural network-based method for seal image ***,neural network-based classification algorithms,such as Residual Networks(ResNet)andVisualGeometryGroup with 16 layers(VGG16)yield suboptimal recognition rates on stamp ***,the fixed training data categories make handling new categories to be a challenging *** paper proposes amulti-stage seal recognition algorithmbased on Siamese network to overcome these ***,the seal image is pre-processed by applying an image rotation correction module based on Histogram of Oriented Gradients(HOG).Secondly,the similarity between input seal image pairs is measured by utilizing a similarity comparison module based on the Siamese ***,we compare the results with the pre-stored standard seal template images in the database to obtain the seal *** evaluate the performance of the proposed method,we further create a new seal image dataset that contains two subsets with 210,000 valid labeled pairs in *** proposed work has a practical significance in industries where automatic seal authentication is essential as in legal,financial,and governmental sectors,where automatic seal recognition can enhance document security and streamline validation ***,the experimental results show that the proposed multi-stage method for seal image recognition outperforms state-of-the-art methods on the two established datasets.

关键词： Seal recognition seal authentication document tampering siamese network spatial transformer network similarity comparison network

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Deleterious variants in RNF111 impair female fertility and induce premature ovarian insufficiency in humans and mice

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Science China(Life Sciences) 2024年第7期67卷 1325-1337页

作者： Chengcheng Song Yingying Qin Yan Li Bingyi Yang Ting Guo Wenqing Ma Dian Xu Keyan Xu Fangfang Fu Li Jin Yanhua Wu Shuyan Tang Xiaojun Chen Feng Zhang Obstetrics and Gynecology Hospital State Key Laboratory of Genetic EngineeringInstitute of Medical Genetics and GenomicsFudan UniversityShanghai 200011China Human Phenome institute Zhangjiang Fudan International Innovation CenterFudan UniversityShanghai 201203China Center for Reproductive Medicine Cheeloo College of MedicineShandong UniversityJinan 250021China state Key Laboratory of Reproductive Medicine and Offspring health Key Laboratory of Reproductive Endocrinology of Ministry of EducationNational Research Center for Assisted Reproductive Technology and Reproductive GeneticsShandong Key Laboratory of Reproductive MedicineShandong Provincial Clinical Research Center for Reproductive HealthShandong UniversityJinan 250021China Department of Obstetrics and Gynecology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China National Demonstration Center for Experimental Biology Education School of Life SciencesFudan UniversityShanghai 200433China Department of Gynecology the Tenth People’s Hospital of Tongji UniversityShanghai 200072China Soong Ching Ling institute of Maternity and Child health International Peace Maternity and Child Health Hospital of China Welfare InstituteShanghai 200030China

Premature ovarian insufficiency(POI)is a heterogeneous female disorder characterized by the loss of ovarian function before the age of *** represents a significant detriment to female ***,the known POI-causative genes currently account for only a fraction of *** elucidate the genetic factors underlying POI,we conducted whole-exome sequencing on a family with three fertile POI patients and identified a deleterious missense variant in *** a subsequent replication study involving 1,030 POI patients,this variant was not only confirmed but also accompanied by the discovery of three additional predicted deleterious RNF111 *** variants collectively account for eight cases,representing 0.78%of the study cohort.A further study involving 500 patients with diminished ovarian reserve also identified two additional RNF111 ***,RNF111 encodes an E3 ubiquitin ligase with a regulatory role in the TGF-β/BMP signaling *** analysis revealed that RNF111/RNF111 is predominantly expressed in the oocytes of mice,monkeys,and *** further investigate the functional implications of RNF111 variants,we generated two mouse models:one with a heterozygous missense mutation(Rnf111+/M)and another with a heterozygous null mutation(Rnf111^(+/-)).Both mouse models exhibited impaired female fertility,characterized by reduced litter sizes and small ovarian ***,RNA-seq and quantitative proteomics analysis unveiled that Rnf111 haploinsufficiency led to dysregulation in female gonad development and negative regulation of the BMP signaling pathway within mouse *** conclusion,our findings strongly suggest that monoallelic deleterious variants in RNF111 can impair female fertility and induce POI in both humans and mice.

关键词： POI RNF111 female fertility ovarian reserve

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Depletion of Kindlin-2 induces cardiac dysfunction in mice

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Science China(Life Sciences) 2016年第11期59卷 1123-1130页

作者： Lihua Qi Yu Yu Xiaochun Chi Danyu Lu Yao Song Youyi Zhang Hongquan Zhang Department of Human Anatomy Histology and Embryology and Key Laboratory of Carcinogenesis and Translational Research Ministry of Education Peking University Health Science and State Key Laboratory of Natural and Biomimetic Drugs Peking University Health Science Center institute of Vascular Medicine Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences Ministry of Education Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides Ministry of Health Peking University Health Science

Kindlin-2, a member of the Kindlin family focal adhesion proteins, plays an important role in cardiac development. It is known that defects in the Z-disc proteins lead to hypertrophic cardiomyopathy(HCM) or dilated cardiomyopathy(DCM). Our previous investigation showed that Kindlin-2 is mainly localized at the Z-disc and depletion of Kindlin-2 disrupts the structure of the Z-Disc. Here, we reported that depletion of Kindlin-2 leads to the disordered myocardial fibers, fractured and vacuolar degeneration in myocardial fibers. Interestingly, depletion of Kindlin-2 in mice induced cardiac myocyte hypertrophy and increased the heart weight. Furthermore, decreased expression of Kindlin-2 led to cardiac dysfunction and also markedly impairs systolic function. Our data indicated that Kindlin-2 not only maintains the cardiac structure but also is required for cardiac function.

关键词： Kindlin-2 depletion myocardial hypertrophy cardiac dysfunction mouse

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An analysis of contributing mining factors in coal workers’pneumoconiosis prevalence in the United states coal mines,1986-2018

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International Journal of Coal Science & Technology 2021年第6期8卷 1227-1237页

作者： Younes Shekarian Elham Rahimi Naser Shekarian Mohammad Rezaee Pedram Roghanchi Department of Mineral Engineering New Mexico Institute of Mining and TechnologySocorroNMUSA Department of Information Systems Business SchoolUniversity of Colorado DenverDenverCOUSA John and Willie Leone family Department of Energy and Mineral Engineering Earth and Mineral Sciences(EMS)Energy InstituteThe Pennsylvania State UniversityUniversity ParkPAUSA

In the United states,an unexpected and severe increase in coal miners’lung diseases in the late 1990s prompted researchers to investigate the causes of the disease *** study aims to scrutinize the effects of various mining parameters,including coal rank,mine size,mine operation type,coal seam height,and geographical location on the prevalence of coal worker’s pneumoconiosis(CWP)in surface and underground coal mines.A comprehensive dataset was created using the *** Safety and health Administration(MSHA)Employment and Accident/Injury *** information was merged based on the mine ID by utilizing SQL data management software.A total number of 123,589 mine-year observations were included in the statistical *** Estimating Equation(GEE)model was used to conduct a statistical analysis on a total of 29,707,and 32,643 mine-year observations for underground and surface coal mines,*** results of the econometrics approach revealed that coal workers in underground coal mines are at a greater risk of CWP comparing to those of surface coal ***,underground coal mines in the Appalachia and Interior regions are at a higher risk of CWP prevalence than the Western *** coal mines in the Appalachian coal region are more likely to CWP development than miners in the Western *** analysis also indicated that coal workers working in smaller mines are more vulnerable to CWP than those in large mine ***,coal workers in thin-seam underground mine operations are more likely to develop CWP.

关键词： Respirable coal mine dust Respiratory diseases Coal worker’s pneumoconiosis(CWP) Occupational exposure

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AI-Based Hematological Age Predictors and the Association Between Biological Age Acceleration and Type 2 Diabetes Mellitus—Chongqing Municipality,China,2015–2021

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China CDC weekly 2024年第45期6卷 1188-1193,I0002-I0005页

作者： Zhe Yin Yingnan Song Junhui Zhang Qiaoyun Dai Xinyuan Zhang Xueying Yang Na Nie Cuixia Chen Zongfu Cao Xu Ma National Human Genetic Resources Center National Research Institute for Family PlanningBeijingChina National Human Genetic Resources Sharing Service Platform National Research Institute for Family PlanningBeijingChina Chinese Academy of Medical Sciences&Peking Union Medical College BeijingChina The First Affiliated Hospital of Chongqing Medical University ChongqingChina

Introduction:Biological age(BA)can represent the actual state of human aging more accurately than chronological age(CA).Methods:Using hematological data from 112,925 participants in southwestern China,collected between 2015 and 2021,this study constructed BA predictors using 7 machine learning(ML)methods(tailored separately for male and female populations).This study then analyzed the association between BA acceleration and type 2 diabetes mellitus(T2DM)within this data using logistic ***,it examined the impact of glycemic control on BA in individuals with ***:Among all ML models,deep neural networks(DNN)delivered the best performance in male[mean absolute error(MAE)=6.89,r=0.75]and female subsets(MAE=6.86,r=0.74).BA acceleration showed positive correlations with T2DM in both male[odds ratio(OR):2.22,95%confidence interval(CI):1.77–2.77]and female subsets(OR:3.10,95%CI:2.16–4.46),while BA deceleration showed negative correlations in both male(OR:0.32,95%CI:0.27–0.39)and female subsets(OR:0.42,95%CI:0.33–0.53).Individuals with diabetes with normal fasting glucose had significantly lower BAs than those with impaired fasting glucose in all CA groups except for patients older than ***:Artificial intelligence(AI)-based hematological BA predictors show promise as advanced tools for assessing aging in epidemiological *** AI-based BA predictors in public health initiatives could facilitate proactive aging management and disease prevention.

关键词： T2DM impaired Chongqing

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An effective method for improving the accuracy of Argo objective analysis

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Acta Oceanologica Sinica 2013年第7期32卷 66-77页

作者： ZHANG Chunling XU Jianping BAO Xianwen WANG Zhenfeng institute of Marine Environment Ocean University of China Second institute of Oceanography State Oceanic Administration state Key Laboratory of Satellite Oceanography Environment Dynamics Second Institute of OceanographyState Oceanic Administration Marine Hydrologic Meteorological Center Command of Navy East China Sea Fleet

Based on the optimal interpolation objective analysis of the Argo data, improvements are made to the em- pirical formula of a background error covariance matrix widely used in data assimilation and objective anal- ysis systems. Specifically, an estimation of correlation scales that can improve effectively the accuracy of Ar- go objective analysis has been developed. This method can automatically adapt to the gradient change of a variable and is referred to as ＂gradient-dependent correlation scale method＂. Its effect on the Argo objective analysis is verified theoretically with Gaussian pulse and spectrum analysis. The results of one-dimensional simulation experiment show that the gradient-dependent correlation scales can improve the adaptability of the objective analysis system, making it possible for the analysis scheme to fully absorb the shortwave information of observation in areas with larger oceanographic gradients. The new scheme is applied to the Argo data obiective analysis system in the Pacific Ocean. The results are obviously improved.

关键词： gradient-dependent correlation scale background error covariance optimal interpolation,spectrum analysis Argo data

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Accuracy of Ebola Information in a Knowledge Exchange Social Website (KESW)

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Open Journal of Preventive Medicine 2017年第10期7卷 210-223页

作者： Fiona Gorman Desa Yadegarians Taufa Islam Simon Tongco Esther Johnston Elma Estrada Nicholas Gorman California state University Long Beach USA California state University Fullerton USA The Wright Center National family Medicine Residency at health Point Auburn USA Keck Graduate institute Claremont USA

Background: Misinformation on interactive Knowledge Exchange Social Websites (KESWs) is concerning since it can influence Internet users’ health behaviors, especially during an infectious disease outbreak. Objective: The present study seeks to examine the accuracy and characteristics of health information posted to a Knowledge Exchange Social Website (KESW). Methods: A sample of 204 answers to Ebola questions were extracted and rated for accuracy. Multiple logistic regression modeling was used to examine whether answer characteristics (best answer, professional background, statistical information, source disclosed, link, and word count) predicted accuracy. Results: Overall, only 27.0% of the posted answers were rated as “accurate”. Accuracy varied across question topics with between 11.8% - 45.5% of answers being rated as accurate. When Yahoo Answers’ “best answers” were examined, the overall accuracy was substantially higher, with 80.0% of “best answers” being rated as accurate compared to 16.0% of all other answers. Conclusion: There is need for tools to help Internet users navigate health information posted on these dynamic user-generated knowledge exchange social websites.

关键词： Online health Information Ebola Infectious Diseases Accuracy Knowledge Exchange Social Websites

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