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GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progresses of gastric cancer

Acta Pharmaceutica Sinica B 2024年第2期14卷 698-711页

作者： Qiwei Jiang Yong Li Songwang Cai Xingyuan Shi Yang Yang Zihao Xing Zhenjie He Shengte Wang Yubin Su Meiwan Chen Zhesheng Chen Zhi Shi Department of Cell Biology&Institute of Biomedicine National Engineering Research Center of Genetic MedicineState Key Laboratory of Bioactive Molecules and Druggability AssessmentMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Department of Gastrointestinal Surgery&General Surgery the Guangdong Provincial People’s HospitalGuangdong Academy of Medical SciencesGuangzhou 510080China Department of Thoracic Surgery The First Affiliated Hospital of Jinan UniversityGuangzhou 510632China Department of Radiation Oncology The Fifth Hospital of Guangzhou Medical UniversityGuangzhou 510150China State Key Laboratory of Quality Research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of MacaoMacao 519000China Department of Pharmaceutical Sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNY 11439USA

Glutamate-ammonia ligase(GLUL, also known as glutamine synthetase) is a crucial enzyme that catalyzes ammonium and glutamate into glutamine in the ATP-dependent condensation. Although GLUL plays a critical role in multiple cancers, the expression and function of GLUL in gastric cancer remain unclear. In the present study, we have found that the expression level of GLUL was significantly lower in gastric cancer tissues compared with adjacent normal tissues, and correlated with N stage and TNM stage, and low GLUL expression predicted poor survival for gastric cancer patients. Knockdown of GLUL promoted the growth, migration, invasion and metastasis of gastric cancer cells in vitro and in vivo, and vice versa, which was independent of its enzyme activity. Mechanistically, GLUL competed with β-Catenin to bind to N-Cadherin, increased the stability of N-Cadherin and decreased the stability of β-Catenin by alerting their ubiquitination. Furthermore, there were lower N-Cadherin and higher β-Catenin expression levels in gastric cancer tissues compared with adjacent normal tissues. GLUL protein expression was correlated with that of N-Cadherin, and could be the independent prognostic factor in gastric cancer. Our findings reveal that GLUL stabilizes N-Cadherin by antagonizing β-Catenin to inhibit the progress of gastric cancer.

关键词： Gastric cancer GLUL N-Cadherin β-Catenin Enzyme

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Effects of Different Culture Conditions and Growth States on the Structure and Hemostatic Properties of Coscinodiscus sp.

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Journal of Ocean University of China 2024年第4期23卷 1121-1134页

作者： HE Zheng LI Qinfeng LIU Jinfeng HUI Guangyan FENG Chao CHENG Xiaojie CHEN Xiguang College of Marine Life Science Sanya Oceanographic InstitutionOcean University of ChinaQingdao 266003China Laboratory for Marine Drugs and Bioproducts Qingdao Marine Science and Technology CenterQingdao 266237China Department of Stomatology Qingdao Women and Children’s HospitalQingdao 266034China Department of Stomatology Qingdao Special Servicemen Recuperation Center of PLA NavyQingdao 266071China

As a renewable marine inorganic material,Coscinodiscus *** significant potential in the field of rapid ***,the low yield of Coscinodiscus *** limits the *** this study,two new culture modes were adopted to increase the production of Coscinodiscus sp.,the effect of changes in culture conditions and growth status on the hemostatic activity of diatoms was *** prevent Coscinodiscus *** sinking in culture,the suspension culture mode was realized by adding0.5%*** semi-continuous high nutrient concentration culture mode increased the cell density of Coscinodiscus *** 11000cells mL^(-1)and shorten the culture cycle to 5 *** terms of coagulation activity,the addition of frustules reduced the in vitro coagulation time by half and the activation time of coagulation by 70%.The hemolysis rate and cytotoxicity of frustules harvested in the two culture modes did not change *** results showed that suspension culture mode and high nutrient concentration culture mode only changed the growth state of Coscinodiscus sp.,while the hemostatic performance remained stable.

关键词： diatom culture Coscinodiscus sp frustule hemostatic material hemorrhage control

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Efficient biosynthesis of creatine by whole-cell catalysis from guanidinoacetic acid in Corynebacterium glutamicum

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Synthetic and Systems Biotechnology 2024年第1期9卷 99-107页

作者： Chunjian Li Pengdong Sun Guoqing Wei Yuqi Zhu Jingyuan Li Yanfeng Liu Jian Chen Yang Deng College of Food Science and Engineering Qingdao Agricultural UniversityQingdao 266109China Key Laboratory of Special Food Processing(Co-construction by Ministry and Province) Ministry of Agriculture Rural AffairsQingdao Agricultural UniversityQingdao 266109China Shandong Technology Innovation center of Special Food Qingdao 266109China Qingdao Special Food Research Institute Qingdao 266109China Qingdao Nuoan Baite Biotechnology Co. Ltd.Qingdao 266109China Science center for Future Foods Engineering Research Center of Ministry of Education on Food Synthetic Biotechnologyand Jiangsu Province Engineering Research Center of Food Synthetic BiotechnologyJiangnan UniversityWuxi 214122China Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of EducationSchool of BiotechnologyJiangnan UniversityWuxi 214122China

Creatine is a naturally occurring derivative of an amino acid commonly utilized in functional foods and ***,the current industrial synthesis of creatine relies on chemical processes,which may hinder its utilization in certain ***,a biological approach was devised that employs whole-cell biocatalysis in the bacterium Corynebacterium glutamicum,which is considered safe for use in food production,to produce safe-for-consumption *** objective of this study was to identify a guanidinoacetate N-methyltransferase(GAMT)with superior catalytic activity for creatine *** employing whole-cell biocatalysis,a gamt gene from Mus caroli(Mcgamt)was cloned and expressed in *** ATCC 13032,resulting in a creatine titer of 3.37 g/***,the study employed a promoter screening strategy that utilized nine native strong promoters in *** to enhance the expression level of *** highest titer was achieved using the P1676 promoter,reaching 4.14 g/*** conditions of whole-cell biocatalysis were further optimized,resulting in a creatine titer of 5.42 g/*** is the first report of successful secretory creatine expression in ***,which provides a safer and eco-friendly approach for the industrial production of creatine.

关键词： Creatine Corynebacterium glutamicum Whole-cell biocatalysis Guanidinoacetate N-Methyltransferase Food additive

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A Cross-Sectional Survey of Iodized Salt Usage in Dining Establishments—13 PLADs,China,2021–2022

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China CDC weekly 2023年第34期5卷 751-755页

作者： Ying Zhang Jichun Wang Xiuwei Li Wei Ma Jianqiang Wang Haiyan Wang Jing Xu national health Commission Key Laboratory of Trace Element Nutrition National Institute for Nutrition and HealthChinese Center for Disease Control and PreventionBeijingChina Science and Technology Department Chinese Center for Disease Control and PreventionBeijingChina.

Summary What is already known about this topic?The national Iodine Deficiency Disease Surveillance system is exclusively focused on monitoring cooking salt used within ***,there is a lack of nationally representative data on the use of iodized salt in dining *** is added by this report?This study evaluated 7,889 salt samples obtained from dining establishments located in 13 provincial-level administrative divisions across *** findings indicated that coverage rate of iodized salt(CRIS)and the consumption rate of adequately iodized salt(CRAIS)were found to be 95.2%and 90.2%,***,880 samples were classified as iodized salt and 804 as adequately iodized *** coastal areas,the CRIS and CRAIS showed a significant decrease to 77.1%and 70.5%,respectively,when compared to the inland regions(P<0.01).

关键词： finding system inland

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Pit density reduction for AlN epilayers grown by molecular beam epitaxy using Al modulation method

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Chinese Physics B 2024年第10期33卷 95-101页

作者： Huan Liu Peng-Fei Shao Song-Lin Chen Tao Tao Yu Yan Zi-Li Xie Bin Liu Dun-Jun Chen Hai Lu Rong Zhang Ke Wang Jiangsu Provincial Key Laboratory of Advanced Photonic and Electronic Materials School of Electronic Science and EngineeringNanjing UniversityNanjing 210093China Hefei national Laboratory Hefei 230088China Xiamen University Xiamen 361005China

We have investigated homoepitaxy of AlN films grown by molecular beam epitaxy on AlN/sapphire templates byadopting both the continuous growth method and the Al modulation epitaxy(AME)growth *** continuous growthmethod encounters significant challenges in controlling the growth *** the precise Al/N=1.0 ratio is difficult toachieve,either the excessive Al-rich or N-rich growth mode *** contrast,by adopting the AME growth method,sucha difficulty has been effectively *** manipulating the supply time of the Al and nitrogen sources,we were able toproduce AlN films with much improved surface *** first step of the AME method,only supplying Al atoms,is important to wet the surface and the Al adatoms can act as a *** of the initial Al supply time caneffectively reduce the pit density on the grown AlN *** pits density dropped from 12 pits/μm^(2)to 1 pit/μm^(2)andthe surface roughness reduced from 0.72 nm to 0.3 nm in a 2×2μm^(2)area for the AME AlN film homoepitaxially grownon an AlN template.

关键词： Al modulation epitaxy molecular beam epitaxy AlN pits

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PHLDA2 reshapes the immune microenvironment and induces drug resistance in hepatocellular carcinoma

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Oncology Research 2024年第6期32卷 1063-1078页

作者： KUN FENG HAO PENG QINGPENG LV YEWEI ZHANG Hepatopancreatobiliary center The Second Affiliated Hospital of Nanjing Medical UniversityNanjing210000China Medical School Southeast UniversityNanjing210000China

Hepatocellular carcinoma(HCC)is a malignancy known for its unfavorable *** dysregulation of the tumor microenvironment(TME)can affect the sensitivity to immunotherapy or chemotherapy,leading to treatment *** elucidation of PHLDA2’s involvement in HCC is imperative,and the clinical value of PHLDA2 is also ***,bioinformatics analysis was performed in multiple cohorts to explore the phenotype and mechanism through which PHLDA2 may affect the progression of ***,the expression and function of PHLDA2 were examined via the qRT-PCR,Western Blot,and MTT *** findings indicate a substantial upregulation of PHLDA2 in HCC,correlated with a poorer *** methylation levels of PHLDA2 were found to be lower in HCC tissues compared to normal liver ***,noteworthy associations were observed between PHLDA2 expression and immune infiltration in *** addition,PHLDA2 upregulation is closely associated with stemness features and immunotherapy or chemotherapy resistance in *** vitro experiments showed that sorafenib or cisplatin significantly up-regulated PHLDA2 mRNA levels,and PHLDA2 knockdown markedly decreased the sensitivity of HCC cells to chemotherapy ***,we found that TGF-βinduced the expression of PHLDA2 in *** GSEA and in vitro experiment indicated that PHLDA2 may promote the HCC progression via activating the AKT signaling *** study revealed the novel role of PHLDA2 as an independent prognostic factor,which plays an essential role in TME remodeling and treatment resistance in HCC.

关键词： HCC Immune infiltration Drug resistance TME PHLDA2

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Ketoconazole Associated Hepatotoxicity: A Systematic Review and Metaanalysis

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Biomedical and Environmental Sciences 2013年第7期26卷 605-610页

作者： YAN Jiang Ying NIE Xiao Lu TAO Qing Mei ZHAN Si Yan ZHANG Yan De national Hepatobilliary & Enteric Surgery Research center Central South University School of Public health Peking University

Objective To evaluate the incidence of Ketoconazole associated hepatotoxicity and related factors Methods Literature retrieval was conducted by using multi-databases for meta-analysis on Ketoconazole associated hepatotoxicity. The data were collected with a standardized form. Overall estimation of incidence of hepatotoxicity for specific study type was calculated by using a DerSimonian-Laird random-effects model owing to the substantial differences among the studies. Results Totally 204 eligible studies were included in the analysis. The incidence of Ketoconazole associated hepatotoxicity was 3.6%-4.2%. The dosage and duration specific subgroup analyses did not show any significant difference among groups, while the age specific subgroup analysis showed the incidence in children and people aged 〉60 years was 1.4% （95% CI 0.5%-4.2%） and 3.2% （95% Cl： 1.1%-8.7%） respectively. Additionally, the incidence of the hepatotoxicity was higher in people who had oral administration of ketoconazole beyond the provisions of the usage instructions, and the incidence was 5.7% （95% CI： 4.5%-7.2%）. Conclusion Ketoconazole associated hepatotoxicity was common. Off-label use might increase the risk of liver damage. Well-designed large sample studies are needed to identify the risk factors in future.

关键词： Ketoconazole Oral treatment Hepatotoxicity Systematic review

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Nickel catalysts with asymmetric steric hindrance for ethylene polymerization

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中国科学技术大学学报 2024年第6期54卷 48-52,59,I0010,I0011页

作者： Wanlu Tian Fuzhou Wang Chen Zou Hefei national Research center for Physical Sciences at the Microscale University of Science and Technology of ChinaHefei 230026China Institutes of Physical Science and Information Technology Anhui UniversityHefei 230601China

α-Diimide catalysts have attracted widespread attention due to their unique chain walking characteristics.A series ofα-diimide nickel/palladium catalysts with different electronic effects and steric hindrances were designed and synthesized for olefin *** this work,we synthesized a series of asymmetricα-diimide nickel complexes with different steric hindrances and used them for ethylene *** nickel catalysts have high ethylene polymerization activity,up to 6.51×10^(6)g·mol^(−1)·h^(−1),and the prepared polyethylene has a moderate melting point and high molecular weight(up to 38.2×10^(4)g·mol^(−1)),with a branching density distribution between 7 and 94 branches per 1000 *** importantly,the polyethylene prepared by these catalysts exhibits excellent tensile properties,with strain and stress reaching 800%and 30 MPa,respectively.

关键词： α-diimine nickel complex polyethylene polymerization asymmetric steric hindrance

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Experimental study on rehydration conditions of freeze-dried platelets

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2009年第5期10卷 697-703页

作者： Ju-li FAN Xian-guo XU Shao-zhi ZHANG Fa-ming ZHU Guang-ming CHEN Li-xing YAN Institute of Refrigeration and Cryogenics Zhejiang Universit Hangzhou 310027 China Key Laboratory of Blood safety Research Ministry of Health Blood Center of Zhejiang Province Hangzhou 310006 China

A rehydration process for freeze-dried human platelets was studied on 1 ml of samples. The effects of prehydration duration, prehydration temperature, an rehydration solution on the recovery rate, mean platelet volume （MPV）, and platelet distribution width （PDW） were investigated. The mass changes during the prehydration process were also studied. Three prehydration durations： 0, 1.5, and 3.5 h, and two rehydration solutions： platelet-poor plasma and phosphate-buffered saline （PBS）, were tested. It was found that：（1） the prehydration was of significance; （2） 1.5 h of prehydration had better effects than 3.5 h of prehydration; （3） as a rehydration solution, the platelet-poor plasma behaved better than the PBS. The impacts of prehydration duration and temperature on the results were studied. There was almost no difference between 35 and 37 ℃. Among all the prehydration durations tested, 15, 30, 60, 90, and 120 min, the best result was achieved with the time duration of 15 min. The weights of prehydrated platelets at the end of each test were measured and the water contents were calculated. After 15 min ofprehydration, the water contents in the samples were about （4.8±0.01）% and （5.27±0.29）% （w/w） corresponding to the conditions of 35 and 37 ℃, respectively. These results will be helpful for further studies on the freeze-drying of mammalian cells.

关键词： Freeze-drying Platelets Rehydration Prehydration Rehydration solution

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A Robust N-Terminal Pro-Brain Natriuretic Peptide Assay for Clinical Diagnosis of Heart Failure in Elderly Patients

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Journal of Analysis and Testing 2024年第1期8卷 74-82页

作者： Xue Gong Jiangling Wu Jiajia Zhang Zhongwei Jiang Yi Wang Pu Zhang Engineering Research center for Biotechnology of Active Substances(Ministry of Education) Chongqing Key Laboratory of Green Synthesis and ApplicationsCollege of ChemistryChongqing Normal UniversityChongqing 401331China Chongqing Research center for Pharmaceutical Engineering College of PharmacyChongqing Medical UniversityChongqing 400016China Department of Clinical Laboratory University Town Hospital of Chongqing Medical UniversityChongqing 401331China

Heart failure(HF)is a clinical hallmark of cardiovascular syndrome leading to substantial morbidity,repeated hospitalization,and enormous healthcare *** elderly populations continue to increase,biomarker-guided diagnosis and treatment for age-related cardiac decline have become *** evidence demonstrates that N-terminal proBNP(NT-proBNP)can provide a unique window into the diagnosis and risk stratification with ***,a simple yet robust aptasensor is developed for on-site recognizing the NT-proBNP by its targeting aptamer,thus achieving the accurate diagnosis of *** aptasensing system is prepared by absorbing the fluorophore-labeled aptamer strand onto the graphene oxide(GO),leading to efficient quenching without possible off-site signal *** aptamer strand can specifically identify target NT-proBNP molecules via a versatile conformational transformation,resulting in the desorption of the aptamer-NTproBNP complexes from GO and re-generation fluorescence signal,thus allowing sensitive detection of NT-proBNP in 37 clinical blood *** advantage of the high specificity of aptamer-guaranteed recognitions of NT-proBNP,this aptasensor system readily achieves better diagnostic performance for HF than commercially adopted chemiluminescence immunoassay(Siemens,CLIA)in hospitals in terms of accuracy(89.2%vs 83.8%),specificity(89.5%vs 84.2%),and positive predictive value(88.9%vs 83.3%).This work provides a stable option for the diagnosis and treatment of elderly HF-related diseases inclinics.

关键词： NT-proBNP Graphene oxide Aptamer Heart failure Clinical diagnosis

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