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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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3'-Sialyllactose regulates glucose and lipid metabolic disorders via the gut–liver axis in mice fed a high-fat die

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Food Science and Human Wellness 2024年

作者： Wei Zhang Meizhen Zhu Kelsang Dekyi Linxi Zheng Yichen Zhang Youping Lv Dongbei Guo Xiaoxuan Chen Lili Pan Xinyue Wang Hongwei Li State Key Laboratory of Vaccines for Infectious Diseases， Xiang An biomedicine Laboratory， School of Public Health， Xiamen University State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics，National Innovation Platform for Industry-Education Integration in Vaccine Research， Xiamen University department of Nutrition， Zhongshan Hospital (Xiamen)， Fudan University Xiamen Clinical Research Center for Cancer Therapy

Recent research has indicated that sialic acid， such as free sialic acid (N-acetylneuraminic acid， Neu5Ac) and bound sialic acid (3'-sialyllactose， 3'-SL)， can ameliorate disorders associated with glycolipid metabolism， although the underlying mechanisms have yet to be determined. We examined the effects of 3'-SL on glycolipid metabolism in mice fed a high-fat diet. Male C57BL/6J mice were divided into six groups: two model control groups (normal and high-fat diets) and four intervention groups [Neu5Ac， and low-，moderate-， and high-dose 3'-SL]. After 8 weeks of continuous gavage intervention， mice in the 3'-SL intervention groups had lower body weight and total fat content; reduced fasting blood glucose， triglycerides， low-density lipoproteins and oxidized-low-density lipoproteins; and increased high-density lipoproteins，but no dosage-dependent of 3'-SL intervention was found， 3’-SL＿M intervention as optimal for further exploration. 3'-SL intervention could increase respiratory exchange ratio， energy expenditure， and amount of exercise performed. 3'-SL increased the colonic abundances of Akkermansia， Lactobacillus， and Bacteroides， and reduced those of Erysipelatoclostridium， Faecalibaculum， and Aldercreutzia. Changes were also observed in colonic metabolites， and liver gene transcript and metabolites， which were mainly enriched in bile secretion， taurine and hypotaurine metabolism， and insulin resistance. Additionally， 3'-SL was observed to regulate genes associated with physiological rhythms， including clock， per2， cry1， and bhihe41. Collectively， our findings indicate that 3'-SL can contribute to the prevention and control of disorders associated with glucose and lipid metabolism caused by high-fat diets. Compared with Neu5Ac， 3'-SL intervention can ameliorate intestinal flora disorders， enhance bile acid circulation， increase tissue energy expenditure， and reduce lipid synthesis， thereby promoting lipid-lowering effects mediated via the liver–gut axis， and can a

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J-shaped association between dietary thiamine intake and the risk of cognitive decline in cognitively healthy,older Chinese individuals

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General Psychiatry 2024年第1期37卷 44-52页

作者： Chengzhang Liu Qiguo Meng Yuanxiu Wei Xinyue Su Yuanyuan Zhang Panpan He Chun Zhou Mengyi Liu Ziliang Ye Xianhui Qin department of Epidemiology and Biostatistics School of Public HealthAnhui Medical UniversityHefeiAnhuiChina institute of biomedicine Anhui Medical UniversityHefeiAnhuiChina Division of Nephrology Nanfang HospitalSouthern Medical UniversityNational Clinical Research Center for Kidney DiseaseState Key Laboratory of Organ Failure ResearchGuangdong Provincial Institute of NephrologyGuangdong Provincial Key Laboratory of Renal Failure ResearchGuangzhou Regenerative Medicine and Health Guangdong LaboratoryGuangzhouGuangdongChina

Background The prospective association of dietary thiamine intake with the risk of cognitive decline among the general older adults remains *** To investigate the association between dietary thiamine intake and cognitive decline in cognitively healthy,older Chinese *** The study included a total of 3106 participants capable of completing repeated cognitive function *** nutrient intake information was collected through 3-day dietary recalls and using a 3-day food-weighed method to assess cooking oil and condiment *** decline was defined as the 5-year decline rate in global or composite cognitive scores based on a subset of items from the Telephone Interview for Cognitive *** The median follow-up duration was 5.9 *** was a J-shaped relationship between dietary thiamine intake and the 5-year decline rate in global and composite cognitive scores,with an inflection point of 0.68 mg/day(95%confidence interval(Cl):0.56 to 0.80)and a minimal risk at 0.60-1.00 mg/day of dietary thiamine *** the inflection point,thiamine intake was not significantly associated with cognitive *** the inflection point,each unit increase in thiamine intake(mg/day)was associated with a significant decrease of 4.24(95%Cl:2.22 to 6.27)points in the global score and 0.49(95%Cl:0.23 to 0.76)standard units in the composite score within 5 years.A stronger positive association between thiamine intake and cognitive decline was observed in those with hypertension,obesity and those who were non-smokers(all p<0.05).Conclusions This study revealed a J-shaped association between dietary thiamine intake and cognitive decline in cognitively healthy,older Chinese individuals,with an inflection point at 0.68 mg/day and a minimal risk at 0.60-1.00 mg/day of dietary thiamine intake.

关键词： intake shaped cognitive

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高吸附电化学纤维传感器用于实时、准确检测颅内一氧化氮

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Science China Materials 2024年第4期67卷 1320-1331页

作者：高睿王列李丹宋杰栗乾明卢江李录河李亦冉叶婷婷王嘉诚焦一丁李方琰何儿任俊烨张晔 National Laboratory of Solid State Microstructures Jiangsu Key Laboratory of Artificial Functional MaterialsChemistry and Biomedicine Innovation CenterCollaborative Innovation Center of Advanced MicrostructuresCollege of Engineering and Applied SciencesNanjing UniversityNanjing 210023China department of Immunology School of Medicine and Holistic Integrative MedicineNanjing University of Chinese MedicineNanjing 210023China

电化学一氧化氮传感器能够实时监测颅内一氧化氮浓度,对于了解大脑中一氧化氮的功能至关重要.然而,在大脑中使用的传统刚性传感电极面临着灵敏度低和植入后神经炎症引起一氧化氮浓度异常的问题.在这里,我们报道了一种结合物理和化学吸... 详细信息

电化学一氧化氮传感器能够实时监测颅内一氧化氮浓度,对于了解大脑中一氧化氮的功能至关重要.然而,在大脑中使用的传统刚性传感电极面临着灵敏度低和植入后神经炎症引起一氧化氮浓度异常的问题.在这里,我们报道了一种结合物理和化学吸附能力、具有高灵敏度和准确性的电化学一氧化氮传感器.其对一氧化氮的物理和化学吸附能力分别来自于电极的高比表面积和丰富的羧基官能团.此外,柔软的电极可以与脑组织的力学性能相匹配,实现了一个高度适应的电极/组织界面.由此设计的颅内一氧化氮传感器表现出迄今为止所报道文献中最高的灵敏度,为3245 pA nmol^(-1)L,检测限为0.1 nmol L^(-1).电极在植入后未观察到显著的炎症反应以及过量的一氧化氮表达,提高了检测的准确性.该传感器成功捕捉了大脑中的一氧化氮波动,并实现了对多个脑区的同时检测,促进了对大脑中一氧化氮生理病理作用的研究.

关键词：一氧化氮浓度生理病理传感电极化学纤维组织界面电化学

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Characterization of the molecular dysfunctions occurring in Aicardi-Goutieres syndrome patients with mutations in ADAR1

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Genes & Diseases 2024年第3期11卷 116-119页

作者： Sofan Al wardat Loredana Frasinlli Elisa Orecchini Federica Rey Silvia Anna Ciafre Silvia Galardi Jessica Garau Stella Gagliardi Simona Orcesi Davide Tonduti Stephana Carelli Cristina Cereda Ernesto Picardi Alessandro Michienzi department of biomedicine and Prevention University of Rome Tor VergataRome 00133Italy Pediatric Clinical Research Center"Romeo ed Enrica Invernizzi" Department of Biomedical and Clinical SciencesUniversity of MilanoMilano 20157Italy Center of Functional Genomics and Rare Diseases Department of PediatricsBuzzi Children's HospitalMilano20154Italy department of Child Neurology and Psychiatry IRccs Mondino FoundationPavia 27100Italy Unit of Pediatric Neurology C.O.A.L.A(Center for Diagnosis and Treatment of Leukodystrophies)Buzzi Children's HospitalMilano 20154Italy department of Biosciences Biotechnologies and EnvironmentUniversityof Bari"AldoMoro"Bari 70125Italy Institute of Biomembranes Bioenergetics and Molecular Biotechnologies(IBIOM)National Research Council(CNR)Bari 70126Italy Biostructures and Biosystems National Institute(INBB) Rome00136Italy Institute of Biochemistry and Cell Biology IBBC-CNRCampus Adriano Buzzati TraversoRome 00015Italy

Aicardi-Goutieres syndrome(AGS)is a systemic inflammatory disorder caused by mutations in any one of the nine different genes,whose deficiency provokes a type I(interferon)IFN response probably central to pathogenesis.^(1) ADAR1,one of the genes mutated in AGS(AGS6),encodes for an enzyme that belongs to the ADAR family(ADAR1,ADAR2,and ADAR3)that catalyzes the conversion of adenosine to inosine within double-stranded RNAs(dsRNAs)(RNA editing A-to-1).

关键词： ADAR1 interferon res

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Supercritical fluid technology:A game-changer for biomacromolecular nanomedicine preparation and biomedical application

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Chinese Chemical Letters 2024年第7期35卷 89-99页

作者： Yating Zheng Yulan Huang Jing Luo Xuqi Peng Xiran Gui Gang Liu Yang Zhang State Key Laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine LaboratoryNational Innovation Platform for Industry-Education Integration in Vaccine ResearchState Key Laboratory of Molecular Vaccinology and Molecular DiagnosticsCenter for Molecular Imaging and Translational MedicineSchool of Public HealthXiamen UniversityXiamen 361102China Shen Zhen Research Institute of Xiamen University Shenzhen 518057China Division of Urology and department of Surgery Brigham and Women's HospitalHarvard Medical SchoolBostonMA 02115United States Innovation Laboratory for Sciences and Technologies of Energy Materials of Fujian Province(IKKEM) Xiamen 361102China

Biomacromolecules are attractive in biomedical applications as therapeutic agents and potential drug carriers due to their natural active components,good biocompatibility,and high ***,their large relative molecular weight,complex structure,susceptibility to degradation,and poor stability limit their *** can address these issues by improving the therapeutic value,bioavailability,permeability,and absorption of biomacromolecules while regulating their retention time in the ***,compelling evidence has been reported that supercritical fluid(SCF)technology has emerged as an alternative that maintains the integrity of biomacromolecules and reduces environmental *** this review,we highlight a set of unique nanosizing strategies based on SCF technology for biomacromolecular nanomedicine,and extensively discuss their characteristics and *** particular,the protein-based,nucleic acid-based,and polysaccharide-based nanomedicine preparations via SCF technology and their biomedical applications are summarized,and the potential for industrial production of biomacromolecular drugs is also *** further provide perspectives on the opportunities and challenges in this excellent field of biomacromolecular drugs nanotechnology.

关键词： Biomacromolecules Supercritical fluid technology Therapeutic proteins Gene therapy Nanomedicine

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Gene replacement therapy in Bietti crystalline corneoretinal dystrophy:an open-label,single-arm,exploratory trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2275-2284页

作者： Jinyuan Wang Jinlu Zhang Shicheng Yu Hongyan Li Shaohong Chen Jingting Luo Haibo Wang Yuxia Guan Haihan Zhang Shiyi Yin Huili Wang Heping Li Junle Liu Jingyuan Zhu Qiong Yang Ying Sha Chuan Zhang Yuhang Yang Xuan Yang Xifang Zhang Xiuli Zhao Likun Wang Liping Yang Wenbin Wei Beijing Tongren Eye Center Beijing Key Laboratory of Intraocular Tumor Diagnosis and TreatmentBeijing Ophthalmology&Visual Sciences Key LabMedical Artificial Intelligence Research and Verification Key Laboratory of the Ministry of Industry and Information TechnologyBeijing Tongren HospitalCapital Medical University100730 BeijingChina School of Clinical Medicine Tsinghua University100084 BeijingChina Chigenovo Co. Ltd.102206 BeijingChina department of Ophthalmology Peking University Third HospitalBeijing Key Laboratory of Restoration of Damaged Ocular NervePeking University Third Hospital100191 BeijingChina department of Ophthalmology The Third People’s Hospital of Dalian116091 DalianChina department of Biomedical Informatics School of Basic Medical SciencesPeking University Health Science Center100191 BeijingChina Institute of Systems biomedicine Department of PathologySchool of Basic Medical SciencesPeking University Health Science Center100191 BeijingChina

Bietti crystalline corneoretinal dystrophy is an inherited retinal disease caused by mutations in CYP4V2,which results in blindness in the working-age population,and there is currently no available ***,we report the results of the first-in-human clinical trial(NCT04722107)of gene therapy for Bietti crystalline corneoretinal dystrophy,including 12 participants who were followed up for 180-365 *** open-label,single-arm exploratory trial aimed to assess the safety and efficacy of a recombinant adeno-associated-virus-serotype-2/8 vector encoding the human CYP4V2 protein(rAAV2/8-hCYP4V2).Participants received a single unilateral subretinal injection of 7.5×10^(10)vector genomes of rAAV2/***,73 treatment-emergent adverse events were reported,with the majority(98.6%)being of mild or moderate intensity and considered to be procedure-or corticosteroid-related;no treatment-related serious adverse events or local/systemic immune toxicities were *** with that measured at baseline,77.8%of the treated eyes showed improvement in best-corrected visual acuity(BCVA)on day 180,with a mean±standard deviation increase of 9.0±10.8 letters in the 9 eyes analyzed(p=0.021).By day 365,80%of the treated eyes showed an increase in BCVA,with a mean increase of 11.0±10.6 letters in the 5 eyes assessed(p=0.125).Importantly,the patients’improvement observed using multifocal electroretinogram,microperimetry,and Visual Function Questionnaire-25 further supported the beneficial effects of the *** conclude that the favorable safety profile and visual improvements identified in this trial encourage the continued development of rAAV2/8-hCYP4V2(named ZVS101e).

关键词： cor dystrophy crystalline

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Blood Calcium as a Protective Factor against Traumatic Fracture

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Journal of Biosciences and Medicines 2024年第3期12卷 328-336页

作者： Xin Zhang Quanquan Zhang Yinjun Luo Tao Feng Yue Hu Ying Li Wenjing Yu Linghan Guo Jinhua Wang Suchan Liao School of Basic Medical Sciences Youjiang Medical University for Nationalities Baise China Modern Industrial College of biomedicine and Great Health Youjiang Medical University for Nationalities Baise China department of Physiology School of Basic Medical Sciences Youjiang Medical University for Nationalities Baise China

Purpose: This study aims to investigate the predictive value of blood calcium in the prognosis of traumatic fracture. Methods: A retrospective experimental design was employed, 112 cases (52 non-fracture and 60 traumatic fracture) were randomly selected. The type of fracture complies with WHO-recommended (2019) diagnostic criteria for osteoporosis combined with fracture. The blood pressure (BP) was measured by OMRON’s HEM-7136 model electronic blood pressure monitor. Blood calcium (Ca2+), and blood phosphorus (P) values were measured using Colorimetric Roche kits on a Roche/Hitachi fully automated biochemical analyzer. Data collection and analysis followed. Results: Higher levels of age, systolic and diastolic blood pressures were found in the traumatic fracture group compared to the control group, whereas weight, height, and blood phosphorus did not differ significantly (P adjusting for age, systolic blood pressure, diastolic blood pressure, and blood phosphorus, binary logistic regression analysis revealed that blood calcium was a protective factor against traumatic fracture (β = -26.85, OR = 0.00, 95% CI = 0.00 -0.02, P = 0.022). Conclusion: The findings suggest that high and low blood calcium levels may serve as useful indicators in predicting the prognosis of fractures resulting from trauma.

关键词： Traumatic Fracture Fracture Biochemical Indicators Blood Calcium Prognostic Value

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Shared genetic architecture highlights the bidirectional association between major depressive disorder and fracture risk

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General Psychiatry 2024年第3期37卷 352-363页

作者： Pianpian Zhao Zhimin Ying Chengda Yuan Haisheng Zhang Ao Dong Jianguo Tao Xiangjiao Yi Mengyuan Yang Wen Jin Weiliang Tian David Karasik Geng Tian Houfeng Zheng The Affiliated Hangzhou First People’s Hospital School of MedicineWestlake UniversityHangzhouZhejiangChina Westlake Laboratory of Life Sciences and biomedicine HangzhouZhejiangChina Diseases&Population(DaP)Geninfo Lab School of Life SciencesWestlake UniversityHangzhouZhejiangChina Institute of Basic Medical Sciences Westlake Institute for Advanced StudyHangzhouZhejiangChina department of Orthopedic Surgery The Second Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina department of Dermatology Hangzhou Hospital of Traditional Chinese MedicineHangzhouZhejiangChina department of Global Statistics Eli Lilly and CompanyBranchburgNew JerseyUSA Azrieli Faculty of Medicine Bar-Ilan UniversitySafedIsrael Binzhou Medical University YantaiShandongChina

Background There is limited evidence suggesting that osteoporosis might exacerbate depressive symptoms,while more studies demonstrate that depression negatively affects bone density and increases fracture *** To explore the relationship between major depressive disorder(MDD)and fracture *** We conducted a nested case-control analysis(32670 patients with fracture and 397017 individuals without fracture)and a matched cohort analysis(16496 patients with MDD and 435492 individuals without MDD)in the same prospective UK Biobank data ***,we investigated the shared genetic architecture between MDD and fracture with linkage disequilibrium score regression and the MiXeR statistical *** used the conditional/conjunctional false discovery rate approach to identify the specific shared *** calculated the weighted genetic risk score for individuals in the UK Biobank and logistic regression was used to confirm the association observed in the prospective *** We found that MDD was associated with a 14%increase in fracture risk(hazard ratio(HR)1.14,95%CI 1.14 to 1.15,p<0.001)in the nested case-control analysis,while fracture was associated with a 72%increase in MDD risk(HR 1.72,95%CI 1.64 to 1.79,p<0.001)in the matched cohort analysis,suggesting a longitudinal and bidirectional ***,genetic summary data suggested a genetic overlap between MDD and ***,we identified four shared genomic loci,with the top signal(rs7554101)near *** protein encoded by SGIP1 is involved in cannabinoid receptor type 1 *** found that genetically predicted MDD was associated with a higher risk of fracture and vice *** addition,we found that the higher expression level of SGIP1 in the spinal cord and muscle was associated with an increased risk of fracture and *** The genetic pleiotropy between MDD and fracture highlights the bidirectional association observed in the epidemiological *** shared ge

关键词： fracture matched osteoporosis

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*** model of riboflavin transporter deficiency(RTD)disorder reveals deficits in synaptic transmission and movement

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Genes & Diseases 2024年第4期11卷 120-123页

作者： Ramesh K.Narayanan Gonzalo Perez-siles Kamila A.Marzec Alexandra Boyling Brent Neumann Manoj P.Menezes Marina L.Kennerson Northcott Neuroscience Laboratory ANZAC Research Institute-Sydney Local Health DistrictSydneyNSW 2139Australia Sydney Medical School University of SydneySydneyNSw 2050Australia ANZAC Research Institute-Sydney Local Health District SydneyNSW 2139Australia Neuroscience Program Monash Biomedicine Discovery Institute and Department of Anatomy and Developmental BiologyMonash UniversityMelbourneVictoria 3800Australia TY Nelson department of Neurology and Neurosurgery and Kids Neuroscience Children's Hospital at WestmeadWestmeadSydneyNSW2145Australia Paediatrics and Child Health The University of SydneySydneySydneyNSW 2145Australia Molecular Medicine Laboratory Concord General Repatriation HospitalSydneyNSW 2139Australia

Riboflavin transporter deficiency(RTD),previously known as Brown-Vialetto-Van Laere syndrome,is a childhoodonset neurodegenerative disorder characterized by sensory and motor neuron degeneration causing ataxia,muscle weakness,optic atrophy,and respiratory *** in SLC52A2 and SLC52A3,solute carrier family members that encode riboflavin(RF)transporters RFVT2 and RFVT3,are known to cause RTD types 2 and 3,respectively.

关键词： RTD degeneration TD

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