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Causal roles of gut microbiota in cholangiocarcinoma etiology suggested by genetic study

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1319-1333页

作者： Zhi-Tao Chen Chen-Chen ding Kai-Lei Chen Yang-Jun Gu chi-Cheng Lu Qi-Yong Li Division of Hepatobiliary and Pancreatic Surgery Shulan(Hangzhou)Hospital Affiliated to Zhejiang Shuren University Shulan International Medical CollegeHangzhou 310000Zhejiang ProvinceChina Pediatric Psychology The Affiliated Mental Health Centre&Hangzhou Seventh People’s HospitalZhejiang University School of MedicineHangzhou 310000Zhejiang ProvinceChina School of Medicine Zhejiang Shuren UniversityHangzhou 310000Zhejiang ProvinceChina School of Medicine Zhejiang Chinese Medical University Zhejiang Shuren CollegeHangzhou 310000Zhejiang ProvinceChina

BACKGROUND Cholangiocarcinoma(CCA)is a highly malignant biliary tract cancer with poor prognosis.Previous studies have implicated the gut microbiota in CCA,but evidence for causal mechanisms is lacking.AIM To investigate the causal relationship between gut microbiota and CCA risk.METHODS We performed a two-sample mendelian randomization study to evaluate potential causal associations between gut microbiota and CCA risk using genome-wide association study summary statistics for 196 gut microbial taxa and CCA.Genetic variants were used as instrumental variables.Multiple sensitivity analyses assessed result robustness.RESULTS Fifteen gut microbial taxa showed significant causal associations with CCA risk.Higher genetically predicted abundance of genus Eubacteriumnodatum group,genus Ruminococcustorques group,genus Coprococcus,genus Dorea,and phylum Actinobacteria were associated with reduced risk of gallbladder cancer and extrahepatic CCA.Increased intrahepatic CCA risk was associated with higher abundance of family Veillonellaceae,genus Alistipes,order Enterobacteriales,and phylum Firmicutes.Protective effects against CCA were suggested for genus Collinsella,genus Eisenbergiella,genus Anaerostipes,genus Paraprevotella,genus Parasutterella,and phylum Verrucomicrobia.Sensitivity analyses indicated these findings were reliable without pleiotropy.CONCLUSION This pioneering study provides novel evidence that specific gut microbiota may play causal roles in CCA risk.Further experimental validation of these candidate microbes is warranted to consolidate causality and mechanisms.

关键词： Cholangiocarcinoma Mendelian randomization Gut microbiota Instrumental variables Sensitivity analyses

Analysis of the joint detection capability of the SMILE satellite and EISCAT-3D radar

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Earth and Planetary Physics 2024年第1期8卷 299-306页

作者： JiaoJiao Zhang TianRan Sun XiZheng Yu DaLin Li Hang Li JiaQi Guo ZongHua ding Tao Chen Jian Wu chi Wang State Key Laboratory of Space Weather National Space Science CenterChinese Academy of SciencesBeijing 100190China Key Laboratory of Solar Activity and Space Weather National Space Science CenterChinese Academy of SciencesBeijing 100190China University of chinese Academy of Sciences Beijing 101408China Key Laboratory of Electronics and Information Technology for Space Systems Chinese Academy of SciencesBeijing 100190China china Research Institute of Radio-wave Propagation Qingdao 266075China

The Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)satellite is a small magnetosphere–ionosphere link explorer developed cooperatively between china and Europe.It pioneers the use of X-ray imaging technology to perform large-scale imaging of the Earth’s magnetosheath and polar cusp regions.It uses a high-precision ultraviolet imager to image the overall configuration of the aurora and monitor changes in the source of solar wind in real time,using in situ detection instruments to improve human understanding of the relationship between solar activity and changes in the Earth’s magnetic field.The SMILE satellite is scheduled to launch in 2025.The European Incoherent Scatter Sciences Association(EISCAT)-3D radar is a new generation of European incoherent scatter radar constructed by EISCAT and is the most advanced ground-based ionospheric experimental device in the high-latitude polar region.It has multibeam and multidirectional quasi-real-time three-dimensional(3D)imaging capabilities,continuous monitoring and operation capabilities,and multiple-baseline interferometry capabilities.Joint detection by the SMILE satellite and the EISCAT-3D radar is of great significance for revealing the coupling process of the solar wind–magnetosphere–ionosphere.Therefore,we performed an analysis of the joint detection capability of the SMILE satellite and EISCAT-3D,analyzed the period during which the two can perform joint detection,and defined the key scientific problems that can be solved by joint detection.In addition,we developed Web-based software to search for and visualize the joint detection period of the SMILE satellite and EISCAT-3D radar,which lays the foundation for subsequent joint detection experiments and scientific research.

关键词： Solar wind Magnetosphere Ionosphere Link Explorer(SMILE)satellite European Incoherent Scatter Sciences Association(EISCAT)-3D radar joint detection

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Blood glucose-lowering activity of protocatechuic acid is mediated by inhibiting a-glucosidase

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Food Science and Human Wellness 2024年第3期13卷 1212-1219页

作者： Huafang ding Shouhe Huang Chui Yiu Chook Erika Kwek chi Yan Kaying Ma Jianhui Liu Hanyue Zhu Zhenyu Chen Food&Nutritional Sciences Programme School of Life SciencesThe Chinese University of Hong KongHong Kong 999077China

α-Glucosidase inhibitors are effective in controlling postprandial hyperglycemia,which play crucial roles in the management of type 2 diabetes.Protocatechuic acid(PCA)is one of phenolic acids existing not only in various plant foods but also as a major microbial metabolite of dietary anthocyanins in the large colon.The present study investigated the inhibitory mechanism of PCA on a-glucosidase in vitro and examined its effect on postprandial blood glucose levels in vivo.Results from in vitro experiments demonstrated that PCA was a mix-type inhibitor of a-glucosidase.Driven by hydrogen bonds and van der Waals interactions,PCA reversibly bound withα-glucosidase to form a stable a-glucosidase-PCA complex in a spontaneous manner.The computational simulation found that PCA could insert into the active cavity of a-glucosidase and establish hydrogen bonds with catalytic amino acid residues.PCA binding aroused the steric hindrance for substrates to enter active sites and caused the structural changes of interacted catalytic amino acid residues.PCA also exhibited postprandial hypoglycemic capacity in diabetic mice.This study may provide the theoretical basis for the application of PCA as an active ingredient of functional foods in dietary management of diabetes.

关键词： Protocatechuic acid α-Glucosidase Postprandial hyperglycemia Inhibition mechanism

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Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

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Journal of Pharmaceutical Analysis 2024年第1期14卷 100-114页

作者： Sze Wan Hung Massimiliano Gaetani Yiran Li Zhouyurong Tan Xu Zheng Ruizhe Zhang Yang ding Gene chi Wai Man Tao Zhang Yi Song Yao Wang Jacqueline Pui Wah Chung Tak Hang Chan Roman A.Zubarev chi chiu Wang Department of Obstetrics&Gynaecology The Chinese University of Hong KongHong KongChina Division of Physiological Chemistry I Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Chemical Proteomics Core Facility Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Unit of Chemical Proteomics Science for Life Laboratory(SciLifeLab)StockholmSE 17177Sweden Center for Reproductive Medicine Henan Key Laboratory of Reproduction and GeneticsThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou450003China Department of Chemistry McGill UniversityMontrealH3A2K6Canada Department of Pharmacological&Technological Chemistry I.M.Sechenov First Moscow State Medical UniversityMoscow119146Russia Reproduction and Development Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong KongChina School of Biomedical Sciences The Chinese University of Hong KongHong KongChina chinese University of Hong Kong-Sichuan University Joint Laboratory in Reproductive Medicine The Chinese University of Hong KongHong KongChina

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus.Angiogenesis is a major pathophysiology in endometriosis.Our previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain unknown.In this study,we demonstrated that oral ProEGCG can be effective in preventing and treating endometriosis.Additionally,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,respectively.Computational simulation and BioLayer interferometry were used to confirm their binding affinity.Our results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)pathway.In vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling pathways.Moreover,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.

关键词： Molecular targets ProEGCG EGCG Angiogenesis Treatment Endometriosis

Recent advances in memristors based on two-dimensional ferroelectric materials

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Frontiers of physics 2024年第1期19卷 195-218页

作者： Wenbiao Niu Guanglong ding Ziqi Jia Xin-Qi Ma JiYu Zhao Kui Zhou Su-Ting Han chi-ching Kuo Ye Zhou Institute for Advanced Study Shenzhen UniversityShenzhen 518060China College of Electronics and Information Engineering Shenzhen UniversityShenzhen 518060China Institute of Organic and Polymeric Materials Research and Development Center of Smart Textile TechnologyTaipei University of TechnologyTaipei 10608TaiwanChina

In this big data era, the explosive growth of information puts ultra-high demands on the data storage/computing, such as high computing power, low energy consumption, and excellent stability. However, facing this challenge, the traditional von Neumann architecture-based computing system is out of its depth owing to the separated memory and data processing unit architecture. One of the most effective ways to solve this challenge is building brain inspired computing system with in-memory computing and parallel processing ability based on neuromorphic devices. Therefore, there is a research trend toward the memristors, that can be applied to build neuromorphic computing systems due to their large switching ratio, high storage density, low power consumption, and high stability. Two-dimensional (2D) ferroelectric materials, as novel types of functional materials, show great potential in the preparations of memristors because of the atomic scale thickness, high carrier mobility, mechanical flexibility, and thermal stability. 2D ferroelectric materials can realize resistive switching (RS) because of the presence of natural dipoles whose direction can be flipped with the change of the applied electric field thus producing different polarizations, therefore, making them powerful candidates for future data storage and computing. In this review article, we introduce the physical mechanisms, characterizations, and synthetic methods of 2D ferroelectric materials, and then summarize the applications of 2D ferroelectric materials in memristors for memory and synaptic devices. At last, we deliberate the advantages and future challenges of 2D ferroelectric materials in the application of memristors devices.

关键词： two-dimensional ferroelectric materials synthesis strategies memristors artificial synapses

Histone demethylase Kdm5c regulates osteogenesis and bone formation via PI3K/Akt/HIF1α and Wnt/β-catenin signaling pathways

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Genes & Diseases 2024年第1期11卷 64-66页

作者： Ying Li Lingli ding Yage Zhang Bingyu Zhou Gene chi Wai Man Min Wang Jinglan Li Yamei Liu Weiping Lin Haibin Wang Sien Lin Liangliang Xu Key Laboratory of Orthopaedics&Traumatology Lingnan Medical Research CenterThe First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou University of Chinese MedicineGuangzhouGuangdong 510000China Department of Orthopaedics&Traumatology Faculty of MedicineThe Chinese University of Hong KongPrince of Wales HospitalShatinHong Kong SAR 999077China Departments of Diagnostics of Traditional chinese Medicine Guangzhou University of Chinese MedicineGuangzhouGuangdong 510000China Orthopaedic Research Lab Affiliated Hospital of Guangdong Medical UniversityGuangdong Medical UniversityZhanjiangGuangdong 524001China

Fractures have an extraordinarily negative impact on individuals'quality of life and functional status.Nonunion or disability of fracture is a major health issue with important clinical,social,and economic implications.1 Mesenchymal stem cells(MSCs)play an indispensable role in the initiation of the fracture repair process including the formation of a callus which is replaced by new bone.The use of MSCs in the treatment of fractures is very attractive as they can reduce the time of healing and occurrence of nonunion.

关键词： PI3K/Akt HIF1α healing

High-energy-density metal nitrides with armchair chains

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Matter and Radiation at Extremes 2022年第3期7卷 47-53页

作者： Jianan Yuan Kang Xia chi ding Xiaomeng Wang Qing Lu Jian Sun National Laboratory of Solid State Microstructures School of Physics and Collaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210093People’s Republic of China Department of Applied Physics College of ScienceNanjing Forestry UniversityNanjing 210037China

Polymeric nitrogen has attracted much attention owing to its possible application as an environmentally safe high-energy-density material.Based on a crystal structure search method accelerated by the use of machine learning and graph theory and on first-principles calculations,we predict a series of metal nitrides with chain-like polynitrogen(P_(21)-AlN_(6),P2_(1)-GaN_(6),P-1-YN_(6),and P_(4)/mnc-TiN_(8)),all of which are estimated to be energetically stable below 40.8 GPa.Phonon calculations and ab initio molecular dynamics simulations at finite temperature suggest that these nitrides are dynamically stable.We find that the nitrogen in these metal nitrides can polymerize into two types of poly-N^(2-)_(4)chains,in which theπelectrons are either extended or localized.Owing to the presence of the polymerized N4 chains,these metal nitrides can store a large amount of chemical energy,which is estimated to range from 4.50 to 2.71 kJ/g.Moreover,these compounds have high detonation pressures and detonation velocities,exceeding those of conventional explosives such as TNT and HMX.

关键词： chains material energy

Dietary oxidized cholesterol causes mucus barrier thinner via decreasing Muc2 expression in the proximal colon and increasing the abundance of mucus-degrading bacteria

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Food Science and Human Wellness 2024年

作者： chi Yan Shou-He Huang Zi-Xing Chen Hua-Fang ding Zhen-Yu Chen School of Life Sciences Faculty of Science The chinese University of Hong Kong

Oxidized cholesterol (OXC) is a harmful dietary substance. Although the consumption of OXC has been associated with colonic inflammation， related underlying mechanisms are still limited. We evaluated the influence of dietary OXC on gut health and ecology by applying the murine model. Results showed that the thickness of the mucus layer was significantly reduced in healthy mice treated with OXC. Short-term intake of OXC did not influence the expression of pro-inflammatory factors in healthy mice but it induced the decrease of Muc2 expression in the proximal colon， accompanied by an increase in the abundance of two mucus-degrading bacteria， namely A. muciniphila and B. acidifaciens. Consistently， oral exposure of OXC promoted mucus barrier erosion in DSS-induced colitis mice and facilitated bacteria infiltration in the colon. The adverse effect of OXC on mucus layer disappeared in antibiotics-treated healthy mice， suggesting that the damaging effect of OXC on the gut mucus layer was not direct and instead was mediated by causing microbiota dysbiosis. Finally， the impact of OXC on the mucus layer and colitis was partly alleviated by green tea catechins. These studies demonstrated that the OXC-induced mucus barrier damage was mainly induced by the dysregulation of gut microbiota at least in this mouse model.

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MAGUS: machine learning and graph theory assisted universal structure searcher

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National Science Review 2023年第7期10卷 213-233页

作者： Junjie Wang Hao Gao Yu Han chi ding Shuning Pan Yong Wang Qiuhan Jia Hui-Tian Wang dingyu Xing Jian Sun National Laboratory of Solid State Microstructures School of Physics and Collaborative Innovation Center of Advanced Microstructures Nanjing University

Crystal structure predictions based on first-principles calculations have gained great success in materials science and solid state physics.However,the remaining challenges still limit their applications in systems with a large number of atoms,especially the complexity of conformational space and the cost of local optimizations for big systems.Here,we introduce a crystal structure prediction method,MAGUS,based on the evolutionary algorithm,which addresses the above challenges with machine learning and graph theory.Techniques used in the program are summarized in detail and benchmark tests are provided.With intensive tests,we demonstrate that on-the-fly machine-learning potentials can be used to significantly reduce the number of expensive first-principles calculations,and the crystal decomposition based on graph theory can efficiently decrease the required configurations in order to find the target structures.We also summarized the representative applications of this method on several research topics,including unexpected compounds in the interior of planets and their exotic states at high pressure and high temperature(superionic,plastic,partially diffusive state,etc.);new functional materials(superhard,high-energy-density,superconducting,photoelectric materials),etc.These successful applications demonstrated that MAGUS code can help to accelerate the discovery of interesting materials and phenomena,as well as the significant value of crystal structure predictions in general.

关键词： crystal structure searching materials design ab-initio calculations density functional theory high-pressure phase transition