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Casual associations between blood metabolites and colon cancer

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World Journal of Gastrointestinal Oncology 2024年第5期16卷 1995-2005页

作者： Ke-Yue Hu Yi-Quan Cheng Zhi-Long Shi fu-Peng Ren gang-Feng Xiao Department of Hematology and Oncology Ningbo No.2 HospitalNingbo 315000Zhejiang ProvinceChina

BACKGROUND Limited knowledge exists regarding the casual associations linking blood metabolites and the risk of developing colorectal cancer.AIM To investigate causal associations between blood metabolites and colon cancer.METHODS The study utilized a two-sample Mendelian randomization(MR)analysis to investigate the causal impact of 486 blood metabolites on colorectal cancer.The primary method of analysis used was the inverse variance weighted model.To further validate the results several sensitivity analyses were performed,including Cochran's Q test,MR-Egger intercept test,and MR robust adjusted profile score.These additional analyses were conducted to ensure the reliability and robustness of the findings.RESULTS After rigorous selection for genetic variation,486 blood metabolites were included in the MR analysis.We found Mannose[odds ratio(OR)=2.09(1.10-3.97),P=0.024],N-acetylglycine[OR=3.14(1.78-5.53),P=7.54×10^(-8)],X-11593-O-methylascorbate[OR=1.68(1.04-2.72),P=0.034],1-arachidonoylglycerophosphocholine[OR=4.23(2.51-7.12),P=6.35×10^(-8)]and 1-arachidonoylglycerophosphoethanolamine 4[OR=3.99(1.17-13.54),P=0.027]were positively causally associated with colorectal cancer,and we also found a negative causal relationship between Tyrosine[OR=0.08(0.01-0.63),P=0.014],Urate[OR=0.25(0.10-0.62),P=0.003],N-acetylglycine[0.73(0.54-0.98),P=0.033],X-12092[OR=0.89(0.81-0.99),P=0.028],Succinylcarnitine[OR=0.48(0.27-0.84),P=0.09]with colorectal cancer.A series of sensitivity analyses were performed to confirm the rigidity of the results.CONCLUSION This study showed a causal relationship between 10 blood metabolites and colorectal cancer,of which 5 blood metabolites were found to be causal for the development of colorectal cancer and were confirmed as risk factors.The other five blood metabolites are protective factors.

关键词： Metabolites Colon cancer Mendelian randomization Genome-wide association studies Casual

Solid particle size characterization by a high-frequency collision response in pneumatic particulate flow

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Particuology 2024年第3期86卷 39-54页

作者： Kai Wang Yichen Li Ziang Chang Min Qin Guangming fu Bangtang Yin gang Wang jiaqi Tian School of Petroleum Engineering China University of Petroleum(East China)Qingdao266580China Key Laboratory of Unconventional Oil&Gas Development China University of Petroleum(East China)Ministry of EducationQingdao266580China National Engineering Research Center of Oil&Gas Drilling and Completion Technology Qingdao266580China Shock and Vibration of Engineering Materials and Structures Key Lab ofSichuan Province Southwest University of Science and TechnologyMianyang621000China

A novel triaxial vibration method is developed for the real-time characterization of the solid particle size distribution(PsD)in pneumatic particulate flow,which is critical for chemical industry.In this work,the particle-wall collision and friction behaviours were analysed by the time-domain statistical and timefrequency joint methods to narrow the high-frequency response range by the initial experiment of free fall for a single particle,interparticle,and multiple particles.Subsequently,verification experiments of PSD characterization in pneumatic flow were performed.First,the quantitative triaxial energy response model that considers the particle size,shape,and mass factors were established.Second,a good agreement of the particle number identification was found between the triaxial vibration energy and mean particle size of 150-550μm.Moreover,the performance with the best accuracy was focused on a range of 42-43 kHz in the x-axis and z-axis and 36.8-38.8 kHz in the y-axis.Finally,the individual particle energy was inversely analysed by the triaxial vibration response within the optimized frequency bands,and the PSD was characterized in real-time by a low error rate,that is,5.2% from the XZ-axis direction of sand(42-43 kHz)and 5.6% from the XYZ-axis of glass(30.9-33.9 kHz,46.2-47.2 kHz,38.3-41.3 kHz for each axis response).Therefore,this research complements the existing approaches for PsD characterization in particulate multiphase flow.

关键词： Solid particulate flow Triaxial vibration High-frequency response Particle wall Particle size distribution

A Transient-Pressure-Based Numerical Approach for Interlayer Identification in Sand Reservoirs

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Fluid Dynamics & Materials Processing 2024年第3期20卷 641-659页

作者： Hao Luo Haibo Deng Honglin Xiao Shaoyang Geng fu Hou gang Luo Yaqi Li Tight Oil and Gas Exploration and Development Project Department PetroChina Southwest Oil and Gas Field CompanyChengdu610051China Energy College Chengdu University of TechnologyChengdu610059China

Almost all sandstone reservoirs contain interlayers. The identification and characterization of these interlayers iscritical for minimizing the uncertainty associated with oilfield development and improving oil and gas recovery.Identifying interlayers outside wells using identification methods based on logging data and machine learning isdifficult and seismic-based identification techniques are expensive. Herein, a numerical model based on seepageand well-testing theories is introduced to identify interlayers using transient pressure data. The proposed modelrelies on the open-source MATLAB Reservoir Simulation Toolbox. The effects of the interlayer thickness, position,and width on the pressure response are thoroughly investigated. A procedure for inverting interlayer parametersin the reservoir using the bottom-hole pressure is also proposed. This method uses only transient pressuredata during well testing and can effectively identify the interlayer distribution near the wellbore at an extremelylow cost. The reliability of the model is verified using effective oilfield examples.

关键词： Sand reservoir interlayer identification transient pressure analysis numerical well test

Förster resonance energy transfer reveals phillygenin and swertiamarin concurrently target AKT on different binding domains to increase the anti-inflammatory effect

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Chinese Chemical Letters 2024年第5期35卷 207-212页

作者： Xiaoyao Ma Jinling Zhang Ge Fang He Gao Jie Gao Li fu Yuanyuan Hou gang Bai State Key Laboratory of Medicinal Chemical Biology College of Pharmacy and Tianjin Key Laboratory of Molecular Drug ResearchNankai UniversityTianjin 300000China College of Life Health Dalian UniversityDalian 116622China Dalian fusheng Pharmaceutical Co. Ltd.Dalian 116000China

The clinical benefit of combination therapy is significant,but it is not easy to define the mechanism of complexity and diversity.Previous studies illustrate that phillygenin(Phi)binds in the allosteric inhibit pocket of protein kinase B(AKT),and swertiamarin(Swe)acts on the pleckstrin homology(PH)domain of AKT.However,the combined synergistic effect of relieving the inflammatory response has yet to be elucidated.Based on high sensitivity,specificity and fast-responsibility fluorescent sensors,the Förster resonance energy transfer(FRET)technique offers a route to provide clear insights into physiological and pathological processes.In the study,molecular docking,the fluorescent probes of Phi and Swe for FRET were designed and synthesized.FRET analysis shown that Swe and Phi concurrently acted on the PH domain and allosterically inhibited pocket of AKT,respectively.The combination of Swe and Phi significantly increased the heat stability of AKT and decreased protease-induced degeneration.In lipopolysaccharides(LPS)-induced mice and cells,the combination arrested AKT activation,nuclear factor kappa-B(NF-κB)phosphorylation,and the expression of tumor necrosis factor-α(TNF-α),interleukin(IL)-6 and IL-8.In conclusion,FRET revealed Phi and Swe concurrently targeted AKT on different domains and the combination of Phi and Swe enhanced the anti-inflammatory effect.

关键词： FRET Swertiamarin Phillygenin AKT Anti-inflammation Combinatorial drug

Thermo-hydro-poro-mechanical responses of a reservoir-induced landslide tracked by high-resolution fiber optic sensing nerves

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第3期16卷 1018-1032页

作者： Xiao Ye Hong-Hu Zhu gang Cheng Hua-fu Pei Bin Shi Luca Schenato Alessandro Pasuto School of Earth Sciences and Engineering Nanjing UniversityNanjing210023China School of Computer Science North China Institute of Science and Technology(National Safety Training Center of Coal Mines)Beijing101601China State Key Lab of Coastal and Offshore Engineering Department of Geotechnical EngineeringDalian University of TechnologyDalian116024China National Research Council-Research Institute for Geo-Hydrological Protection(CNR-IRPI) Padova35127Italy Department of Information Engineering University of PadovaPadova35131Italy

Thermo-poro-mechanical responses along sliding zone/surface have been extensively studied.However,it has not been recognized that the potential contribution of other crucial engineering geological interfaces beyond the slip surface to progressive failure.Here,we aim to investigate the subsurface multiphysics of reservoir landslides under two extreme hydrologic conditions(i.***.wet and dry),particularly within sliding masses.Based on ultra-weak fiber Bragg grating(UWFBG)technology,we employ specialpurpose fiber optic sensing cables that can be implanted into boreholes as“nerves of the Earth”to collect data on soil temperature,water content,pore water pressure,and strain.The Xinpu landslide in the middle reach of the Three Gorges Reservoir Area in China was selected as a case study to establish a paradigm for in situ thermo-hydro-poro-mechanical monitoring.These UWFBG-based sensing cables were vertically buried in a 31 m-deep borehole at the foot of the landslide,with a resolution of 1 m except for the pressure sensor.We reported field measurements covering the period 2021 and 2022 and produced the spatiotemporal profiles throughout the borehole.Results show that wet years are more likely to motivate landslide motions than dry years.The annual thermally active layer of the landslide has a critical depth of roughly 9 m and might move downward in warmer years.The dynamic groundwater table is located at depths of 9e15 m,where the peaked strain undergoes a periodical response of leap and withdrawal to annual hydrometeorological cycles.These interface behaviors may support the interpretation of the contribution of reservoir regulation to slope stability,allowing us to correlate them to local damage events and potential global destabilization.This paper also offers a natural framework for interpreting thermo-hydro-poro-mechanical signatures from creeping reservoir bank slopes,which may form the basis for a landslide monitoring and early warning system.

关键词： Reservoir landslide Thermo-hydro-poro-mechanical response Ultra-weak fiber bragg grating(UWFBG) subsurface evolution Engineering geological interface Geotechnical monitoring

In-situ synthesis of quantum dots in the nucleus of live cells

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National Science Review 2024年第3期11卷 172-182页

作者： Yusi Hu Zhi-gang Wang Haohao fu Chuanzheng Zhou Wensheng Cai Xueguang Shao Shu-Lin Liu Dai-Wen Pang State Key Laboratory of Medicinal Chemical Biology Frontiers Science Centre for New Organic MatterTianjin Key Laboratory of Biosensing and Molecular Recognition Research Centre for Analytical Sciences College of Chemistry School of Medicine and Frontiers Science Centre for Cell Responses Nankai University Haihe Laboratory of Sustainable Chemical Transformations

The cell nucleus is the main site for the storage and replication of genetic material, and the synthesis of substances in the nucleus is rhythmic, regular and strictly regulated by physiological processes. However,whether exogenous substances, such as nanoparticles, can be synthesized in situ in the nucleus of live cells has not been reported. Here, we have achieved in-situ synthesis of CdSxSe1-xquantum dots（QDs） in the nucleus by regulation of the glutathione（GSH） metabolic pathway. High enrichment of GSH in the nucleus can be accomplished by the addition of GSH with the help of the Bcl-2 protein. Then, high-valence Se is reduced to low-valence Se by glutathione-reductase-catalyzed GSH, and interacts with the Cd precursor formed through Cd and thiol-rich proteins, eventually generating QDs in the nucleus. Our work contributes to a new understanding of the syntheses of substances in the cell nucleus and will pave the way for the development of advanced ‘supercells’.

关键词： glutathione live cell nucleus quantum dot intracellular synthesis

Myosteatosis is associated with coronary artery calcification in patients with type 2 diabetes

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World Journal of Diabetes 2024年第3期15卷 429-439页

作者： fu-Peng Liu Mu-Jie Guo Qing Yang Yan-Ying Li Yan-gang Wang Mei Zhang The Affiliated Hospital of Medical College Qingdao University Qingdao UniversityQingdao 266071Shandong ProvinceChina Department of Endocrinology The Affiliated Hospital of Jining Medical UniversityJining 272029Shandong ProvinceChina Department of Medical Imaging The Affiliated Hospital of Jining Medical UniversityJining 272029Shandong ProvinceChina Department of Clinical Nutrition The Affiliated Hospital of Jining Medical UniversityJining 272029Shandong ProvinceChina Department of Endocrinology The Affiliated Hospital of Qingdao UniversityQingdao 266003Shandong ProvinceChina

BACKGROUND Myosteatosis,rather than low muscle mass,is the primary etiologic factor of sarcopenia in patients with type 2 diabetes mellitus(T2DM).Myosteatosis may lead to a series of metabolic dysfunctions,such as insulin resistance,systematic inflammation,and oxidative stress,and all these dysfunctions are closely associated with the acceleration of T2DM and atherosclerosis.AIM To investigate the association between myosteatosis and coronary artery calcification(CAC)in patients with T2DM.METHODS Patients with T2DM,who had not experienced major cardiovascular events and had undergone both abdominal and thoracic computed tomography(CT)scans,were included.The mean skeletal muscle attenuation was assessed using abdominal CT images at the L3 level.The CAC score was determined from thoracic CT images using the Agatston scoring method.Myosteatosis was diagnosed according to Martin’s criteria.Severe CAC(SCAC)was defined when the CAC score exceeded 300.Logistic regression and decision tree analyses were performed.RESULTS A total of 652 patients with T2DM were enrolled.Among them,167(25.6%)patients had SCAC.Logistic regression analysis demonstrated that myosteatosis,age,duration of diabetes,cigarette smoking,and alcohol consumption were independent risk factors of SCAC.Myosteatosis was significantly associated with an increased risk of SCAC(OR=2.381,P=0.003).The association between myosteatosis and SCAC was significant in the younger patients(OR=2.672,95%CI:1.477-4.834,P=0.002),but not the older patients(OR=1.456,95%CI:0.863-2.455,P=0.188),and was more prominent in the population with lower risks of atherosclerosis.The decision tree analyses prioritized older age as the primary variable for SCAC.In older patients,cigarette smoking was the main contributing factor for SCAC,while in younger patients,it was myosteatosis.CONCLUSION Myosteatosis is a novel risk factor for atherosclerosis in patients with T2DM,especially in the population with younger ages and fewer traditional risk factors.

关键词： Type 2 diabetes Myosteatosis Muscle quality Coronary artery calcification Atherosclerosis Cardiovascular diseases

Comparison of immune responses and intestinal flora in epicutaneously sensitized BALB/c or C57BL/6 mouse models of food allergy

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Food Science and Human Wellness 2024年第2期13卷 668-680页

作者： gang Yu Yuhao Jiang Shuifeng Zhang Pengpeng Liu Shunyu Wang Huadong Sheng Yanbo Wang Qiaozhi Zhang Linglin fu Food Safety Key Laboratory of Zhejiang Province School of Food Science and BiotechnologyZhejiang Gongshang UniversityHangzhou 310018China Zhejiang Fangyuan Test Group Co. Ltd.Hangzhou 310018China Key Laboratory of Biosafety Detection for Zhejiang Market Regulation Hangzhou 310018China Zhejiang Liziyuan Food Co. LtdJinhua 321031China

Cutaneous exposure to food allergens through a disrupted skin barrier is recognized as an important cause of food allergy,and the cutaneous sensitized mouse model has been established to investigate relevant allergic disorders.However,the role of different genetic backgrounds of mice on immune responses to food allergens upon epicutaneous sensitization is largely unknown.In this study,two strains of mice,i.e.,the BALB/c and C57BL/6 mice,were epicutaneously sensitized with ovalbumin on atopic dermatitis(AD)-like skin lesions,followed by intragastric challenge to induce IgE-mediated food allergy.Allergic outcomes were measured as clinical signs,specific antibodies and cytokines,and immune cell subpopulations,as well as changes in intestinal barrier function and gut microbiota.Results showed that both strains of mice exhibited typical food-allergic symptoms with a Th2-skewed response.The C57BL/6 mice,rather than the BALB/c mice,were fitter for establishing an epicutaneously sensitized model of food allergy since a stronger Th2-biased response and severer disruptions in the intestinal barrier and gut homeostasis were observed.This study provides knowledge for selecting an appropriate mouse model to study food-allergic responses associated with AD-like skin lesions and highlights the role of genetic variations in the immune mechanism underlying pathogenesis of food allergy.

关键词： Food allergy Mouse models Epicutaneous sensitization Th2 response Gut microbiota

A novel alternative for pyrogen detection based on a transgenic cell line

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1221-1229页

作者： Qing He Chuan-Fei Yu gang Wu Kai-Qin Wang Yong-Bo Ni Xiao Guo Zhi-Hao fu Lan Wang De-Jiang Tan Hua Gao Can Wang gang Chen Xu-Hong Chen Bo Chen Jun-Zhi Wang National Institutes for Food and Drug Control BeijingChina School of Life Science and Biopharmaceutics Shenyang Pharmaceutical UniversityShenyangChina Shanghai Institute for Food and Drug Control ShanghaiChina KeyMed Biosciences Inc. ChengduChina

Pyrogen,often as a contaminant,is a key indicator affecting the safety of almost all parenteral drugs(including biologicals,chemicals,traditional Chinese medicines and medical devices).It has become a goal to completely replace the in vivo rabbit pyrogen test by using the in vitro pyrogen test based on the promoted‘reduction,replacement and refinement’principle,which has been highly considered by regulatory agencies from different countries.We used NF-κB,a central signalling molecule mediating inflammatory responses,as a pyrogenic marker and the monocyte line THP-1 transfected with a luciferase reporter gene regulated by NF-κB as an in vitro model to detect pyrogens by measuring the intensity of a fluorescence signal.Here,we show that this test can quantitatively and sensitively detect endotoxin(lipopolysaccharide from different strains)and nonendotoxin(lipoteichoic acid,zymosan,peptidoglycan,lectin and glucan),has good stability in terms of NF-κB activity and cell phenotypes at 39 cell passages and can be applied to detect pyrogens in biologicals(group A&C meningococcal polysaccharide vaccine;basiliximab;rabies vaccine(Vero cells)for human use,freeze-dried;Japanese encephalitis vaccine(Vero cells),inactivated;insulin aspart injection;human albumin;recombinant human erythropoietin injection(CHO Cell)).The within-laboratory reproducibility of the test in three independent laboratories was 85%,80%and 80%and the interlaboratory reproducibility among laboratories was 83.3%,95.6%and 86.7%.The sensitivity(true positive rate)and specificity(true negative rate)of the test were 89.9%and 90.9%,respectively.In summary,the test provides a novel alternative for pyrogen detection.

关键词： pyrogen rabbit replace