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Mitochondrial dysfunction affects hepatic immune and metabolic remodeling in patients with hepatitis B virus-related acute-onchronic liver failure

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World Journal of Gastroenterology 2024年第8期30卷 881-900页

作者： Yu Zhang Xiao-ling tian Jie-Qun li Dong-sheng Wu Qiang li Bin Chen Department of Hepatology Institute of HepatologyThe First Affiliated Hospital of Hunan University of Chinese MedicineChangsha 410021Hunan ProvinceChina Department of liver Transplant Transplant Medical Research CenterThe Second Xiangya Hospital of Central South UniversityChangsha 410011Hunan ProvinceChina Department of Surgery The First Affiliated Hospital of Hunan University of Chinese MedicineChangsha 410021Hunan ProvinceChina

BACKGROUND Immune dysregulation and metabolic derangement have been recognized as key factors that contribute to the progression of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).However,the mechanisms underlying immune and metabolic derangement in patients with advanced HBV-ACLF are unclear.AIM To identify the bioenergetic alterations in the liver of patients with HBV-ACLF causing hepatic immune dysregulation and metabolic disorders.METHODS liver samples were collected from 16 healthy donors(HDs)and 17 advanced HBV-ACLF patients who were eligible for liver transplantation.The mitochondrial ultrastructure,metabolic characteristics,and immune microenvironment of the liver were assessed.More focus was given to organic acid metabolism as well as the function and subpopulations of macrophages in patients with HBV-ACLF.RESULTS Compared with HDs,there was extensive hepatocyte necrosis,immune cell infiltration,and ductular reaction in patients with ACLF.In patients,the liver suffered severe hypoxia,as evidenced by increased expression of hypoxia-inducible factor-1α.Swollen mitochondria and cristae were observed in the liver of patients.The number,length,width,and area of mitochondria were adaptively increased in hepatocytes.Targeted metabolomics analysis revealed that mitochondrial oxidative phosphorylation decreased,while anaerobic glycolysis was enhanced in patients with HBV-ACLF.These findings suggested that,to a greater extent,hepa-tocytes used the extra-mitochondrial glycolytic pathway as an energy source.Patients with HBV-ACLF had elevated levels of chemokine C-C motif ligand 2 in the liver homogenate,which stimulates peripheral monocyte infiltration into the liver.Characterization and functional analysis of macrophage subsets revealed that patients with ACLF had a high abundance of CD68^(+)HLA-DR^(+)macrophages and elevated levels of both interleukin-1βand transforming growth factor-β1 in their livers.The abundance of CD206^(+)CD163^(+)macrophages and expression of interleukin-10 decreased.Th

关键词： Acute-on-chronic liver failure Hypoxia-inducible factor-1α Mitochondria Metabolic phenotype Immune cells

Interpretation and characterization of rate of penetration intelligent prediction model

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Petroleum Science 2024年第1期21卷 582-596页

作者： Zhi-Jun Pei Xian-Zhi Song Hai-Tao Wang Yi-Qi Shi Shou-Ceng tian Gen-sheng li College of Petroleum Engineering China University of Petroleum(Beijing)Beijing102249China State Key Laboratory of Petroleum Resources and Prospecting Beijing102249China Kunlun Digital Technology Co. Ltd.Beijing102206China

Accurate prediction of the rate of penetration(ROP)is significant for drilling optimization.While the intelligent ROP prediction model based on fully connected neural networks(FNN)outperforms traditional ROP equations and machine learning algorithms,its lack of interpretability undermines its credibility.This study proposes a novel interpretation and characterization method for the FNN ROP prediction model using the Rectified linear Unit(ReLU)activation function.By leveraging the derivative of the ReLU function,the FNN function calculation process is transformed into vector operations.The FNN model is linearly characterized through further simplification,enabling its interpretation and analysis.The proposed method is applied in ROP prediction scenarios using drilling data from three vertical wells in the Tarim Oilfield.The results demonstrate that the FNN ROP prediction model with ReLU as the activation function performs exceptionally well.The relative activation frequency curve of hidden layer neurons aids in analyzing the overfitting of the FNN ROP model and determining drilling data similarity.In the well sections with similar drilling data,averaging the weight parameters enables linear characterization of the FNN ROP prediction model,leading to the establishment of a corresponding linear representation equation.Furthermore,the quantitative analysis of each feature's influence on ROP facilitates the proposal of drilling parameter optimization schemes for the current well section.The established linear characterization equation exhibits high precision,strong stability,and adaptability through the application and validation across multiple well sections.

关键词： Fully connected neural network Explainable artificial intelligence Rate of penetration ReLU active function Deep learning Machine learning

Icariin plus curcumol enhances autophagy through the mTOR pathway and promotes cathepsin B-mediated pyroptosis of prostate cancer cells

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Asian Pacific Journal of Tropical Biomedicine 2024年第2期14卷 55-64页

作者： Xu-Yun Wang Wen-Jing Xu Bo-Nan li tian-Song Sun Wen sheng Department of Andrology Beijing Hospital of Traditional Chinese MedicineCapital Medical UniversityBeijing100010China Department of Dermatology The First Affiliated Hospital of Hunan University of Chinese MedicineChangsha410021China School of Integrated Chinese and Western Medicine Hunan University of Chinese MedicineChangsha410208China Andrology Laboratory Hunan University of Chinese MedicineChangsha410208China School of Rehabilitation Medicine and Health Care Hunan University of MedicineHuaihua418000China School of Traditional Chinese Medicine Hunan University of MedicineHuaihua418000China

Objective:To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying mechanisms.Methods:We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell viability and proliferation.Autophagy expression was analyzed using monodansylcadaverine staining.Immunofluorescence and Western blot analyses were used to evaluate protein expressions related to autophagy,pyroptosis,and the mTOR pathway.Cellular damage was examined using the lactate dehydrogenase assay.Moreover,cathepsin B and NLRP3 were detected by co-immunoprecipitation.Results:Icariin plus curcumol led to a decrease in PC3 cell proliferation and an enhancement of autophagy.The levels of LC3-Ⅱ/LC3-Ⅰand beclin-1 were increased,while the levels of p62 and mTOR were decreased after treatment with icariin plus curcumol.These changes were reversed upon overexpression of mTOR.Furthermore,3-methyladenine resulted in a decrease in inflammatory cytokines,pyroptosis-related protein levels,and lactate dehydrogenase concentration,compared to the icariin plus curcumol group.Inhibiting cathepsin B reversed the regulatory effects of icariin plus curcumol.Conclusions:Icariin plus curcumol demonstrates great potential as a therapeutic agent for castration-resistant prostate cancer by enhancing autophagy via the mTOR pathway and promoting pyroptosis mediated by cathepsin B.These findings provide valuable insights into the molecular mechanisms underlying the therapeutic potential of icariin and curcumol for prostate cancer treatment.

关键词： Icariin Curcumol Autophagy mTOR Cathepsin B Pyroptosis Prostate cancer

Recent advances in promising drugs for primary prevention of gastroesophageal variceal bleeding with cirrhotic portal hypertension

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 4-13页

作者： Ji-Yao sheng Zi-Fan Meng Qiao li Yong-sheng Yang Department of Hepatobiliary and Pancreatic Surgery the Second Hospital of Jilin UniversityChangchun 130041China Jilin Engineering Laboratory for Translational Medicine of Hepatobiliary and Pancreatic Diseases the Second Hospital of Jilin UniversityChangchun 130041China

Background:Gastroesophageal variceal bleeding is one of the most severe complications of patients with cirrhosis.Although primary prevention drugs,including non-selectiveβ-blockers,have effectively reduced the incidence of bleeding,their efficacy is limited due to side effects and related contraindications.With recent advances in precision medicine,precise drug treatment provides better treatment efficacy.Data sources:literature search was conducted in PubMed,MEDliNE and Web of Science for relevant articles published up to May 2022.Information on clinical trials was obtained from https://clinicaltrials.gov/and http://***/.Results:The in-depth understanding of the pathogenesis and advances of portal hypertension has enabled the discovery of multiple molecular targets for promising drugs.According to the site of action,these drugs could be classified into four classes:intrahepatic,extrahepatic,both intrahepatic and extrahepatic targets and others.All these classes of drugs offer advantages over traditional treatments in prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.Conclusions:This review classified and summarized the promising drugs,which prevent gastroesophageal variceal bleeding by targeting specific markers of pathogenesis of portal hypertension,demonstrating the significance of using the precision medicine strategy to discover and develop promising drugs for the primary prevention of gastroesophageal variceal bleeding in patients with cirrhotic portal hypertension.

关键词： Cirrhotic portal hypertension Target drug Primary prevention Bleeding

Gut microbiota intervention attenuates thermogenesis in broilers exposed to high temperature through modulation of the hypothalamic 5‑HT pathway

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Journal of Animal Science and Biotechnology 2024年第2期15卷 679-698页

作者： sheng li Xiaoqing li Kai Wang Yansen li Kentaro Nagaoka Chunmei li Research Centre for livestock Environmental Control and Smart Production College of Animal Science and TechnologyNanjing Agricultural UniversityNanjing 210095China Laboratory of Veterinary Physiology Department of Veterinary MedicineFaculty of AgricultureTokyo University of Agriculture and TechnologyTokyo 183‑8509Japan

Background Broilers have a robust metabolism and high body temperature,which make them less tolerant to hightemperature(HT)environments and more susceptible to challenges from elevated temperatures.Gut microbes,functioning as symbionts within the host,possess the capacity to significantly regulate the physiological functions and environmental adaptability of the host.This study aims to investigate the effects of gut microbial intervention on the body temperature and thermogenesis of broilers at different ambient temperatures,as well as the underlying mechanism involving the"gut-brain"axis.Methods Broilers were subjected to gut microbiota interference with or without antibiotics(control or ABX)starting at 1 day of age.At 21 day of age,they were divided into 4 groups and exposed to different environments for 7 d:The control and ABX groups at room temperature(RT,24±1℃,60%relative humidity(RH),24 h/d)and the control-HT and ABX-HT groups at high temperature(HT,32±1℃,60%RH,24 h/d).Results The results demonstrated that the antibiotic-induced gut microbiota intervention increased body weight and improved feed conversion in broiler chickens(Pliver(Plistipes was enriched in control chickens.In contrast,antibioticinduced gut microbiota intervention resulted in a decrease in the relative abundance of Alistipes(P<0.05).Moreover,this difference was accompanied by increased hypothalamic 5-hydroxytryptamine(5-HT)content and TPH2 expression(P<0.05).Conclusions These findings underscore the critical role

关键词： 5-HT Broiler chickens Gut microbiota Thermogenesis Thermoregulation

SIRT1 inhibits apoptosis of human lens epithelial cells through suppressing endoplasmic reticulum stress in vitro and in vivo

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1205-1216页

作者： Hui Cui Di Sun sheng Meng tian-Ju Ma Zi Ye Zhao-Hui li Medical School of Chinese PLA Beijing 100089China Senior Department of Ophthalmology the Third Medical Center of PLA General HospitalBeijing 100853China

AIM:To explore the effect of silent information regulator factor 2-related enzyme 1(SIRT1)on modulating apoptosis of human lens epithelial cells(HLECs)and alleviating lens opacification of rats through suppressing endoplasmic reticulum(ER)stress.METHODS:HLECs(SRA01/04)were treated with varying concentrations of tunicamycin(TM)for 24h,and the expression of SIRT1 and C/EBP homologous protein(CHOP)was assessed using real-time quantitative polymerase chain reaction(RT-PCR),Western blotting,and immunofluorescence.Cell morphology and proliferation was evaluated using an inverted microscope and cell counting kit-8(CCK-8)assay,respectively.In the SRA01/04 cell apoptosis model,which underwent siRNA transfection for SIRT1 knockdown and SRT1720 treatment for its activation,the expression levels of SIRT1,CHOP,glucose regulated protein 78(GRP78),and activating transcription factor 4(ATF4)were examined.The potential reversal of SIRT1 knockdown effects by 4-phenyl butyric acid(4-PBA;an ER stress inhibitor)was investigated.In vivo,age-related cataract(ARC)rat models were induced by sodium selenite injection,and the protective role of SIRT1,activated by SRT1720 intraperitoneal injections,was evaluated through morphology observation,hematoxylin and eosin(H&E)staining,Western blotting,and RT-PCR.RESULTS:SIRT1 expression was downregulated in TMinduced SRA01/04 cells.Besides,in SRA01/04 cells,both cell apoptosis and CHOP expression increased with the rising doses of TM.ER stress was stimulated by TM,as evidenced by the increased GRP78 and ATF4 in the SRA01/04 cell apoptosis model.Inhibition of SIRT1 by siRNA knockdown increased ER stress activation,whereas SRT1720 treatment had opposite results.4-PBA partly reverse the adverse effect of SIRT1 knockdown on apoptosis.In vivo,SRT1720 attenuated the lens opacification and weakened the ER stress activation in ARC rat models.CONCLUSION:SIRT1 plays a protective role against TM-induced apoptosis in HLECs and slows the progression of cataract in rats by inhibiting ER stress.These findings sug

关键词： silent information regulator factor 2-related enzyme 1 endoplasmic reticulum stress apoptosis human lens epithelial cells cataract

The origins of catalytic selectivity for the electrochemical conversion of carbon dioxide to methanol

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Nano Research 2024年第1期17卷 5-17页

作者： tian Wang Yating Wang Yuhang li Chunzhong li Key Laboratory for Ultrafine Materials of Ministry of Education Shanghai Engineering Research Center of Hierarchical NanomaterialsFrontiers Science Center for Materiobiology and Dynamic ChemistrySchool of Materials Science and EngineeringEast China University of Science&TechnologyShanghai 200237China School of Chemical Engineering East China University of Science&TechnologyShanghai 200237China

The electrocatalytic conversion of carbon dioxide(CO_(2))into useful fuels and chemical feedstocks is an emerging route to alleviate global warming and reduce reliance on fossil fuels.Methanol(CH_(3)OH),as one of the most significant and widely used liquid fuels that can be generated by CO_(2)reduction,is essential in the chemical industry.In this minireview,we unravel the origins of the selective formation of CH_(3)OH via CO_(2)reduction,including catalyst composition designs,local structure modulations,and electrolyte/catalyst interface regulations.Finally,the remaining challenges and perspectives for the CO_(2)-to-CH_(3)OH reduction are proposed.

关键词： methanol carbon dioxide(CO_(2))reduction reaction electrochemistry electrocatalyst catalyst-electrolyte interface

Fracture geometry and breakdown pressure of radial borehole fracturing in multiple layers

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Petroleum Science 2024年第1期21卷 430-444页

作者： Yu-Ning Yong Zhao-Quan Guo Shou-Ceng tian Lu-Yao Ma tian-Yu Wang Mao sheng National Key Laboratory of Petroleum Resources and Engineering China University of Petroleum(Beijing)Beijing102249China Beijing Petroleum Machinery Company limited CNPC Engineering Technology R&D Company LimitedBeijing102206China Smart Energy Co. LtdChina Xiongan GroupXiong’an New Area071000HebeiChina

Radial borehole fracturing that combines radial boreholes with hydraulic fracturing is anticipated to improve the output of tight oil and gas reservoirs.This paper aims to investigate fracture propagation and pressure characteristics of radial borehole fracturing in multiple layers.A series of laboratory experiments with artificial rock samples(395 mm×395 mm×395 mm)was conducted using a true triaxial fracturing device.Three crucial factors corresponding to the vertical distance of adjacent radial borehole layers(vertical distance),the azimuth and diameter of the radial borehole are examined.Experimental results show that radial borehole fracturing in multiple layers generates diverse fracture geometries.Four types of fractures are identified based on the connectivity between hydraulic fractures and radial boreholes.The vertical distance significantly influences fracture propagation perpendicular to the radial borehole axis.An increase in the vertical distance impedes fracture connection across multiple radial borehole layers and reduces the fracture propagation distance along the radial borehole axis.The azimuth also influences fracture propagation along the radial borehole axis.Increasing the azimuth reduces the guiding ability of radial boreholes,which makes the fracture quickly curve to the maximum horizontal stress direction.The breakdown pressure correlates with diverse fracture geometries observed.When the fractures connect multi-layer radial boreholes,increasing the vertical distance decreases the breakdown pressure.Decreasing the azimuth and increasing the diameter also decrease the breakdown pressure.The extrusion force exists between the adjacent fractures generated in radial boreholes in multiple rows,which plays a crucial role in enhancing the guiding ability of radial boreholes and results in higher breakdown pressure.The research provides valuable theoretical insights for the field application of radial borehole fracturing technology in tight oil and gas reservoirs.

关键词： Multi-layer radial boreholes Hydraulic fracturing Fracture propagation Pressure characteristic

Improving the Forecasts of Coastal Wind Speeds in tianjin, China Based on the WRF Model with Machine Learning Algorithms

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Journal of Meteorological Research 2024年第3期38卷 570-585页

作者： Weihang ZHANG Meng tian Shangfei HAI Fei WANG Xiadong AN Wanju li Xiaodong li lifang sheng College of Oceanic and Atmospheric Sciences Ocean University of China tianjin Key Laboratory for Oceanic Meteorology Tianjin Institute of Meteorological Science CMA Earth System Modeling and Prediction Centre China Meteorological Administration (CMA) Qingdao Meteorological Bureau

Characterized by sudden changes in strength, complex influencing factors, and significant impacts, the wind speed in the circum-Bohai Sea area is relatively challenging to forecast. On the western side of Bohai Bay, as the economic center of the circum-Bohai Sea, tianjin exhibits a high demand for accurate wind forecasting. In this study, three machine learning algorithms were employed and compared as post-processing methods to correct wind speed forecasts by the Weather Research and Forecast（WRF） model for tianjin. The results showed that the random forest（RF）achieved better performance in improving the forecasts because it substantially reduced the model bias at a lower computing cost, while the support vector machine（SVM） performed slightly worse（especially for stronger winds）,but it required an approximately 15 times longer computing time. The back propagation（BP） neural network produced an average forecast significantly closer to the observed forecast but insufficiently reduced the RMSE. In regard to wind speed frequency forecasting, the RF method commendably corrected the forecasts of the frequency of moderate（force 3） wind speeds, while the BP method showed a desirable capability for correcting the forecasts of stronger（force > 6） winds. In addition, the 10-m u and v components of wind(u10and v10), 2-m relative humidity（RH2） and temperature（T2）, 925-hPa u(u925), sea level pressure（SLP）, and 500-hPa temperature(T500) were identified as the main factors leading to bias in wind speed forecasting by the WRF model in tianjin, indicating the importance of local dynamical/thermodynamic processes in regulating the wind speed. This study demonstrates that the combination of numerical models and machine learning techniques has important implications for refined local wind forecasting.

关键词： machine learning Weather Research and Forecast (WRF) model wind speed forecasting coastal region