This paper proposes a cascade deep convolutional neural network to address the loosening detection problem of bolts on axlebox covers.Firstly,an SSD network based on ResNet50 and CBAM module by improving bolt image fe...This paper proposes a cascade deep convolutional neural network to address the loosening detection problem of bolts on axlebox covers.Firstly,an SSD network based on ResNet50 and CBAM module by improving bolt image features is proposed for locating bolts on axlebox covers.And then,theA2-PFN is proposed according to the slender features of the marker lines for extracting more accurate marker lines regions of the bolts.Finally,a rectangular approximationmethod is proposed to regularize themarker line regions asaway tocalculate the angle of themarker line and plot all the angle values into an angle table,according to which the criteria of the angle table can determine whether the bolt with the marker line is in danger of loosening.Meanwhile,our improved algorithm is compared with the pre-improved algorithmin the object localization stage.The results show that our proposed method has a significant improvement in both detection accuracy and detection speed,where ourmAP(IoU=0.75)reaches 0.77 and fps reaches 16.6.And in the saliency detection stage,after qualitative comparison and quantitative comparison,our method significantly outperforms other state-of-the-art methods,where our MAE reaches 0.092,F-measure reaches 0.948 and AUC reaches 0.943.Ultimately,according to the angle table,out of 676 bolt samples,a total of 60 bolts are loose,69 bolts are at risk of loosening,and 547 bolts are tightened.展开更多
Objective:The aim of this study was to investigate the molecular mechanism of anti-apoptotic action of survivin to the hepatoma-cellular carcinoma cell line HepG2.Methods:Design and synthesize siRNA gene sequence spec...Objective:The aim of this study was to investigate the molecular mechanism of anti-apoptotic action of survivin to the hepatoma-cellular carcinoma cell line HepG2.Methods:Design and synthesize siRNA gene sequence specifically targeting at HepG2 cell.HepG2 cells cultures were divided into five groups:blank control group,negative control group,low dose group,medium dose group and high dose group.HepG2 cells were treated respectively by pshRNA-survivin-387 of different concentrations.The apoptosis index(AI) was determined by flow cytometry(FCM).Cells were stained with rhodomine-123(Rh123) to detect changes of mitochondrial membrane potentials.The concentration of cytoplasmic cytochrome C(Cyt.C) was continuously determined by ELISA.Relative activities of caspase-9 and caspase-3 were assessed by colorimetric assay.Results:Compared with the control group,due to the function of short interference RNAs(SiRNAs) that suppresses the survivin gene expression,the apoptotic index of transfected groups were significantly higher than those of control groups(F = 13568.68,q = 110.47-327.16,P < 0.01),the apoptosis index of high concentration of transfected cells was higher than the low concentration transfected group(q = 39.63-168.22,P < 0.01).The apoptosis index of high concentrations transfected HepG2 cells was 25.54%,higher than that of blank control group,negative control group,low dose group and medium dose group(5.24%,6.61%,12.63% and 15.64%,respectively).HepG2 cells transfected with SiRNA exhibit gradually decreasing mitochondrial membrane potentials,which then lead to the releasing of Cyt C,following it were the activation of caspase-9 and caspase-3.Conclusion:Survivin performs the function of anti-apoptosis to the HepG2 cells via modulating the apoptosis of mitochondrial.HepG2 cells transfected with SiRNA survivin can significantly induce apoptosis.展开更多
RNA-binding proteins (RBPs) play an important role in post-transcriptional gene regulation. However, the functions of RBPs in plants remain poorly understood. Maize kernel mutant dek42 has small defective kernels and ...RNA-binding proteins (RBPs) play an important role in post-transcriptional gene regulation. However, the functions of RBPs in plants remain poorly understood. Maize kernel mutant dek42 has small defective kernels and lethal seedlings. Dek42 was cloned by Mutator tag isolation and further confirmed by an independent mutant allele and clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 materials. Dek42 encodes an RRM_RBM48 type RNA-binding protein that localizes to the nucleus. Dek42 is constitutively expressed in various maize tissues. The dek42 mutation caused a significant reduction in the accumulation of DEK42 protein in mutant kernels. RNA-seq analysis showed that the dek42 mutation significantly disturbed the expression of thousands of genes during maize kernel development. Sequence analysis also showed that the dek42 mutation significantly changed alternative splicing in expressed genes, which were especially enriched for the U12-type intron-retained type. Yeast two-hybrid screening identified SF3a1 as a DEK42-interacting protein. DEK42 also interacts with the spliceosome component U1-70K. These results suggested that DEK42 participates in the regulation of pre-messenger RNA splicing through its interaction with other spliceosome components. This study showed the function of a newly identified RBP and provided insights into alternative splicing regulation during maize kernel development.展开更多
Obesity and associated metabolic diseases are characterized by a chronic low-grade inflammatory state with the infiltration of many inflammatory cells,especially macrophages.Immune molecules,including some cytokines,h...Obesity and associated metabolic diseases are characterized by a chronic low-grade inflammatory state with the infiltration of many inflammatory cells,especially macrophages.Immune molecules,including some cytokines,have a close relationship with metabolism.Interleukin(IL)-25 is a member of the IL-17 cytokine family that can regulate macrophages and alleviate some metabolic dysfunction;however,its role and mechanisms in lipid metabolism remain to be extensively clarified.Human serum and liver biopsy specimens,high-fat diet-induced obesity mice and DB/DB(Lepr−/−)animal models were used to examine IL-25 expression in obesity and nonalcoholic fatty liver diseases(NAFLD).To observe the role of IL-25 in lipid metabolism,model mice were administered with IL-25 or adoptively transferred with IL-25-educated macrophages in vivo,whereas bone marrow-derived macrophages,the macrophage cell line RAW264.7 and adipocytes differentiated from 3T3-L1 were used in vitro.IL-25 was decreased in NAFLD patients and obese mice.In addition,IL-25 reduced body weight gain and lipid accumulation,enhanced lipid uptake by macrophages and increased the expression of lipolysis andβ-oxidation enzymes via alternatively activating macrophages.IL-25 also promoted lipolysis and suppressed lipogenesis in adipocytes co-cultured with the IL-25-educated macrophages.Furthermore,IL-25 improved the mitochondrial respiratory capacity and oxygen consumption rate of macrophages and produced more NAD+/NADH and ATP.In conclusion,IL-25 can stimulate M2 macrophage polarization and thereby promote lipolysis and mitochondrial respiratory capacity,highlighting the potential for IL-25 to be used as a therapeutic agent against obesity and associated metabolic syndromes.展开更多
In plants, Vacuole H^+-PPases(VPPs) are important Aproton pumps and encoded by multiple genes. In addition to full-length VPPs, several truncated forms are expressed, but their biological functions are unknown. In thi...In plants, Vacuole H^+-PPases(VPPs) are important Aproton pumps and encoded by multiple genes. In addition to full-length VPPs, several truncated forms are expressed, but their biological functions are unknown. In this study, we functionally characterized maize vacuole H^+-PPase 5(ZmVPP5), a truncated VPP in the maize genome. Although ZmVPP5 shares high sequence similarity with ZmVPP1 ZmVPP5 lacks the complete structure of the conserved proton transport and the inorganic pyrophosphatase-related domain. Phylogenetic analysis suggests that ZmVPP5 might be derived from an incomplete gene duplication event. ZmVPP5 is expressed in multiple tissues, and ZmVPP5 was detected in the plasma membrane, vacuole membrane and nuclei of maize cells. The overexpression of ZmVPP5 in yeast cells caused a hypersensitivity to salt stress. Transgenic maize lines with overexpressed ZmVPP5 also exhibited the salt hypersensitivity phenotype. A yeast two-hybrid analysis identified the ZmBag6 like protein as a putative ZmVPP5-interacting protein. The results of bimolecular luminescence complementation(Bi LC)assay suggest an interaction between ZmBag6-like protein and ZmVPP5 in vivo. Overall, this study suggests that ZmVPP5 might act as a VPP antagonist and participate in the cellular response to salt stress. Our study of ZmVPP5 has expanded the understanding of the origin and functions of truncated forms of plant VPPs.展开更多
The present paper is devoted to a preliminary study towards the establishment of an ergodic theory for stochastic di erential equations(SDEs)with less regular coecients and degenerate noises.These equations are often ...The present paper is devoted to a preliminary study towards the establishment of an ergodic theory for stochastic di erential equations(SDEs)with less regular coecients and degenerate noises.These equations are often derived as mesoscopic limits of complex or huge microscopic systems.By studying the associated Fokker-Planck equation(FPE),we prove the convergence of the time average of globally de ned weak solutions of such an SDE to the set of stationary measures of the FPE under Lyapunov conditions.In the case where the set of stationary measures consists of a single element,the unique stationary measure is shown to be physical.Similar convergence results for the solutions of the FPE are established as well.Some of our convergence results,while being special cases of those contained in Ji et al.(2019)for SDEs with periodic coecients,have weaken the required Lyapunov conditions and are of much simpli ed proofs.Applications to stochastic damping Hamiltonian systems and stochastic slow-fast systems are given.展开更多
To the Editor:Previous studies have demonstrated the efficacy of bictegravir(B),emtricitabine(F),and tenofovir alafenamide(TAF)in achieving virological suppression in human immunodeficiency virus(HIV)-infected patient...To the Editor:Previous studies have demonstrated the efficacy of bictegravir(B),emtricitabine(F),and tenofovir alafenamide(TAF)in achieving virological suppression in human immunodeficiency virus(HIV)-infected patients.Virological suppression can be influenced by various factors,with baseline HIV-1 RNA being a critical consideration.Guidelines often use a baseline HIV RNA level of>500,000 copies/mL as the primary reference indicator for drug selection.[1]However,previous studies on the effectiveness of B/F/TAF have not specifically analyzed patients with baseline HIV RNA>500,000 copies/mL.In Chongqing,China,where the prevalence of advanced HIV among hospitalized patients living with HIV exceeds 70%,[2]up to 25%of patients have baseline HIV-1 RNA>500,000 copies/mL in our study,and many patients have opportunistic infections.In such a complex medical setting,the virological suppression rates of patients using B/F/TAF remain uncertain.展开更多
Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide,and the development of nonalcoholic steatohepatitis(NASH)might cause irreversible hepatic damage.Hyperlipidemia(HLP)is the lea...Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide,and the development of nonalcoholic steatohepatitis(NASH)might cause irreversible hepatic damage.Hyperlipidemia(HLP)is the leading risk factor for NAFLD.This study aims to illuminate the causative contributor and potential mechanism of Kallistatin(KAL)mediating HLP to NAFLD.221 healthy control and 253 HLP subjects,62 healthy control and 44 NAFLD subjects were enrolled.The plasma KAL was significantly elevated in HLP subjects,especially in hypertriglyceridemia(HTG)subjects,and positively correlated with liver injury.Further,KAL levels of NAFLD patients were significantly up-regulated.KAL transgenic mice induced hepatic steatosis,inflammation,and fibrosis with time and accelerated inflammation development in high-fat diet(HFD)mice.In contrast,KAL knockout ameliorated steatosis and inflammation in high-fructose diet(HFruD)and methionine and choline-deficient(MCD)diet-induced NAFLD rats.Mechanistically,KAL induced hepatic steatosis and NASH by down-regulating adipose triglyceride lipase(ATGL)and comparative gene identification 58(CGl-58)by LRP6/Gas/PKA/GSK3βpathway through down-regulating peroxisome proliferator-activated receptor(PPARy)and up-regulating kruppel-like factor four(KLF4),respectively.CGl-58 is bound to NF-kB p65 in the cytoplasm,and diminishing CGl-58 facilitated p65 nuclear translocation and TNFa induction.Meanwhile,hepatic CGl-58-overexpress reverses NASH in KAL transgenic mice.Further,free fatty acids up-regulated KAL against thyroid hormone in hepatocytes.Moreover,Fenofibrate,one triglyceride-lowering drug,could reverse hepatic steatosis by down-regulating KAL.These results demonstrate that elevated KAL plays a crucial role in the development of HLP to NAFLD and may be served as a potential preventive and therapeutic target.展开更多
文摘This paper proposes a cascade deep convolutional neural network to address the loosening detection problem of bolts on axlebox covers.Firstly,an SSD network based on ResNet50 and CBAM module by improving bolt image features is proposed for locating bolts on axlebox covers.And then,theA2-PFN is proposed according to the slender features of the marker lines for extracting more accurate marker lines regions of the bolts.Finally,a rectangular approximationmethod is proposed to regularize themarker line regions asaway tocalculate the angle of themarker line and plot all the angle values into an angle table,according to which the criteria of the angle table can determine whether the bolt with the marker line is in danger of loosening.Meanwhile,our improved algorithm is compared with the pre-improved algorithmin the object localization stage.The results show that our proposed method has a significant improvement in both detection accuracy and detection speed,where ourmAP(IoU=0.75)reaches 0.77 and fps reaches 16.6.And in the saliency detection stage,after qualitative comparison and quantitative comparison,our method significantly outperforms other state-of-the-art methods,where our MAE reaches 0.092,F-measure reaches 0.948 and AUC reaches 0.943.Ultimately,according to the angle table,out of 676 bolt samples,a total of 60 bolts are loose,69 bolts are at risk of loosening,and 547 bolts are tightened.
文摘Objective:The aim of this study was to investigate the molecular mechanism of anti-apoptotic action of survivin to the hepatoma-cellular carcinoma cell line HepG2.Methods:Design and synthesize siRNA gene sequence specifically targeting at HepG2 cell.HepG2 cells cultures were divided into five groups:blank control group,negative control group,low dose group,medium dose group and high dose group.HepG2 cells were treated respectively by pshRNA-survivin-387 of different concentrations.The apoptosis index(AI) was determined by flow cytometry(FCM).Cells were stained with rhodomine-123(Rh123) to detect changes of mitochondrial membrane potentials.The concentration of cytoplasmic cytochrome C(Cyt.C) was continuously determined by ELISA.Relative activities of caspase-9 and caspase-3 were assessed by colorimetric assay.Results:Compared with the control group,due to the function of short interference RNAs(SiRNAs) that suppresses the survivin gene expression,the apoptotic index of transfected groups were significantly higher than those of control groups(F = 13568.68,q = 110.47-327.16,P < 0.01),the apoptosis index of high concentration of transfected cells was higher than the low concentration transfected group(q = 39.63-168.22,P < 0.01).The apoptosis index of high concentrations transfected HepG2 cells was 25.54%,higher than that of blank control group,negative control group,low dose group and medium dose group(5.24%,6.61%,12.63% and 15.64%,respectively).HepG2 cells transfected with SiRNA exhibit gradually decreasing mitochondrial membrane potentials,which then lead to the releasing of Cyt C,following it were the activation of caspase-9 and caspase-3.Conclusion:Survivin performs the function of anti-apoptosis to the HepG2 cells via modulating the apoptosis of mitochondrial.HepG2 cells transfected with SiRNA survivin can significantly induce apoptosis.
基金supported by the National Key Research and Development Program of China (2016YFD0101003)the National Natural Science Foundation of China (91635303 and 31425019)
文摘RNA-binding proteins (RBPs) play an important role in post-transcriptional gene regulation. However, the functions of RBPs in plants remain poorly understood. Maize kernel mutant dek42 has small defective kernels and lethal seedlings. Dek42 was cloned by Mutator tag isolation and further confirmed by an independent mutant allele and clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 materials. Dek42 encodes an RRM_RBM48 type RNA-binding protein that localizes to the nucleus. Dek42 is constitutively expressed in various maize tissues. The dek42 mutation caused a significant reduction in the accumulation of DEK42 protein in mutant kernels. RNA-seq analysis showed that the dek42 mutation significantly disturbed the expression of thousands of genes during maize kernel development. Sequence analysis also showed that the dek42 mutation significantly changed alternative splicing in expressed genes, which were especially enriched for the U12-type intron-retained type. Yeast two-hybrid screening identified SF3a1 as a DEK42-interacting protein. DEK42 also interacts with the spliceosome component U1-70K. These results suggested that DEK42 participates in the regulation of pre-messenger RNA splicing through its interaction with other spliceosome components. This study showed the function of a newly identified RBP and provided insights into alternative splicing regulation during maize kernel development.
基金supported by the National Nature Science Foundation of China:81272338,81272515,81370945,81471033,81570871,81570764 and 81600641the National Key Sci-Tech Special Project of China:2013ZX09102-053,2015GKS-355+7 种基金the Program for Doctoral Station in University:20130171110053the Key Project of the Nature Science Foundation of Guangdong Province,China:2015A030311043,2016A030311035the Guangdong Natural Science Fund:2014A020212023,2014A030313073,2015A030313103 and 2015A030313029the Guandong Science and Technology Project(2014A020212023,2015B090903063 and 2016A020214001)the Guangzhou Science and Technology Project:2014J4100162,201508020033 and 201510010052the Pearl River Nova Program of Guangzhou Municipality,China,Grant Number:201610010186the Chang jiang Scholars and Innovative Research Team in University:985 project PCSIRT 0947the Fundamental Research Funds for the Central Universities of China(Youth Program 13ykpy06,16ykpy24 and 31610046).
文摘Obesity and associated metabolic diseases are characterized by a chronic low-grade inflammatory state with the infiltration of many inflammatory cells,especially macrophages.Immune molecules,including some cytokines,have a close relationship with metabolism.Interleukin(IL)-25 is a member of the IL-17 cytokine family that can regulate macrophages and alleviate some metabolic dysfunction;however,its role and mechanisms in lipid metabolism remain to be extensively clarified.Human serum and liver biopsy specimens,high-fat diet-induced obesity mice and DB/DB(Lepr−/−)animal models were used to examine IL-25 expression in obesity and nonalcoholic fatty liver diseases(NAFLD).To observe the role of IL-25 in lipid metabolism,model mice were administered with IL-25 or adoptively transferred with IL-25-educated macrophages in vivo,whereas bone marrow-derived macrophages,the macrophage cell line RAW264.7 and adipocytes differentiated from 3T3-L1 were used in vitro.IL-25 was decreased in NAFLD patients and obese mice.In addition,IL-25 reduced body weight gain and lipid accumulation,enhanced lipid uptake by macrophages and increased the expression of lipolysis andβ-oxidation enzymes via alternatively activating macrophages.IL-25 also promoted lipolysis and suppressed lipogenesis in adipocytes co-cultured with the IL-25-educated macrophages.Furthermore,IL-25 improved the mitochondrial respiratory capacity and oxygen consumption rate of macrophages and produced more NAD+/NADH and ATP.In conclusion,IL-25 can stimulate M2 macrophage polarization and thereby promote lipolysis and mitochondrial respiratory capacity,highlighting the potential for IL-25 to be used as a therapeutic agent against obesity and associated metabolic syndromes.
基金supported by the National Natural Sciences Foundation of China (31425019 and 91335208)the Ministry of Science and Technology of China (2014CB138204)
文摘In plants, Vacuole H^+-PPases(VPPs) are important Aproton pumps and encoded by multiple genes. In addition to full-length VPPs, several truncated forms are expressed, but their biological functions are unknown. In this study, we functionally characterized maize vacuole H^+-PPase 5(ZmVPP5), a truncated VPP in the maize genome. Although ZmVPP5 shares high sequence similarity with ZmVPP1 ZmVPP5 lacks the complete structure of the conserved proton transport and the inorganic pyrophosphatase-related domain. Phylogenetic analysis suggests that ZmVPP5 might be derived from an incomplete gene duplication event. ZmVPP5 is expressed in multiple tissues, and ZmVPP5 was detected in the plasma membrane, vacuole membrane and nuclei of maize cells. The overexpression of ZmVPP5 in yeast cells caused a hypersensitivity to salt stress. Transgenic maize lines with overexpressed ZmVPP5 also exhibited the salt hypersensitivity phenotype. A yeast two-hybrid analysis identified the ZmBag6 like protein as a putative ZmVPP5-interacting protein. The results of bimolecular luminescence complementation(Bi LC)assay suggest an interaction between ZmBag6-like protein and ZmVPP5 in vivo. Overall, this study suggests that ZmVPP5 might act as a VPP antagonist and participate in the cellular response to salt stress. Our study of ZmVPP5 has expanded the understanding of the origin and functions of truncated forms of plant VPPs.
基金The first author was supported by China Scholarship Council.The second author was supported by University of Alberta,and Natural Sciences and Engineering Research Council of Canada(Grant Nos.RGPIN-2018-04371 and DGECR-2018-00353)The third author was supported by Pacific Institute for the Mathematical Sciences-Canadian Statistical Sciences Institute Postdoctoral Fellowship,Pacific Institute for the Mathematical Sciences-Collaborative Research Group Grant,National Natural Science Foundation of China(Grant Nos.11771026 and 11471344)+2 种基金the Pacific Institute for the Mathematical Sciences-University of Washington site through National Science Foundation of USA(Grant No.DMS-1712701)The fourth author was supported by Natural Sciences and Engineering Research Council of Canada Discovery(Grant No.1257749)Pacific Institute for the Mathematical Sciences-Collaborative Research Group Grant,University of Alberta,and Jilin University.
文摘The present paper is devoted to a preliminary study towards the establishment of an ergodic theory for stochastic di erential equations(SDEs)with less regular coecients and degenerate noises.These equations are often derived as mesoscopic limits of complex or huge microscopic systems.By studying the associated Fokker-Planck equation(FPE),we prove the convergence of the time average of globally de ned weak solutions of such an SDE to the set of stationary measures of the FPE under Lyapunov conditions.In the case where the set of stationary measures consists of a single element,the unique stationary measure is shown to be physical.Similar convergence results for the solutions of the FPE are established as well.Some of our convergence results,while being special cases of those contained in Ji et al.(2019)for SDEs with periodic coecients,have weaken the required Lyapunov conditions and are of much simpli ed proofs.Applications to stochastic damping Hamiltonian systems and stochastic slow-fast systems are given.
基金supported by grants from the first batch of Key Public Health Key Discipline Construction Project(Junior College),Chongqing Science and Technology Bureau(No.CSTB2022TIAD-KPX0180)the Joint Medical Research Projects of Chongqing Municipal Health Committee and Chongqing Municipal Science and Technology Bureau(No.2022QNXM032)+2 种基金Chongqing Talent Cultivation Program(No.cstc2021 ycjh-bgzxm0275)the Joint Medical Research Projects of Chongqing Municipal Health Committee and Chongqing Municipal Science and Technology Bureau(No.2020FYYX066)Chongqing Medical Scientific Research Project(Joint project of Chongqing Health Commission and Science and Technology Bureau)(No.2020FYYX118)
文摘To the Editor:Previous studies have demonstrated the efficacy of bictegravir(B),emtricitabine(F),and tenofovir alafenamide(TAF)in achieving virological suppression in human immunodeficiency virus(HIV)-infected patients.Virological suppression can be influenced by various factors,with baseline HIV-1 RNA being a critical consideration.Guidelines often use a baseline HIV RNA level of>500,000 copies/mL as the primary reference indicator for drug selection.[1]However,previous studies on the effectiveness of B/F/TAF have not specifically analyzed patients with baseline HIV RNA>500,000 copies/mL.In Chongqing,China,where the prevalence of advanced HIV among hospitalized patients living with HIV exceeds 70%,[2]up to 25%of patients have baseline HIV-1 RNA>500,000 copies/mL in our study,and many patients have opportunistic infections.In such a complex medical setting,the virological suppression rates of patients using B/F/TAF remain uncertain.
基金supported by The National Natural Science Foundation of China (Grants 82070888,82100917,82070882,82273116,and 82203661)National Key R&D Program of China (Grant 2018YFA0800403)+5 种基金Guangdong Special Support Program for Young Top Scientist (Grant 201629046)Guangdong Natural Science Fund (Grant 2021A1515010434,2022A1515012423,2022A1515012513 and 2023A1515010316)Key Sci-Tech Research Project of Guangzhou Municipality (202201010820)China Postdoctoral Science Foundation (Grant 2021M703679)Guangzhou Key Laboratory for Metabolic Diseases (202102100004)2019 Milstein Medical Asian American Partnership Foundation Research Project Award in Translational Medicine.
文摘Non-alcoholic fatty liver disease(NAFLD)is the most common chronic liver disease worldwide,and the development of nonalcoholic steatohepatitis(NASH)might cause irreversible hepatic damage.Hyperlipidemia(HLP)is the leading risk factor for NAFLD.This study aims to illuminate the causative contributor and potential mechanism of Kallistatin(KAL)mediating HLP to NAFLD.221 healthy control and 253 HLP subjects,62 healthy control and 44 NAFLD subjects were enrolled.The plasma KAL was significantly elevated in HLP subjects,especially in hypertriglyceridemia(HTG)subjects,and positively correlated with liver injury.Further,KAL levels of NAFLD patients were significantly up-regulated.KAL transgenic mice induced hepatic steatosis,inflammation,and fibrosis with time and accelerated inflammation development in high-fat diet(HFD)mice.In contrast,KAL knockout ameliorated steatosis and inflammation in high-fructose diet(HFruD)and methionine and choline-deficient(MCD)diet-induced NAFLD rats.Mechanistically,KAL induced hepatic steatosis and NASH by down-regulating adipose triglyceride lipase(ATGL)and comparative gene identification 58(CGl-58)by LRP6/Gas/PKA/GSK3βpathway through down-regulating peroxisome proliferator-activated receptor(PPARy)and up-regulating kruppel-like factor four(KLF4),respectively.CGl-58 is bound to NF-kB p65 in the cytoplasm,and diminishing CGl-58 facilitated p65 nuclear translocation and TNFa induction.Meanwhile,hepatic CGl-58-overexpress reverses NASH in KAL transgenic mice.Further,free fatty acids up-regulated KAL against thyroid hormone in hepatocytes.Moreover,Fenofibrate,one triglyceride-lowering drug,could reverse hepatic steatosis by down-regulating KAL.These results demonstrate that elevated KAL plays a crucial role in the development of HLP to NAFLD and may be served as a potential preventive and therapeutic target.