In modern terminology,“organoids”refer to cells that grow in a specific three-dimensional(3D)environment in vitro,sharing similar structures with their source organs or tissues.Observing themorphology or growth char...In modern terminology,“organoids”refer to cells that grow in a specific three-dimensional(3D)environment in vitro,sharing similar structures with their source organs or tissues.Observing themorphology or growth characteristics of organoids through a microscope is a commonly used method of organoid analysis.However,it is difficult,time-consuming,and inaccurate to screen and analyze organoids only manually,a problem which cannot be easily solved with traditional technology.Artificial intelligence(AI)technology has proven to be effective in many biological and medical research fields,especially in the analysis of single-cell or hematoxylin/eosin stained tissue slices.When used to analyze organoids,AI should also provide more efficient,quantitative,accurate,and fast solutions.In this review,we will first briefly outline the application areas of organoids and then discuss the shortcomings of traditional organoid measurement and analysis methods.Secondly,we will summarize the development from machine learning to deep learning and the advantages of the latter,and then describe how to utilize a convolutional neural network to solve the challenges in organoid observation and analysis.Finally,we will discuss the limitations of current AI used in organoid research,as well as opportunities and future research directions.展开更多
BACKGROUND Chronic hepatitis B virus(HBV)infection is often associated with increased lipid deposition in hepatocytes.However,when combined with non-alcoholic fatty liver disease or hyperlipidemia,it tends to have a l...BACKGROUND Chronic hepatitis B virus(HBV)infection is often associated with increased lipid deposition in hepatocytes.However,when combined with non-alcoholic fatty liver disease or hyperlipidemia,it tends to have a lower HBV deoxyribonucleic acid(DNA)load.The relationship between lipid metabolism and HBV DNA replication and its underlying mechanisms are not well understood.AIM To investigate the relationship between lipid metabolism and HBV DNA replication and its underlying mechanisms.METHODS 1603 HBsAg-seropositive patients were included in the study.We first explored the relationship between patients'lipid levels,hepatic steatosis,and HBV DNA load.Also,we constructed an HBV infection combined with a hepatic steatosis cell model in vitro by fatty acid stimulation of HepG2.2.15 cells to validate the effect of lipid metabolism on HBV DNA replication in vitro.By knocking down and overexpressing Plin2,we observed whether Plin2 regulates autophagy and HBV replication.By inhibiting both Plin2 and cellular autophagy under high lipid stimulation,we examined whether the Plin2-autophagy pathway regulates HBV replication.RESULTS The results revealed that serum triglyceride levels,high-density lipoprotein levels,and hepatic steatosis ratio were significantly lower in the HBV-DNA high load group.Logistic regression analysis indicated that hepatic steatosis and serum triglyceride levels were negatively correlated with HBV-DNA load.Stratified analysis by HBeAg showed significant negative correlations between HBV-DNA load and hepatic steatosis ratio in both HBeAgpositive and HBeAg-negative groups.An in vitro cell model was developed by stimulating HepG2.2.15 cells with palmitic acid and oleic acid to study the relationship between HBV-DNA load and lipid metabolism.The results of the in vitro experiments suggested that fatty acid treatment increased lipid droplet deposition and decreased the expression of cell supernatant HBsAg,HBeAg,and HBV DNA load.Western blot and polymerase chain reaction analysis showed that fatty acid stimulation significantly induced Plin2 protein expression and inhibited the expression of hepatocyte autophagy proteins.Inhibition of Plin2 protein expression under fatty acid stimulation reversed the reduction in HBsAg and HBeAg expression and HBV DNA load induced by fatty acid stimulation and the inhibition of cellular autophagy.Knocking down Plin2 and blocking autophagy with 3-methyladenine(3-MA)inhibited HBV DNA replication.CONCLUSION In conclusion,lipid metabolism is a significant factor affecting HBV load in patients with HBV infection.The in vitro experiments established that fatty acid stimulation inhibits HBV replication via the Plin2-autophagy pathway.展开更多
BACKGROUND Non-alcoholic fatty liver disease has become the most common chronic liver disease worldwide,which originates from the accumulation of triglyceride(TG)in the liver.Patients with type 2 diabetes mellitus(T2D...BACKGROUND Non-alcoholic fatty liver disease has become the most common chronic liver disease worldwide,which originates from the accumulation of triglyceride(TG)in the liver.Patients with type 2 diabetes mellitus(T2DM)are considered to have a predisposition to hepatic steatosis.However,the influencing factors for hepatic fat accumulation in T2DM patients remain unclear.AIM To investigate the influencing factors for hepatic fat accumulation in T2DM patients.METHODS We enrolled 329 T2DM patients admitted to the Endocrinology Department of the First Affiliated Hospital of Soochow University,who underwent MR mDIXONQuant examination to quantify the hepatic fat fraction(HFF).According to body mass index(BMI),the patients were divided into normal weight,overweight,and obese groups.The differences in general statistics,biochemical parameters,islet function,and HFF were compared among the three groups.The associations between HFF and other parameters and the influences of various parameters on the severity of hepatic fat accumulation were analyzed.RESULTS The HFF of T2DM patients gradually increased in the normal weight,overweight,and obese groups(P<0.05).Spearman correlation analysis showed that in T2DM patients,HFF was negatively correlated with age and high-density lipoprotein cholesterol(P<0.05),whereas it was positively correlated with BMI,waist-hip ratio,fasting plasma glucose,alanine aminotransferase(ALT),aspartate aminotransferase,bilirubin,glutamyl transpeptidase,lactate dehydrogenase,albumin(ALB),uric acid(UA),total cholesterol,TG,low-density lipoprotein cholesterol(LDL-C),C-reactive protein,free triiodothyronine,fasting insulin,fasting C-peptide,and homeostasis model assessment of insulin resistance(P<0.05).Multiple linear regression analysis showed significant positive influences of BMI,ALT,LDL-C,UA,and ALB on HFF in T2DM patients(P<0.05).Binary logistic regression analysis showed that BMI,ALT,ALB,and LDL-C were independent risk factors for moderate to severe fatty liver in T2DM patients,and obesity increased the risk of being complicated with moderate to severe fatty liver by 4.03 times(P<0.05).CONCLUSION The HFF of T2DM patients increases with BMI.Higher BMI,ALT,ALB,and LDLC are independent risk factors for moderate to severe fatty liver in T2DM patients.展开更多
BACKGROUND The elevation of plasma von Willebrand factor(vWF)has been proposed to be a predictor of lung cancer.Type 2 diabetes mellitus(T2DM)causes endothelial activation,resulting in the secretion of vWF.However,the...BACKGROUND The elevation of plasma von Willebrand factor(vWF)has been proposed to be a predictor of lung cancer.Type 2 diabetes mellitus(T2DM)causes endothelial activation,resulting in the secretion of vWF.However,the role of vWF in patients with T2DM complicated with lung cancer remains unclear.AIM To investigate the clinical value of serum vWF as a tumor marker in patients with T2DM combined with lung adenocarcinoma in situ(AIS).METHODS This study enrolled 43 patients with T2DM combined with lung AIS(T2DM+AIS group),43 patients with T2DM alone(T2DM group),43 patients with lung AIS alone(AIS group),and 43 healthy volunteers(control group).The serum levels of vWF,insulin-like growth factor 1,and insulin-like growth factor binding protein 3 were determined.Multiple linear stepwise regression was performed to determine the correlations among variables.RESULTS Serum concentration of vWF in the T2DM+AIS group was significantly higher than those in the T2DM,AIS,and control groups(P<0.05).Serum vWF levels in the T2DM and AIS groups were significantly higher than that in the control group(P<0.05).There was no significant difference in serum vWF level between the T2DM and AIS groups.In the T2DM+AIS group,serum vWF was independently associated and positively correlated with serum levels of insulinlike growth factor 1 and insulin-like growth factor binding protein 3(P<0.05).CONCLUSION Serum vWF level may represent a novel biomarker for the early diagnosis of lung AIS.展开更多
In China, the health risk from overexposure to particles is becoming an important public health concern. To investigate daily exposure characteristics to PM 2.5 with high ambient concentration in urban area, a persona...In China, the health risk from overexposure to particles is becoming an important public health concern. To investigate daily exposure characteristics to PM 2.5 with high ambient concentration in urban area, a personal exposure study was conducted for school children, and office workers in Beijing, China. For all participants (N = 114), the mean personal 24-hr exposure concentration was 102.5, 14.7, 0.093, 0.528, 0.934, 0.174 and 0.703 μg/m 3 for PM 2.5 , black carbon, Mn, Al, Ca, Pb, and Fe. Children's exposure concentrations of PM 2.5 were 4-5 times higher than those in related studies. The ambient concentration of PM 2.5 (128.5 μg/m 3 ) was significantly higher than the personal exposure concentration (P < 0.05), and exceed the reference concentration (25 μg/m 3 ) of WHO air quality guideline. Good correlation relationships and significant differences were identified between ambient concentration and personal exposure concentration. The relationships indicate that the ambient concentration is the main factor influencing personal exposure concentration, but is not a good indicator of personal exposure concentration. Outdoor activities (commute mode, exposure to heating, workday or weekend travel) influenced personal exposure concentrations significantly, but the magnitude of the influence from indoor activities (exposure to cooking) was masked by the high ambient concentrations.展开更多
Minichromosome Maintenance protein 10(MCM10)is essential for DNA replication initiation and DNA elongation in yeasts and animals.Although the functions of MCM10 in DNA replication and repair have been well documented,...Minichromosome Maintenance protein 10(MCM10)is essential for DNA replication initiation and DNA elongation in yeasts and animals.Although the functions of MCM10 in DNA replication and repair have been well documented,the detailed mechanisms for MCM10 in these processes are not well known.Here,we identified AtMCM10 gene through a forward genetic screening for releasing a silenced marker gene.Although plant MCM10 possesses a similar crystal structure as animal MCM10,AtMCM10 is not essential for plant growth or development in Arabidopsis.AtMCM10 can directly bind to histone H3-H4 and promotes nucleosome assembly in vitro.The nucleosome density is decreased in Atmcm10,and most of the nucleosome density decreased regions in Atmcm10 are also regulated by newly synthesized histone chaperone Chromatin Assembly Factor-1(CAF-1).Loss of both AtMCM10 and CAF-1 is embryo lethal,indicating that AtM CM10 and CAF-1 are indispensable for replication-coupled nucleosome assembly.AtMCM10 interacts with both new and parental histones.Atmcm10 mutants have lower H3.1abundance and reduced H3K27me1/3 levels with releasing some silenced transposons.We propose that AtM CM10 deposits new and parental histones during nucleosome assembly,maintaining proper epigenetic modifications and genome stability during DNA replication.展开更多
VerticiUium wilt disease becomes a major threat to many economically important crops.It is unclear whether and how plant immunity takes place during cotton-Verticillium interaction due to the lack of marker genes.Taki...VerticiUium wilt disease becomes a major threat to many economically important crops.It is unclear whether and how plant immunity takes place during cotton-Verticillium interaction due to the lack of marker genes.Taking advantage of cotton(Gossypium hirsutum) genome,we discovered pathogenesis-related(PR) gene families,which have been widely used as markers of immune responses in plants.To profile the expression of G.hirsutum PR genes in the process of plant immunity,we treated cotton roots with two immunogenic peptides,flg22 and nlp20 known as pathogen-associated molecular patterns,as well as three VerticiUium dahliae-derived peptides,nlp20^(Vd2),nlp23^(Vd3),and nlp23^(Vd4) which are highly identical to nlp20.Quantitative real-time PCR results revealed that 14 G hirsutum PR gene(GhPR) families were induced or suppressed independently in response to flg22,nlp20,nlp20^(Vd2),nlp23^(Vd3),and nlp23^(Vd4).Most GhPR genes are expressed highest at 3 h post incubation of immunogenic peptides.Compared to flg22 and nlp20,nlp20^(Vd2) is more effective to trigger up-regulated expression of GhPR genes.Notably,both nlp23^(Vd3) and nlp23^(Vd4) are able to induce GhPR gene up-regulation,although they do not induce necrosis on cotton leaves.Thus,our results provide marker genes and new immunogenic peptides for further investigation of cotton-V.dahliae interaction.展开更多
RNA-directed DNA methylation(Rd DM) is a plant-specific de novo DNA methylation pathway,which has extensive cross-talk with histone modifications. Here, we report that the maize RdDM regulator SAWADEE HOMEODOMAIN HOMO...RNA-directed DNA methylation(Rd DM) is a plant-specific de novo DNA methylation pathway,which has extensive cross-talk with histone modifications. Here, we report that the maize RdDM regulator SAWADEE HOMEODOMAIN HOMOLOG 2(SHH2) is an H3 K9 me1 reader. Our structural studies reveal that H3 K9 me1 recognition is achieved by recognition of the methyl group via a classic aromatic cage and hydrogen-bonding and salt-bridge interactions with the free protons of the mono-methyllysine. The di-and tri-methylation states disrupt the polar interactions, decreasing the binding affinity. Our study reveals a monomethyllysine recognition mechanism which potentially links RdDM to H3 K9 me1 in maize.展开更多
The(2 + 1)-dimensional Ito equation is extended to a general form including some nonintegrable effects via introducing generalized bilinear operators. It is pointed out that the nonintegrable(2 + 1)-dimensional Ito eq...The(2 + 1)-dimensional Ito equation is extended to a general form including some nonintegrable effects via introducing generalized bilinear operators. It is pointed out that the nonintegrable(2 + 1)-dimensional Ito equation contains lump solutions and interaction solutions between lump and stripe solitons. The result shows that the lump soliton will be swallowed or arisen by a stripe soliton in a fixed time. Furthermore, by the interaction between a lump and a paired resonant stripe soliton, the lump will be transformed to an instanton or a rogue wave.展开更多
DNA methylation,a conserved epigenetic mark,is critical for tuning temporal and spatial gene expression.The Arabidopsis thaliana DNA glycosylase/lyase REPRESSOR OF SILENCING 1(ROS1)initiates active DNA demethylation a...DNA methylation,a conserved epigenetic mark,is critical for tuning temporal and spatial gene expression.The Arabidopsis thaliana DNA glycosylase/lyase REPRESSOR OF SILENCING 1(ROS1)initiates active DNA demethylation and is required to prevent DNA hypermethylation at thousands of genomic loci.However,how ROS1 is recruited to specific loci is not well understood.Here,we report the discovery of Arabidopsis AGENET Domain Containing Protein 3(AGDP3)as a cellular factor that is required to prevent gene silencing and DNA hypermethylation.AGDP3 binds to H3K9me2 marks in its target DNA via its AGD12 cassette.Analysis of the crystal structure of the AGD12 cassette of AGDP3 in complex with an H3K9me2 peptide revealed that dimethylated H3 K9 and unmodified H3 K4 are specifically anchored into two different surface pockets.A histidine residue located in the methyllysine binding aromatic cage provides AGDP3 with pH-dependent H3K9me2 binding capacity.Our results uncover a molecular mechanism for the regulation of DNA demethylation by the gene silencing mark H3K9me2.展开更多
Conservation management practices e including agroforestry,cover cropping,no-till,reduced tillage,and residue return e have been applied for decades to control surface runoff and soil erosion,yet results have not been...Conservation management practices e including agroforestry,cover cropping,no-till,reduced tillage,and residue return e have been applied for decades to control surface runoff and soil erosion,yet results have not been integrated and evaluated across cropping systems.In this study we collected data comparing agricultural production with and without conservation management strategies.We used a bootstrap resampling analysis to explore interactions between practice type,soil texture,surface runoff,and soil erosion.We then used a correlation analysis to relate changes in surface runoff and soil erosion to 13 other soil health and agronomic indicators,including soil organic carbon,soil aggregation,infil-tration,porosity,subsurface leaching,and cash crop yield.Across all conservation management practices,surface runoff and erosion had respective mean decreases of 67%and 80%compared with controls.Use of cover cropping provided the largest decreases in erosion and surface runoff,thus emphasizing the importance of maintaining continuous vegetative cover on soils.Coarse-and medium-textured soils had greater decreases in both erosion and runoff than fine-textured soils.Changes in surface runoff and soil erosion under conservation management were highly correlated with soil organic carbon,aggregation,porosity,infiltration,leaching,and yield,showing that conservation practices help drive important in-teractions between these different facets of soil health.This study offers the first large-scale comparison of how different conservation agriculture practices reduce surface runoff and soil erosion,and at the same time provides new insight into how these interactions influence the improvement or loss of soil health。展开更多
Phosphatidylinositol 3-kinase(PI3K)is a crucial cell survival pathway implicated in tumorigenesis because of its role in stimulating cell proliferation and suppressing apoptosis.This study was to investigate the regul...Phosphatidylinositol 3-kinase(PI3K)is a crucial cell survival pathway implicated in tumorigenesis because of its role in stimulating cell proliferation and suppressing apoptosis.This study was to investigate the regulation of proliferation and apoptosis by LY294002,an inhibitor of PI3K in cervical cancer cells and the expression of FLICE-like inhibitory protein(c-FLIP)in vitro.Human cervical cancer HeLa cells were used in this experiment and cultured.The cultured cells were treated with LY294002 at different concentrations(10,25,50 and 100µmol/L)for 6,12,24,and 48 h before harvesting for evaluation.Cell viability was measured by 3-(4,5)-dimethylthiazol(-2-y1)-3,5-di-phenyltetrazoliumbromide(MTT)assay.Apoptosis was analyzed byflow cytometry.The expression of c-FLIP was detected by Western blot.Cell viability was inhibited by LY294002 significantly(P<0.05).Flow cytometry analysis revealed that cell apoptosis was significantly increased in the presence of LY294002 as compared with the control group.Although the expression of c-FLIP was increased in a short time,the expression of c-FLIP was markedly suppressed after the treatment of LY294002 for 48 h.These results suggested that the PI3K/Akt signal pathway might be involved in the regulation of cell apoptosis in cervical cancer cells.Moreover,the regulation of c-FLIP expression through PI3K/Akt signal pathway in cervical cancer cells was observed in vitro.展开更多
infection model for studying inflammation and the innate immune response.We investigated the genes and signaling pathways activated by static immersion and caudal vein microinjection infection using transcriptome prof...infection model for studying inflammation and the innate immune response.We investigated the genes and signaling pathways activated by static immersion and caudal vein microinjection infection using transcriptome profiling and reverse-transcription quantitative PCR(RT-qPCR)to compare the innate immune response in 3 days post-fertilization(dpf)zebrafish larvae infected by Vibrio parahaemolyticus Vp13 strain.The median lethal dose(LD50)values at 96 h following immersion and microinjection were 3.63×107 CFU/mL and 5.76×102 CFU/nL,respectively.An innate immune response was initiated after 2 h of incubation with the respective LD50 for each infection method.Six hundred and two genes in the immersion group and 359 genes in the microinjection group were activated and differentially expressed post-infection.Sixty-three Gene Ontology(GO)terms and four Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were significantly enriched in the immersion group,compared with only three GO terms and no KEGG pathways in the microinjection group.Two genes,tnfb and ccl20a.3,were significantly up-regulated in both groups.We speculated that immersion infection may affect initial dorsal determination,cytochromes,and fatty acid-binding proteins,as well as inflammation,while microinjection infection may mainly directly affect the immune response.Infection with doses>LD50(1.09×109 CFU/mL and 1.09×103 CFU/nL by immersion and microinjection,respectively)caused more significant up-regulation of il11a,tnfa,tnfb,il1b,ccl34a.4,ccl20a.3,irak3,cxcl18b,and ccl35.1,suggesting that in addition to the classical innate immunity genes tnfa,tnfb,il1b,and il6,the genes il11a,ccl34a.4,ccl20a.3,cxcl18b,and ccl35.1 were also important for defending against Vp13 infection.These findings highlight the genes involved in the responses of zebrafish to Vp13 infection via different routes and doses,and thus provide the basis for further analyses of immune response signaling pathways.展开更多
基金the National Key R&D Program of China(No.2017YFA0700500)the National Natural Science Foundation of China(No.62172202)+1 种基金the Experiment Project of ChinaManned Space Program(No.HYZHXM01019)the Fundamental Research Funds for the Central Universities from Southeast University(No.3207032101C3).
文摘In modern terminology,“organoids”refer to cells that grow in a specific three-dimensional(3D)environment in vitro,sharing similar structures with their source organs or tissues.Observing themorphology or growth characteristics of organoids through a microscope is a commonly used method of organoid analysis.However,it is difficult,time-consuming,and inaccurate to screen and analyze organoids only manually,a problem which cannot be easily solved with traditional technology.Artificial intelligence(AI)technology has proven to be effective in many biological and medical research fields,especially in the analysis of single-cell or hematoxylin/eosin stained tissue slices.When used to analyze organoids,AI should also provide more efficient,quantitative,accurate,and fast solutions.In this review,we will first briefly outline the application areas of organoids and then discuss the shortcomings of traditional organoid measurement and analysis methods.Secondly,we will summarize the development from machine learning to deep learning and the advantages of the latter,and then describe how to utilize a convolutional neural network to solve the challenges in organoid observation and analysis.Finally,we will discuss the limitations of current AI used in organoid research,as well as opportunities and future research directions.
文摘BACKGROUND Chronic hepatitis B virus(HBV)infection is often associated with increased lipid deposition in hepatocytes.However,when combined with non-alcoholic fatty liver disease or hyperlipidemia,it tends to have a lower HBV deoxyribonucleic acid(DNA)load.The relationship between lipid metabolism and HBV DNA replication and its underlying mechanisms are not well understood.AIM To investigate the relationship between lipid metabolism and HBV DNA replication and its underlying mechanisms.METHODS 1603 HBsAg-seropositive patients were included in the study.We first explored the relationship between patients'lipid levels,hepatic steatosis,and HBV DNA load.Also,we constructed an HBV infection combined with a hepatic steatosis cell model in vitro by fatty acid stimulation of HepG2.2.15 cells to validate the effect of lipid metabolism on HBV DNA replication in vitro.By knocking down and overexpressing Plin2,we observed whether Plin2 regulates autophagy and HBV replication.By inhibiting both Plin2 and cellular autophagy under high lipid stimulation,we examined whether the Plin2-autophagy pathway regulates HBV replication.RESULTS The results revealed that serum triglyceride levels,high-density lipoprotein levels,and hepatic steatosis ratio were significantly lower in the HBV-DNA high load group.Logistic regression analysis indicated that hepatic steatosis and serum triglyceride levels were negatively correlated with HBV-DNA load.Stratified analysis by HBeAg showed significant negative correlations between HBV-DNA load and hepatic steatosis ratio in both HBeAgpositive and HBeAg-negative groups.An in vitro cell model was developed by stimulating HepG2.2.15 cells with palmitic acid and oleic acid to study the relationship between HBV-DNA load and lipid metabolism.The results of the in vitro experiments suggested that fatty acid treatment increased lipid droplet deposition and decreased the expression of cell supernatant HBsAg,HBeAg,and HBV DNA load.Western blot and polymerase chain reaction analysis showed that fatty acid stimulation significantly induced Plin2 protein expression and inhibited the expression of hepatocyte autophagy proteins.Inhibition of Plin2 protein expression under fatty acid stimulation reversed the reduction in HBsAg and HBeAg expression and HBV DNA load induced by fatty acid stimulation and the inhibition of cellular autophagy.Knocking down Plin2 and blocking autophagy with 3-methyladenine(3-MA)inhibited HBV DNA replication.CONCLUSION In conclusion,lipid metabolism is a significant factor affecting HBV load in patients with HBV infection.The in vitro experiments established that fatty acid stimulation inhibits HBV replication via the Plin2-autophagy pathway.
基金Suzhou Health Committee and Science and Technology Bureau,No.KJXW2019005.
文摘BACKGROUND Non-alcoholic fatty liver disease has become the most common chronic liver disease worldwide,which originates from the accumulation of triglyceride(TG)in the liver.Patients with type 2 diabetes mellitus(T2DM)are considered to have a predisposition to hepatic steatosis.However,the influencing factors for hepatic fat accumulation in T2DM patients remain unclear.AIM To investigate the influencing factors for hepatic fat accumulation in T2DM patients.METHODS We enrolled 329 T2DM patients admitted to the Endocrinology Department of the First Affiliated Hospital of Soochow University,who underwent MR mDIXONQuant examination to quantify the hepatic fat fraction(HFF).According to body mass index(BMI),the patients were divided into normal weight,overweight,and obese groups.The differences in general statistics,biochemical parameters,islet function,and HFF were compared among the three groups.The associations between HFF and other parameters and the influences of various parameters on the severity of hepatic fat accumulation were analyzed.RESULTS The HFF of T2DM patients gradually increased in the normal weight,overweight,and obese groups(P<0.05).Spearman correlation analysis showed that in T2DM patients,HFF was negatively correlated with age and high-density lipoprotein cholesterol(P<0.05),whereas it was positively correlated with BMI,waist-hip ratio,fasting plasma glucose,alanine aminotransferase(ALT),aspartate aminotransferase,bilirubin,glutamyl transpeptidase,lactate dehydrogenase,albumin(ALB),uric acid(UA),total cholesterol,TG,low-density lipoprotein cholesterol(LDL-C),C-reactive protein,free triiodothyronine,fasting insulin,fasting C-peptide,and homeostasis model assessment of insulin resistance(P<0.05).Multiple linear regression analysis showed significant positive influences of BMI,ALT,LDL-C,UA,and ALB on HFF in T2DM patients(P<0.05).Binary logistic regression analysis showed that BMI,ALT,ALB,and LDL-C were independent risk factors for moderate to severe fatty liver in T2DM patients,and obesity increased the risk of being complicated with moderate to severe fatty liver by 4.03 times(P<0.05).CONCLUSION The HFF of T2DM patients increases with BMI.Higher BMI,ALT,ALB,and LDLC are independent risk factors for moderate to severe fatty liver in T2DM patients.
文摘BACKGROUND The elevation of plasma von Willebrand factor(vWF)has been proposed to be a predictor of lung cancer.Type 2 diabetes mellitus(T2DM)causes endothelial activation,resulting in the secretion of vWF.However,the role of vWF in patients with T2DM complicated with lung cancer remains unclear.AIM To investigate the clinical value of serum vWF as a tumor marker in patients with T2DM combined with lung adenocarcinoma in situ(AIS).METHODS This study enrolled 43 patients with T2DM combined with lung AIS(T2DM+AIS group),43 patients with T2DM alone(T2DM group),43 patients with lung AIS alone(AIS group),and 43 healthy volunteers(control group).The serum levels of vWF,insulin-like growth factor 1,and insulin-like growth factor binding protein 3 were determined.Multiple linear stepwise regression was performed to determine the correlations among variables.RESULTS Serum concentration of vWF in the T2DM+AIS group was significantly higher than those in the T2DM,AIS,and control groups(P<0.05).Serum vWF levels in the T2DM and AIS groups were significantly higher than that in the control group(P<0.05).There was no significant difference in serum vWF level between the T2DM and AIS groups.In the T2DM+AIS group,serum vWF was independently associated and positively correlated with serum levels of insulinlike growth factor 1 and insulin-like growth factor binding protein 3(P<0.05).CONCLUSION Serum vWF level may represent a novel biomarker for the early diagnosis of lung AIS.
基金supported by the National Natural Science Foundation of China(No.50778100) funded in part by Afton Chemical Corporation
文摘In China, the health risk from overexposure to particles is becoming an important public health concern. To investigate daily exposure characteristics to PM 2.5 with high ambient concentration in urban area, a personal exposure study was conducted for school children, and office workers in Beijing, China. For all participants (N = 114), the mean personal 24-hr exposure concentration was 102.5, 14.7, 0.093, 0.528, 0.934, 0.174 and 0.703 μg/m 3 for PM 2.5 , black carbon, Mn, Al, Ca, Pb, and Fe. Children's exposure concentrations of PM 2.5 were 4-5 times higher than those in related studies. The ambient concentration of PM 2.5 (128.5 μg/m 3 ) was significantly higher than the personal exposure concentration (P < 0.05), and exceed the reference concentration (25 μg/m 3 ) of WHO air quality guideline. Good correlation relationships and significant differences were identified between ambient concentration and personal exposure concentration. The relationships indicate that the ambient concentration is the main factor influencing personal exposure concentration, but is not a good indicator of personal exposure concentration. Outdoor activities (commute mode, exposure to heating, workday or weekend travel) influenced personal exposure concentrations significantly, but the magnitude of the influence from indoor activities (exposure to cooking) was masked by the high ambient concentrations.
基金supported by National Natural Science Foundation of China (31921001)。
文摘Minichromosome Maintenance protein 10(MCM10)is essential for DNA replication initiation and DNA elongation in yeasts and animals.Although the functions of MCM10 in DNA replication and repair have been well documented,the detailed mechanisms for MCM10 in these processes are not well known.Here,we identified AtMCM10 gene through a forward genetic screening for releasing a silenced marker gene.Although plant MCM10 possesses a similar crystal structure as animal MCM10,AtMCM10 is not essential for plant growth or development in Arabidopsis.AtMCM10 can directly bind to histone H3-H4 and promotes nucleosome assembly in vitro.The nucleosome density is decreased in Atmcm10,and most of the nucleosome density decreased regions in Atmcm10 are also regulated by newly synthesized histone chaperone Chromatin Assembly Factor-1(CAF-1).Loss of both AtMCM10 and CAF-1 is embryo lethal,indicating that AtM CM10 and CAF-1 are indispensable for replication-coupled nucleosome assembly.AtMCM10 interacts with both new and parental histones.Atmcm10 mutants have lower H3.1abundance and reduced H3K27me1/3 levels with releasing some silenced transposons.We propose that AtM CM10 deposits new and parental histones during nucleosome assembly,maintaining proper epigenetic modifications and genome stability during DNA replication.
基金supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB11040500) to Hui-Shan GuoNational Natural Science Foundation(31500119) to Chenlei HuaNational Natural Science Foundation(31600124) to Jian-Hua Zhao
文摘VerticiUium wilt disease becomes a major threat to many economically important crops.It is unclear whether and how plant immunity takes place during cotton-Verticillium interaction due to the lack of marker genes.Taking advantage of cotton(Gossypium hirsutum) genome,we discovered pathogenesis-related(PR) gene families,which have been widely used as markers of immune responses in plants.To profile the expression of G.hirsutum PR genes in the process of plant immunity,we treated cotton roots with two immunogenic peptides,flg22 and nlp20 known as pathogen-associated molecular patterns,as well as three VerticiUium dahliae-derived peptides,nlp20^(Vd2),nlp23^(Vd3),and nlp23^(Vd4) which are highly identical to nlp20.Quantitative real-time PCR results revealed that 14 G hirsutum PR gene(GhPR) families were induced or suppressed independently in response to flg22,nlp20,nlp20^(Vd2),nlp23^(Vd3),and nlp23^(Vd4).Most GhPR genes are expressed highest at 3 h post incubation of immunogenic peptides.Compared to flg22 and nlp20,nlp20^(Vd2) is more effective to trigger up-regulated expression of GhPR genes.Notably,both nlp23^(Vd3) and nlp23^(Vd4) are able to induce GhPR gene up-regulation,although they do not induce necrosis on cotton leaves.Thus,our results provide marker genes and new immunogenic peptides for further investigation of cotton-V.dahliae interaction.
基金supported by National Natural Science Foundation of China(31770782)the Ministry of Science and Technology of China(2016YFA0503200)+1 种基金the Shenzhen Science and Technology Program(JCYJ20200109110403829 and KQTD20190929173906742)Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes(2019KSYS006)to J.D.
文摘RNA-directed DNA methylation(Rd DM) is a plant-specific de novo DNA methylation pathway,which has extensive cross-talk with histone modifications. Here, we report that the maize RdDM regulator SAWADEE HOMEODOMAIN HOMOLOG 2(SHH2) is an H3 K9 me1 reader. Our structural studies reveal that H3 K9 me1 recognition is achieved by recognition of the methyl group via a classic aromatic cage and hydrogen-bonding and salt-bridge interactions with the free protons of the mono-methyllysine. The di-and tri-methylation states disrupt the polar interactions, decreasing the binding affinity. Our study reveals a monomethyllysine recognition mechanism which potentially links RdDM to H3 K9 me1 in maize.
基金Supported by the National Natural Science Foundation of China under Grant No.1143505sponsored by K.C.Wong Magna Fund in Ningbo University
文摘The(2 + 1)-dimensional Ito equation is extended to a general form including some nonintegrable effects via introducing generalized bilinear operators. It is pointed out that the nonintegrable(2 + 1)-dimensional Ito equation contains lump solutions and interaction solutions between lump and stripe solitons. The result shows that the lump soliton will be swallowed or arisen by a stripe soliton in a fixed time. Furthermore, by the interaction between a lump and a paired resonant stripe soliton, the lump will be transformed to an instanton or a rogue wave.
基金the Chinese Academy of Sciences and the National Natural Science Foundation of China(31970580)to M.L.the National Key R&D Program(2016YFA0503200)+1 种基金Shenzhen Science and Technology Program(JCYJ20200109110403829 and KQTD20190929173906742)Key Laboratory of Molecular Design for Plant Cell Factory of Guangdong Higher Education Institutes(2019KSYS006)to J.D.
文摘DNA methylation,a conserved epigenetic mark,is critical for tuning temporal and spatial gene expression.The Arabidopsis thaliana DNA glycosylase/lyase REPRESSOR OF SILENCING 1(ROS1)initiates active DNA demethylation and is required to prevent DNA hypermethylation at thousands of genomic loci.However,how ROS1 is recruited to specific loci is not well understood.Here,we report the discovery of Arabidopsis AGENET Domain Containing Protein 3(AGDP3)as a cellular factor that is required to prevent gene silencing and DNA hypermethylation.AGDP3 binds to H3K9me2 marks in its target DNA via its AGD12 cassette.Analysis of the crystal structure of the AGD12 cassette of AGDP3 in complex with an H3K9me2 peptide revealed that dimethylated H3 K9 and unmodified H3 K4 are specifically anchored into two different surface pockets.A histidine residue located in the methyllysine binding aromatic cage provides AGDP3 with pH-dependent H3K9me2 binding capacity.Our results uncover a molecular mechanism for the regulation of DNA demethylation by the gene silencing mark H3K9me2.
基金the conservation management and soil erosion project funded by the Yangling Vocational&Technical College,grant number:A2019009Jinshi Jian was supported by the Strategic Priority Research Program of Chinese Academy of Sci-ences,under contract number XDA20040202+3 种基金the US Depart-ment of Energy,Office of Science,Biological and Environmental Research as part of the Terrestrial Ecosystem Sciences Program,under contract DE-AC05-76RL01830Can Du was supported by the Yangling Vocational&Technical College 2019 Natural Science Research Fund Project,under grant number:A2019048Ryan Stewart was supported by the U.S.Department of Agriculture NRCS Conservation Innovation Grant(No.69-3A75-14-260)the Vir-ginia Agricultural Experiment Station and the Hatch Program of the National Institute of Food and Agriculture,U.S.Department of Agriculture.
文摘Conservation management practices e including agroforestry,cover cropping,no-till,reduced tillage,and residue return e have been applied for decades to control surface runoff and soil erosion,yet results have not been integrated and evaluated across cropping systems.In this study we collected data comparing agricultural production with and without conservation management strategies.We used a bootstrap resampling analysis to explore interactions between practice type,soil texture,surface runoff,and soil erosion.We then used a correlation analysis to relate changes in surface runoff and soil erosion to 13 other soil health and agronomic indicators,including soil organic carbon,soil aggregation,infil-tration,porosity,subsurface leaching,and cash crop yield.Across all conservation management practices,surface runoff and erosion had respective mean decreases of 67%and 80%compared with controls.Use of cover cropping provided the largest decreases in erosion and surface runoff,thus emphasizing the importance of maintaining continuous vegetative cover on soils.Coarse-and medium-textured soils had greater decreases in both erosion and runoff than fine-textured soils.Changes in surface runoff and soil erosion under conservation management were highly correlated with soil organic carbon,aggregation,porosity,infiltration,leaching,and yield,showing that conservation practices help drive important in-teractions between these different facets of soil health.This study offers the first large-scale comparison of how different conservation agriculture practices reduce surface runoff and soil erosion,and at the same time provides new insight into how these interactions influence the improvement or loss of soil health。
文摘Phosphatidylinositol 3-kinase(PI3K)is a crucial cell survival pathway implicated in tumorigenesis because of its role in stimulating cell proliferation and suppressing apoptosis.This study was to investigate the regulation of proliferation and apoptosis by LY294002,an inhibitor of PI3K in cervical cancer cells and the expression of FLICE-like inhibitory protein(c-FLIP)in vitro.Human cervical cancer HeLa cells were used in this experiment and cultured.The cultured cells were treated with LY294002 at different concentrations(10,25,50 and 100µmol/L)for 6,12,24,and 48 h before harvesting for evaluation.Cell viability was measured by 3-(4,5)-dimethylthiazol(-2-y1)-3,5-di-phenyltetrazoliumbromide(MTT)assay.Apoptosis was analyzed byflow cytometry.The expression of c-FLIP was detected by Western blot.Cell viability was inhibited by LY294002 significantly(P<0.05).Flow cytometry analysis revealed that cell apoptosis was significantly increased in the presence of LY294002 as compared with the control group.Although the expression of c-FLIP was increased in a short time,the expression of c-FLIP was markedly suppressed after the treatment of LY294002 for 48 h.These results suggested that the PI3K/Akt signal pathway might be involved in the regulation of cell apoptosis in cervical cancer cells.Moreover,the regulation of c-FLIP expression through PI3K/Akt signal pathway in cervical cancer cells was observed in vitro.
基金This work was supported by the Ministry of Education Returnees Research Fund(D-8002-15-0042)the China-US Ocean Research Center Fund(A1-3201-19-3013)the Shanghai First-Class Discipline Construction Fund.
文摘infection model for studying inflammation and the innate immune response.We investigated the genes and signaling pathways activated by static immersion and caudal vein microinjection infection using transcriptome profiling and reverse-transcription quantitative PCR(RT-qPCR)to compare the innate immune response in 3 days post-fertilization(dpf)zebrafish larvae infected by Vibrio parahaemolyticus Vp13 strain.The median lethal dose(LD50)values at 96 h following immersion and microinjection were 3.63×107 CFU/mL and 5.76×102 CFU/nL,respectively.An innate immune response was initiated after 2 h of incubation with the respective LD50 for each infection method.Six hundred and two genes in the immersion group and 359 genes in the microinjection group were activated and differentially expressed post-infection.Sixty-three Gene Ontology(GO)terms and four Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways were significantly enriched in the immersion group,compared with only three GO terms and no KEGG pathways in the microinjection group.Two genes,tnfb and ccl20a.3,were significantly up-regulated in both groups.We speculated that immersion infection may affect initial dorsal determination,cytochromes,and fatty acid-binding proteins,as well as inflammation,while microinjection infection may mainly directly affect the immune response.Infection with doses>LD50(1.09×109 CFU/mL and 1.09×103 CFU/nL by immersion and microinjection,respectively)caused more significant up-regulation of il11a,tnfa,tnfb,il1b,ccl34a.4,ccl20a.3,irak3,cxcl18b,and ccl35.1,suggesting that in addition to the classical innate immunity genes tnfa,tnfb,il1b,and il6,the genes il11a,ccl34a.4,ccl20a.3,cxcl18b,and ccl35.1 were also important for defending against Vp13 infection.These findings highlight the genes involved in the responses of zebrafish to Vp13 infection via different routes and doses,and thus provide the basis for further analyses of immune response signaling pathways.
