Dolomites and eruptive rocks are well-developed in the Permian Fengcheng Formation in Junggar Basin in China, in which oil and gas are accumulated extensively. Until now, high-yield industrial oil and gas flows have b...Dolomites and eruptive rocks are well-developed in the Permian Fengcheng Formation in Junggar Basin in China, in which oil and gas are accumulated extensively. Until now, high-yield industrial oil and gas flows have been obtained in the dolomitic tuff of the second unit of the Fengcheng Formation, which demonstrates the huge exploration potential of the thick layer of massive dolomitic tuff. The lithology of the second unit of the Fengcheng Formation in this area has gradually transformed from the dolomite, dolomitic tuff to siltstone from east to west. Moreover, the well testing shows that the reservoir is oil-saturated, and the production rate mainly depends on the reservoir’s physical properties and fracture development. In this study, different types of data including core data, well log and seismic data are used cooperatively to characterize the sedimentary, structure and fracture features of the Fengcheng Formation, and then characterize the promising target zone in the study area. The result indicates that hydrocarbons are most accumulated along the deep fault in the Wu-Xia fault zone, which will be the favorable zone for the next progressive exploration.展开更多
The mud shale of Qingshankou Formation in Songliao Basin is the main rock source and contains rich shale oil resources. The successful development of shale oil depends on evaluating and optimizing the “sweet spots”....The mud shale of Qingshankou Formation in Songliao Basin is the main rock source and contains rich shale oil resources. The successful development of shale oil depends on evaluating and optimizing the “sweet spots”. To accurately identify and optimize the favorable sweet spots of shale oil in Qingshankou Formation, Songliao Basin, the original logging data were preprocessed in this paper. Then the thin mud shale interlayer of Qingshankou Formation was identified effectively by using the processed logging data. Based on the artificial neural network method, the mineral content of mud shale in Qingshankou Formation was predicted. The lithofacies were identified according to the mineral and TOC content. Finally, a three-dimensional (3-D) model of total organic carbon (TOC), vitrinite reflectance (Ro), mineral content, and rock of Qingshankou Formation in Songliao Basin was established to evaluate and predict the favorable sweet spots of shale oil in the study area. The results show that there are a lot of calcareous and siliceous thin interlayers in Qingshankou Formation, and TOC content is generally between 2% and 3%. Ro is the highest in Gulong sag, followed by Sanzhao sag. The lithofacies mainly consists of felsic shale and mixed shale, mainly in the first member of Qingshankou Formation. Comprehensive analysis shows that shale oil development potential is enormous in the eastern part of Sanzhao Sag and the northern part of Gulong Sag.展开更多
Objective This study aimed to develop a nomogram to predict the overall survival(OS)of patients with acinar-predominant adenocarcinoma(APA).Methods Data from patients with APA obtained from the Surveillance,Epidemiolo...Objective This study aimed to develop a nomogram to predict the overall survival(OS)of patients with acinar-predominant adenocarcinoma(APA).Methods Data from patients with APA obtained from the Surveillance,Epidemiology,and End Results(SEER)database between 2008 and 2016 were used.Significant prognostic factors were incorporated to construct a nomogram for predicting the 1-,3-,and 5-year OS in these patients.The discrimination and calibration abilities of the nomogram were assessed using a C-index and calibration curves,respectively.Results A total of 2242 patients with APA were randomly divided into a training cohort(n=1576)and validation cohort(n=666).The independent prognostic factors for OS incorporated into the nomogram included marital status,age,gender,differentiation grade,T stage,N stage,and M stage.The nomogram showed good prediction capability,as indicated by the C-index[0.713,95%confidence interval(CI):0.705–0.721 in the training cohort,and 0.662,95%CI:0.649–0.775 in the validation cohort].The calibration curves demonstrated that the 1-,3-,and 5-year OS probabilities were consistent between the observed and predicted outcome frequencies.Patients were divided into the high-risk and low-risk groups with the former showing significantly worse survival than the latter(P<0.001).Conclusion Using the SEER database,a nomogram was established to predict the 1-,3-,and 5-year OS of patients with APA and was superior to the tumor size,lymph node,and metastasis staging system in terms of evaluating long-term prognosis.展开更多
AIM: To investigate the effects of (dietary) glycine against oxidant-induced injury caused by bile duct ligation (BDL).METHODS: Either a diet containing 5% glycine or a standard diet was fed to male Sprague-Dawl...AIM: To investigate the effects of (dietary) glycine against oxidant-induced injury caused by bile duct ligation (BDL).METHODS: Either a diet containing 5% glycine or a standard diet was fed to male Sprague-Dawley (SD) rats. Three days later, BDL or sham-operation was performed. Rats were sacrificed 1 to 3 d after BDL. The influence of deoxycholic acid (DCA) in the presence or absence of glycine on liver cells was determined by measurement of calcium and chloride influx in cultivated Kupffer cells and lactate dehydrogenase (LDH) activity was determined in the supernatant of cultivated hepatocytes.RESULTS: Serum alanine transaminase levels increased to about 600 U/L 1 d alter BDL. However, enzyme release was blunted by about two third in rats receiving glycine. Release of the alkaline phosphatase and aspartate aminotransferase was also blocked significantly in the group fed glycine. Focal necrosis was observed 2 d after BDL. Glycine partially blocked the histopathological changes. Incubation of Kupffer cells with DCA led to increased intracellular calcium that could be blocked by incubation with glycine. However, systemic blockage of Kupffer cells with gadolinium chloride had no effects on transaminase release. Incubation of isolated hepatocytes with DCA led to a significant release of LDH after 4 h. This release was largely blocked when incubation with glycine was performed.CONCLUSION: These data indicate that glycine significantly decreased liver injury, most likely by a direct effect on hepatocytes. Kupffer cells do not appear to play an important role in the pathological changes caused by cholestasis.展开更多
Previous studies have shown that hepatocyte-like cells can be generated from fibroblasts using either lineage-specific transcription factors or chemical induction methods.However,these methods have their own deficienc...Previous studies have shown that hepatocyte-like cells can be generated from fibroblasts using either lineage-specific transcription factors or chemical induction methods.However,these methods have their own deficiencies that restrict the therapeutic applications of such induced hepatocytes.In this study,we present a transgene-free,highly efficient chemical-induced direct reprogramming approach to generate hepatocyte-like cells from mouse embryonic fibroblasts(MEFs).Using a small molecule cocktail(SMC)as an inducer,MEFs can be directly reprogrammed into hepatocyte-like cells,bypassing the intermediate stages of pluripotent and immature hepatoblasts.These chemical-induced hepatocyte-like cells(ciHeps)closely resemble mature primary hepatocytes in terms of morphology,biological behavior,gene expression patterns,marker expression levels,and hepatic functions.Furthermore,transplanted ciHeps can integrate into the liver,promote liver regeneration,and improve survival rates in mice with acute liver damage.ciHeps can also ameliorate liver fibrosis caused by chronic injuries and enhance liver function.Notably,ciHeps exhibit no tumorigenic potential either in vitro or in vivo.Mechanistically,SMC-induced mesenchymal-to-epithelial transition and suppression of SNAI1 contribute to the fate conversion of fibroblasts into ciHeps.These results indicate that this transgene-free,chemical-induced direct reprogramming technique has the potential to serve as a valuable means of producing alternative hepatocytes for both research and therapeutic purposes.Additionally,this method also sheds light on the direct reprogramming of other cell types under chemical induction.展开更多
Mitophagy(mitochondrial autophagy)in hepatocytes is an essential quality control mechanism that removes for lysosomal digestion damaged,effete and superfluous mitochondria.Mitophagy has distinct variants.In type 1 mit...Mitophagy(mitochondrial autophagy)in hepatocytes is an essential quality control mechanism that removes for lysosomal digestion damaged,effete and superfluous mitochondria.Mitophagy has distinct variants.In type 1 mitophagy,typical of nutrient deprivation,cup-shaped sequestration membranes(phagophores)grow,surround and sequester individual mitochondria into mitophagosomes,often in coordination with mitochondrial fission.After sequestration,the outer compartment of the mitophagosome acidifies and the entrapped mitochondrion depolarizes,followed by fusion with lysosomes.By contrast,mitochondrial depolarization stimulates type 2 mitophagy,which is characterized by coalescence of autophagic microtubule-associated protein 1A/1B-light chain 3(LC3)-containing structures on mitochondrial surfaces without the formation of a phagophore or mitochondrial fission.Oppositely to type 1 mitophagy,the inhibition of phosphoinositide-3-kinase(PI3K)does not block type 2 mitophagy.In type 3 mitophagy,or micromitophagy,mitochondria-derived vesicles(MDVs)enriched in oxidized proteins bud off from mitochondrial inner and outer membranes and incorporate into multivesicular bodies by vesicle scission into the lumen.In response to ethanol feeding,widespread ethanol-induced hepatocellular mitochondrial depolarization occurs to facilitate hepatic ethanol metabolism.As a consequence,type 2 mitophagy develops in response to the mitochondrial depolarization.After chronic high ethanol feeding,processing of depolarized mitochondria by mitophagy becomes compromised,leading to release of mitochondrial damage-associated molecular patterns(mtDAMPs)that promote inflammatory and profibrogenic responses.We propose that the persistence of mitochondrial responses for acute ethanol metabolism links initial adaptive ethanol metabolism to mitophagy and then to chronic maladaptive changes initiating onset and the progression of alcoholic liver disease(ALD).展开更多
The poly(ethylene glycol) (PEG, with Mw 2000)-urea inclusion compound (IC) crystallized at high temperature region showed two typical orientations, flat-on and edge-on crystals. 2D-XRD and polarized FTIR spectro...The poly(ethylene glycol) (PEG, with Mw 2000)-urea inclusion compound (IC) crystallized at high temperature region showed two typical orientations, flat-on and edge-on crystals. 2D-XRD and polarized FTIR spectroscopy revealed that the PEG chains within urea channels were perpendicular to the substrate in fiat-on oriented crystals, while PEG chain axes were parallel to the substrate and lay along the growth direction in the edge-on crystals. FT1R absorption bands of PEG in the ICs are sensitive to orientation of the crystals. A scheme of PEG chain packing in the urea IC channel was proposed, which could explain the orientation of the crystal nucleus causing the two types of morphologies. Furthermore, functioning of PEG2000 chain end with analine had significantly influence on the morphology and orientation of the inclusion compound crystals, due to the defects caused by large terminal groups included in the urea channel.展开更多
The solid form of drugs plays a central role in optimizing the physicochemical properties of drugs,and new solid forms will provide more options to achieve the desirable pharmaceutical profiles of drugs.Recently,certa...The solid form of drugs plays a central role in optimizing the physicochemical properties of drugs,and new solid forms will provide more options to achieve the desirable pharmaceutical profiles of drugs.Recently,certain drugs have been found to form crystalline inclusion complexes(ICs) with multiple types of linear polymers,representing a new subcategory of pharmaceutical solids.In this study,we used diflunisal(DIF) as the model drug host and extended the guest of drug/polymer ICs from homopolymers to block copolymers of poly(ethylene glycol)(PEG) and poly(s-caprolactone)(PCL).The block length in the guest copolymers showed a significant influence on the formation,thermal stability and dissolution behavior of the DIF ICs.Though the PEG block could hardly be included alone,it could indeed be included in the DIF ICs when the PCL block was long enough.The increase of the PCL block length produced IC crystals with improved thermal stability.The dissolution profiles of DIF/block copolymer ICs exhibited gradually decreased aqueous solubility and dissolution rate with the increasing PCL block length.These results demonstrate the possibility of using drug/polymer ICs to modulate the desired pharmaceutical profiles of drugs in a predictable and controllable manner.展开更多
The solid forms of drugs play a central role in controlling their physicochemical properties and consequently the bioavailability. Multiple types of drug solid forms have been developed to achieve the desirable pharma...The solid forms of drugs play a central role in controlling their physicochemical properties and consequently the bioavailability. Multiple types of drug solid forms have been developed to achieve the desirable pharmaceutical profiles, but new solid forms will provide more options for the solid-state property optimization and hence are highly desirable. This review focuses on a new pharmaceutical solid form, drug-polymer inclusion complexes (ICs), and summarizes their structural features, structure- property relationships, as well as potential pharmaceutical applications展开更多
文摘Dolomites and eruptive rocks are well-developed in the Permian Fengcheng Formation in Junggar Basin in China, in which oil and gas are accumulated extensively. Until now, high-yield industrial oil and gas flows have been obtained in the dolomitic tuff of the second unit of the Fengcheng Formation, which demonstrates the huge exploration potential of the thick layer of massive dolomitic tuff. The lithology of the second unit of the Fengcheng Formation in this area has gradually transformed from the dolomite, dolomitic tuff to siltstone from east to west. Moreover, the well testing shows that the reservoir is oil-saturated, and the production rate mainly depends on the reservoir’s physical properties and fracture development. In this study, different types of data including core data, well log and seismic data are used cooperatively to characterize the sedimentary, structure and fracture features of the Fengcheng Formation, and then characterize the promising target zone in the study area. The result indicates that hydrocarbons are most accumulated along the deep fault in the Wu-Xia fault zone, which will be the favorable zone for the next progressive exploration.
文摘The mud shale of Qingshankou Formation in Songliao Basin is the main rock source and contains rich shale oil resources. The successful development of shale oil depends on evaluating and optimizing the “sweet spots”. To accurately identify and optimize the favorable sweet spots of shale oil in Qingshankou Formation, Songliao Basin, the original logging data were preprocessed in this paper. Then the thin mud shale interlayer of Qingshankou Formation was identified effectively by using the processed logging data. Based on the artificial neural network method, the mineral content of mud shale in Qingshankou Formation was predicted. The lithofacies were identified according to the mineral and TOC content. Finally, a three-dimensional (3-D) model of total organic carbon (TOC), vitrinite reflectance (Ro), mineral content, and rock of Qingshankou Formation in Songliao Basin was established to evaluate and predict the favorable sweet spots of shale oil in the study area. The results show that there are a lot of calcareous and siliceous thin interlayers in Qingshankou Formation, and TOC content is generally between 2% and 3%. Ro is the highest in Gulong sag, followed by Sanzhao sag. The lithofacies mainly consists of felsic shale and mixed shale, mainly in the first member of Qingshankou Formation. Comprehensive analysis shows that shale oil development potential is enormous in the eastern part of Sanzhao Sag and the northern part of Gulong Sag.
基金supported in part by the National Key Research and Development Program of China(No.2016YFC1303201).
文摘Objective This study aimed to develop a nomogram to predict the overall survival(OS)of patients with acinar-predominant adenocarcinoma(APA).Methods Data from patients with APA obtained from the Surveillance,Epidemiology,and End Results(SEER)database between 2008 and 2016 were used.Significant prognostic factors were incorporated to construct a nomogram for predicting the 1-,3-,and 5-year OS in these patients.The discrimination and calibration abilities of the nomogram were assessed using a C-index and calibration curves,respectively.Results A total of 2242 patients with APA were randomly divided into a training cohort(n=1576)and validation cohort(n=666).The independent prognostic factors for OS incorporated into the nomogram included marital status,age,gender,differentiation grade,T stage,N stage,and M stage.The nomogram showed good prediction capability,as indicated by the C-index[0.713,95%confidence interval(CI):0.705–0.721 in the training cohort,and 0.662,95%CI:0.649–0.775 in the validation cohort].The calibration curves demonstrated that the 1-,3-,and 5-year OS probabilities were consistent between the observed and predicted outcome frequencies.Patients were divided into the high-risk and low-risk groups with the former showing significantly worse survival than the latter(P<0.001).Conclusion Using the SEER database,a nomogram was established to predict the 1-,3-,and 5-year OS of patients with APA and was superior to the tumor size,lymph node,and metastasis staging system in terms of evaluating long-term prognosis.
基金Grants from the National Institute of Alcohol Abuse and Alcoholism (NIAAA)by a grant from the Deutsche Forschungsgemeinschaft,No.FR 1644/4-1
文摘AIM: To investigate the effects of (dietary) glycine against oxidant-induced injury caused by bile duct ligation (BDL).METHODS: Either a diet containing 5% glycine or a standard diet was fed to male Sprague-Dawley (SD) rats. Three days later, BDL or sham-operation was performed. Rats were sacrificed 1 to 3 d after BDL. The influence of deoxycholic acid (DCA) in the presence or absence of glycine on liver cells was determined by measurement of calcium and chloride influx in cultivated Kupffer cells and lactate dehydrogenase (LDH) activity was determined in the supernatant of cultivated hepatocytes.RESULTS: Serum alanine transaminase levels increased to about 600 U/L 1 d alter BDL. However, enzyme release was blunted by about two third in rats receiving glycine. Release of the alkaline phosphatase and aspartate aminotransferase was also blocked significantly in the group fed glycine. Focal necrosis was observed 2 d after BDL. Glycine partially blocked the histopathological changes. Incubation of Kupffer cells with DCA led to increased intracellular calcium that could be blocked by incubation with glycine. However, systemic blockage of Kupffer cells with gadolinium chloride had no effects on transaminase release. Incubation of isolated hepatocytes with DCA led to a significant release of LDH after 4 h. This release was largely blocked when incubation with glycine was performed.CONCLUSION: These data indicate that glycine significantly decreased liver injury, most likely by a direct effect on hepatocytes. Kupffer cells do not appear to play an important role in the pathological changes caused by cholestasis.
基金supported by the National Natural Science Foundation of China(81472772)the Natural Science Foundation of Shanghai(14ZR1408900)the Major National Science and Technology Projects(2018ZX10302207).
文摘Previous studies have shown that hepatocyte-like cells can be generated from fibroblasts using either lineage-specific transcription factors or chemical induction methods.However,these methods have their own deficiencies that restrict the therapeutic applications of such induced hepatocytes.In this study,we present a transgene-free,highly efficient chemical-induced direct reprogramming approach to generate hepatocyte-like cells from mouse embryonic fibroblasts(MEFs).Using a small molecule cocktail(SMC)as an inducer,MEFs can be directly reprogrammed into hepatocyte-like cells,bypassing the intermediate stages of pluripotent and immature hepatoblasts.These chemical-induced hepatocyte-like cells(ciHeps)closely resemble mature primary hepatocytes in terms of morphology,biological behavior,gene expression patterns,marker expression levels,and hepatic functions.Furthermore,transplanted ciHeps can integrate into the liver,promote liver regeneration,and improve survival rates in mice with acute liver damage.ciHeps can also ameliorate liver fibrosis caused by chronic injuries and enhance liver function.Notably,ciHeps exhibit no tumorigenic potential either in vitro or in vivo.Mechanistically,SMC-induced mesenchymal-to-epithelial transition and suppression of SNAI1 contribute to the fate conversion of fibroblasts into ciHeps.These results indicate that this transgene-free,chemical-induced direct reprogramming technique has the potential to serve as a valuable means of producing alternative hepatocytes for both research and therapeutic purposes.Additionally,this method also sheds light on the direct reprogramming of other cell types under chemical induction.
基金This work was supported,in part,by Grants AA025379,AA021191,AA022815,and DK073336 from the USA National Institutes of Health(NIH).Imaging facilities were supported,in part,by P30 CA138313 and 1S10OD018113.
文摘Mitophagy(mitochondrial autophagy)in hepatocytes is an essential quality control mechanism that removes for lysosomal digestion damaged,effete and superfluous mitochondria.Mitophagy has distinct variants.In type 1 mitophagy,typical of nutrient deprivation,cup-shaped sequestration membranes(phagophores)grow,surround and sequester individual mitochondria into mitophagosomes,often in coordination with mitochondrial fission.After sequestration,the outer compartment of the mitophagosome acidifies and the entrapped mitochondrion depolarizes,followed by fusion with lysosomes.By contrast,mitochondrial depolarization stimulates type 2 mitophagy,which is characterized by coalescence of autophagic microtubule-associated protein 1A/1B-light chain 3(LC3)-containing structures on mitochondrial surfaces without the formation of a phagophore or mitochondrial fission.Oppositely to type 1 mitophagy,the inhibition of phosphoinositide-3-kinase(PI3K)does not block type 2 mitophagy.In type 3 mitophagy,or micromitophagy,mitochondria-derived vesicles(MDVs)enriched in oxidized proteins bud off from mitochondrial inner and outer membranes and incorporate into multivesicular bodies by vesicle scission into the lumen.In response to ethanol feeding,widespread ethanol-induced hepatocellular mitochondrial depolarization occurs to facilitate hepatic ethanol metabolism.As a consequence,type 2 mitophagy develops in response to the mitochondrial depolarization.After chronic high ethanol feeding,processing of depolarized mitochondria by mitophagy becomes compromised,leading to release of mitochondrial damage-associated molecular patterns(mtDAMPs)that promote inflammatory and profibrogenic responses.We propose that the persistence of mitochondrial responses for acute ethanol metabolism links initial adaptive ethanol metabolism to mitophagy and then to chronic maladaptive changes initiating onset and the progression of alcoholic liver disease(ALD).
基金This work was financially supported by the National Natural Science Foundation of China(No.21374054)the SinoGerman Center for Research Promotion
文摘The poly(ethylene glycol) (PEG, with Mw 2000)-urea inclusion compound (IC) crystallized at high temperature region showed two typical orientations, flat-on and edge-on crystals. 2D-XRD and polarized FTIR spectroscopy revealed that the PEG chains within urea channels were perpendicular to the substrate in fiat-on oriented crystals, while PEG chain axes were parallel to the substrate and lay along the growth direction in the edge-on crystals. FT1R absorption bands of PEG in the ICs are sensitive to orientation of the crystals. A scheme of PEG chain packing in the urea IC channel was proposed, which could explain the orientation of the crystal nucleus causing the two types of morphologies. Furthermore, functioning of PEG2000 chain end with analine had significantly influence on the morphology and orientation of the inclusion compound crystals, due to the defects caused by large terminal groups included in the urea channel.
基金financially supported by the National Natural Science Foundation of China(Nos.21434008,21374054)National Basic Research Program of China(973 Program,No.2014CB932202)
文摘The solid form of drugs plays a central role in optimizing the physicochemical properties of drugs,and new solid forms will provide more options to achieve the desirable pharmaceutical profiles of drugs.Recently,certain drugs have been found to form crystalline inclusion complexes(ICs) with multiple types of linear polymers,representing a new subcategory of pharmaceutical solids.In this study,we used diflunisal(DIF) as the model drug host and extended the guest of drug/polymer ICs from homopolymers to block copolymers of poly(ethylene glycol)(PEG) and poly(s-caprolactone)(PCL).The block length in the guest copolymers showed a significant influence on the formation,thermal stability and dissolution behavior of the DIF ICs.Though the PEG block could hardly be included alone,it could indeed be included in the DIF ICs when the PCL block was long enough.The increase of the PCL block length produced IC crystals with improved thermal stability.The dissolution profiles of DIF/block copolymer ICs exhibited gradually decreased aqueous solubility and dissolution rate with the increasing PCL block length.These results demonstrate the possibility of using drug/polymer ICs to modulate the desired pharmaceutical profiles of drugs in a predictable and controllable manner.
基金supported by the National Natural Science Foundation of China (No. 21434008)
文摘The solid forms of drugs play a central role in controlling their physicochemical properties and consequently the bioavailability. Multiple types of drug solid forms have been developed to achieve the desirable pharmaceutical profiles, but new solid forms will provide more options for the solid-state property optimization and hence are highly desirable. This review focuses on a new pharmaceutical solid form, drug-polymer inclusion complexes (ICs), and summarizes their structural features, structure- property relationships, as well as potential pharmaceutical applications