Hydrogen sulfide(H_(2)S)is a toxic,essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter.These studies have mainly focus...Hydrogen sulfide(H_(2)S)is a toxic,essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter.These studies have mainly focused on the production and pharmacological side effects caused by H_(2)S.Therefore,effective strategies to remove H_(2)S has become a key research topic.Furthermore,the development of novel nanoplatforms has provided new tools for the targeted removal of H_(2)S.This paper was performed to review the association between H_(2)S anddisease,relatedH_(2)S inhibitory drugs,aswell as H_(2)S responsive nanoplatforms(HRNs).This review first analyzed the role of H_(2)S in multiple tissues and conditions.Second,common drugs used to eliminate H_(2)S,as well as their potential for combination with anticancer agents,were summarized.Not only the existing studies on HRNs,but also the inhibition H_(2)S combined with different therapeutic methods were both sorted out in this review.Furthermore,this review provided in-depth analysis of the potential of HRNs about treatment or detection in detail.Finally,potential challenges of HRNs were proposed.This study demonstrates the excellent potential of HRNs for biomedical applications.展开更多
The Gravitational wave burst high-energy Electromagnetic Counterpart All-sky Monitor(GECAM)is a dedicated mission for monitoring high-energy transients.Here we report the design of the GECAM Scientific Ground Segment(...The Gravitational wave burst high-energy Electromagnetic Counterpart All-sky Monitor(GECAM)is a dedicated mission for monitoring high-energy transients.Here we report the design of the GECAM Scientific Ground Segment(GSGS)in terms of the scientific requirements,including the architecture,the external interfaces,the main function,and workflow.Judging from the analysis and verification results during the commissioning phase,the GSGS functions well and is able to monitor the status of the payloads,adjust the parameters,develop the scientific observation plans,generate the scientific data products,analyze the data,etc.Thus,the on-orbit operation and scientific researches of GECAM are guaranteed.展开更多
The prevention and early diagnosis of liver cancer remains a global medical challenge.During the malignant transformation of hepatocytes,a variety of oncogenic cellular signalling molecules,such as novel high mobility...The prevention and early diagnosis of liver cancer remains a global medical challenge.During the malignant transformation of hepatocytes,a variety of oncogenic cellular signalling molecules,such as novel high mobility group-Box 3,angiopoietin-2,Golgi protein 73,glypican-3,Wnt3a(a signalling molecule in the Wnt/β-catenin pathway),and secretory clusterin,can be expressed and secreted into the blood.These signalling molecules are derived from different signalling pathways and may not only participate in the malignant transformation of hepatocytes but also become early diagnostic indicators of hepatocarcinogenesis or specific targeted molecules for hepatocellular carcinoma therapy.This article reviews recent progress in the study of several signalling molecules as sensitive biomarkers for monitoring hepatocarcinogenesis.展开更多
[Objectives]This study was conducted to breed special pig breeds resistant to diarrhea by using modern biotechnology.[Methods]From Guizhou local breeds,such as Nuogu pigs,Kele pig,Yorkshire pigs and Duroc pigs,190 sam...[Objectives]This study was conducted to breed special pig breeds resistant to diarrhea by using modern biotechnology.[Methods]From Guizhou local breeds,such as Nuogu pigs,Kele pig,Yorkshire pigs and Duroc pigs,190 samples were collected for the analysis of anti-diarrhea gene.[Results]The anti-diarrhea genotype frequency of Kele pigs was 70.00%,which was higher than that of Nuogu pigs(67.37%)and Yorkshire pigs(Yorkshire pigs and Duroc pigs)(50.59%).The favorable anti-diarrhea gene of all Nuogu pigs,Kele pigs,and Yorkshire pigs and Duroc pigs was G,with gene frequencies of 0.7355,0.8368 and 0.8500,respectively,and the frequencies of allele A were 0.2645,0.1632 and 0.1500,respectively.In the process of generation selection,combination selection of GG♂×GG♀,GG♂×GA♀,GA♂×GG♀and GA♂×GA♀was conducted,and GG individuals were selected while gradually phasing out GA and AA individuals.The anti-diarrhea genotypes of 98 pigs in the offspring were tested,and it was found that the frequency of genotype GG was greatly improved,and the frequencies in Nuogu pigs,Kele pigs,Yorkshire pigs and Duroc pigs were increased to 73.91%,81.82%,85.25%and 66.67%respectively,thus forming a special anti-diarrhea breed.[Conclusions]This study provides a basis for selecting excellent breeding pigs,establishing core populations and screening resistance genes in the core populations and their offspring.展开更多
AIM: To interfere with the activation of nuclear factor-κB(NF-κB) with metformin and explore its effect in reversing multidrug resistance(MDR) of hepatocellular carcinoma(HCC) cells.METHODS: Expression of P-glycopro...AIM: To interfere with the activation of nuclear factor-κB(NF-κB) with metformin and explore its effect in reversing multidrug resistance(MDR) of hepatocellular carcinoma(HCC) cells.METHODS: Expression of P-glycoprotein(P-gp) and NF-κB in human HepG 2 or HepG 2/adriamycin(ADM) cells treated with pC MV-NF-κB-small interference RNA(siR NA) with or without metformin, was analyzed by Western blot or fluorescence quantitative PCR. Cell viability was tested by CCK-8 assay. Cell cycle and apoptosis were measured by flow cytometry and Annexin-V-PE/7-AnnexinV apoptosis detection double staining assay, respectively. RESULTS: P-gp overexpression in HepG 2 and HepG 2/ADM cells was closely related to mdr1 mR NA(3.310 ± 0.154) and NF-κB mR NA(2.580 ± 0.040) expression. NF-κB gene transcription was inhibited by specific siR NA with significant down-regulation of P-gp and enhanced HCC cell chemosensitivity to doxorubicin. After pretreatment with metformin, Hep G2/ADM cells were sensitized to doxorubicin and P-gp was decreased through the NF-κB signaling pathway. The synergistic effect of metformin and NF-κB siR NA were found in HepG 2/ADM cells with regard to proliferation inhibition, cell cycle arrest and inducing cell apoptosis. CONCLUSION: Metformin via silencing NF-κB signaling could effectively reverse MDR of HCC cells by downregulating MDR1/P-gp expression.展开更多
Coal ash melting characteristics has a direct impact on the smooth operation of entrained gasifier.Mineral conversion of coal ash is very significant to be investigated,because the mineral can affect the melting tempe...Coal ash melting characteristics has a direct impact on the smooth operation of entrained gasifier.Mineral conversion of coal ash is very significant to be investigated,because the mineral can affect the melting temperature and viscosity under high temperature conditions.In this paper,the effects of different Al2O3/CaO on the mineral conversion,melting temperature and viscosity of Ningdong coal ash are studied by the combination of experiment and simulation.The trend of melting temperature decreases firstly and rises with increasing Al_(2)O_(3)/CaO.The ashmelting point reached to the lowestwhen the ratio is 1.23.XRD and Factsage software are used to analyze crystallization behavior of samples.The results showthat the content of anorthite,albite and corundumincreases and subsequently decreases,while the content of mullite decreases firstly and then rises with increasing Al_(2)O_(3)/CaO.High content with CaO can contribute to form albite and anorthite of low-melting.Besides,high content with Al_(2)O_(3) can tend to produce mullite of high-melting.The results of experimental and simulation are basically the same,which lays a foundation for the melting characteristics of Ningdong coal ash and can provide technical support for the smooth operation of the entrained-gasifier.展开更多
Chronic spinal cord compression(CSCC)is induced by disc herniation and other reasons,leading to movement and sensation dysfunction,with a serious impact on quality of life.Spontaneous disc herniation rarely occurs in ...Chronic spinal cord compression(CSCC)is induced by disc herniation and other reasons,leading to movement and sensation dysfunction,with a serious impact on quality of life.Spontaneous disc herniation rarely occurs in rodents,and therefore establishing a chronic spinal cord compression(CSCC)animal model is of crucial importance to explore the pathogenesis and treatment of CSCC.The absence of secreted protein,acidic,and rich in cysteine(SPARC)leads to spontaneous intervertebral disc degeneration in mice,which resembles human disc degeneration.In this study,we evaluated whether SPARC-null mice may serve as an animal model for CSCC.We performed rod rotation test,pain threshold test,gait analysis,and Basso Mouse Scale score.Our results showed that the motor function of SPARC-null mice was weakened,and magnetic resonance images revealed compression at different spinal cord levels,particularly in the lumbar segments.Immunofluorescence staining and western blot assay showed that the absence of SPARC induced apoptosis of neurons and oligodendrocytes,activation of microglia/macrophages with M1/M2 phenotype and astrocytes with A1/A2 phenotype;it also activated the expression of the NOD-like receptor protein 3 inflammasome and inhibited brain-derived neurotrophic factor/tyrosine kinase B signaling pathway.Notably,these findings are characteristics of CSCC.Therefore,we propose that SPARC-null mice may be an animal model for studying CSCC caused by disc herniation.展开更多
Background:The effective treatment for hepatocellular carcinoma(HCC)depends on early diagnosis.Previously,the abnormal expression of Wnt3a as the key signaling molecule in the Wnt/β-catenin pathway was found in HCC c...Background:The effective treatment for hepatocellular carcinoma(HCC)depends on early diagnosis.Previously,the abnormal expression of Wnt3a as the key signaling molecule in the Wnt/β-catenin pathway was found in HCC cells and could be released into the circulation.In this study,we used rat model of hepatocarcinogenesis to dynamically investigate the alteration of oncogenic Wnt3a and to explore its early monitor value for HCC.Methods:Sprague-Dawley rats(SD)were fed with diet 2-fluorenylacetamide(2-FAA,0.05%)for inducing hepatocarcinogenesis,and grouped based on liver morphological alteration by Hematoxylin&Eosin(H&E)staining;rats fed with normal chow were used as normal control(NC).Total RNA and protein were purified from rat livers.Differently expressed genes(DEGs)or Wnt3a m RNA,cellular distribution,and Wnt3a protein levels were analyzed by whole genome microarray with signal logarithm ratio(SLR log 2 cy5/cy3),immunohistochemistry,and enzyme-linked immunosorbent assay,respectively.Results:Models of rat hepatocarcinogenesis were successfully established based on liver histopathological H&E staining.Rats were divided into the cell degeneration(r Deg),precancerosis(r Pre-C)and HCC(r HCC)groups.Total numbers of the up-and down-regulated DEGs with SLR≥8 were 55 and 48 in the r Deg group,268 and 57 in the r Pre-C group,and 312 and 201 in the r HCC group,respectively.Significantly altered genes were involved in cell proliferation,signal transduction,tumor metastasis,and apoptosis.Compared with the NC group,Wnt3a m RNA was increased by 4.6 folds(P<0.001)in the r Deg group,7.4 folds(P<0.001)in the r Pre-C group,and 10.4 folds(P<0.001)in the r HCC group;the positive rates of liver Wnt3a were 66.7%(P=0.001)in the r Deg group,100%(P<0.001)in the r Pre-C group,and 100%(P<0.001)in the r HCC group,respectively.Also,there were significant differences of liver Wnt3a(P<0.001)or serum Wnt3a(P<0.001)among different groups.Conclusions:Overexpression of Wnt3a was associated with rat hepatocarcinogenesis and it should be expected to be a promising monitoring biomarker for HCC occurrence at early stage.展开更多
Nonalcoholic fatty liver disease(NAFLD)or metabolic-associated fatty liver disease has been characterized by the lipid accumulation with injury of hepatocytes and has become one of the most common chronic liver diseas...Nonalcoholic fatty liver disease(NAFLD)or metabolic-associated fatty liver disease has been characterized by the lipid accumulation with injury of hepatocytes and has become one of the most common chronic liver diseases in the world.The complex mechanisms of NAFLD formation are still under identification.Carnitine palmitoyltransferase-Ⅱ(CPT-Ⅱ)on inner mitochondrial membrane(IMM)regulates long chain fatty acidβ-oxidation,and its abnormality has had more and more attention paid to it by basic and clinical research in NAFLD.The sequences of its peptide chain and DNA nucleotides have been identified,and the catalytic activity of CPT-Ⅱ is affected on its gene mutations,deficiency,enzymatic thermal instability,circulating carnitine level and so on.Recently,the CPT-Ⅱ dysfunction has been discovered in models of liver lipid accumulation.Meanwhile,the malignant transformation of hepatocyte-related CD44^(+) stem T cell activation,high levels of tumor-related biomarkers(AFP,GPC3)and abnormal activation of Wnt3a expression as a key signal molecule of the Wnt/β-catenin pathway run parallel to the alterations of hepatocyte pathology.This review focuses on some of the progress of CPT-Ⅱ inactivity on IMM with liver fatty accumulation as a possible novel pathogenesis for NAFLD in hepatocarcinogenesis.展开更多
AIM: TO investigate the characteristics and diagnostic value of annexin A2 (ANXA2) expression in cancerous tissues and sera of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METH...AIM: TO investigate the characteristics and diagnostic value of annexin A2 (ANXA2) expression in cancerous tissues and sera of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: Levels of liver ANXA2 gene transcription or protein expression were analyzed in HCC-, their self- controlled precancerous-, and distant cancerous- tissues from 30 HCC. Serum levels of ANXA2 expression in 115 patients with HCC, 25 with metastatic liver can cer, 35 with chronic hepatitis, 28 with acute hepatitis, 38 with cirrhosis, and 30 healthy controls were deter- mined. Clinicopathological characteristics of circulating ANXA2 expression were analyzed, and its diagnostic efficiency and clinical values in HCC were evaluated. RESULTS: ANXA2 expression was localized in both cell membrane and cytoplasm in HCC tissue, mainly in the cytoplasm of matched adjacent cancerous tissue, and there was almost no positive staining in matched distant cancerous tissue. Abnormal expression of liver ANXA2 was present in HCC tissues compared with self-con- trolled adjacent- and distant-cancerous tissues at pro- tein or mRNA level. Circulating ANXA2 in HCC patients was significantly higher than that of other liver diseases (P 〈 0.01) except metastatic liver cancer. If the diag- nostic cutoff value of ANXA2 level was more than 18 ng/ mL, the incidence of serum ANXA2 was 86.96% in the HCC group, 80% in the metastatic liver cancer group, 31.58% in the liver cirrhosis group, none in the chronic hepatitis or acute hepatitis or normal control group, respectively. Serum ANXA2 expression in HCC patients was correlated with HBV infection (27.38 ± 5.67 ng/mL vs 18.58 ± 7.83 ng/mL, P 〈 0.01), extrahepatic metas- tasis (26.11±5.43 ng/mL ys 22.79 ± 5.64 ng/mL, P 〈 0.01), and portal vein thrombus (26.03 ± 5.99 ng/mL vs 23.06 ± 5.03 ng/mL, P 〈 0.01), and was significantly higher (P 〈 0.01) in the moderately- (26.19±5.34 ng/ mL) or the poorly- differentiated group (27.05 ± 5.13 ng/mL) than in the well differentiated group (20.43 ± 4.97 ng/mL), and in the tumor node metastasis stages Ⅲ-Ⅳ(P 〈 0.01) than in stages Ⅰ-Ⅱ. ANXA2 was not correlated with patient sex, age, size or α-fetoprotein (AFP) level. Area under the receiver operating charac- teristic curve for the whole range of sensitivities and specificities was 0.796 for ANXA2 and 0.782 for AFP. Combining detection of serum ANXA2 and AFP substan- tially improved the diagnostic efficiency (96.52%) and the neclative predictive value ('96.61%) for HCC.of ANXA2 expression has good diagnostic potential for HCC diagnosis.展开更多
Two ligand oligopeptides GV1 and GV2 were designed according to the putative binding region of VEGF to its receptors. GV1, GV2 and endosome releasing oligopeptide HA20 were conjugated with poly-L-lysine or protamine a...Two ligand oligopeptides GV1 and GV2 were designed according to the putative binding region of VEGF to its receptors. GV1, GV2 and endosome releasing oligopeptide HA20 were conjugated with poly-L-lysine or protamine and the resulting conjugates could interact with DNA in a noncovalent bond to form a complex. Using pSV2-β-galactosidase as a reporter gene, it has been demonstrated that exogenous gene was transferred into bovine aortic arch-derived endothelial cells (ABAE) andhuman malignant melanoma cell lines (A375) in vitro. In vivo experiments, exogenous gene was transferred into tumor vascular endothelial cells and tumor cells of subcutaneously transplanted human colon cancer LOVO, human malignant melanoma A375 and human hepatoma graft in nude mice. This system could also target gene to intrahepatically transplanted human hepatoma injected via portal vein in nude mice. These results are correlated with theGene delivery system targeting VEGF receptors relevant receptors (flt-1, flk-1/KDR) expression on the targeted cells and tissues.展开更多
基金supported by National Key Research and Development Program of China(contract No.2019YFA0904800)National Nature Science Foundation of China(32030065,31722033,92049304 to Y.Z.)+5 种基金Shanghai Sailing Program(contract No.21YF1410300)Science and Technology Commission of Shanghai Municipality(contract No.10DZ2220500)The Shanghai Committee of Science and Technology(grant No.11DZ2260600)Shanghai Frontiers Science Center of Optogenetic Techniques for CellMetabolism(Y.Z.)Research Unit of New Techniques for Live-cell Metabolic Imaging(Chinese Academy of Medical Sciences,2019-I2M-5-013 to Y.Z.)the State Key Laboratory of Bioreactor Engineering,the Fundamental Research Funds for the Central Universities.
文摘Hydrogen sulfide(H_(2)S)is a toxic,essential gas used in various biological and physical processes and has been the subject of many targeted studies on its role as a new gas transmitter.These studies have mainly focused on the production and pharmacological side effects caused by H_(2)S.Therefore,effective strategies to remove H_(2)S has become a key research topic.Furthermore,the development of novel nanoplatforms has provided new tools for the targeted removal of H_(2)S.This paper was performed to review the association between H_(2)S anddisease,relatedH_(2)S inhibitory drugs,aswell as H_(2)S responsive nanoplatforms(HRNs).This review first analyzed the role of H_(2)S in multiple tissues and conditions.Second,common drugs used to eliminate H_(2)S,as well as their potential for combination with anticancer agents,were summarized.Not only the existing studies on HRNs,but also the inhibition H_(2)S combined with different therapeutic methods were both sorted out in this review.Furthermore,this review provided in-depth analysis of the potential of HRNs about treatment or detection in detail.Finally,potential challenges of HRNs were proposed.This study demonstrates the excellent potential of HRNs for biomedical applications.
基金supported by the National Key R&D Program of China(2022YFF0711404,2021YFA0718500)International Partnership Program of Chinese Academy of Sciences(grant No.113111KYSB20190020)+2 种基金the National Natural Science Foundation of China(NSFC,Grant No.U1938106)the open subject of the National HEP Data Center(E029S2S1)support from the Strategic Priority Research Program on Space Science,the Chinese Academy of Sciences(grant Nos.XDA15360102,XDA15360300,XDA15052700 and E02212A02S)。
文摘The Gravitational wave burst high-energy Electromagnetic Counterpart All-sky Monitor(GECAM)is a dedicated mission for monitoring high-energy transients.Here we report the design of the GECAM Scientific Ground Segment(GSGS)in terms of the scientific requirements,including the architecture,the external interfaces,the main function,and workflow.Judging from the analysis and verification results during the commissioning phase,the GSGS functions well and is able to monitor the status of the payloads,adjust the parameters,develop the scientific observation plans,generate the scientific data products,analyze the data,etc.Thus,the on-orbit operation and scientific researches of GECAM are guaranteed.
基金Supported by National Natural Science Foundation of China,No.81673241 and No.31872738Nantong Infectious Disease Alliance Fund,No.202308001.
文摘The prevention and early diagnosis of liver cancer remains a global medical challenge.During the malignant transformation of hepatocytes,a variety of oncogenic cellular signalling molecules,such as novel high mobility group-Box 3,angiopoietin-2,Golgi protein 73,glypican-3,Wnt3a(a signalling molecule in the Wnt/β-catenin pathway),and secretory clusterin,can be expressed and secreted into the blood.These signalling molecules are derived from different signalling pathways and may not only participate in the malignant transformation of hepatocytes but also become early diagnostic indicators of hepatocarcinogenesis or specific targeted molecules for hepatocellular carcinoma therapy.This article reviews recent progress in the study of several signalling molecules as sensitive biomarkers for monitoring hepatocarcinogenesis.
基金Supported by Guizhou Provincial Department of Agriculture and Rural Affairs Project(QNYZZZ[2017]No.12)2024 Quality Supervision and Sampling Project of Normal Temperature Semen for Breeding Pigs.
文摘[Objectives]This study was conducted to breed special pig breeds resistant to diarrhea by using modern biotechnology.[Methods]From Guizhou local breeds,such as Nuogu pigs,Kele pig,Yorkshire pigs and Duroc pigs,190 samples were collected for the analysis of anti-diarrhea gene.[Results]The anti-diarrhea genotype frequency of Kele pigs was 70.00%,which was higher than that of Nuogu pigs(67.37%)and Yorkshire pigs(Yorkshire pigs and Duroc pigs)(50.59%).The favorable anti-diarrhea gene of all Nuogu pigs,Kele pigs,and Yorkshire pigs and Duroc pigs was G,with gene frequencies of 0.7355,0.8368 and 0.8500,respectively,and the frequencies of allele A were 0.2645,0.1632 and 0.1500,respectively.In the process of generation selection,combination selection of GG♂×GG♀,GG♂×GA♀,GA♂×GG♀and GA♂×GA♀was conducted,and GG individuals were selected while gradually phasing out GA and AA individuals.The anti-diarrhea genotypes of 98 pigs in the offspring were tested,and it was found that the frequency of genotype GG was greatly improved,and the frequencies in Nuogu pigs,Kele pigs,Yorkshire pigs and Duroc pigs were increased to 73.91%,81.82%,85.25%and 66.67%respectively,thus forming a special anti-diarrhea breed.[Conclusions]This study provides a basis for selecting excellent breeding pigs,establishing core populations and screening resistance genes in the core populations and their offspring.
基金Supported by Projects of Jiangsu Elitist Peak in Six Fields,Nos.2013-WSN-078,2013-WSW-011,and 2014-YY-028the QingL an Program of Jiangsu Higher Education,the Youth Science Foundation of Nantong Health Department,No.WQ2014005the International Science and Technology Cooperation Program,No.2013DFA32150
文摘AIM: To interfere with the activation of nuclear factor-κB(NF-κB) with metformin and explore its effect in reversing multidrug resistance(MDR) of hepatocellular carcinoma(HCC) cells.METHODS: Expression of P-glycoprotein(P-gp) and NF-κB in human HepG 2 or HepG 2/adriamycin(ADM) cells treated with pC MV-NF-κB-small interference RNA(siR NA) with or without metformin, was analyzed by Western blot or fluorescence quantitative PCR. Cell viability was tested by CCK-8 assay. Cell cycle and apoptosis were measured by flow cytometry and Annexin-V-PE/7-AnnexinV apoptosis detection double staining assay, respectively. RESULTS: P-gp overexpression in HepG 2 and HepG 2/ADM cells was closely related to mdr1 mR NA(3.310 ± 0.154) and NF-κB mR NA(2.580 ± 0.040) expression. NF-κB gene transcription was inhibited by specific siR NA with significant down-regulation of P-gp and enhanced HCC cell chemosensitivity to doxorubicin. After pretreatment with metformin, Hep G2/ADM cells were sensitized to doxorubicin and P-gp was decreased through the NF-κB signaling pathway. The synergistic effect of metformin and NF-κB siR NA were found in HepG 2/ADM cells with regard to proliferation inhibition, cell cycle arrest and inducing cell apoptosis. CONCLUSION: Metformin via silencing NF-κB signaling could effectively reverse MDR of HCC cells by downregulating MDR1/P-gp expression.
基金supported by the Key Research and Development Program of Ningxia(2018BCE01004)Natural Science Foundation of Ningxia(2018AAC03013)Discipline Project of Ningxia(NXYLXK2017A04).
文摘Coal ash melting characteristics has a direct impact on the smooth operation of entrained gasifier.Mineral conversion of coal ash is very significant to be investigated,because the mineral can affect the melting temperature and viscosity under high temperature conditions.In this paper,the effects of different Al2O3/CaO on the mineral conversion,melting temperature and viscosity of Ningdong coal ash are studied by the combination of experiment and simulation.The trend of melting temperature decreases firstly and rises with increasing Al_(2)O_(3)/CaO.The ashmelting point reached to the lowestwhen the ratio is 1.23.XRD and Factsage software are used to analyze crystallization behavior of samples.The results showthat the content of anorthite,albite and corundumincreases and subsequently decreases,while the content of mullite decreases firstly and then rises with increasing Al_(2)O_(3)/CaO.High content with CaO can contribute to form albite and anorthite of low-melting.Besides,high content with Al_(2)O_(3) can tend to produce mullite of high-melting.The results of experimental and simulation are basically the same,which lays a foundation for the melting characteristics of Ningdong coal ash and can provide technical support for the smooth operation of the entrained-gasifier.
基金supported by the National Natural Science Foundation of China,Nos.82074454(to XJC),82174409(to MY),81930116(to YJW),81873317(to XJC)the National Key R&D Program of China,No.2018YFC1704300(to YJW)the Natural Science Foundation of Shanghai,No.20ZR1459000(to MY)。
文摘Chronic spinal cord compression(CSCC)is induced by disc herniation and other reasons,leading to movement and sensation dysfunction,with a serious impact on quality of life.Spontaneous disc herniation rarely occurs in rodents,and therefore establishing a chronic spinal cord compression(CSCC)animal model is of crucial importance to explore the pathogenesis and treatment of CSCC.The absence of secreted protein,acidic,and rich in cysteine(SPARC)leads to spontaneous intervertebral disc degeneration in mice,which resembles human disc degeneration.In this study,we evaluated whether SPARC-null mice may serve as an animal model for CSCC.We performed rod rotation test,pain threshold test,gait analysis,and Basso Mouse Scale score.Our results showed that the motor function of SPARC-null mice was weakened,and magnetic resonance images revealed compression at different spinal cord levels,particularly in the lumbar segments.Immunofluorescence staining and western blot assay showed that the absence of SPARC induced apoptosis of neurons and oligodendrocytes,activation of microglia/macrophages with M1/M2 phenotype and astrocytes with A1/A2 phenotype;it also activated the expression of the NOD-like receptor protein 3 inflammasome and inhibited brain-derived neurotrophic factor/tyrosine kinase B signaling pathway.Notably,these findings are characteristics of CSCC.Therefore,we propose that SPARC-null mice may be an animal model for studying CSCC caused by disc herniation.
基金supported by grants from the Natural Science Foundation of China(81873915,31872738 and 81673241)Nantong S&T Key Plan(MS12019021)NTU Medical Program of China(TDYX2021010)。
文摘Background:The effective treatment for hepatocellular carcinoma(HCC)depends on early diagnosis.Previously,the abnormal expression of Wnt3a as the key signaling molecule in the Wnt/β-catenin pathway was found in HCC cells and could be released into the circulation.In this study,we used rat model of hepatocarcinogenesis to dynamically investigate the alteration of oncogenic Wnt3a and to explore its early monitor value for HCC.Methods:Sprague-Dawley rats(SD)were fed with diet 2-fluorenylacetamide(2-FAA,0.05%)for inducing hepatocarcinogenesis,and grouped based on liver morphological alteration by Hematoxylin&Eosin(H&E)staining;rats fed with normal chow were used as normal control(NC).Total RNA and protein were purified from rat livers.Differently expressed genes(DEGs)or Wnt3a m RNA,cellular distribution,and Wnt3a protein levels were analyzed by whole genome microarray with signal logarithm ratio(SLR log 2 cy5/cy3),immunohistochemistry,and enzyme-linked immunosorbent assay,respectively.Results:Models of rat hepatocarcinogenesis were successfully established based on liver histopathological H&E staining.Rats were divided into the cell degeneration(r Deg),precancerosis(r Pre-C)and HCC(r HCC)groups.Total numbers of the up-and down-regulated DEGs with SLR≥8 were 55 and 48 in the r Deg group,268 and 57 in the r Pre-C group,and 312 and 201 in the r HCC group,respectively.Significantly altered genes were involved in cell proliferation,signal transduction,tumor metastasis,and apoptosis.Compared with the NC group,Wnt3a m RNA was increased by 4.6 folds(P<0.001)in the r Deg group,7.4 folds(P<0.001)in the r Pre-C group,and 10.4 folds(P<0.001)in the r HCC group;the positive rates of liver Wnt3a were 66.7%(P=0.001)in the r Deg group,100%(P<0.001)in the r Pre-C group,and 100%(P<0.001)in the r HCC group,respectively.Also,there were significant differences of liver Wnt3a(P<0.001)or serum Wnt3a(P<0.001)among different groups.Conclusions:Overexpression of Wnt3a was associated with rat hepatocarcinogenesis and it should be expected to be a promising monitoring biomarker for HCC occurrence at early stage.
基金Supported by the National Natural Science Foundation of China,No.81873915 and No.31872738the Key Plan of Nantong S&T Development,No.MS12020021the S&T Program of Medical School of Nantong University,No.TDYX2021010.
文摘Nonalcoholic fatty liver disease(NAFLD)or metabolic-associated fatty liver disease has been characterized by the lipid accumulation with injury of hepatocytes and has become one of the most common chronic liver diseases in the world.The complex mechanisms of NAFLD formation are still under identification.Carnitine palmitoyltransferase-Ⅱ(CPT-Ⅱ)on inner mitochondrial membrane(IMM)regulates long chain fatty acidβ-oxidation,and its abnormality has had more and more attention paid to it by basic and clinical research in NAFLD.The sequences of its peptide chain and DNA nucleotides have been identified,and the catalytic activity of CPT-Ⅱ is affected on its gene mutations,deficiency,enzymatic thermal instability,circulating carnitine level and so on.Recently,the CPT-Ⅱ dysfunction has been discovered in models of liver lipid accumulation.Meanwhile,the malignant transformation of hepatocyte-related CD44^(+) stem T cell activation,high levels of tumor-related biomarkers(AFP,GPC3)and abnormal activation of Wnt3a expression as a key signal molecule of the Wnt/β-catenin pathway run parallel to the alterations of hepatocyte pathology.This review focuses on some of the progress of CPT-Ⅱ inactivity on IMM with liver fatty accumulation as a possible novel pathogenesis for NAFLD in hepatocarcinogenesis.
基金We are thankful to the National Natural Science Foundation of China(22174110 and 22127803)the Industrial Support Plan of Gansu Provincial Department of Education(2021cyzc-01)the Special Fund Project for Guiding Local Scientific and Technological Development by the Central Government(2020-2060503-17).
基金Supported by Priority Academic Program Development of Jiangsu Higher Education Institution (PAPD)the Project of Jiangsu Clinical Medicine (BL2012053)+1 种基金the Programs of Nantong Society Undertaking and Technological Innovation,No.HS2012034 and HS2011012the International S and T Cooperation Program of China
文摘AIM: TO investigate the characteristics and diagnostic value of annexin A2 (ANXA2) expression in cancerous tissues and sera of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). METHODS: Levels of liver ANXA2 gene transcription or protein expression were analyzed in HCC-, their self- controlled precancerous-, and distant cancerous- tissues from 30 HCC. Serum levels of ANXA2 expression in 115 patients with HCC, 25 with metastatic liver can cer, 35 with chronic hepatitis, 28 with acute hepatitis, 38 with cirrhosis, and 30 healthy controls were deter- mined. Clinicopathological characteristics of circulating ANXA2 expression were analyzed, and its diagnostic efficiency and clinical values in HCC were evaluated. RESULTS: ANXA2 expression was localized in both cell membrane and cytoplasm in HCC tissue, mainly in the cytoplasm of matched adjacent cancerous tissue, and there was almost no positive staining in matched distant cancerous tissue. Abnormal expression of liver ANXA2 was present in HCC tissues compared with self-con- trolled adjacent- and distant-cancerous tissues at pro- tein or mRNA level. Circulating ANXA2 in HCC patients was significantly higher than that of other liver diseases (P 〈 0.01) except metastatic liver cancer. If the diag- nostic cutoff value of ANXA2 level was more than 18 ng/ mL, the incidence of serum ANXA2 was 86.96% in the HCC group, 80% in the metastatic liver cancer group, 31.58% in the liver cirrhosis group, none in the chronic hepatitis or acute hepatitis or normal control group, respectively. Serum ANXA2 expression in HCC patients was correlated with HBV infection (27.38 ± 5.67 ng/mL vs 18.58 ± 7.83 ng/mL, P 〈 0.01), extrahepatic metas- tasis (26.11±5.43 ng/mL ys 22.79 ± 5.64 ng/mL, P 〈 0.01), and portal vein thrombus (26.03 ± 5.99 ng/mL vs 23.06 ± 5.03 ng/mL, P 〈 0.01), and was significantly higher (P 〈 0.01) in the moderately- (26.19±5.34 ng/ mL) or the poorly- differentiated group (27.05 ± 5.13 ng/mL) than in the well differentiated group (20.43 ± 4.97 ng/mL), and in the tumor node metastasis stages Ⅲ-Ⅳ(P 〈 0.01) than in stages Ⅰ-Ⅱ. ANXA2 was not correlated with patient sex, age, size or α-fetoprotein (AFP) level. Area under the receiver operating charac- teristic curve for the whole range of sensitivities and specificities was 0.796 for ANXA2 and 0.782 for AFP. Combining detection of serum ANXA2 and AFP substan- tially improved the diagnostic efficiency (96.52%) and the neclative predictive value ('96.61%) for HCC.of ANXA2 expression has good diagnostic potential for HCC diagnosis.
文摘Two ligand oligopeptides GV1 and GV2 were designed according to the putative binding region of VEGF to its receptors. GV1, GV2 and endosome releasing oligopeptide HA20 were conjugated with poly-L-lysine or protamine and the resulting conjugates could interact with DNA in a noncovalent bond to form a complex. Using pSV2-β-galactosidase as a reporter gene, it has been demonstrated that exogenous gene was transferred into bovine aortic arch-derived endothelial cells (ABAE) andhuman malignant melanoma cell lines (A375) in vitro. In vivo experiments, exogenous gene was transferred into tumor vascular endothelial cells and tumor cells of subcutaneously transplanted human colon cancer LOVO, human malignant melanoma A375 and human hepatoma graft in nude mice. This system could also target gene to intrahepatically transplanted human hepatoma injected via portal vein in nude mice. These results are correlated with theGene delivery system targeting VEGF receptors relevant receptors (flt-1, flk-1/KDR) expression on the targeted cells and tissues.