The autotetraploid Carassius auratus(4nRR,4n=200,RRRR)is derived from whole-genome duplication of Carassius auratus red var.(RCC,2n=100,RR).In the current study,we demonstrated that chromatophores and pigment changes ...The autotetraploid Carassius auratus(4nRR,4n=200,RRRR)is derived from whole-genome duplication of Carassius auratus red var.(RCC,2n=100,RR).In the current study,we demonstrated that chromatophores and pigment changes directly caused the coloration and variation of 4nRR skin(red in RCC,brownish-yellow in4nRR).To further explore the molecular mechanisms underlying coloration formation and variation in 4nRR,we performed transcriptome profiling and molecular functional verification in RCC and 4nRR.Results revealed that scarb1,associated with carotenoid metabolism,underwent significant down-regulation in 4nRR.Efficient editing of this candidate pigment gene provided clear evidence of its significant role in RCC coloration.Subsequently,we identified four divergent scarb1 homeologs in 4nRR:two original scarb1 homeologs from RCC and two duplicated ones.Notably,three of these homeologs possessed two highly conserved alleles,exhibiting biased and allelespecific expression in the skin.Remarkably,after precise editing of both the original and duplicated scarb1homeologs and/or alleles,4nRR individuals,whether singly or multiply mutated,displayed a transition from brownishyellow skin to a cyan-gray phenotype.Concurrently,the proportional areas of the cyan-gray regions displayed a gene-dose correlation.These findings illustrate the subfunctionalization of duplicated scarb1,with all scarb1genes synergistically and equally contributing to the pigmentation of 4nRR.This is the first report concerning the functional differentiation of duplicated homeologs in an autopolyploidfish,substantiallyenrichingour understanding of coloration formation and change within this group of organisms.展开更多
BACKGROUND:Plasma exchange(PE)-centered artificial liver support system reduced the high mortality rate of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).But the data were diverse in different med...BACKGROUND:Plasma exchange(PE)-centered artificial liver support system reduced the high mortality rate of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).But the data were diverse in different medical centers.The present prospective nationwide study was to evaluate the effects of PE on patients with HBV-ACLF at different stages.METHODS:From December 2009 to December 2011,we evaluated 250 patients at different stages of HBV-ACLF from 10 major medical centers in China.All the laboratory parameters were collected at admission,before and after PE.RESULTS:Among the 250 patients who underwent 661 rounds of PE,one-month survival rate was 61.6%; 141(56.4%) showed improvement after PE.Variables such as age(P=0.000),levels of total bilirubin(TB,P=0.000),direct bilirubin(P=0.000),total triglycerides(P=0.000),low-density lipoprotein(P=0.022),Na+(P=0.014),Cl–(P=0.038),creatinine(Cr,P=0.007),fibrinogen(P=0.000),prothrombin time(PT,P=0.000),white blood cell(P=0.000),platelet(P=0.003) and MELD(P=0.000) were significantly related to prognosis.Multivariate logistic regression analysis showed that age,disease stage,TB,Cr and PT levels were independent risk factors of mortality among HBV-ACLF patients.CONCLUSIONS:PE can improve the clinical outcome of patients with HBV-ACLF.Levels of TB,Cr and PT,age and disease stage help to predict prognosis.展开更多
AIM: To observe the effect of response-guided add-on therapy with adefovir(ADV) and lamivudine(LAM) in cirrhotic hepatitis B(CHB) patients.METHODS: A total of 100 patients with CHB and cirrhosis were divided into thre...AIM: To observe the effect of response-guided add-on therapy with adefovir(ADV) and lamivudine(LAM) in cirrhotic hepatitis B(CHB) patients.METHODS: A total of 100 patients with CHB and cirrhosis were divided into three arms according to hepatitis B virus(HBV) DNA level after 24 wk LAM monotherapy: Arm A(complete response, HBV DNA ≤ 60 IU/m L, n = 49), Arm B(partial response, HBV DNA: 60-2000 IU/m L, n = 31) and Arm C(inadequate response, HBV DNA > 2000 IU/m L, n = 20). ADV was added to LAM at week 48 in Arms A and B, but at week 24 in Arm C. Virological response, YMDD mutations, biochemical response, and liver function were evaluated.RESULTS: Comparison of the three arms demonstrated that early complete virologic response at week 24was associated with maintained viral suppression(undetectable rate of HBV DNA at week 144 was 95.96%, 66.67% and 35.29%, respectively, P = 0.000) and reduced YMDD mutations(mutation rate at week 144 was 0%, 3.23% and 15%, respectively, P = 0.015) after 144 wk treatment. For patients who failed to achieve complete virological response at week 24, switching to combination therapy further decreased HBV DNA level by 1 log10 IU/m L. All three arms obtained biochemical benefits including decline of alanine aminotransferase and elevation of albumin. In patients who developed HBV DNA breakthrough for YMDD mutations, ADV add-on therapy did not induce further multiple drug resistance to LAM or ADV.CONCLUSION: Optimized response-guided add-on therapy of ADV and LAM maintains long-term suppression of HBV DNA and improves liver function in CHB patients with compensated liver cirrhosis.展开更多
Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.T...Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.The present study aimed to determine whether the HBV-ACLF treatment has significantly improved during the past decade.Methods:This study retrospectively compared short-term(28/56 days)survival rates of two different nationwide cohorts(cohort I:2008-2011 and cohort II:2012-2015).Eligible HBV-ACLF patients were enrolled retrospectively.Patients in the cohorts I and II were assigned either to the standard medical therapy(SMT)group(cohort I-SMT,cohort II-SMT)or artificial liver support system(ALSS)group(cohort IALSS,cohort II-ALSS).Propensity score matching analysis was conducted to eliminate baseline differences,and multivariate logistic regression analysis was used to explore the independent factors for 28-day survival.Results:Short-term(28/56 days)survival rates were significantly higher in the ALSS group than those in the SMT group(P<0.05)and were higher in the cohort II than those in the cohort I(P<0.001).After propensity score matching,short-term(28/56 days)survival rates were higher in the cohort II than those in the cohort I for both SMT(60.7%vs.53.0%,50.0%vs.39.8%,P<0.05)and ALSS(66.1%vs.56.5%,53.0%vs.44.4%,P<0.05)treatments.The 28-day survival rate was higher in patients treated with nucleos(t)ide analogs than in patients without such treatments(P=0.046).Multivariate logistic regression analysis revealed that ALSS(OR=0.962,95%CI:0.951-0.973,P=0.038),nucleos(t)ide analogs(OR=0.927,95%CI:0.871-0.983,P=0.046),old age(OR=1.028,95%CI:1.015-1.041,P<0.001),total bilirubin(OR=1.002,95%CI:1.001-1.003,P=0.004),INR(OR=1.569,95%CI:1.044-2.358,P<0.001),COSSH-ACLF grade(OR=2.683,95%CI:1.792-4.017,P<0.001),and albumin(OR=0.952,95%CI:0.924-0.982,P=0.002)were independent factors for 28-day mortality.Conclusions:The treatment for patients with HBV-ACLF has improved in the past decade.展开更多
Severe deterioration of liver function in patients can be characterized by coagulation disorders, jaundice, hepatic encephalopathy, ascites, and other symptoms. Severe liver injury can develop as acute liver failure, ...Severe deterioration of liver function in patients can be characterized by coagulation disorders, jaundice, hepatic encephalopathy, ascites, and other symptoms. Severe liver injury can develop as acute liver failure, subacute liver failure, acute-on-chronic liver failure, or further worsening of end-stage liver disease [1].展开更多
Oral squamous cell carcinoma (OSCC) is the most common malignant tumour in oral and maxillofacial region. The interaction between stromal cells and tumor cells is involved in the proliferation, differentiation, apopto...Oral squamous cell carcinoma (OSCC) is the most common malignant tumour in oral and maxillofacial region. The interaction between stromal cells and tumor cells is involved in the proliferation, differentiation, apoptosis, adhesion and migration of tumor cells, and is closely related to the malignant degree and prognosis of tumors. The development of OSCC is of great significance to the treatment of OSCC. This paper summarizes the sources of several important stromal cells and their effects on tumor cells, which provides a theoretical basis for the treatment of OSCC.展开更多
The stability of anion exchange membranes(AEMs) is an important feature of alkaline exchange membrane fuel cells(AEMFCs), which has been extensively studied. However it remains a real challenge due to the harsh workin...The stability of anion exchange membranes(AEMs) is an important feature of alkaline exchange membrane fuel cells(AEMFCs), which has been extensively studied. However it remains a real challenge due to the harsh working condition. Herein, we developed a novel type of polysulfone-based AEMs with three modified 1,2-dimethylbenzimidazoliums containing different substitutes at C4-and C7-position. The results showed that the introduction of the substitutes could obviously improve the dimensional and alkaline stabilities of the corresponding membranes. The swelling ratios of resultant AEMs were all lower than 10% after water immersion. The membrane with 4,7-dimethoxy-1,2-dimethylbenzimidazolium group exhibited the highest alkaline stability. Only 9.2% loss of hydroxide conductivity was observed after treating the membrane in 1 mol·L^(-1) KOH solution at 80 °C for 336 h. Furthermore, the density functional theory(DFT) study on the three functional group models showed that the substitutes at C4-and C7-position affected the lowest unoccupied molecular orbital(LUMO) energies of the different 1,2-dimethylbenzimidazolium groups.展开更多
Due to the nature of the solute redistribution,the reduction in the solidification rate with time in a square root relationship,and the multiphase melt flow during the solidification,casting defects such as macrosegre...Due to the nature of the solute redistribution,the reduction in the solidification rate with time in a square root relationship,and the multiphase melt flow during the solidification,casting defects such as macrosegregation,shrinkage cavity,and porosity will inevitably occur in the steel ingot and intensify with the increase in ingot size.These defects directly affect the performance of the final product and severely restrict the choice of subsequent thermal processing methods and process windows.Therefore,the solidification defects including macrosegregation,shrinkage/porosity,and inclusions encountered in the preparation of large steel ingots and their formation mechanisms were reviewed.The development progress and the latest development of the macrosegregation model for steel ingots were introduced in detail,especially the latest progress in the coupling prediction of macrosegregation and shrinkage as well as macrosegregation and inclusions.Some methods to reduce macrosegregation of ingots were discussed as well.Finally,a new casting method called layered casting was introduced in detail.This method can effectively improve the uniformity of the macrostructure and reduce the macrosegregation of the large ingots and therefore is a promising method for preparing large ingots with high homogeneity.展开更多
基金supported by the National Natural Science Foundation of China (32172972,U19A2040)Science and Technology Innovation Program of Hunan Province (2021RC4028)+4 种基金Earmarked Fund for China Agriculture Research System (CARS-45)Hunan Provincial Science and Technology Department (2019RS5001)Special Funds for Construction of Innovative Provinces in Hunan Province (2021NK1010)Special Science Found of Nansha-South China Agricultural University Fishery Research Institute,Guangzhou (NSYYKY202305,NSYYKY202306)Aid Program for Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Province。
文摘The autotetraploid Carassius auratus(4nRR,4n=200,RRRR)is derived from whole-genome duplication of Carassius auratus red var.(RCC,2n=100,RR).In the current study,we demonstrated that chromatophores and pigment changes directly caused the coloration and variation of 4nRR skin(red in RCC,brownish-yellow in4nRR).To further explore the molecular mechanisms underlying coloration formation and variation in 4nRR,we performed transcriptome profiling and molecular functional verification in RCC and 4nRR.Results revealed that scarb1,associated with carotenoid metabolism,underwent significant down-regulation in 4nRR.Efficient editing of this candidate pigment gene provided clear evidence of its significant role in RCC coloration.Subsequently,we identified four divergent scarb1 homeologs in 4nRR:two original scarb1 homeologs from RCC and two duplicated ones.Notably,three of these homeologs possessed two highly conserved alleles,exhibiting biased and allelespecific expression in the skin.Remarkably,after precise editing of both the original and duplicated scarb1homeologs and/or alleles,4nRR individuals,whether singly or multiply mutated,displayed a transition from brownishyellow skin to a cyan-gray phenotype.Concurrently,the proportional areas of the cyan-gray regions displayed a gene-dose correlation.These findings illustrate the subfunctionalization of duplicated scarb1,with all scarb1genes synergistically and equally contributing to the pigmentation of 4nRR.This is the first report concerning the functional differentiation of duplicated homeologs in an autopolyploidfish,substantiallyenrichingour understanding of coloration formation and change within this group of organisms.
基金supported by grants from the National Science and Technology Major Project(2012ZX10002004)Scientific Research Fund of Zhejiang Provincial Education Department(Y201328037)the opening foundation of the State Key Laboratory for Diagnosis and Treatment of Infectious Diseases and Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases,First Affiliated Hospital,Zhejiang University School of Medicine(2015KF04)
文摘BACKGROUND:Plasma exchange(PE)-centered artificial liver support system reduced the high mortality rate of hepatitis B virus(HBV)-related acute-on-chronic liver failure(ACLF).But the data were diverse in different medical centers.The present prospective nationwide study was to evaluate the effects of PE on patients with HBV-ACLF at different stages.METHODS:From December 2009 to December 2011,we evaluated 250 patients at different stages of HBV-ACLF from 10 major medical centers in China.All the laboratory parameters were collected at admission,before and after PE.RESULTS:Among the 250 patients who underwent 661 rounds of PE,one-month survival rate was 61.6%; 141(56.4%) showed improvement after PE.Variables such as age(P=0.000),levels of total bilirubin(TB,P=0.000),direct bilirubin(P=0.000),total triglycerides(P=0.000),low-density lipoprotein(P=0.022),Na+(P=0.014),Cl–(P=0.038),creatinine(Cr,P=0.007),fibrinogen(P=0.000),prothrombin time(PT,P=0.000),white blood cell(P=0.000),platelet(P=0.003) and MELD(P=0.000) were significantly related to prognosis.Multivariate logistic regression analysis showed that age,disease stage,TB,Cr and PT levels were independent risk factors of mortality among HBV-ACLF patients.CONCLUSIONS:PE can improve the clinical outcome of patients with HBV-ACLF.Levels of TB,Cr and PT,age and disease stage help to predict prognosis.
基金Supported by Grants from Key Medical Specialties Fund of Shanghai Municipal Health Bureau(partially),No.05II 011 2-1Glaxo Smith Kline(China)Investment Co,Ltd,Project 110353
文摘AIM: To observe the effect of response-guided add-on therapy with adefovir(ADV) and lamivudine(LAM) in cirrhotic hepatitis B(CHB) patients.METHODS: A total of 100 patients with CHB and cirrhosis were divided into three arms according to hepatitis B virus(HBV) DNA level after 24 wk LAM monotherapy: Arm A(complete response, HBV DNA ≤ 60 IU/m L, n = 49), Arm B(partial response, HBV DNA: 60-2000 IU/m L, n = 31) and Arm C(inadequate response, HBV DNA > 2000 IU/m L, n = 20). ADV was added to LAM at week 48 in Arms A and B, but at week 24 in Arm C. Virological response, YMDD mutations, biochemical response, and liver function were evaluated.RESULTS: Comparison of the three arms demonstrated that early complete virologic response at week 24was associated with maintained viral suppression(undetectable rate of HBV DNA at week 144 was 95.96%, 66.67% and 35.29%, respectively, P = 0.000) and reduced YMDD mutations(mutation rate at week 144 was 0%, 3.23% and 15%, respectively, P = 0.015) after 144 wk treatment. For patients who failed to achieve complete virological response at week 24, switching to combination therapy further decreased HBV DNA level by 1 log10 IU/m L. All three arms obtained biochemical benefits including decline of alanine aminotransferase and elevation of albumin. In patients who developed HBV DNA breakthrough for YMDD mutations, ADV add-on therapy did not induce further multiple drug resistance to LAM or ADV.CONCLUSION: Optimized response-guided add-on therapy of ADV and LAM maintains long-term suppression of HBV DNA and improves liver function in CHB patients with compensated liver cirrhosis.
基金supported by grants from the Science&Technology Key Program of Zhejiang China(2017C03051)the National Science&Technology Major Project of China(2017ZX10203201)。
文摘Background:Hepatitis B virus-related acute-on-chronic liver failure(HBV-ACLF)has a high short-term mortality.However,the treatment progression for HBV-ACLF in China in the past decade has not been well characterized.The present study aimed to determine whether the HBV-ACLF treatment has significantly improved during the past decade.Methods:This study retrospectively compared short-term(28/56 days)survival rates of two different nationwide cohorts(cohort I:2008-2011 and cohort II:2012-2015).Eligible HBV-ACLF patients were enrolled retrospectively.Patients in the cohorts I and II were assigned either to the standard medical therapy(SMT)group(cohort I-SMT,cohort II-SMT)or artificial liver support system(ALSS)group(cohort IALSS,cohort II-ALSS).Propensity score matching analysis was conducted to eliminate baseline differences,and multivariate logistic regression analysis was used to explore the independent factors for 28-day survival.Results:Short-term(28/56 days)survival rates were significantly higher in the ALSS group than those in the SMT group(P<0.05)and were higher in the cohort II than those in the cohort I(P<0.001).After propensity score matching,short-term(28/56 days)survival rates were higher in the cohort II than those in the cohort I for both SMT(60.7%vs.53.0%,50.0%vs.39.8%,P<0.05)and ALSS(66.1%vs.56.5%,53.0%vs.44.4%,P<0.05)treatments.The 28-day survival rate was higher in patients treated with nucleos(t)ide analogs than in patients without such treatments(P=0.046).Multivariate logistic regression analysis revealed that ALSS(OR=0.962,95%CI:0.951-0.973,P=0.038),nucleos(t)ide analogs(OR=0.927,95%CI:0.871-0.983,P=0.046),old age(OR=1.028,95%CI:1.015-1.041,P<0.001),total bilirubin(OR=1.002,95%CI:1.001-1.003,P=0.004),INR(OR=1.569,95%CI:1.044-2.358,P<0.001),COSSH-ACLF grade(OR=2.683,95%CI:1.792-4.017,P<0.001),and albumin(OR=0.952,95%CI:0.924-0.982,P=0.002)were independent factors for 28-day mortality.Conclusions:The treatment for patients with HBV-ACLF has improved in the past decade.
基金supported by grants from Key Research and Development Project of Department of Science and Technology of Zhejiang Province(2017C03051)Science Fund for Creative Research Groups of the National Natural Science Foundation of China(81721091)
文摘Severe deterioration of liver function in patients can be characterized by coagulation disorders, jaundice, hepatic encephalopathy, ascites, and other symptoms. Severe liver injury can develop as acute liver failure, subacute liver failure, acute-on-chronic liver failure, or further worsening of end-stage liver disease [1].
基金National Natural Science Foundation of China(81320108011)Provincial Industrial Innovation Project 2016C044-3 in Jilin ProvinceJilin Natural Science Foundation 20170101093JC.
文摘Oral squamous cell carcinoma (OSCC) is the most common malignant tumour in oral and maxillofacial region. The interaction between stromal cells and tumor cells is involved in the proliferation, differentiation, apoptosis, adhesion and migration of tumor cells, and is closely related to the malignant degree and prognosis of tumors. The development of OSCC is of great significance to the treatment of OSCC. This paper summarizes the sources of several important stromal cells and their effects on tumor cells, which provides a theoretical basis for the treatment of OSCC.
基金financially supported by the National Natural Science Foundation of China (No. 21404018)Fundamental Research Funds for the Central Universities (No. DUT16RC(4)79)+2 种基金Education Department of the Liaoning Province (No. LT2015007)Fundamental Research Funds for the Central Universities (No. DUT16TD19)Chang Jiang Scholar Program (No. T2012049)
文摘The stability of anion exchange membranes(AEMs) is an important feature of alkaline exchange membrane fuel cells(AEMFCs), which has been extensively studied. However it remains a real challenge due to the harsh working condition. Herein, we developed a novel type of polysulfone-based AEMs with three modified 1,2-dimethylbenzimidazoliums containing different substitutes at C4-and C7-position. The results showed that the introduction of the substitutes could obviously improve the dimensional and alkaline stabilities of the corresponding membranes. The swelling ratios of resultant AEMs were all lower than 10% after water immersion. The membrane with 4,7-dimethoxy-1,2-dimethylbenzimidazolium group exhibited the highest alkaline stability. Only 9.2% loss of hydroxide conductivity was observed after treating the membrane in 1 mol·L^(-1) KOH solution at 80 °C for 336 h. Furthermore, the density functional theory(DFT) study on the three functional group models showed that the substitutes at C4-and C7-position affected the lowest unoccupied molecular orbital(LUMO) energies of the different 1,2-dimethylbenzimidazolium groups.
基金This work is sponsored by the National Natural Science Foundation of China(Grant No.52074182)Natural Science Foundation of Shanghai(Grant No.22ZR1430700).
文摘Due to the nature of the solute redistribution,the reduction in the solidification rate with time in a square root relationship,and the multiphase melt flow during the solidification,casting defects such as macrosegregation,shrinkage cavity,and porosity will inevitably occur in the steel ingot and intensify with the increase in ingot size.These defects directly affect the performance of the final product and severely restrict the choice of subsequent thermal processing methods and process windows.Therefore,the solidification defects including macrosegregation,shrinkage/porosity,and inclusions encountered in the preparation of large steel ingots and their formation mechanisms were reviewed.The development progress and the latest development of the macrosegregation model for steel ingots were introduced in detail,especially the latest progress in the coupling prediction of macrosegregation and shrinkage as well as macrosegregation and inclusions.Some methods to reduce macrosegregation of ingots were discussed as well.Finally,a new casting method called layered casting was introduced in detail.This method can effectively improve the uniformity of the macrostructure and reduce the macrosegregation of the large ingots and therefore is a promising method for preparing large ingots with high homogeneity.
