Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chem...Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.展开更多
目的:探讨高效液相色谱法(HPLC)血红蛋白A2/F/A1c检测在β-地中海贫血筛查中的应用。方法:收集本院2020年7月-2022年7月在本院行婚前检验的2642人次临床资料,均采用全自动血红蛋白分析仪检测红细胞指数及异常血红蛋白、RDB法分析β-地...目的:探讨高效液相色谱法(HPLC)血红蛋白A2/F/A1c检测在β-地中海贫血筛查中的应用。方法:收集本院2020年7月-2022年7月在本院行婚前检验的2642人次临床资料,均采用全自动血红蛋白分析仪检测红细胞指数及异常血红蛋白、RDB法分析β-地贫基因型,并分别应用HPLC血红蛋白A2/F/A1c检测试剂(研究试剂盒)及对比试剂盒(VARIANTⅡβ-thalassemia Short Program)进行HbA2检测,评估血红蛋白A2/F/A1c试剂筛查β-地中海贫血效果。结果:共筛查2642人次,筛查β-地中海贫血阳性率7.0%,其中β-地贫轻型177例,中间型4例,重型3例;根据HPLC中异常Hb滞留时间、总Hb占比及色谱图形特征,共发现5种异常Hb;采用RDB法共检测到7种β-地贫基因型,以CD41-42(-TCTT)、IVS-Ⅱ-654(C-T)、CD17(A-T)和-28(A-G)最为常见,重型β-地贫基因型为IVS-Ⅱ-654(C-T),中间型基因型为-28(A-G)纯合子;研究试剂盒与对照试剂盒检测阳性符合率为97.8%,阴性符合率为99.9%,总体符合率为99.7%。结论:HPLC技术人为因素影响小,适用于大规模人群筛查;血红蛋白A2/F/A1c试剂检测HbA2具有方便快捷、费用低廉、准确性高等优势,在临床筛查β-地贫应用效果较好。展开更多
KVPO_(4)F(KVPF)has been extensively investigated as the potential cathode material for potassium-ion batteries(PIBs)owing to its high theoretical capacity,superior operating voltage,and three-dimensional Kt conduction...KVPO_(4)F(KVPF)has been extensively investigated as the potential cathode material for potassium-ion batteries(PIBs)owing to its high theoretical capacity,superior operating voltage,and three-dimensional Kt conduction pathway.Nevertheless,the electrochemical behavior of KVPF is limited by the inherent poor electronic conductivity of the phosphate framework and unstable electrode/electrolyte interface.To address the above issues,this work proposes an infiltration-calcination method to confine the in-situ grown KVPF into the mesoporous carbon CMK-3(denoted KVPF@CMK-3).The assembled KVPF@CMK-3 nanocomposite features three-dimensional interconnected carbon channels,which not only offer abundant active sites and significantly accelerate K t/electron transport,but also prevent the growth of KVPF nanoparticle agglomerates,hence stabilizing the structure of the material.Additionally,V–F–C bonds are created at the interface of KVPF and CMK-3,which reduce the loss of F and stabilize the electrode interface.Thus,when tested as a cathode material for PIBs,the KVPF@CMK-3 nanocomposite delivers superior reversible capacitiy(103.2 mAh g^(-1) at 0.2 C),outstanding rate performance(90.1 mAh g^(-1) at 20 C),and steady cycling performance(92.2 mAh g^(-1) at 10 C and with the retention of 88.2%after 500 cycles).Moreover,its potassium storage mechanism is further examined by ex-situ XRD and ex-situ XPS techniques.The above synthetic strategy demonstrates the potential of KVPF@CMK-3 to be applied as the cathode for PIBs.展开更多
Background:Exercise training protects against heart failure.However,the mechanism underlying the protective effect of exercise training on angiotensinⅡ(AngⅡ)-induced cardiac fibrosis remains unclear.Methods:An exerc...Background:Exercise training protects against heart failure.However,the mechanism underlying the protective effect of exercise training on angiotensinⅡ(AngⅡ)-induced cardiac fibrosis remains unclear.Methods:An exercise model involving C57BL/6N mice and 6 weeks of treadmill training was used.AngⅡ(1.44 mg/kg/day)was administered to induce cardiac fibrosis.RNA sequencing and bioinformatic analysis were used to identify the key factors mediating the effects of exercise training on cardiac fibrosis.Primary adult mouse cardiac fibroblasts(CFs)were used in vitro.Adeno-associated virus serotype 9 was used to overexpress POU domain,class 2,transcription factor 1(POU2F1)in vivo.Results:Exercise training attenuated AngⅡ-induced cardiac fibrosis and reversed 39 gene expression changes.The transcription factor regulating the largest number of these genes was POU2F1.Compared to controls,POU2F1 was shown to be signififcantly upregulated by AngⅡ,which is itself reduced by exercise training.In vivo,POU2F1 overexpression nullified the benefits of exercise training on cardiac fibrosis.In CFs,POU2F1 promoted cardiac fibrosis.CCAAT enhancer-binding proteinβ(C/EBPβ)was predicted to be the transcription factor of POU2F1and verified using a dual-luciferase reporter assay.In vivo,exercise training activated AMP-activated protein kinase(AMPK)and alleviated the increase in C/EBPβinduced by AngⅡ.In CFs,AMPK agonist inhibited the increase in C/EBPβand POU2F1 induced by Ang II,whereas AMPK inhibitor reversed this effect.Conclusion:Exercise training attenuates AngⅡ-induced cardiac fibrosis by reducing POU2F1.Exercise training inhibits POU2F1 by activating AMPK,which is followed by the downregulation of C/EBPβ,the transcription factor of POU2F1.展开更多
基金National Yang Ming Chiao Tung University Far Eastern Memorial Hospital Joint Research Programs(NYCU-FEMH 109DN03,110DN06,111DN04,112DN05).
文摘Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.
文摘目的:探讨高效液相色谱法(HPLC)血红蛋白A2/F/A1c检测在β-地中海贫血筛查中的应用。方法:收集本院2020年7月-2022年7月在本院行婚前检验的2642人次临床资料,均采用全自动血红蛋白分析仪检测红细胞指数及异常血红蛋白、RDB法分析β-地贫基因型,并分别应用HPLC血红蛋白A2/F/A1c检测试剂(研究试剂盒)及对比试剂盒(VARIANTⅡβ-thalassemia Short Program)进行HbA2检测,评估血红蛋白A2/F/A1c试剂筛查β-地中海贫血效果。结果:共筛查2642人次,筛查β-地中海贫血阳性率7.0%,其中β-地贫轻型177例,中间型4例,重型3例;根据HPLC中异常Hb滞留时间、总Hb占比及色谱图形特征,共发现5种异常Hb;采用RDB法共检测到7种β-地贫基因型,以CD41-42(-TCTT)、IVS-Ⅱ-654(C-T)、CD17(A-T)和-28(A-G)最为常见,重型β-地贫基因型为IVS-Ⅱ-654(C-T),中间型基因型为-28(A-G)纯合子;研究试剂盒与对照试剂盒检测阳性符合率为97.8%,阴性符合率为99.9%,总体符合率为99.7%。结论:HPLC技术人为因素影响小,适用于大规模人群筛查;血红蛋白A2/F/A1c试剂检测HbA2具有方便快捷、费用低廉、准确性高等优势,在临床筛查β-地贫应用效果较好。
基金This work was supported by the National Natural Science Foundation of China(22179063).
文摘KVPO_(4)F(KVPF)has been extensively investigated as the potential cathode material for potassium-ion batteries(PIBs)owing to its high theoretical capacity,superior operating voltage,and three-dimensional Kt conduction pathway.Nevertheless,the electrochemical behavior of KVPF is limited by the inherent poor electronic conductivity of the phosphate framework and unstable electrode/electrolyte interface.To address the above issues,this work proposes an infiltration-calcination method to confine the in-situ grown KVPF into the mesoporous carbon CMK-3(denoted KVPF@CMK-3).The assembled KVPF@CMK-3 nanocomposite features three-dimensional interconnected carbon channels,which not only offer abundant active sites and significantly accelerate K t/electron transport,but also prevent the growth of KVPF nanoparticle agglomerates,hence stabilizing the structure of the material.Additionally,V–F–C bonds are created at the interface of KVPF and CMK-3,which reduce the loss of F and stabilize the electrode interface.Thus,when tested as a cathode material for PIBs,the KVPF@CMK-3 nanocomposite delivers superior reversible capacitiy(103.2 mAh g^(-1) at 0.2 C),outstanding rate performance(90.1 mAh g^(-1) at 20 C),and steady cycling performance(92.2 mAh g^(-1) at 10 C and with the retention of 88.2%after 500 cycles).Moreover,its potassium storage mechanism is further examined by ex-situ XRD and ex-situ XPS techniques.The above synthetic strategy demonstrates the potential of KVPF@CMK-3 to be applied as the cathode for PIBs.
基金supported by the National Natural Science Foundation of China(82030072 to HX,81871850 to HY,81972149 to WG,and 81830009 to YZ)Beijing Natural Science Foundation(No.7212125 to HY)+2 种基金National Key R&D Program of China(Grant No.2020YFA0803800 to HY)the Key Clinical Projects of Peking University Third Hospital(BYSYZD2019022 to HX)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(No.2021-I2M-5-003 to HX and YZ)。
文摘Background:Exercise training protects against heart failure.However,the mechanism underlying the protective effect of exercise training on angiotensinⅡ(AngⅡ)-induced cardiac fibrosis remains unclear.Methods:An exercise model involving C57BL/6N mice and 6 weeks of treadmill training was used.AngⅡ(1.44 mg/kg/day)was administered to induce cardiac fibrosis.RNA sequencing and bioinformatic analysis were used to identify the key factors mediating the effects of exercise training on cardiac fibrosis.Primary adult mouse cardiac fibroblasts(CFs)were used in vitro.Adeno-associated virus serotype 9 was used to overexpress POU domain,class 2,transcription factor 1(POU2F1)in vivo.Results:Exercise training attenuated AngⅡ-induced cardiac fibrosis and reversed 39 gene expression changes.The transcription factor regulating the largest number of these genes was POU2F1.Compared to controls,POU2F1 was shown to be signififcantly upregulated by AngⅡ,which is itself reduced by exercise training.In vivo,POU2F1 overexpression nullified the benefits of exercise training on cardiac fibrosis.In CFs,POU2F1 promoted cardiac fibrosis.CCAAT enhancer-binding proteinβ(C/EBPβ)was predicted to be the transcription factor of POU2F1and verified using a dual-luciferase reporter assay.In vivo,exercise training activated AMP-activated protein kinase(AMPK)and alleviated the increase in C/EBPβinduced by AngⅡ.In CFs,AMPK agonist inhibited the increase in C/EBPβand POU2F1 induced by Ang II,whereas AMPK inhibitor reversed this effect.Conclusion:Exercise training attenuates AngⅡ-induced cardiac fibrosis by reducing POU2F1.Exercise training inhibits POU2F1 by activating AMPK,which is followed by the downregulation of C/EBPβ,the transcription factor of POU2F1.
