Benzo[a]pyrene(B[a]P)is a food contaminant toxic for cardiovascular diseases.The nuclear translocation of Arylhydrocarbon receptor(AhR)plays an important role in B[a]P-induced oxidative stress and vascular diseases.We...Benzo[a]pyrene(B[a]P)is a food contaminant toxic for cardiovascular diseases.The nuclear translocation of Arylhydrocarbon receptor(AhR)plays an important role in B[a]P-induced oxidative stress and vascular diseases.We confi rmed that B[a]P promoted ROS production in vascular smooth muscle cells(VSMCs)in vitro and in vivo,associated with the nuclear translocation of AhR.It is known that phosphorylation inhibits while dephosphorylation of AhR promotes nuclear translocation of AhR.However,from the posttranslational modifi cation level,the mechanism by which B[a]P activates and regulates the nuclear translocation of AhR is unclear.Co-immunoprecipitation results showed that cytoplasmic AhR was phosphorylated before B[a]P stimulation,and switched to O-GlcNAcylation upon B[a]P 1-h stimulation in VSMCs,suggesting there may be a competitively inhibitory relationship between O-GlcNAcylation and phosphorylation of AhR.Next,siRNAs of O-linked N-acetylglucosamine transferase(OGT),O-GlcNAcase(OGA)and OGA inhibitor PUGNAc were used.SiOGT blocks but siOGA and PUGNAc promote B[a]P-dependent AhR nuclear translocation and oxidative stress.Ser11 may be the competitive binding site for phosphorylation and O-GlcNAcylation of AhR.Phosphorylation-mimic variant inhibits but O-GlcNAcylation of AhR promotes AhR nuclear translocation and oxidative stress.Our fi ndings highlight a new perspective for AhR nuclear translocation regulated by the competitive modifi cation between phosphorylation and O-GlcNAcylation.展开更多
基于文献计量分析方法,利用Citespace及Excel软件工具,通过对2012-2022年Web of Science核心数据库和知网学术期刊数据库中的文献进行分析,了解花生育种及栽培相关研究的热点和趋势。中国、印度和美国是花生研究的主要国家,其中中国的...基于文献计量分析方法,利用Citespace及Excel软件工具,通过对2012-2022年Web of Science核心数据库和知网学术期刊数据库中的文献进行分析,了解花生育种及栽培相关研究的热点和趋势。中国、印度和美国是花生研究的主要国家,其中中国的发文数量持续攀升,显示出中国花生研究在国际上的强劲势头。国际合作网络也日益密切,中国、印度和美国为合作中心,合作伙伴数量逐渐扩大,合作方式逐渐多样化。在国内方面,山东省农业科学院等机构主导了花生研究,国内机构合作网络密切,表现出活跃的合作关系,体现了全国各地花生研究的广泛分布和协同发展。研究热点方面,英文文献从基础特性和遗传抗性逐步过渡到分子水平、脂肪酸含量,最终拓展至生态系统和生长机制;中文文献则强调花生作物在特定环境下的适应性,包括对抗旱、连作等压力的关注。本文的研究结果为深入了解花生科研热点与发展趋势提供了有益参考。展开更多
BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy ...BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.展开更多
Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed ...Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast cancer.During this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor microenvironment.Interestingly,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic targets.Mechanistic investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of G-MDSC.On the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)subsets.In summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.展开更多
目的研究高效价IgG血型抗体孕妇血清中IgG亚型与胎儿新生儿溶血病(hemolytic disease of the fetus and newborn,HDFN)及高胆红素血症发生率的相关性,评价IgG亚型检测的临床价值。方法对2020年1月~2021年10月在西安大兴医院进行产前免...目的研究高效价IgG血型抗体孕妇血清中IgG亚型与胎儿新生儿溶血病(hemolytic disease of the fetus and newborn,HDFN)及高胆红素血症发生率的相关性,评价IgG亚型检测的临床价值。方法对2020年1月~2021年10月在西安大兴医院进行产前免疫血清学检测的225例高效价IgG抗体孕妇(其中ABO血型系统217例,Rh血型系统8例),采用微柱凝胶技术检测其IgG亚型,对新生儿脐血进行新生儿溶血系列检测,生化分析仪检测新生儿血清胆红素水平,分析孕妇血清IgG亚型与HDFN及高胆红素血症发生率的相关性。结果217例高效价IgG抗-A(B)孕妇血清中IgG1/IgG3亚型134例(占比61.75%),IgG1/IgG3混合型18例(占比8.29%),IgG2/IgG4亚型检出65例(占比29.95%);8例高效价Rh系统IgG抗体均为IgG1和/或IgG3亚型,未检出IgG2或IgG4亚型。IgG1/IgG3亚型组中HDFN发生率为79.29%(111/140),高胆红素血症发生率为55.71%(78/140);IgG1/IgG3混合型组中HDFN发生率为90.00%(18/20),高胆红素血症发生率为70.00%(14/20);IgG2/IgG4亚型组中HDFN发生率为15.38%(10/65),未发生高胆红素血症。IgG1/IgG3亚型组与IgG1/IgG3混合型组HDFN及高胆红素血症发生率比较差异无统计学意义(χ^(2)=0.692,1.461,均P>0.05);IgG抗体效价1∶256及效价1∶512,HDFN发生率分别为64.28%,56.94%,IgG1/IgG3单独存在组、混合型组和IgG2/IgG4组随抗体效价增高HDFN发生率未增加,差异均无统计学意义(χ^(2)=0.231,2.813,均P>0.05)。结论血型抗体高效价孕妇血清中IgG亚型类别与HDFN及高胆红素血症发生率具有相关性,产前检测血型抗体IgG亚型,对HDFN及高胆红素血症的精准预防和治疗具有指导意义。展开更多
基金supported by the National Key Research Project of China(2022YFF1100300)National Natural Science Foundation of China(32272328)+5 种基金Natural Science Foundation of Hebei Province(B2022321001)Major Public Welfare Projects in Henan Province(201300110200)National Key Research Project of Hebei Province(20375502D)National Key Research Project of Hebei Province(H2021206427)University Science and Technology Research Project of Hebei Province(QN2017107)Postdoctoral Research Funds of Hebei Medical University(307050100163759).
文摘Benzo[a]pyrene(B[a]P)is a food contaminant toxic for cardiovascular diseases.The nuclear translocation of Arylhydrocarbon receptor(AhR)plays an important role in B[a]P-induced oxidative stress and vascular diseases.We confi rmed that B[a]P promoted ROS production in vascular smooth muscle cells(VSMCs)in vitro and in vivo,associated with the nuclear translocation of AhR.It is known that phosphorylation inhibits while dephosphorylation of AhR promotes nuclear translocation of AhR.However,from the posttranslational modifi cation level,the mechanism by which B[a]P activates and regulates the nuclear translocation of AhR is unclear.Co-immunoprecipitation results showed that cytoplasmic AhR was phosphorylated before B[a]P stimulation,and switched to O-GlcNAcylation upon B[a]P 1-h stimulation in VSMCs,suggesting there may be a competitively inhibitory relationship between O-GlcNAcylation and phosphorylation of AhR.Next,siRNAs of O-linked N-acetylglucosamine transferase(OGT),O-GlcNAcase(OGA)and OGA inhibitor PUGNAc were used.SiOGT blocks but siOGA and PUGNAc promote B[a]P-dependent AhR nuclear translocation and oxidative stress.Ser11 may be the competitive binding site for phosphorylation and O-GlcNAcylation of AhR.Phosphorylation-mimic variant inhibits but O-GlcNAcylation of AhR promotes AhR nuclear translocation and oxidative stress.Our fi ndings highlight a new perspective for AhR nuclear translocation regulated by the competitive modifi cation between phosphorylation and O-GlcNAcylation.
文摘基于文献计量分析方法,利用Citespace及Excel软件工具,通过对2012-2022年Web of Science核心数据库和知网学术期刊数据库中的文献进行分析,了解花生育种及栽培相关研究的热点和趋势。中国、印度和美国是花生研究的主要国家,其中中国的发文数量持续攀升,显示出中国花生研究在国际上的强劲势头。国际合作网络也日益密切,中国、印度和美国为合作中心,合作伙伴数量逐渐扩大,合作方式逐渐多样化。在国内方面,山东省农业科学院等机构主导了花生研究,国内机构合作网络密切,表现出活跃的合作关系,体现了全国各地花生研究的广泛分布和协同发展。研究热点方面,英文文献从基础特性和遗传抗性逐步过渡到分子水平、脂肪酸含量,最终拓展至生态系统和生长机制;中文文献则强调花生作物在特定环境下的适应性,包括对抗旱、连作等压力的关注。本文的研究结果为深入了解花生科研热点与发展趋势提供了有益参考。
基金Supported by Shanghai Hospital Development Center Foundation,No.SHDC2022CRS033.
文摘BACKGROUND Hepatocellular carcinoma(HCC)is one of the leading causes of death due to its complexity,heterogeneity,rapid metastasis and easy recurrence after surgical resection.We demonstrated that combination therapy with transcatheter arterial chemoembolization(TACE),hepatic arterial infusion chemotherapy(HAIC),Epclusa,Lenvatinib and Sintilimab is useful for patients with advanced HCC.CASE SUMMARY A 69-year-old man who was infected with hepatitis C virus(HCV)30 years previously was admitted to the hospital with abdominal pain.Enhanced computed tomography(CT)revealed a low-density mass in the right lobe of the liver,with a volume of 12.9 cm×9.4 cm×15 cm,and the mass exhibited a“fast-in/fast-out”pattern,with extensive filling defect areas in the right branch of the portal vein and an alpha-fetoprotein level as high as 657 ng/mL.Therefore,he was judged to have advanced HCC.During treatment,the patient received three months of Epclusa,three TACE treatments,two HAIC treatments,three courses of sintilimab,and twenty-one months of lenvatinib.In the third month of treatment,the patient developed severe side effects and had to stop immunotherapy,and the Lenvatinib dose had to be halved.Postoperative pathological diagnosis indicated a complete response.The patient recovered well after the operation,and no tumor recurrence was found.CONCLUSION Multidisciplinary conversion therapy for advanced enormous HCC caused by HCV infection has a significant effect.Individualized drug adjustments should be made during any treatment according to the patient's tolerance to treatment.
基金supported by the Postdoctoral Research Funds of Hebei Medical University(30705010016-3759)Natural Science Foundation of China(32272328)+4 种基金Natural Science Foundation of Hebei Province(B2022321001)National Key Research Project of Hebei Province(20375502D)Postdoctoral Research Project of Hebei Province(B2022003031)Science and Technology Research Program of Hebei Provincial Colleges(QN2023229)Hebei Provincial Key Laboratory of Nutrition and Health(2023YDYY-KF05)。
文摘Intermittent fasting can benefit breast cancer patients undergoing chemotherapy or immunotherapy.However,it is still uncertain how to select immunotherapy drugs to combine with intermittent fasting.Herein we observed that two cycles of fasting treatment significantly inhibited breast tumor growth and lung tissue metastasis,as well as prolonged overall survival in mice bearing 4T1 and 4T07 breast cancer.During this process,both the immunosuppressive monocytic-(M-)and granulocytic-(G-)myeloid-derived suppressor cell(MDSC)decreased,accompanied by an increase in interleukin(IL)7R^(+)and granzyme B^(+)T cells in the tumor microenvironment.Interestingly,we observed that Ly6G^(low)G-MDSC sharply decreased after fasting treatment,and the cell surface markers and protein mass spectrometry data showed potential therapeutic targets.Mechanistic investigation revealed that glucose metabolism restriction suppressed the splenic granulocytemonocyte progenitor and the generation of colony-stimulating factors and IL-6,which both contributed to the accumulation of G-MDSC.On the other hand,glucose metabolism restriction can directly induce the apoptosis of Ly6G^(low)G-MDSC,but not Ly6G^(high)subsets.In summary,these results suggest that glucose metabolism restriction induced by fasting treatment attenuates the immune-suppressive milieu and enhances the activation of CD3^(+)T cells,providing potential solutions for enhancing immune-based cancer interventions.
文摘目的研究高效价IgG血型抗体孕妇血清中IgG亚型与胎儿新生儿溶血病(hemolytic disease of the fetus and newborn,HDFN)及高胆红素血症发生率的相关性,评价IgG亚型检测的临床价值。方法对2020年1月~2021年10月在西安大兴医院进行产前免疫血清学检测的225例高效价IgG抗体孕妇(其中ABO血型系统217例,Rh血型系统8例),采用微柱凝胶技术检测其IgG亚型,对新生儿脐血进行新生儿溶血系列检测,生化分析仪检测新生儿血清胆红素水平,分析孕妇血清IgG亚型与HDFN及高胆红素血症发生率的相关性。结果217例高效价IgG抗-A(B)孕妇血清中IgG1/IgG3亚型134例(占比61.75%),IgG1/IgG3混合型18例(占比8.29%),IgG2/IgG4亚型检出65例(占比29.95%);8例高效价Rh系统IgG抗体均为IgG1和/或IgG3亚型,未检出IgG2或IgG4亚型。IgG1/IgG3亚型组中HDFN发生率为79.29%(111/140),高胆红素血症发生率为55.71%(78/140);IgG1/IgG3混合型组中HDFN发生率为90.00%(18/20),高胆红素血症发生率为70.00%(14/20);IgG2/IgG4亚型组中HDFN发生率为15.38%(10/65),未发生高胆红素血症。IgG1/IgG3亚型组与IgG1/IgG3混合型组HDFN及高胆红素血症发生率比较差异无统计学意义(χ^(2)=0.692,1.461,均P>0.05);IgG抗体效价1∶256及效价1∶512,HDFN发生率分别为64.28%,56.94%,IgG1/IgG3单独存在组、混合型组和IgG2/IgG4组随抗体效价增高HDFN发生率未增加,差异均无统计学意义(χ^(2)=0.231,2.813,均P>0.05)。结论血型抗体高效价孕妇血清中IgG亚型类别与HDFN及高胆红素血症发生率具有相关性,产前检测血型抗体IgG亚型,对HDFN及高胆红素血症的精准预防和治疗具有指导意义。