The Global Leaders’Meeting on Women was held in Beijing,the capital of China,on 13-14 October.South African Minister in the Presidency for Women,Youth and Persons with Disabilities Sindisiwe Chikunga,attended the eve...The Global Leaders’Meeting on Women was held in Beijing,the capital of China,on 13-14 October.South African Minister in the Presidency for Women,Youth and Persons with Disabilities Sindisiwe Chikunga,attended the event.ChinAfrica spoke with her in an exclusive interview about the messages she brought to the meeting,South Africa’s progress in women’s empowerment,how the G20 presidency can contribute to this cause,and China’s role.An edited excerpt of the interview follows.展开更多
嵌合抗原受体T细胞(chimeric antigen receptor T cells,CAR-T)的出现使得多发性骨髓瘤(multiple myeloma,MM)患者的治疗进入了一个新的阶段,但大多数患者都难逃原发耐药或疾病复发的不良结局。G蛋白偶联受体C类5组成员D(G protein-coup...嵌合抗原受体T细胞(chimeric antigen receptor T cells,CAR-T)的出现使得多发性骨髓瘤(multiple myeloma,MM)患者的治疗进入了一个新的阶段,但大多数患者都难逃原发耐药或疾病复发的不良结局。G蛋白偶联受体C类5组成员D(G protein-coupled receptor class C group 5 member D,GPRC5D)是目前MM患者的一个有前景的治疗靶点,与GPRC5D CAR-T相关的Ⅰ期临床研究也都显示出较高的反应率和疗效。文章将对现有的靶向GPRC5D CAR-T细胞最新研究进行综述,旨在通过总结讨论目前不同GPRC5D CAR-T细胞治疗复发难治性MM的研究现状,对今后的临床治疗提供更多参考。展开更多
Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects ...Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.展开更多
Multi-nucleotide variants(MNVs)are critical genetic variants associated with various genetic diseases.However,tools for precisely installing MNVs are limited.In this study,we present the development of a dual-base edi...Multi-nucleotide variants(MNVs)are critical genetic variants associated with various genetic diseases.However,tools for precisely installing MNVs are limited.In this study,we present the development of a dual-base editor,BDBE,by integrating TadA-dual and engineered human N-methylpurine DNA glycosylase(eMPG)into nCas9(D10A).Our results demonstrate that BDBE effectively converts A-to-G/C/T(referred to as A-to-B)and C-to-T/G/A(referred to as C-to-D)simultaneously,yielding nine types of dinucleotides from adjacent CA nucleotides while maintaining minimal off-target effects.Notably,BDBE4 exhibits exceptional performance across multiple human cell lines and successfully simulated all nine dinucleotide MNVs from the gnomAD database.These findings indicate that BDBE significantly expands the product range of base editors and offers a valuable resource for advancing MNV research.展开更多
Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex ster...Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs proliferation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.展开更多
文摘The Global Leaders’Meeting on Women was held in Beijing,the capital of China,on 13-14 October.South African Minister in the Presidency for Women,Youth and Persons with Disabilities Sindisiwe Chikunga,attended the event.ChinAfrica spoke with her in an exclusive interview about the messages she brought to the meeting,South Africa’s progress in women’s empowerment,how the G20 presidency can contribute to this cause,and China’s role.An edited excerpt of the interview follows.
文摘嵌合抗原受体T细胞(chimeric antigen receptor T cells,CAR-T)的出现使得多发性骨髓瘤(multiple myeloma,MM)患者的治疗进入了一个新的阶段,但大多数患者都难逃原发耐药或疾病复发的不良结局。G蛋白偶联受体C类5组成员D(G protein-coupled receptor class C group 5 member D,GPRC5D)是目前MM患者的一个有前景的治疗靶点,与GPRC5D CAR-T相关的Ⅰ期临床研究也都显示出较高的反应率和疗效。文章将对现有的靶向GPRC5D CAR-T细胞最新研究进行综述,旨在通过总结讨论目前不同GPRC5D CAR-T细胞治疗复发难治性MM的研究现状,对今后的临床治疗提供更多参考。
基金supported by the National Key Research and Development Program of China(Grant No.2019YFC1605000)National Natural Science Foundation of China(Grant No.31871806)the Beijing Livestock Industry Innovation Team(BAIC05-2023)。
文摘Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.
基金supported by the National Key Research and Development Program of China(2021YFC2700904,2021YFF0702601,2021YFA0805300)the National Natural Science Foundation of China(82071723,82100482,82101733)+2 种基金Guangdong Basic and Applied Basic Research Foundation(2021B1515020069)Guangzhou Science and Technology Planning Project(2023A03J0377)Research Unit of Generation of Large Animal Disease Models,Chinese Academy of Medical Sciences(2019-I2M-5-025)。
文摘Multi-nucleotide variants(MNVs)are critical genetic variants associated with various genetic diseases.However,tools for precisely installing MNVs are limited.In this study,we present the development of a dual-base editor,BDBE,by integrating TadA-dual and engineered human N-methylpurine DNA glycosylase(eMPG)into nCas9(D10A).Our results demonstrate that BDBE effectively converts A-to-G/C/T(referred to as A-to-B)and C-to-T/G/A(referred to as C-to-D)simultaneously,yielding nine types of dinucleotides from adjacent CA nucleotides while maintaining minimal off-target effects.Notably,BDBE4 exhibits exceptional performance across multiple human cell lines and successfully simulated all nine dinucleotide MNVs from the gnomAD database.These findings indicate that BDBE significantly expands the product range of base editors and offers a valuable resource for advancing MNV research.
基金supported by the National Natural Science Foundation of China(Grant Nos.:82073906 and 82273987)Priority Academic Program Development(PAPD)of Jiangsu Higher Education Institutions,and Postgraduate Research Practice Innovation Program of Jiangsu Province(Grant Nos.:KYCX22-2966 and KYCX23-2967).
文摘Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs proliferation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.
