Studies on diabetes have long been hampered by a lack of authentic disease models that,ideally,should be unlimited and able to recapitulate the abnormalities involved in the development,structure,and function of human...Studies on diabetes have long been hampered by a lack of authentic disease models that,ideally,should be unlimited and able to recapitulate the abnormalities involved in the development,structure,and function of human pancreatic islets under pathological conditions.Stem cell-based islet organoids faithfully recapitulate islet development in vitro and provide large amounts of three-dimensional functional islet biomimetic materials with a morphological structure and cellular composition similar to those of native islets.Thus,islet organoids hold great promise for modeling islet development and function,deciphering the mechanisms underlying the onset of diabetes,providing an in vitro human organ model for infection of viruses such as SARS-CoV-2,and contributing to drug screening and autologous islet transplantation.However,the currently established islet organoids are generally immature compared with native islets,and further efforts should be made to improve the heterogeneity and functionality of islet organoids,making it an authentic and informative disease model for diabetes.Here,we review the advances and challenges in the generation of islet organoids,focusing on human pluripotent stem cell-derived islet organoids,and the potential applications of islet organoids as disease models and regenerative therapies for diabetes.展开更多
AIM:To investigate the relationship between blood riboflavin levels and riboflavin transporter 2(RFT2) gene expression in gastric carcinoma(GC) development.METHODS:High-performance liquid chromatography was used to de...AIM:To investigate the relationship between blood riboflavin levels and riboflavin transporter 2(RFT2) gene expression in gastric carcinoma(GC) development.METHODS:High-performance liquid chromatography was used to detect blood riboflavin levels in patients with GC.Real-time fluorogenic quantitative polymerase chain reaction and immunohistochemistry were used to analyze the expression of RFT2 mRNA and protein in samples from 60 GC patients consisting of both tumor and normal tissue.RESULTS:A significant decrease in the RFT2 mRNA levels was detected in GC samples compared with those in the normal mucous membrane(0.398 ± 0.149 vs 1.479 ± 0.587;P = 0.040).Tumors exhibited low RFT2 protein expression(75%,16.7%,8.3% and 0% for no RFT2 staining,weak staining,medium staining and strong staining,respectively),which was significantly lower than that in the normal mucous membrane(10%,16.7%,26.7% and 46.7% for no RFT2 staining,weak staining,medium staining and strong staining,respectively;P < 0.05).Tumors with low RFT2 expression were significantly associated with tumor stage and histological grade.Moreover,a significantly decrease in Uyghur patients was observed compared with Han patients.However,other parameters-gender,tumor location and lymph node metastasis-showed no significant relationship with RFT2 expression.Blood riboflavin levels were reverse correlated with development of GC(1.2000 ± 0.97 569 ng/mL in high tumor stage patients vs 2.5980 ± 1.31 129 ng/mL in low tumor stage patients;P < 0.05).A positive correlation of plasma riboflavin levels with defective expression of RFT2 protein was found in GC patients(2 = 2.619;P = 0.019).CONCLUSION:Defective expression of RFT2 is associated with the development of GC and this may represent a mechanism underlying the decreased plasma riboflavin levels in GC.展开更多
Dear Editor,As the most prevalent DNA methylation modification in prokaryotes,DNA N6 methyladenosine(6mA)in eukaryotic genomes has recently been observed in diverse species including Caenorhabditis elegans(Greer et al...Dear Editor,As the most prevalent DNA methylation modification in prokaryotes,DNA N6 methyladenosine(6mA)in eukaryotic genomes has recently been observed in diverse species including Caenorhabditis elegans(Greer et al.,2015),Dro-sophila melanogaster(Zhang et al,2015),mouse(Wu et al,2016)and human(Xiao et al,2018).6mA has been reported to associate with multiple physiological processes including embryonic development and tumorigenesis(Greer et al.,2015;Zhang et al.,2015;Xie et al.,2018),yet some con-troversies exist.In contrast to the findings showing that ALKBH1(alkB homolog 1)is a primary 6mA demethylase in mouse and human cells(Wu et al.,2016;Xiao et al.,2018;Xie et al..2018),other studies indicate that ALKBH1 is prone to demethylate 6mA on bubbled or bulged DNAs that are often featured by a locally unpairing region with flanking duplex,such as D-loop,R-loop as well as DNA or RNA stem-loop,and single-stranded DNAs at a lower efficiency.展开更多
Dear Editor, Endocytosis is a crucial process employed by cells to internal- ize nutrients and turnover membrane components and is essential for many functions, including nutrient uptake, signal transduction, cytokine...Dear Editor, Endocytosis is a crucial process employed by cells to internal- ize nutrients and turnover membrane components and is essential for many functions, including nutrient uptake, signal transduction, cytokinesis, morphogenesis, cell adhesion and migration. Endocytosis is classified as clathrin-dependent endocytosis （CDE） or clathrin-independent endocytosis （CIE） according to its dependence on clathrin. Several different CIE pathways have been proposed, including caveolin-dependent endocytosis, flotillin-dependent endocytosis, the clathrin-inde- pendent carrier pathway, ARF6-dependent endocytosis, phagocytosis, macropinocytosis, the IL2RI3 pathway （Doherty and McMahon, 2009）, the newly identified fast endophilin-me- diated endocytosis pathway （Boucrot et al., 2015） and the EGFR-NCE pathway （Caldieri et al., 2017）.展开更多
Caenorhabditis elegans hid-1 gene was first identified in a screen for mutants with a high-temperature-induced dauer formation(Hid)phenotype.Despite the fact that the hid-1 gene encodes a novel protein(HID-1)which is ...Caenorhabditis elegans hid-1 gene was first identified in a screen for mutants with a high-temperature-induced dauer formation(Hid)phenotype.Despite the fact that the hid-1 gene encodes a novel protein(HID-1)which is highly conserved from Caenorhabditis elegans to mammals,the domain structure,subcellular localization,and exact function of HID-1 remain unknown.Previous studies and various bioinformatic softwares predicted that HID-1 contained many transmembrane domains but no known functional domain.In this study,we revealed that mammalian HID-1 localized to the medial-and transGolgi apparatus as well as the cytosol,and the localization was sensitive to brefeldin A treatment.Next,we demonstrated that HID-1 was a peripheral membrane protein and dynamically shuttled between the Golgi apparatus and the cytosol.Finally,we verified that a conserved N-terminal myristoylation site was required for HID-1 binding to the Golgi apparatus.We propose that HID-1 is probably involved in the intracellular trafficking within the Golgi region.展开更多
Dear Editor, Intracellular trafficking is a basis of cellular activities, including cell migration, immune response, and development （Lebreton et al., 2003; Lu（;in et al., 2014; Ulrich and Heisenberg, 2009）. In hea...Dear Editor, Intracellular trafficking is a basis of cellular activities, including cell migration, immune response, and development （Lebreton et al., 2003; Lu（;in et al., 2014; Ulrich and Heisenberg, 2009）. In healthy tissue, intracellular trafficking is highly regulated, con- trolling the form and function of cells （Furthauer and Gonzalez- Gaitan, 2009）.展开更多
The regionally proximal relation of order d along arithmetic progressions,namely AP[d]for d 2 N,is introduced and investigated.It turns out that if(X;T)is a topological dynamical system with AP[d]=Δ,then each ergodic...The regionally proximal relation of order d along arithmetic progressions,namely AP[d]for d 2 N,is introduced and investigated.It turns out that if(X;T)is a topological dynamical system with AP[d]=Δ,then each ergodic measure of(X;T)is isomorphic to a d-step pro-nilsystem,and thus(X;T)has zero entropy.Moreover,it is shown that if(X;T)is a strictly ergodic distal system with the property that the maximal topological and measurable d-step pro-nilsystems are isomorphic,then AP[d]=RP[d]for each d 2 N.It follows that for a minimal 1-pro-nilsystem,AP[d]=RP[d]for each d 2 N.An example which is a strictly ergodic distal system with discrete spectrum whose maximal equicontinuous factor is not isomorphic to the Kronecker factor is constructed.展开更多
Endocytosis is a fundamental cellular activity that plays crucial roles in a variety of biological processes,including nutrient uptake,signal transduction,immune response,morphogenesis,neurotransmission,cell migration...Endocytosis is a fundamental cellular activity that plays crucial roles in a variety of biological processes,including nutrient uptake,signal transduction,immune response,morphogenesis,neurotransmission,cell migration and tissue development[1–3].Endocytosis has been classified into two subtypes:the展开更多
基金This work was supported by grants from the Ministry of Science and Technology of the People’s Republic of China(2018YFA0507101,2016YFA0500203)the National Natural Science Foundation of China(31770900,31730054)+1 种基金the Beijing Natural Science Foundation(5212016)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(2011087).
文摘Studies on diabetes have long been hampered by a lack of authentic disease models that,ideally,should be unlimited and able to recapitulate the abnormalities involved in the development,structure,and function of human pancreatic islets under pathological conditions.Stem cell-based islet organoids faithfully recapitulate islet development in vitro and provide large amounts of three-dimensional functional islet biomimetic materials with a morphological structure and cellular composition similar to those of native islets.Thus,islet organoids hold great promise for modeling islet development and function,deciphering the mechanisms underlying the onset of diabetes,providing an in vitro human organ model for infection of viruses such as SARS-CoV-2,and contributing to drug screening and autologous islet transplantation.However,the currently established islet organoids are generally immature compared with native islets,and further efforts should be made to improve the heterogeneity and functionality of islet organoids,making it an authentic and informative disease model for diabetes.Here,we review the advances and challenges in the generation of islet organoids,focusing on human pluripotent stem cell-derived islet organoids,and the potential applications of islet organoids as disease models and regenerative therapies for diabetes.
基金Supported by The National Natural Science Foundation of China,No.81160459
文摘AIM:To investigate the relationship between blood riboflavin levels and riboflavin transporter 2(RFT2) gene expression in gastric carcinoma(GC) development.METHODS:High-performance liquid chromatography was used to detect blood riboflavin levels in patients with GC.Real-time fluorogenic quantitative polymerase chain reaction and immunohistochemistry were used to analyze the expression of RFT2 mRNA and protein in samples from 60 GC patients consisting of both tumor and normal tissue.RESULTS:A significant decrease in the RFT2 mRNA levels was detected in GC samples compared with those in the normal mucous membrane(0.398 ± 0.149 vs 1.479 ± 0.587;P = 0.040).Tumors exhibited low RFT2 protein expression(75%,16.7%,8.3% and 0% for no RFT2 staining,weak staining,medium staining and strong staining,respectively),which was significantly lower than that in the normal mucous membrane(10%,16.7%,26.7% and 46.7% for no RFT2 staining,weak staining,medium staining and strong staining,respectively;P < 0.05).Tumors with low RFT2 expression were significantly associated with tumor stage and histological grade.Moreover,a significantly decrease in Uyghur patients was observed compared with Han patients.However,other parameters-gender,tumor location and lymph node metastasis-showed no significant relationship with RFT2 expression.Blood riboflavin levels were reverse correlated with development of GC(1.2000 ± 0.97 569 ng/mL in high tumor stage patients vs 2.5980 ± 1.31 129 ng/mL in low tumor stage patients;P < 0.05).A positive correlation of plasma riboflavin levels with defective expression of RFT2 protein was found in GC patients(2 = 2.619;P = 0.019).CONCLUSION:Defective expression of RFT2 is associated with the development of GC and this may represent a mechanism underlying the decreased plasma riboflavin levels in GC.
基金This work was supported by the National Key Research and Development Program of China(2017YFA0102802)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16010100)+9 种基金the National Key Research and Development(2018YFC2000100,2017YFA0103304,National Natural Science Foundation 81625009,91749202,81861168034,91949209,91749123,81671377,Program of China 2018YFA0107203)the of China(Grant Nos.81921006,31671429,81822018,81870228,81922027,31900524,81701388,31770900,and 31730054)the Program of the Beijing Municipal Science and Technology Commission(Z191100001519005)Beijing Natural Science Foundation(Z190019)Beijing Municipal Commission of Health and Family Planning(PXM2018_026283_000002)Advanced Innovation Center for Human Brain Protection(3500-1192012)the Key Research Program of the Chinese Academy of Sciences(KFZD-SW-221)K.C.Wong Education Foundation(GJTD-2019-06,GJTD-2019-08)Young Elite Scientists Sponsorship Program by CAST,Youth Innovation Promotion Association of CASthe State Key Laboratory of Stem Cell and Reproductive Biology and the State Key Laboratory of Membrane Biology.
文摘Dear Editor,As the most prevalent DNA methylation modification in prokaryotes,DNA N6 methyladenosine(6mA)in eukaryotic genomes has recently been observed in diverse species including Caenorhabditis elegans(Greer et al.,2015),Dro-sophila melanogaster(Zhang et al,2015),mouse(Wu et al,2016)and human(Xiao et al,2018).6mA has been reported to associate with multiple physiological processes including embryonic development and tumorigenesis(Greer et al.,2015;Zhang et al.,2015;Xie et al.,2018),yet some con-troversies exist.In contrast to the findings showing that ALKBH1(alkB homolog 1)is a primary 6mA demethylase in mouse and human cells(Wu et al.,2016;Xiao et al.,2018;Xie et al..2018),other studies indicate that ALKBH1 is prone to demethylate 6mA on bubbled or bulged DNAs that are often featured by a locally unpairing region with flanking duplex,such as D-loop,R-loop as well as DNA or RNA stem-loop,and single-stranded DNAs at a lower efficiency.
文摘Dear Editor, Endocytosis is a crucial process employed by cells to internal- ize nutrients and turnover membrane components and is essential for many functions, including nutrient uptake, signal transduction, cytokinesis, morphogenesis, cell adhesion and migration. Endocytosis is classified as clathrin-dependent endocytosis （CDE） or clathrin-independent endocytosis （CIE） according to its dependence on clathrin. Several different CIE pathways have been proposed, including caveolin-dependent endocytosis, flotillin-dependent endocytosis, the clathrin-inde- pendent carrier pathway, ARF6-dependent endocytosis, phagocytosis, macropinocytosis, the IL2RI3 pathway （Doherty and McMahon, 2009）, the newly identified fast endophilin-me- diated endocytosis pathway （Boucrot et al., 2015） and the EGFR-NCE pathway （Caldieri et al., 2017）.
基金the National Science Foundation of China(Grant Nos.30870564,and 30900268),The Beijing Natural Science Foundation(No.5092017)the Major State Basic Research Program of China(No.2010CB833701)the CAS Project(KSCX2-SW-224 and Novo Nordisk-CAS to P Xu).
文摘Caenorhabditis elegans hid-1 gene was first identified in a screen for mutants with a high-temperature-induced dauer formation(Hid)phenotype.Despite the fact that the hid-1 gene encodes a novel protein(HID-1)which is highly conserved from Caenorhabditis elegans to mammals,the domain structure,subcellular localization,and exact function of HID-1 remain unknown.Previous studies and various bioinformatic softwares predicted that HID-1 contained many transmembrane domains but no known functional domain.In this study,we revealed that mammalian HID-1 localized to the medial-and transGolgi apparatus as well as the cytosol,and the localization was sensitive to brefeldin A treatment.Next,we demonstrated that HID-1 was a peripheral membrane protein and dynamically shuttled between the Golgi apparatus and the cytosol.Finally,we verified that a conserved N-terminal myristoylation site was required for HID-1 binding to the Golgi apparatus.We propose that HID-1 is probably involved in the intracellular trafficking within the Golgi region.
基金This work was supported by grants from the National Natural Sci- ence Foundation （Grant No. 31270884）, the Beijing Natural Science Foundation （5122026）, and Youth Innovation Promotion Association, Chinese Academy of Sciences.
文摘Dear Editor, Intracellular trafficking is a basis of cellular activities, including cell migration, immune response, and development （Lebreton et al., 2003; Lu（;in et al., 2014; Ulrich and Heisenberg, 2009）. In healthy tissue, intracellular trafficking is highly regulated, con- trolling the form and function of cells （Furthauer and Gonzalez- Gaitan, 2009）.
基金This work was supported by National Natural Science Foundation of China(Grant Nos.11431012,11971455,11571335 and 11371339).
文摘The regionally proximal relation of order d along arithmetic progressions,namely AP[d]for d 2 N,is introduced and investigated.It turns out that if(X;T)is a topological dynamical system with AP[d]=Δ,then each ergodic measure of(X;T)is isomorphic to a d-step pro-nilsystem,and thus(X;T)has zero entropy.Moreover,it is shown that if(X;T)is a strictly ergodic distal system with the property that the maximal topological and measurable d-step pro-nilsystems are isomorphic,then AP[d]=RP[d]for each d 2 N.It follows that for a minimal 1-pro-nilsystem,AP[d]=RP[d]for each d 2 N.An example which is a strictly ergodic distal system with discrete spectrum whose maximal equicontinuous factor is not isomorphic to the Kronecker factor is constructed.
基金supported by the National Natural Science Foundation of China(31770900,31270884,30900268)the Beijing Natural Science Foundation(5122026,5092017)the Youth Innovation Promotion Association of the Chinese Academy of Sciences(2011087)
文摘Endocytosis is a fundamental cellular activity that plays crucial roles in a variety of biological processes,including nutrient uptake,signal transduction,immune response,morphogenesis,neurotransmission,cell migration and tissue development[1–3].Endocytosis has been classified into two subtypes:the
