Circular RNAs(circRNAs)are a type of non coding RNA that possess unique single stranded circular structures formed through reverse splicing mechanisms.Due to the lack of a free end that is typically susceptible to deg...Circular RNAs(circRNAs)are a type of non coding RNA that possess unique single stranded circular structures formed through reverse splicing mechanisms.Due to the lack of a free end that is typically susceptible to degradation by nucleases,circular RNAs exhibit resistance to ribonuclease R,making them highly stable in eukaryotic cells.The complex relationship between circRNA dysregulation and various pathophysiological conditions,especially cancer.Tumor microenvironment(TME)is a collective term for various components surrounding tumors and is an important factor affecting tumor development.Simultaneous infiltration of TME by different types of immune cells;These immune cells interact with the TME,collectively forming the so-called“tumor immune microenvironment”.The complex interactions between tumor cells and TME profoundly affect the behavior of malignant tumors,and circRNAs derived from tumor cells and TME cell components have become important mediators of immune response and evasion within the TME.CircRNAs can directly or indirectly regulate immune cells,thereby modulating anti-tumor immunity.This review highlights how circRNAs,especially those encapsulated in extracellular vesicles like exosomes,influence the differentiation,chemotaxis,and anti-tumor immune functions of immune cells within the TME.Metabolic reprogramming plays an important role in this process.The process of circRNAs regulating tumor immunity is affected by multiple factors,such as hypoxia and viral infection.This review emphasizes the roles of the interaction between circRNAs and the TME in tumor immune regulation and prospects the guiding significance of circRNAs in tumor immune checkpoint therapy.展开更多
Key distribution is one of the most important and often also the most difficult parts in cryptography[1].In symmetric key cryptography,both of the sender and the recipient must share the same secure key for successful...Key distribution is one of the most important and often also the most difficult parts in cryptography[1].In symmetric key cryptography,both of the sender and the recipient must share the same secure key for successful communication.Traditionally key distribution is achieved by establishing a separate‘‘secure channel".The‘‘secure channel"can be a specially-built communication link,展开更多
In a perfect security case of symmetric encryption,the secure key is generated from a true random number generator and cannot be reused.Moreover,it has the same code length as the total message.Furthermore,we require ...In a perfect security case of symmetric encryption,the secure key is generated from a true random number generator and cannot be reused.Moreover,it has the same code length as the total message.Furthermore,we require the secure key to be distributed by employing unconditionally secure methods.Apart from quantum secure direct communication(QSDC)that directly achieves the confidential transmission of secure information over a quantum channel without key distribution procedure[1–3],secure key generation and secure key distribution(SKD)are the two most remarkable challenges restricting the efficiency and security of a cryptosystem[4]in conventional secure communication systems.展开更多
Drug-induced hyperglycemia/diabetes is a global issue. Some drugs induce hyperglycemia by activating the pregnane X receptor(PXR), but the mechanism is unclear. Here, we report that PXR activation induces hyperglycemi...Drug-induced hyperglycemia/diabetes is a global issue. Some drugs induce hyperglycemia by activating the pregnane X receptor(PXR), but the mechanism is unclear. Here, we report that PXR activation induces hyperglycemia by impairing hepatic glucose metabolism due to inhibition of the hepatocyte nuclear factor 4-alpha(HNF4 a)-glucose transporter 2(GLUT2) pathway. The PXR agonists atorvastatin and rifampicin significantly downregulated GLUT2 and HNF4 a expression, and impaired glucose uptake and utilization in HepG2 cells. Overexpression of PXR downregulated GLUT2 and HNF4 a expression, while silencing PXR upregulated HNF4 a and GLUT2 expression.Silencing HNF4 a decreased GLUT2 expression, while overexpressing HNF4 a increased GLUT2 expression and glucose uptake. Silencing PXR or overexpressing HNF4 a reversed the atorvastatininduced decrease in GLUT2 expression and glucose uptake. In human primary hepatocytes, atorvastatin downregulated GLUT2 and HNF4 a mRNA expression, which could be attenuated by silencing PXR. Silencing HNF4 a downregulated GLUT2 mRNA expression. These findings were reproduced with mouse primary hepatocytes. Hnf4 a plasmid increased Slc2 a2 promoter activity. Hnf4 a silencing or pregnenolone-16 a-carbonitrile(PCN) suppressed the Slc2 a2 promoter activity by decreasing HNF4 a recruitment to the Slc2 a2 promoter. Liver-specific Hnf4 a deletion and PCN impaired glucose tolerance and hepatic glucose uptake, and decreased the expression of hepatic HNF4 a and GLUT2. In conclusion, PXR activation impaired hepatic glucose metabolism partly by inhibiting the HNF4 aGLUT2 pathway. These results highlight the molecular mechanisms by which PXR activators induce hyperglycemia/diabetes.展开更多
基金supported by the National Natural Science Foundation of China(82103298)Basic Research Project of Science and Technology Cooperation in Qiandongnan Prefecture(No.2023-16).
文摘Circular RNAs(circRNAs)are a type of non coding RNA that possess unique single stranded circular structures formed through reverse splicing mechanisms.Due to the lack of a free end that is typically susceptible to degradation by nucleases,circular RNAs exhibit resistance to ribonuclease R,making them highly stable in eukaryotic cells.The complex relationship between circRNA dysregulation and various pathophysiological conditions,especially cancer.Tumor microenvironment(TME)is a collective term for various components surrounding tumors and is an important factor affecting tumor development.Simultaneous infiltration of TME by different types of immune cells;These immune cells interact with the TME,collectively forming the so-called“tumor immune microenvironment”.The complex interactions between tumor cells and TME profoundly affect the behavior of malignant tumors,and circRNAs derived from tumor cells and TME cell components have become important mediators of immune response and evasion within the TME.CircRNAs can directly or indirectly regulate immune cells,thereby modulating anti-tumor immunity.This review highlights how circRNAs,especially those encapsulated in extracellular vesicles like exosomes,influence the differentiation,chemotaxis,and anti-tumor immune functions of immune cells within the TME.Metabolic reprogramming plays an important role in this process.The process of circRNAs regulating tumor immunity is affected by multiple factors,such as hypoxia and viral infection.This review emphasizes the roles of the interaction between circRNAs and the TME in tumor immune regulation and prospects the guiding significance of circRNAs in tumor immune checkpoint therapy.
基金supported by the National Key Research and Development Program of China (2016YFE0129400)the Youth Innovation Promotion Association (2016290)the Strategic Priority Research Program of the Chinese Academy of Sciences (XDA06010705)
文摘Key distribution is one of the most important and often also the most difficult parts in cryptography[1].In symmetric key cryptography,both of the sender and the recipient must share the same secure key for successful communication.Traditionally key distribution is achieved by establishing a separate‘‘secure channel".The‘‘secure channel"can be a specially-built communication link,
基金This work was supported by the National Key Research and Development Program of China(2016YFE0129400)Youth Innovation Promotion Association(2016290)+1 种基金Strategic Priority Research Program of the Chinese Academy of Sciences(XDC02010800)National Cryptography Development Fund during the 13th Five-Year Plan Period(MMJJ20180112).
文摘In a perfect security case of symmetric encryption,the secure key is generated from a true random number generator and cannot be reused.Moreover,it has the same code length as the total message.Furthermore,we require the secure key to be distributed by employing unconditionally secure methods.Apart from quantum secure direct communication(QSDC)that directly achieves the confidential transmission of secure information over a quantum channel without key distribution procedure[1–3],secure key generation and secure key distribution(SKD)are the two most remarkable challenges restricting the efficiency and security of a cryptosystem[4]in conventional secure communication systems.
基金supported by the National Natural Science Foundation of China (Nos.81673505,81872930,and 82073922)the “Double First-Class” university project (No.CPU2018GY22,China)“333” Project of Jiangsu Province (No.BRA2020287,China)。
文摘Drug-induced hyperglycemia/diabetes is a global issue. Some drugs induce hyperglycemia by activating the pregnane X receptor(PXR), but the mechanism is unclear. Here, we report that PXR activation induces hyperglycemia by impairing hepatic glucose metabolism due to inhibition of the hepatocyte nuclear factor 4-alpha(HNF4 a)-glucose transporter 2(GLUT2) pathway. The PXR agonists atorvastatin and rifampicin significantly downregulated GLUT2 and HNF4 a expression, and impaired glucose uptake and utilization in HepG2 cells. Overexpression of PXR downregulated GLUT2 and HNF4 a expression, while silencing PXR upregulated HNF4 a and GLUT2 expression.Silencing HNF4 a decreased GLUT2 expression, while overexpressing HNF4 a increased GLUT2 expression and glucose uptake. Silencing PXR or overexpressing HNF4 a reversed the atorvastatininduced decrease in GLUT2 expression and glucose uptake. In human primary hepatocytes, atorvastatin downregulated GLUT2 and HNF4 a mRNA expression, which could be attenuated by silencing PXR. Silencing HNF4 a downregulated GLUT2 mRNA expression. These findings were reproduced with mouse primary hepatocytes. Hnf4 a plasmid increased Slc2 a2 promoter activity. Hnf4 a silencing or pregnenolone-16 a-carbonitrile(PCN) suppressed the Slc2 a2 promoter activity by decreasing HNF4 a recruitment to the Slc2 a2 promoter. Liver-specific Hnf4 a deletion and PCN impaired glucose tolerance and hepatic glucose uptake, and decreased the expression of hepatic HNF4 a and GLUT2. In conclusion, PXR activation impaired hepatic glucose metabolism partly by inhibiting the HNF4 aGLUT2 pathway. These results highlight the molecular mechanisms by which PXR activators induce hyperglycemia/diabetes.
