Background:Renal cell carcinoma(RCC)is a prevalent malignancy characterized by a rising incidence and significant mortality.Interleukins(ILs)are crucial in regulating immune cell trafficking and exhibit anti-tumor pro...Background:Renal cell carcinoma(RCC)is a prevalent malignancy characterized by a rising incidence and significant mortality.Interleukins(ILs)are crucial in regulating immune cell trafficking and exhibit anti-tumor properties.However,limited research has explored the expression levels and prognostic significance of interleukins in RCC.Methods:In this comprehensive study,we performed a detailed analysis of interleukins in RCC patients using multiple bioinformatics tools,including Oncomine,UALCAN,GEPIA,Kaplan-Meier plotter,cBioPortal,GeneMANIA,TRRUST,STRING,and Linked Omics.Results:Our analysis demonstrated a significant upregulation in the transcriptional levels of IL4,IL7,IL15,IL16,IL23A,IL26,and IL32 were significantly upregulated in RCC tissues,indicating their potential involvement in the pathogenesis of this malignancy.In contrast,IL1A,IL11,and IL27 were downregulated,indicating their potential function as tumor suppressors.Significant correlations were identified between the expression levels of IL11,IL23A,IL27,IL32,and the pathological stage of RCC patients.The expression levels of IL1A,IL4,IL11,IL15,IL16,IL23A,IL26,IL27,and IL32 were significantly correlated with improved prognosis.The differentially expressed interleukins primarily function in cytokine-cytokine receptor interactions and immune response-regulating signaling pathways.homeobox A10(HOXA10),v-myb myeloblastosis viral oncogene homolog(avian)(MYB),v-rel reticuloendotheliosis viral oncogene homolog A(avian)(RELA),and nuclear factor of kappa light polypeptide gene enhancer in B-cells 1(NFKB1)are key transcription factors for ILs,while LCK proto-oncogene(LCK),LYN proto-oncogene(LYN),spleen associated tyrosine kinase(SYK),Janus kinase 3(JAK3),and FER tyrosine kinase(FER)are IL targets.IL expression significantly correlated with the infiltration of six distinct immune cell types.IL1A potentially exerts an anti-tumor effect in RCC prognosis by inducing neutrophil extracellular traps(NETs).Additionally,NFKB1 may positively regulate IL1A,providing a rationale for further in vivo and clinical studies.Conclusion:In conclusion,our study demonstrates the potential role of IL 1A in the prognosis of RCC and establishes a theoretical foundation for subsequent in vivo and clinical investigations.展开更多
Protein phosphatase 2A(PP2A)is a major serine/threonine phosphatase which participates in the regulation of multiple cellular processes.As a confirmed tumor suppressor,PP2A activity is downregulated in tumors and its ...Protein phosphatase 2A(PP2A)is a major serine/threonine phosphatase which participates in the regulation of multiple cellular processes.As a confirmed tumor suppressor,PP2A activity is downregulated in tumors and its re-activation can induce apoptosis of cancer cells.In the brains of Alzheimer's disease(AD)patients,decreased PP2A activity also plays a key role in promoting tau hyperphosphorylation and A0 generation.In this review,we discussed compounds aiming at modulating PP2A activity in the treatment of cancer or AD.The upstream factors that inactivate PP2A in diseases have not been fully elucidated and further studies are needed.It will help for the refinement and development of novel and clinically tractable PP2A-targeted compounds or therapies for the treatment of tumor and AD.展开更多
Objective The prevalence of carbapenem-resistant Klebsiella pneumoniae(CR-KP)is a global public health problem.It is mainly caused by the plasmid-carried carbapenemase gene.Outer membrane vesicles(OMVs)contain toxins ...Objective The prevalence of carbapenem-resistant Klebsiella pneumoniae(CR-KP)is a global public health problem.It is mainly caused by the plasmid-carried carbapenemase gene.Outer membrane vesicles(OMVs)contain toxins and other factors involved in various biological processes,includingβ-lactamase and antibiotic-resistance genes.This study aimed to reveal the transmission mechanism of OMV-mediated drug resistance of Klebsiella(K.)pneumoniae.Methods We selected CR-KP producing K.pneumoniae carbapenemase-2(KPC-2)to study whether they can transfer resistance genes through OMVs.The OMVs of CR-KP were obtained by ultracentrifugation,and incubated with carbapenem-sensitive K.pneumoniae for 4 h.Finally,the carbapenem-sensitive K.pneumoniae was tested for the presence of bla_(KPC-2)resistance gene and its sensitivity to carbapenem antibiotics.Results The existence of OMVs was observed by the electron microscopy.The extracted OMVs had bla_(KPC-2)resistance gene.After incubation with OMVs,bla_(KPC-2)resistance gene was detected in sensitive K.pneumoniae,and it became resistant to imipenem and meropenem.Conclusion This study demonstrated that OMVs isolated from KPC-2-producing CR-KP could deliver bla_(KPC-2)to sensitive K.pneumoniae,allowing the bacteria to produce carbapenemase,which may provide a novel target for innovative therapies in combination with conventional antibiotics for treating carbapenem-resistant Enterobacteriaceae.展开更多
The article“Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer's Disease”,written by Hui WEI,Hui-liang ZHANG,Jia-zhao XIE,Dong-li MENG,Xiao-chuan WANG,Dan KE,Ji ZENG,Rong LIU,was or...The article“Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer's Disease”,written by Hui WEI,Hui-liang ZHANG,Jia-zhao XIE,Dong-li MENG,Xiao-chuan WANG,Dan KE,Ji ZENG,Rong LIU,was originally published electronically on the publisher's internet portal on 13 March 2020 without open access.With the author(s)'decision to opt for Open Choice the copyright of the article changed to O The Author(s)2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License(https://creativecommons.org/licenses/by/4.0/),which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons license,and indicate if changes were made.展开更多
Letα(F_(q)^(d),p)denote the maximum size of a general position set in a p-random subset of F_(q)^(d).We determine the order of magnitude ofα(F_(q)^(2),p)up to polylogarithmic factors for all possible values of p,imp...Letα(F_(q)^(d),p)denote the maximum size of a general position set in a p-random subset of F_(q)^(d).We determine the order of magnitude ofα(F_(q)^(2),p)up to polylogarithmic factors for all possible values of p,improving the previous results obtained by Roche-Newton and Warren(2022)and Bhowmick and Roche-Newton(2024).For d≥3,we prove upper bounds forα(F_(q)^(d),p)that are essentially tight within certain ranges for p.We establish the upper bound 2^((1+o(1))q) for the number of general position sets in F_(q)^(d),which matches the trivial lower bound 2q asymptotically in the exponent.We also refine this counting result by proving an asymptotically tight(in the exponent)upper bound for the number of general position sets with a fixed size.The latter result for d=2 improves the result of Roche-Newton and Warren(2022).Our proofs are grounded in the hypergraph container method.In addition,for d=2,we also leverage the pseudorandomness of the point-line incidence graph of F_(q)^(2).展开更多
Clostridioides difficile is a leading cause of healthcare-associated infections,causing billions of economic losses every year.Its symptoms range from mild diarrhea to life-threatening damage to the colon.Transmission...Clostridioides difficile is a leading cause of healthcare-associated infections,causing billions of economic losses every year.Its symptoms range from mild diarrhea to life-threatening damage to the colon.Transmission and recurrence of c.difficile infection(CDl)are mediated by the metabolically dormant spores,while the virulence of C.difficile is mainly due to the two large clostridial toxins,TcdA and TcdB.Producing toxins or forming spores are two different strategies for C.difficile to cope with harsh environmental conditions.It is of great significance to understand the molecular mechanisms for C.difficile to skew to either of the cellular processes.Here,we summarize the current understanding of the regulation and connections between toxin production and sporulation in C.difficile and further discuss the potential solutions for yet-to-be-answered questions.展开更多
The aim of this study is to investigate the effect of tyrosine kinase Src on Tyrosine 307(Y307)phosphor-ylation,protein phosphatase 2A(PP2A)activity,and on tau phosphorylation.Specific Src siRNA was transfected into c...The aim of this study is to investigate the effect of tyrosine kinase Src on Tyrosine 307(Y307)phosphor-ylation,protein phosphatase 2A(PP2A)activity,and on tau phosphorylation.Specific Src siRNA was transfected into cultured mouse neuroblastoma N2a cells to inhibit the expression of Src protein,and the phosphorylation levels of PP2A Y307 and tau at different sites,as well as PP2A activity were detected at different time points after siRNA transfection.Twelve hours after siRNA transfec-tion,the protein level of Src was dramatically decreased,with decreased PP2A Y307 phosphorylation.However,the total PP2A protein level was also decreased,together with a decreased PP2A activity.Tau was hyperpho-sphorylated at the Ser198/199/202 sites.Multiple factors may be involved in the cellular regulation of PP2A activ-ity.Inhibiting Src expression could induce inactivation of PP2A and tau hyperphosphorylation.展开更多
基金supported by Natural Science Foundation of Anhui Province(2008085MH273)Anhui Fund for Distinguished Young Scholars(2022AH020050)+3 种基金the Scientific Research Platform Improvement Project of Anhui Medical University(2022xkjT045)the Natural Science Foundation of Anhui Province(No.2108085MH278)Graduate Research and Practice Innovation Project of Anhui Medical University(YJS20230110)the Science and Technology Program of Ma’anshan City(No.YL-2022-8)。
文摘Background:Renal cell carcinoma(RCC)is a prevalent malignancy characterized by a rising incidence and significant mortality.Interleukins(ILs)are crucial in regulating immune cell trafficking and exhibit anti-tumor properties.However,limited research has explored the expression levels and prognostic significance of interleukins in RCC.Methods:In this comprehensive study,we performed a detailed analysis of interleukins in RCC patients using multiple bioinformatics tools,including Oncomine,UALCAN,GEPIA,Kaplan-Meier plotter,cBioPortal,GeneMANIA,TRRUST,STRING,and Linked Omics.Results:Our analysis demonstrated a significant upregulation in the transcriptional levels of IL4,IL7,IL15,IL16,IL23A,IL26,and IL32 were significantly upregulated in RCC tissues,indicating their potential involvement in the pathogenesis of this malignancy.In contrast,IL1A,IL11,and IL27 were downregulated,indicating their potential function as tumor suppressors.Significant correlations were identified between the expression levels of IL11,IL23A,IL27,IL32,and the pathological stage of RCC patients.The expression levels of IL1A,IL4,IL11,IL15,IL16,IL23A,IL26,IL27,and IL32 were significantly correlated with improved prognosis.The differentially expressed interleukins primarily function in cytokine-cytokine receptor interactions and immune response-regulating signaling pathways.homeobox A10(HOXA10),v-myb myeloblastosis viral oncogene homolog(avian)(MYB),v-rel reticuloendotheliosis viral oncogene homolog A(avian)(RELA),and nuclear factor of kappa light polypeptide gene enhancer in B-cells 1(NFKB1)are key transcription factors for ILs,while LCK proto-oncogene(LCK),LYN proto-oncogene(LYN),spleen associated tyrosine kinase(SYK),Janus kinase 3(JAK3),and FER tyrosine kinase(FER)are IL targets.IL expression significantly correlated with the infiltration of six distinct immune cell types.IL1A potentially exerts an anti-tumor effect in RCC prognosis by inducing neutrophil extracellular traps(NETs).Additionally,NFKB1 may positively regulate IL1A,providing a rationale for further in vivo and clinical studies.Conclusion:In conclusion,our study demonstrates the potential role of IL 1A in the prognosis of RCC and establishes a theoretical foundation for subsequent in vivo and clinical investigations.
基金grants from National Natural Science Foundation of China(No.31970964 and No.31771189)Natural Science Foundation of Hubei Province,China(No.2017CFA065)Wuhan Health and Family Planning Commission(No.WX18C17).
文摘Protein phosphatase 2A(PP2A)is a major serine/threonine phosphatase which participates in the regulation of multiple cellular processes.As a confirmed tumor suppressor,PP2A activity is downregulated in tumors and its re-activation can induce apoptosis of cancer cells.In the brains of Alzheimer's disease(AD)patients,decreased PP2A activity also plays a key role in promoting tau hyperphosphorylation and A0 generation.In this review,we discussed compounds aiming at modulating PP2A activity in the treatment of cancer or AD.The upstream factors that inactivate PP2A in diseases have not been fully elucidated and further studies are needed.It will help for the refinement and development of novel and clinically tractable PP2A-targeted compounds or therapies for the treatment of tumor and AD.
基金supported by the National Natural Science Foundation of China(No.31771189)the Wuhan Health Commission(No.WX18C17 and No.WX19Q31)the Natural Science Foundation of Hubei Province,China(No.2017CFA065 and No.WJ2019H378).
文摘Objective The prevalence of carbapenem-resistant Klebsiella pneumoniae(CR-KP)is a global public health problem.It is mainly caused by the plasmid-carried carbapenemase gene.Outer membrane vesicles(OMVs)contain toxins and other factors involved in various biological processes,includingβ-lactamase and antibiotic-resistance genes.This study aimed to reveal the transmission mechanism of OMV-mediated drug resistance of Klebsiella(K.)pneumoniae.Methods We selected CR-KP producing K.pneumoniae carbapenemase-2(KPC-2)to study whether they can transfer resistance genes through OMVs.The OMVs of CR-KP were obtained by ultracentrifugation,and incubated with carbapenem-sensitive K.pneumoniae for 4 h.Finally,the carbapenem-sensitive K.pneumoniae was tested for the presence of bla_(KPC-2)resistance gene and its sensitivity to carbapenem antibiotics.Results The existence of OMVs was observed by the electron microscopy.The extracted OMVs had bla_(KPC-2)resistance gene.After incubation with OMVs,bla_(KPC-2)resistance gene was detected in sensitive K.pneumoniae,and it became resistant to imipenem and meropenem.Conclusion This study demonstrated that OMVs isolated from KPC-2-producing CR-KP could deliver bla_(KPC-2)to sensitive K.pneumoniae,allowing the bacteria to produce carbapenemase,which may provide a novel target for innovative therapies in combination with conventional antibiotics for treating carbapenem-resistant Enterobacteriaceae.
文摘The article“Protein Phosphatase 2A as a Drug Target in the Treatment of Cancer and Alzheimer's Disease”,written by Hui WEI,Hui-liang ZHANG,Jia-zhao XIE,Dong-li MENG,Xiao-chuan WANG,Dan KE,Ji ZENG,Rong LIU,was originally published electronically on the publisher's internet portal on 13 March 2020 without open access.With the author(s)'decision to opt for Open Choice the copyright of the article changed to O The Author(s)2020 and the article is forthwith distributed under a Creative Commons Attribution 4.0 International License(https://creativecommons.org/licenses/by/4.0/),which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons license,and indicate if changes were made.
基金supported by European Research Council Advanced Grant(Grant No.101020255)Leverhulme Research Project Grant(Grant No.RPG-2018-424)+3 种基金supported by National Natural Science Foundation of China(Grant No.123B2012)supported by European Research Council Advanced Grants“GeoScape”(Grant No.882971)and“ERMiD”(Grant No.101054936)Jonathan Tidor for stimulating discussions at 2023 University of California San Diego Workshop on Ramsey Theoryinitiated while Ji Zeng was visiting Shanghai Center for Mathematical Sciences at the kind invitation of Hehui Wu.
文摘Letα(F_(q)^(d),p)denote the maximum size of a general position set in a p-random subset of F_(q)^(d).We determine the order of magnitude ofα(F_(q)^(2),p)up to polylogarithmic factors for all possible values of p,improving the previous results obtained by Roche-Newton and Warren(2022)and Bhowmick and Roche-Newton(2024).For d≥3,we prove upper bounds forα(F_(q)^(d),p)that are essentially tight within certain ranges for p.We establish the upper bound 2^((1+o(1))q) for the number of general position sets in F_(q)^(d),which matches the trivial lower bound 2q asymptotically in the exponent.We also refine this counting result by proving an asymptotically tight(in the exponent)upper bound for the number of general position sets with a fixed size.The latter result for d=2 improves the result of Roche-Newton and Warren(2022).Our proofs are grounded in the hypergraph container method.In addition,for d=2,we also leverage the pseudorandomness of the point-line incidence graph of F_(q)^(2).
文摘Clostridioides difficile is a leading cause of healthcare-associated infections,causing billions of economic losses every year.Its symptoms range from mild diarrhea to life-threatening damage to the colon.Transmission and recurrence of c.difficile infection(CDl)are mediated by the metabolically dormant spores,while the virulence of C.difficile is mainly due to the two large clostridial toxins,TcdA and TcdB.Producing toxins or forming spores are two different strategies for C.difficile to cope with harsh environmental conditions.It is of great significance to understand the molecular mechanisms for C.difficile to skew to either of the cellular processes.Here,we summarize the current understanding of the regulation and connections between toxin production and sporulation in C.difficile and further discuss the potential solutions for yet-to-be-answered questions.
基金supported by the National Natural Science Foundation of China(Grant Nos.30500188,30471922 and 30731160621)Gamla Tja¨narinnor Foundation and Gun och Bertil Stohnes Stiftelse.
文摘The aim of this study is to investigate the effect of tyrosine kinase Src on Tyrosine 307(Y307)phosphor-ylation,protein phosphatase 2A(PP2A)activity,and on tau phosphorylation.Specific Src siRNA was transfected into cultured mouse neuroblastoma N2a cells to inhibit the expression of Src protein,and the phosphorylation levels of PP2A Y307 and tau at different sites,as well as PP2A activity were detected at different time points after siRNA transfection.Twelve hours after siRNA transfec-tion,the protein level of Src was dramatically decreased,with decreased PP2A Y307 phosphorylation.However,the total PP2A protein level was also decreased,together with a decreased PP2A activity.Tau was hyperpho-sphorylated at the Ser198/199/202 sites.Multiple factors may be involved in the cellular regulation of PP2A activ-ity.Inhibiting Src expression could induce inactivation of PP2A and tau hyperphosphorylation.
