An increasing number of studies have shown that many alpine lakes have experienced rapid ecosystem transformations over the past^200 years[1–3].However,the mechanisms responsible for triggering these changes are ofte...An increasing number of studies have shown that many alpine lakes have experienced rapid ecosystem transformations over the past^200 years[1–3].However,the mechanisms responsible for triggering these changes are often ambiguous in paleolimnological records and hence they are often debated.A major reason for this is that lake ecosystems are under increasing pressure from both anthropogenic activities and climate change.Possible means of distinguishing the effects of different regional drivers of lake ecosystem changes include the study of paleolimnological contexts which predate human activity,or the study of alpine lakes which are still largely unaffected by local human activity.展开更多
Metabolic dysfunction-associated steatohepatitis(MASH)is one of the most common chronic liver diseases and is mainly caused by metabolic disorders and systemic inflammatory responses.Recent studies have indicated that...Metabolic dysfunction-associated steatohepatitis(MASH)is one of the most common chronic liver diseases and is mainly caused by metabolic disorders and systemic inflammatory responses.Recent studies have indicated that the activation of the mammalian(or mechanistic)target of rapamycin(mTOR)signaling participates in MASH progression by facilitating lipogenesis and regulating the immune microenvironment.Although several molecular medicines have been demonstrated to inhibit the phosphorylation or activation of mTOR,their poor specificity and side effects limit their clinical application in MASH treatment.Phytic acid(PA),as an endogenous and natural antioxidant in the liver,presents significant anti-inflammatory and lipid metabolism-inhibiting functions to alleviate MASH.In this study,considering the unique phosphate-rich structure of PA,we developed a cerium-PA(CePA)nanocom-plex by combining PA with cerium ions possessing phosphodiesterase activity.CePA intervened in the S2448 phosphorylation of mTOR through the occupation effect of phosphate groups,thereby inhibiting the inflammatory response and mTOR-sterol regulatory element-binding protein 1(SREBP1)regulation axis.The in vivo experiments suggested that CePA alleviated MASH progression and fat accumulation in high-fat diet-fed mice.Mechanistic studies validated that CePA exerts a liver-targeted mTOR repressive function,making it a promising candidate for MASH and other mTOR-related disease treatments.展开更多
Objective Colorectal cancer(CRC)is a common cancer worldwide.Although there are several treatments for cancer,the therapeutic effect on CRC remains unsatisfactory,and it is imperative to identify new therapeutic targe...Objective Colorectal cancer(CRC)is a common cancer worldwide.Although there are several treatments for cancer,the therapeutic effect on CRC remains unsatisfactory,and it is imperative to identify new therapeutic targets.Design Prefoldin(PFDN)is mainly used in the cytoskeleton assembly during the folding of actin and tubulin monomers.However,whether PFDN subunits are involved in regulating the development of CRC remains to be elucidated.In this study,molecular biology,cell culture,transcriptome sequencing and other experimental techniques,combined with bioinformatics,were used to verify the regulatory effects of PFDN6 on CRC.Results PFDN6 expression is elevated in patients with CRC and is closely associated with the development of CRC.Knockdown of PFDN6 reduced the tumour cell number,promoted apoptosis,and inhibited the migration and invasion of CRC cells in HCT-116 and RKO cell lines.Mechanistically,differentially expressed genes and related signalling pathways in RKO cells after PFDN6 knockdown were analysed by transcriptome sequencing.Conclusion PFDN6 was found to regulate the generation and development of CRC by targeting ZNF575.These results open new avenues for therapeutic interventions for patients with CRC.展开更多
基金supported by the National Natural Science Foundation of China (41790421, 41722105).
文摘An increasing number of studies have shown that many alpine lakes have experienced rapid ecosystem transformations over the past^200 years[1–3].However,the mechanisms responsible for triggering these changes are often ambiguous in paleolimnological records and hence they are often debated.A major reason for this is that lake ecosystems are under increasing pressure from both anthropogenic activities and climate change.Possible means of distinguishing the effects of different regional drivers of lake ecosystem changes include the study of paleolimnological contexts which predate human activity,or the study of alpine lakes which are still largely unaffected by local human activity.
基金supported by the National Natural Science Foundation of China(82373409,82173143,and 82173082)the Top Young Talents Project of“Special Support Program for High Level Talents”in Shaanxi Province(TZ0422,2020−2025)+3 种基金the 2023 program for training talented pilots upon graduation(LHRCYB23009)support from the National Key Research and Development Program of China(2021YFB3500904)the Key Research and Development Program of Shaanxi(2024SF-YBXM-439)the support from the Fundamental Research Funds for the Central Universities(D5000210635 and D5000210829).
文摘Metabolic dysfunction-associated steatohepatitis(MASH)is one of the most common chronic liver diseases and is mainly caused by metabolic disorders and systemic inflammatory responses.Recent studies have indicated that the activation of the mammalian(or mechanistic)target of rapamycin(mTOR)signaling participates in MASH progression by facilitating lipogenesis and regulating the immune microenvironment.Although several molecular medicines have been demonstrated to inhibit the phosphorylation or activation of mTOR,their poor specificity and side effects limit their clinical application in MASH treatment.Phytic acid(PA),as an endogenous and natural antioxidant in the liver,presents significant anti-inflammatory and lipid metabolism-inhibiting functions to alleviate MASH.In this study,considering the unique phosphate-rich structure of PA,we developed a cerium-PA(CePA)nanocom-plex by combining PA with cerium ions possessing phosphodiesterase activity.CePA intervened in the S2448 phosphorylation of mTOR through the occupation effect of phosphate groups,thereby inhibiting the inflammatory response and mTOR-sterol regulatory element-binding protein 1(SREBP1)regulation axis.The in vivo experiments suggested that CePA alleviated MASH progression and fat accumulation in high-fat diet-fed mice.Mechanistic studies validated that CePA exerts a liver-targeted mTOR repressive function,making it a promising candidate for MASH and other mTOR-related disease treatments.
基金supported by Doctoral‘Direct Access’Research Project of Chongqing(CSTB2022BSXM-JCX0012)the National Natural Science Foundation of Chongqing(cstc2021jcyj-msxmX0127)the 2023 programme for training talented pilots upon graduation(LHRCYB23009).
文摘Objective Colorectal cancer(CRC)is a common cancer worldwide.Although there are several treatments for cancer,the therapeutic effect on CRC remains unsatisfactory,and it is imperative to identify new therapeutic targets.Design Prefoldin(PFDN)is mainly used in the cytoskeleton assembly during the folding of actin and tubulin monomers.However,whether PFDN subunits are involved in regulating the development of CRC remains to be elucidated.In this study,molecular biology,cell culture,transcriptome sequencing and other experimental techniques,combined with bioinformatics,were used to verify the regulatory effects of PFDN6 on CRC.Results PFDN6 expression is elevated in patients with CRC and is closely associated with the development of CRC.Knockdown of PFDN6 reduced the tumour cell number,promoted apoptosis,and inhibited the migration and invasion of CRC cells in HCT-116 and RKO cell lines.Mechanistically,differentially expressed genes and related signalling pathways in RKO cells after PFDN6 knockdown were analysed by transcriptome sequencing.Conclusion PFDN6 was found to regulate the generation and development of CRC by targeting ZNF575.These results open new avenues for therapeutic interventions for patients with CRC.
