Ubiquitination,a multifaceted post-translational modification,regulates protein function,degradation,and gene expression.The pivotal role of ubiquitination in the pathogenesis and progression of cancer,including color...Ubiquitination,a multifaceted post-translational modification,regulates protein function,degradation,and gene expression.The pivotal role of ubiquitination in the pathogenesis and progression of cancer,including colorectal,breast,and liver cancer,is well-established.Osteosarcoma,an aggressive bone tumor predominantly affecting adolescents,also exhibits dysregulation of the ubiquitination system,encompassing both ubiquitination and deubiquitination processes.This dysregulation is now recognized as a key driver of osteosarcoma development,progression,and chemoresistance.This review highlights recent progress in elucidating how ubiquitination modulates tumor behavior across signaling pathways.We then focus on the mechanisms by which ubiquitination influences osteosarcoma cell function.Finally,we discuss the potential for targeting the ubiquitin-proteasome system in osteosarcoma therapy.By unraveling the impact of ubiquitination on osteosarcoma cell physiology,we aim to facilitate the development of novel strategies for prognosis,staging,treatment,and overcoming chemoresistance.展开更多
Stimulus-responsive polymers containing dynamic bonds enable fascinating properties of self-healing,recycling and reprocessing due to enhanced relaxation of polymer chain/network with labile linkages.Here,we study the...Stimulus-responsive polymers containing dynamic bonds enable fascinating properties of self-healing,recycling and reprocessing due to enhanced relaxation of polymer chain/network with labile linkages.Here,we study the structure and properties of a new type of thermoplastic polyurethanes(TPUs)with trapped dynamic covalent bonds in the hard-phase domain and report the frustrated relaxation of TPUs containing weak dynamic bond andπ-πinteraction in hard segments.As detected by rheometry,the aromatic TPUs with alkyl disulfide in the hard segments possess the maximum network relaxation time in contrast to those without dynamic bonds and alicyclic TPUs.In situ FTIR and small-angle scattering results reveal that the alkyl disulfide facilitates stronger intermolecular interaction and more stable micro-phase morphology inπ-πinteraction based aromatic TPUs.Molecular dynamics simulation for pure hard segments of model molecules verify that the presence of disulfide bonds leads to strongerπ-πstacking of aromatic rings due to both enhanced assembling thermodynamics and kinetics.The enhancedπ-πpacking and micro-phase structure in TPUs further kinetically immobilize the dynamic bond.This kinetically interlocking between the weak dynamic bonds and strong molecular interaction in hard segments leads to much slower network relaxation of TPU.This work provides a new insight in tuning the network relaxation and heat resistance as well as molecular self-assembly in stimulus-responsive dynamic polymers by both molecular design and micro-phase control toward the functional applications of advanced materials.展开更多
基金the Sichuan Provincial Central Leading Local Science and Technology Development Special Project(Grant No.2023ZYD0072)the National Natural Science Foundation of China(Grant No.82301785)the Guangdong Basic and Applied Basic Research Foundation(Grant No.2019A1515111078).
文摘Ubiquitination,a multifaceted post-translational modification,regulates protein function,degradation,and gene expression.The pivotal role of ubiquitination in the pathogenesis and progression of cancer,including colorectal,breast,and liver cancer,is well-established.Osteosarcoma,an aggressive bone tumor predominantly affecting adolescents,also exhibits dysregulation of the ubiquitination system,encompassing both ubiquitination and deubiquitination processes.This dysregulation is now recognized as a key driver of osteosarcoma development,progression,and chemoresistance.This review highlights recent progress in elucidating how ubiquitination modulates tumor behavior across signaling pathways.We then focus on the mechanisms by which ubiquitination influences osteosarcoma cell function.Finally,we discuss the potential for targeting the ubiquitin-proteasome system in osteosarcoma therapy.By unraveling the impact of ubiquitination on osteosarcoma cell physiology,we aim to facilitate the development of novel strategies for prognosis,staging,treatment,and overcoming chemoresistance.
基金financially supported by the National Natural Science Foundation of China(No.21774135)。
文摘Stimulus-responsive polymers containing dynamic bonds enable fascinating properties of self-healing,recycling and reprocessing due to enhanced relaxation of polymer chain/network with labile linkages.Here,we study the structure and properties of a new type of thermoplastic polyurethanes(TPUs)with trapped dynamic covalent bonds in the hard-phase domain and report the frustrated relaxation of TPUs containing weak dynamic bond andπ-πinteraction in hard segments.As detected by rheometry,the aromatic TPUs with alkyl disulfide in the hard segments possess the maximum network relaxation time in contrast to those without dynamic bonds and alicyclic TPUs.In situ FTIR and small-angle scattering results reveal that the alkyl disulfide facilitates stronger intermolecular interaction and more stable micro-phase morphology inπ-πinteraction based aromatic TPUs.Molecular dynamics simulation for pure hard segments of model molecules verify that the presence of disulfide bonds leads to strongerπ-πstacking of aromatic rings due to both enhanced assembling thermodynamics and kinetics.The enhancedπ-πpacking and micro-phase structure in TPUs further kinetically immobilize the dynamic bond.This kinetically interlocking between the weak dynamic bonds and strong molecular interaction in hard segments leads to much slower network relaxation of TPU.This work provides a new insight in tuning the network relaxation and heat resistance as well as molecular self-assembly in stimulus-responsive dynamic polymers by both molecular design and micro-phase control toward the functional applications of advanced materials.
