Bromodomain and extra-terminal domain(BET)proteins,which function partly through MYC proto-oncogene(MYC),are critical epigenetic readers and emerging therapeutic targets in cancer.Whether and how BET inhibition simult...Bromodomain and extra-terminal domain(BET)proteins,which function partly through MYC proto-oncogene(MYC),are critical epigenetic readers and emerging therapeutic targets in cancer.Whether and how BET inhibition simultaneously induces metabolic remodeling in cancer cells remains unclear.Here we find that even transient BET inhibition by JQ-1 and other pan-BET inhibitors(pan-BETis)blunts liver cancer cell proliferation and tumor growth.BET inhibition decreases glycolytic gene expression but enhances mitochondrial glucose and glutamine oxidative metabolism revealed by metabolomics and isotope labeling analysis.Specifically,BET inhibition downregulates miR-30a to upregulate glutamate dehydrogenase 1(GDH1)independent of MYC,which producesα-ketoglutarate for mitochondrial oxidative phosphorylation(OXPHOS).Targeting GDH1 or OXPHOS is synthetic lethal to BET inhibi-tion,and combined BET and OXPHOS inhibition therapeutically prevents liver tumor growth in vitro and in vivo.Together,we uncover an important epigenetic-metabolic crosstalk whereby BET inhibition induces MYC-independent and GDH1-dependent glutamine metabolic remodeling that can be exploited for innovative combination therapy of liver cancer.展开更多
Lysine lactylation is a recently discovered post-translational modification with emerging roles in both physiology and disease.A recent study published in Cell shows that lactate-induced lactylation of the homologous ...Lysine lactylation is a recently discovered post-translational modification with emerging roles in both physiology and disease.A recent study published in Cell shows that lactate-induced lactylation of the homologous recombination(HR)protein meiotic recombination 11 results in HR hyperactivation and chemoresistance in cancer cells,establishing a previously unrecognized link between cellular metabolism and deoxyribonucleic acid(DNA)damage repair and providing new insights into how altered glucose metabolism can impact DNA damage response in cancer.展开更多
Nonlinear optical (NLO) crystals are pivotal in laser application technology, which can convert the laser frequency to generate coherent light in the deep-ultraviolet (deep-UV, wavelengthλ≤200 nm) to far-infrared sp...Nonlinear optical (NLO) crystals are pivotal in laser application technology, which can convert the laser frequency to generate coherent light in the deep-ultraviolet (deep-UV, wavelengthλ≤200 nm) to far-infrared spectral range, and widely used in solid-state system detection, tissue imaging, quantum information,and more [1]. To expand the diversity of optical functional units and then discover novel NLO materials.展开更多
The design and synthesis of new deep-ultraviolet(DUV)optical materials are important but challenging.It is well known that the polarizability anisotropy of linear[BO_(2)]^(−)is larger than those of[BO_(3)]^(3−)and[BO_...The design and synthesis of new deep-ultraviolet(DUV)optical materials are important but challenging.It is well known that the polarizability anisotropy of linear[BO_(2)]^(−)is larger than those of[BO_(3)]^(3−)and[BO_(4)]^(5−),which is the better choice for exploring excellent optical materials.Here,we search for such crystals in borate systems based on the unusual fundamental structural unit[BO_(2)]^(−).By combining the linear[BO_(2)]^(−)with the traditional triangular[BO_(3)]^(3−)and tetrahedral[BO_(4)]^(5−)units,a new mixed metal borate,Rb_(5)Ba_(2)(B_(10)O_(17))_(2)(BO_(2))was obtained via high-temperature solution method.It exhibits excellent optical properties including a DUV transmission window(188 nm)and suitable birefringence(0.06).It also has good thermal stability and its crystal plates can be prepared easily.Furthermore,the strategies of designing borates with[BO_(2)]^(−)units have been proposed from the transformation of crystal framework and the preparation method.展开更多
基金supported by the National Natural Science Foundation of China(82273223 to F.L.,32270798 to P.L.)the National Key Research and Development Program of China(2022YFA1103900 to F.L.).
文摘Bromodomain and extra-terminal domain(BET)proteins,which function partly through MYC proto-oncogene(MYC),are critical epigenetic readers and emerging therapeutic targets in cancer.Whether and how BET inhibition simultaneously induces metabolic remodeling in cancer cells remains unclear.Here we find that even transient BET inhibition by JQ-1 and other pan-BET inhibitors(pan-BETis)blunts liver cancer cell proliferation and tumor growth.BET inhibition decreases glycolytic gene expression but enhances mitochondrial glucose and glutamine oxidative metabolism revealed by metabolomics and isotope labeling analysis.Specifically,BET inhibition downregulates miR-30a to upregulate glutamate dehydrogenase 1(GDH1)independent of MYC,which producesα-ketoglutarate for mitochondrial oxidative phosphorylation(OXPHOS).Targeting GDH1 or OXPHOS is synthetic lethal to BET inhibi-tion,and combined BET and OXPHOS inhibition therapeutically prevents liver tumor growth in vitro and in vivo.Together,we uncover an important epigenetic-metabolic crosstalk whereby BET inhibition induces MYC-independent and GDH1-dependent glutamine metabolic remodeling that can be exploited for innovative combination therapy of liver cancer.
文摘Lysine lactylation is a recently discovered post-translational modification with emerging roles in both physiology and disease.A recent study published in Cell shows that lactate-induced lactylation of the homologous recombination(HR)protein meiotic recombination 11 results in HR hyperactivation and chemoresistance in cancer cells,establishing a previously unrecognized link between cellular metabolism and deoxyribonucleic acid(DNA)damage repair and providing new insights into how altered glucose metabolism can impact DNA damage response in cancer.
基金supported by Key Research Program of Frontier Sciences,Chinese Academy of Sciences (ZDBS-LY-SLH035)the National Natural Science Foundation of China (22193044and 52002397)+3 种基金the National Key R&D Program of China(2021YFB3601502)Natural Science Foundation of Xinjiang(2021D01E05)Tianshan Basic Research Talents (2022TSYCJU0001)Chinese Academy of Sciences Project for Young Scientists in Basic Research (YSBR-024)。
文摘Nonlinear optical (NLO) crystals are pivotal in laser application technology, which can convert the laser frequency to generate coherent light in the deep-ultraviolet (deep-UV, wavelengthλ≤200 nm) to far-infrared spectral range, and widely used in solid-state system detection, tissue imaging, quantum information,and more [1]. To expand the diversity of optical functional units and then discover novel NLO materials.
基金supported by the National Natural Science Foundation of China(51872325,51922014,61835014,51972336)the Shanghai Cooperation Organization Science and Technology Partnership Program(2020E01039)+6 种基金Xinjiang Tianshan Youth Program-Outstanding Young Science and Technology Talents(2020Q004)the CAS Youth Interdisciplinary Team(JCTD-2021-18)the West Light Foundation of Chinese Academy of Sciences(2021-XBQNXZ-004)the Scientific Instrument Developing Project,Chinese Academy of Sciences(YJKYYQ20210033)Fujian Innovation Academy,Chinese Academy of Sciences,Key Research Program of Frontier Sciences,Chinese Academy of Sciences(ZDBS-LY-SLH035)Xinjiang Outstanding Young Scientific and Technological Talents(2020Q004)the International Partnership Program of CAS(1A1365kysb20200008)。
文摘The design and synthesis of new deep-ultraviolet(DUV)optical materials are important but challenging.It is well known that the polarizability anisotropy of linear[BO_(2)]^(−)is larger than those of[BO_(3)]^(3−)and[BO_(4)]^(5−),which is the better choice for exploring excellent optical materials.Here,we search for such crystals in borate systems based on the unusual fundamental structural unit[BO_(2)]^(−).By combining the linear[BO_(2)]^(−)with the traditional triangular[BO_(3)]^(3−)and tetrahedral[BO_(4)]^(5−)units,a new mixed metal borate,Rb_(5)Ba_(2)(B_(10)O_(17))_(2)(BO_(2))was obtained via high-temperature solution method.It exhibits excellent optical properties including a DUV transmission window(188 nm)and suitable birefringence(0.06).It also has good thermal stability and its crystal plates can be prepared easily.Furthermore,the strategies of designing borates with[BO_(2)]^(−)units have been proposed from the transformation of crystal framework and the preparation method.
