Graded hypoxia is a common microenvironment in malignant solid tumors.As a central regulator in the hypoxic response,hypoxia-inducible factor-1(HIF-1)can induce multiple cellular processes including glycolysis,angioge...Graded hypoxia is a common microenvironment in malignant solid tumors.As a central regulator in the hypoxic response,hypoxia-inducible factor-1(HIF-1)can induce multiple cellular processes including glycolysis,angiogenesis,and necroptosis.How cells exploit the HIF-1 pathway to coordinate different processes to survive hypoxia remains unclear.We developed an integrated model of the HIF-1αnetwork to elucidate the mechanism of cellular adaptation to hypoxia.By numerical simulations and bifurcation analysis,we found that HIF-1αis progressively activated with worsening hypoxia due to the sequential deactivation of the hydroxylases prolyl hydroxylase domain enzymes and factor inhibiting HIF(FIH).Bistable switches control the activation and deactivation processes.As a result,glycolysis,immunosuppression,angiogenesis,and necroptosis are orderly elicited in aggravating hypoxia.To avoid the excessive accumulation of lactic acid during glycolysis,HIF-1αinduces monocarboxylate transporter and carbonic anhydrase 9 sequentially to export intracellular hydrogen ions,facilitating tumor cell survival.HIF-1α-induced miR-182 facilitates vascular endothelial growth factor production to promote angiogenesis under moderate hypoxia.The imbalance between accumulation and removal of lactic acid in severe hypoxia may result in acidosis and induce cell necroptosis.In addition,the deactivation of FIH results in the destabilization of HIF-1αin anoxia.Collectively,HIF-1αorchestrates the adaptation of tumor cells to hypoxia by selectively inducing its targets according to the severity of hypoxia.Our work may provide clues for tumor therapy by targeting the HIF-1 pathway.展开更多
The interaction of alkoxysilanes with nanoscaled giant polyoxoclusters is a challenging route for efficiently building blocks for supramolecular smart design.3-Aminopropyltrimethoxysilane(APTMS)treatment grafts amino ...The interaction of alkoxysilanes with nanoscaled giant polyoxoclusters is a challenging route for efficiently building blocks for supramolecular smart design.3-Aminopropyltrimethoxysilane(APTMS)treatment grafts amino groups onto the surface of the Keplerate{Mo_(132)}in a controlled manner.By means of XPS and elemental analysis,we studied the influence of the component ratio,the solvent nature,acidity and mixture preparation on the stoichiometry of POM-APTMS conjugates.The reaction mechanism shows the role of{Mo_(2)}bridging units as reactive sites for APTMS binding.展开更多
Replacing lithium ions with sodium ions as the charge carriers in rechargeable batteries can induce noticeable differences in the electrochemical storage mechanisms of electrode materials.Many material parameters,such...Replacing lithium ions with sodium ions as the charge carriers in rechargeable batteries can induce noticeable differences in the electrochemical storage mechanisms of electrode materials.Many material parameters,such as particle size,morphology,and the presence of defects,are known to further affect the storage mechanism.Here,we report an investigation of how the introduction of titanium vacancies into anatase TiO_(2)affects the sodium storage mechanism.From pair distribution function analysis,we observe that sodium ions are inserted into titanium vacancies at the early stage of the discharge process.This is supported by density functional theory calculations,which predict that sodium insertion is more favourable at vacancies than at interstitial sites.Our calculations also show that the intercalation voltage is sensitive to the anion coordination environment of the vacancy.Sodiation to higher concentrations induces a phase transition toward a disordered rhombohedral structure,similar to that observed in defect-free TiO_(2).Finally,we find that the X-ray diffraction pattern of the rhombohedral phase drastically changes depending on the composition and degree of disorder,providing further comprehension on the sodium storage mechanism of anatase.展开更多
Interferon regulatory factors(IRFs)are transcription factors with a conserved N-terminal helix-loop-helix DNA-binding domain 1.IRF family plays a pivotal role in regulating interferon transcription,immune cell develop...Interferon regulatory factors(IRFs)are transcription factors with a conserved N-terminal helix-loop-helix DNA-binding domain 1.IRF family plays a pivotal role in regulating interferon transcription,immune cell development,cell growth,apoptosis,and oncogenesis.2 Despite considerable research,the roles of IRFs in cancer development,metastasis,drug resistance,and prognosis remain unclear.Through multidimensional correlation analysis,we examined the association between IRFs and various cancer characteristics,including clinical and immune subtype analysis,stemness,tumor microenvironment(TME),and drug sensitivity,by utilizing The Cancer Genome Atlas(TCGA)data.Moreover,the classification and prognostic role of IRF1 were further validated through immunohistochemistry staining of kidney renal papillary cell carcinoma(KIRP)clinical tissues.This research enriches our understanding of the IRFs’roles in cancer and their clinical applications.展开更多
The enigmatic phenomenon of colossal volumetric and uniaxial negative thermal expansion(NTE)in Ca_(2)RuO_(4)has long challenged understanding due to its intertwined electronic,structural,and magnetic degrees of freedo...The enigmatic phenomenon of colossal volumetric and uniaxial negative thermal expansion(NTE)in Ca_(2)RuO_(4)has long challenged understanding due to its intertwined electronic,structural,and magnetic degrees of freedom.Through ab initio molecular dynamics(AIMD),normal-mode decomposition techniques,and anharmonic Grüneisen analysis,we reveal the microscopic origin of its anisotropic expansion.The uniaxial NTE near the metal-to-insulator transition(MIT)arises from phonons with negative Grüneisen parameters coupled to pronounced elastic anisotropy.Octahedral tilts are central yet non-rigid,involving intrinsic shape changes rather than rigid unit modes.AIMD captures the thermal evolution of RuO_(6)rotations,tilts,and antipolar Ca displacements,which modify local tetragonal distortions of the RuO_(6)octahedra and drive the MIT.Our findings provide microscopic insight into NTE in Ca_(2)RuO_(4)and highlight strategies to engineer phase transitions and thermal responses in A_(2)BO_(4)oxides via tailored octahedral distortions.展开更多
基金supported by the National Natural Science Foundation of China(nos.12090052,11874209,11574139,and 11934008).
文摘Graded hypoxia is a common microenvironment in malignant solid tumors.As a central regulator in the hypoxic response,hypoxia-inducible factor-1(HIF-1)can induce multiple cellular processes including glycolysis,angiogenesis,and necroptosis.How cells exploit the HIF-1 pathway to coordinate different processes to survive hypoxia remains unclear.We developed an integrated model of the HIF-1αnetwork to elucidate the mechanism of cellular adaptation to hypoxia.By numerical simulations and bifurcation analysis,we found that HIF-1αis progressively activated with worsening hypoxia due to the sequential deactivation of the hydroxylases prolyl hydroxylase domain enzymes and factor inhibiting HIF(FIH).Bistable switches control the activation and deactivation processes.As a result,glycolysis,immunosuppression,angiogenesis,and necroptosis are orderly elicited in aggravating hypoxia.To avoid the excessive accumulation of lactic acid during glycolysis,HIF-1αinduces monocarboxylate transporter and carbonic anhydrase 9 sequentially to export intracellular hydrogen ions,facilitating tumor cell survival.HIF-1α-induced miR-182 facilitates vascular endothelial growth factor production to promote angiogenesis under moderate hypoxia.The imbalance between accumulation and removal of lactic acid in severe hypoxia may result in acidosis and induce cell necroptosis.In addition,the deactivation of FIH results in the destabilization of HIF-1αin anoxia.Collectively,HIF-1αorchestrates the adaptation of tumor cells to hypoxia by selectively inducing its targets according to the severity of hypoxia.Our work may provide clues for tumor therapy by targeting the HIF-1 pathway.
基金supported by the Russian Science Foundation:Project No.19-73-00177 as part of the investigation of Keplerate conjugation with alkoxysilanesProject No.21-73-00311 as part of conjugation with fluorescence dyes with POM and investigation of photophysical properties.
文摘The interaction of alkoxysilanes with nanoscaled giant polyoxoclusters is a challenging route for efficiently building blocks for supramolecular smart design.3-Aminopropyltrimethoxysilane(APTMS)treatment grafts amino groups onto the surface of the Keplerate{Mo_(132)}in a controlled manner.By means of XPS and elemental analysis,we studied the influence of the component ratio,the solvent nature,acidity and mixture preparation on the stoichiometry of POM-APTMS conjugates.The reaction mechanism shows the role of{Mo_(2)}bridging units as reactive sites for APTMS binding.
基金support from the Royal Society(UF130329)funded by EPSRC grant EP/L000202.
文摘Replacing lithium ions with sodium ions as the charge carriers in rechargeable batteries can induce noticeable differences in the electrochemical storage mechanisms of electrode materials.Many material parameters,such as particle size,morphology,and the presence of defects,are known to further affect the storage mechanism.Here,we report an investigation of how the introduction of titanium vacancies into anatase TiO_(2)affects the sodium storage mechanism.From pair distribution function analysis,we observe that sodium ions are inserted into titanium vacancies at the early stage of the discharge process.This is supported by density functional theory calculations,which predict that sodium insertion is more favourable at vacancies than at interstitial sites.Our calculations also show that the intercalation voltage is sensitive to the anion coordination environment of the vacancy.Sodiation to higher concentrations induces a phase transition toward a disordered rhombohedral structure,similar to that observed in defect-free TiO_(2).Finally,we find that the X-ray diffraction pattern of the rhombohedral phase drastically changes depending on the composition and degree of disorder,providing further comprehension on the sodium storage mechanism of anatase.
基金supported in part by the National Natural Science Foundation of China(No.82002923,82203505).
文摘Interferon regulatory factors(IRFs)are transcription factors with a conserved N-terminal helix-loop-helix DNA-binding domain 1.IRF family plays a pivotal role in regulating interferon transcription,immune cell development,cell growth,apoptosis,and oncogenesis.2 Despite considerable research,the roles of IRFs in cancer development,metastasis,drug resistance,and prognosis remain unclear.Through multidimensional correlation analysis,we examined the association between IRFs and various cancer characteristics,including clinical and immune subtype analysis,stemness,tumor microenvironment(TME),and drug sensitivity,by utilizing The Cancer Genome Atlas(TCGA)data.Moreover,the classification and prognostic role of IRF1 were further validated through immunohistochemistry staining of kidney renal papillary cell carcinoma(KIRP)clinical tissues.This research enriches our understanding of the IRFs’roles in cancer and their clinical applications.
基金supported by JSPS KAKENHI JP24H00374,JST-CREST(JPMJCR22O1)the Kanagawa Institute of Industrial Science and Technology and Design and Engineering by Joint Inverse Innovation for Materials Architecture of the Ministry of Education,Culture,Sports,Science and Technology.The numerical calculations partially were carried out on the TSUBAME4.0 supercomputer at the Institute of Science Tokyo.
文摘The enigmatic phenomenon of colossal volumetric and uniaxial negative thermal expansion(NTE)in Ca_(2)RuO_(4)has long challenged understanding due to its intertwined electronic,structural,and magnetic degrees of freedom.Through ab initio molecular dynamics(AIMD),normal-mode decomposition techniques,and anharmonic Grüneisen analysis,we reveal the microscopic origin of its anisotropic expansion.The uniaxial NTE near the metal-to-insulator transition(MIT)arises from phonons with negative Grüneisen parameters coupled to pronounced elastic anisotropy.Octahedral tilts are central yet non-rigid,involving intrinsic shape changes rather than rigid unit modes.AIMD captures the thermal evolution of RuO_(6)rotations,tilts,and antipolar Ca displacements,which modify local tetragonal distortions of the RuO_(6)octahedra and drive the MIT.Our findings provide microscopic insight into NTE in Ca_(2)RuO_(4)and highlight strategies to engineer phase transitions and thermal responses in A_(2)BO_(4)oxides via tailored octahedral distortions.
