Growing evidence suggests that exercise can provide neuroprotection by improving mitochondrial quality control(MQC)on the aged brain.Adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK)signaling responsiven...Growing evidence suggests that exercise can provide neuroprotection by improving mitochondrial quality control(MQC)on the aged brain.Adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK)signaling responsiveness declines with aging.However,whether AMPK plays a role in the exercise-mediated improvement of memory and MQC in the aged hippocampus remains to be established.5-Aminoimidazole 4-carboxamide ribonucleoside(AICAR),a pharmacological agonist of AMPK,has been proposed to be an exercise mimetic recently.However,it has not been clarified whether AICAR could mimic the effects of exercise on the aged hippocampus through improvement of MQC.In this study,AICAR(AMPK agonist)and Compound C(AMPK inhibitor)were used to investigate if AMPK plays a key role in exercise-induced improvement of MQC and if AICAR could act as an exercise mimetic through improvement of MQC in aged hippocampus.Both exercise and AICAR improved the memory of aged mice and increased AMPK phosphorylation in the aged hippocampus.Exercise,but not AICAR,improved mitochondrial respiratory function in the aged hippocampus and increased the microtubule associated protein 1 light chain 3(LC3)-II/LC3-I ratio and the protein expression of LC3-II and autophagy related protein 7(ATG7)in the lysate of whole hippocampal tissue.Both exercise and AICAR increased the ratio of LC3-II/LC3-I and the protein expression of LC3-II in the mitochondrial fractions of the hippocampus.Regarding mitochondrial dynamics,neither exercise training nor AICAR changed the protein level of mitofusin 2(Mfn2).Exercise,but not AICAR,increased the protein level of dynamin-related protein 1(Drp1).Furthermore,both exercise training and AICAR increased the protein level of peroxisome proliferator-activated receptor γ coactivator 1α(PGC-1α),a modulator of mitochondrial biogenesis.Compound C abolished the exercise-induced effects on memory in aged mice,AMPK phosphorylation,autophagy,mitophagy,and mitochondrial fission in the aged hippocampus.However,Compound C did not reverse the exercise-induced increase in PGC-1α protein levels in the aged hippocampus.Our data provide evidence that AMPK plays an important role in the exercise-induced improvement of memory and MQC in the hippocampus of aged mice.Importantly,we demonstrated for the first time that AICAR could partially mimetic the beneficial effects of endurance exercise on memory and MQC in the hippocampus of aged mice,and thus may be a promising exercise mimetic for counteracting brain aging.展开更多
Maize(Zea mays L.)is recognized as one of the most significant cereal crops worldwide,serving as a primary source of human food,animal feed,and industrial raw materials.With increasing diversification of market demand...Maize(Zea mays L.)is recognized as one of the most significant cereal crops worldwide,serving as a primary source of human food,animal feed,and industrial raw materials.With increasing diversification of market demands for specialty maize varieties,distinctive fresh produce cultivars characterized by unique textures have gained considerable popularity among consumers(Boyer and Shannon 1984).Notably,sweet maize is often referred to as the‘King of fruits and vegetables'due to its richness in polysaccharides,dietary fiber,trace elements,vitamins,linoleic acid,and other essential nutrients(Revilla et al.2021).展开更多
Kinesin-8 motors can move with a high processivity on microtubule lattices toward the plus end.After reaching the plus end,the kinesin-8 motors can pause for a long time and promote the microtubule depolymerization.He...Kinesin-8 motors can move with a high processivity on microtubule lattices toward the plus end.After reaching the plus end,the kinesin-8 motors can pause for a long time and promote the microtubule depolymerization.Here,using atomistic molecular dynamics simulations we studied the structural changes of the kinesin-8 head in different nucleotide states bound to the straight and curved tubulins and the corresponding interactions between them.We found that the kinesin-8 head in ATP and/or ADP–Pi state has the similar strong affinity while in ADP state has the similar weak affinity to both the straight and curved tubulins,which is strongly implicated in the mechanism of the long but very different residence times of the kinesin-8 motor on the microtubule lattice and at the end.Moreover,we found that loop-2 of the kinesin-8 head bound strongly to the curved tubulin in the stable state has a large interference with its neck linker pulled in the minusended orientation.This is contrary to the case of the head bound strongly to the straight tubulin,where loop-2 has little interference with its neck linker pulled in the minus-ended orientation.The large interference can induce a larger internal force between the two heads and thus can induce the two curved tubulins bound strongly by the two heads to be more curved relative to each other.This is strongly implicated in the mechanism of the depolymerase activity of the kinesin-8motors and explains the origin of loop-2 playing a facilitating role in the depolymerase activity.展开更多
In this work,we develop an extended dissipaton theory that generalizes the environmental couplings beyond the conventional linear and quadratic forms,enabling the treatment of ar-bitrary order of bath couplings.Ap-ply...In this work,we develop an extended dissipaton theory that generalizes the environmental couplings beyond the conventional linear and quadratic forms,enabling the treatment of ar-bitrary order of bath couplings.Ap-plying this theoretical framework to the condensed-phase non-Condon spectroscopy,we demonstrate the in-terplay of anharmonicity,non-Con-don and solvent effects on optical spectra,where the higher-order cou-plings arise from the anharmonicity of nuclear potential surface of the excited state.Precise simulations are carried out with high efficiency on linear absorption spectra involving the above mentioned correlated effects.We exhibit how an anharmonic potential modulates the vibronic feature,offering insights into the role of nonlinear environmental couplings in spectroscopic signatures and exemplifying the success of the extended dissipaton formalism as an exact and efficient method for higher-or-der bath couplings.展开更多
Aqueous hydrogen(H_(2))gas batteries with unmatched lifespan are ideal for grid-scale energy storage,yet their deployment remains limited by the lack of low-cost,efficient,and durable hydrogen electrodes.Here,we repor...Aqueous hydrogen(H_(2))gas batteries with unmatched lifespan are ideal for grid-scale energy storage,yet their deployment remains limited by the lack of low-cost,efficient,and durable hydrogen electrodes.Here,we report a high-throughput and durable gas diffusion electrode(GDE)based on a simply preparable carbon-coated nickel(Ni@C)catalyst and the design of H_(2) diffusion channels.By optimizing the carbon layer structure,a balance between the intrinsic activity and stability of the catalyst can be achieved.This Ni@C catalyst exhibits a hydrogen oxidation reaction(HOR)activity of 44 A g^(-1) as well as remarkable hydrogen evolution reaction(HER)performance.Experimental results and theoretical calculations confirm the electronic interaction between the carbon shell and Ni.In combination with a hydrophobic design,a robust and durable Ni@C-GDE has been fabricated.This electrode achieves a low HOR polarization of only 91 mV at 30 mA cm^(-2),outperforming Pt/C-GDE(154 mV),and operates stably over 4500cycles(3200 h)for HOR/HER reversing.Enabled by this electrode,a 10 Ah Ni-H_(2) battery with an energy density of 156.3 Wh kg^(-1) and cost of 62.2$kWh^(-1) is demonstrated.This work offers a viable strategy for practical and scalable hydrogen gas batteries.展开更多
Artificial intelligence(AI)is significantly advancing precision medicine,particularly in the fields of immunogenomics,radiomics,and pathomics.In immunogenomics,AI can process vast amounts of genomic and multi-omic dat...Artificial intelligence(AI)is significantly advancing precision medicine,particularly in the fields of immunogenomics,radiomics,and pathomics.In immunogenomics,AI can process vast amounts of genomic and multi-omic data to identify biomarkers associated with immunotherapy responses and disease prognosis,thus providing strong support for personalized treatments.In radiomics,AI can analyze high-dimensional features from computed tomography(CT),magnetic resonance imaging(MRI),and positron emission tomography/computed tomography(PET/CT)images to discover imaging biomarkers associated with tumor heterogeneity,treatment response,and disease progression,thereby enabling non-invasive,real-time assessments for personalized therapy.Pathomics leverages AI for deep analysis of digital pathology images,and can uncover subtle changes in tissue microenvironments,cellular characteristics,and morphological features,and offer unique insights into immunotherapy response prediction and biomarker discovery.These AI-driven technologies not only enhance the speed,accuracy,and robustness of biomarker discovery but also significantly improve the precision,personalization,and effectiveness of clinical treatments,and are driving a shift from empirical to precision medicine.Despite challenges such as data quality,model interpretability,integration of multi-modal data,and privacy protection,the ongoing advancements in AI,coupled with interdisciplinary collaboration,are poised to further enhance AI’s roles in biomarker discovery and immunotherapy response prediction.These improvements are expected to lead to more accurate,personalized treatment strategies and ultimately better patient outcomes,marking a significant step forward in the evolution of precision medicine.展开更多
In order to solve the problems of high coupling and poor scalability of the traditional monomer early warning release system architecture,multi-level deployment in a complex network environment will lead to high inves...In order to solve the problems of high coupling and poor scalability of the traditional monomer early warning release system architecture,multi-level deployment in a complex network environment will lead to high investment in software and hardware and cannot achieve intensive multi-level deployment.This paper realizes the goal of system scalability by introducing micro service architecture and technology stack and realizes the goal of resource intensification by introducing the idea of a data forwarding agent.The designed architecture scheme has been practically applied in the“Jiangxi emergency early warning information release system software platform(phase I)project”(hereinafter referred to as“provincial emergency”),which meets the needs of flexible deployment of multi-level applications across meteorological wide area network(WAN),business private network of other commissions,offices,and bureaus,government extranet,Internet and other complex networks,and fully verifies the scientificity and rationality of the scheme.It has achieved the goal of intensive and scalable construction of provincial emergencies under the complex network environment,greatly improved the early warning capacity and communication capacity of emergencies and comprehensive disasters,provided a reliable guarantee for disaster prevention and reduction,and provided a reference for the construction of current and future early warning release system and capacity improvement project.展开更多
This study investigated the regulatory potential of salidroside(SAL),a primary active compound in Rhodiola rosea L.,on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha(HIF-1α)pathway in o...This study investigated the regulatory potential of salidroside(SAL),a primary active compound in Rhodiola rosea L.,on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha(HIF-1α)pathway in osteoblasts.Luciferase reporter assay and chromatin immunoprecipitation(Ch IP)assay were employed to validate whether the receptor activator of nuclear factor-κB ligand(RANKL)is the downstream target gene of HIF-1αin osteoblasts.The study also utilized lipopolysaccharide(LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo.Furthermore,conditioned medium(CM)from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1αpathway.Hypoxic condition-induced overexpression of HIF-1αupregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells.In vivo,SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1αby downregulating the expression of RANKL,vascular endothelial growth factor(VEGF),interleukin 6(IL-6),and angiopoietin-like 4(ANGPTL4).In the paracrine experiment,conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1α/RANKL,VEGF,IL-6,and ANGPTL4 pathways.RANKL emerges as the downstream target gene regulated by HIF-1αin osteoblasts.SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1α/RANKL,VEGF,IL-6,and ANGPTL4 pathways.SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.展开更多
基金supported by grants from the National Natural Science Foundation of China(81301128,81771500,82202789,82205065)the 2022 Suzhou Health Youth Backbone Talent“National Tutorial System”Training Project(Qngg2022024)+2 种基金the Science and Technology Project of Suzhou City of China(SKJYD2021195)the Science,Technology and Innovation Commission of Shenzhen(JCYJ20220530165211026)the Postgraduate Research and Practice Innovation Program in Jiangsu Province(KYCX22_3157,KYCX24_3371,YCX25_3517).
文摘Growing evidence suggests that exercise can provide neuroprotection by improving mitochondrial quality control(MQC)on the aged brain.Adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK)signaling responsiveness declines with aging.However,whether AMPK plays a role in the exercise-mediated improvement of memory and MQC in the aged hippocampus remains to be established.5-Aminoimidazole 4-carboxamide ribonucleoside(AICAR),a pharmacological agonist of AMPK,has been proposed to be an exercise mimetic recently.However,it has not been clarified whether AICAR could mimic the effects of exercise on the aged hippocampus through improvement of MQC.In this study,AICAR(AMPK agonist)and Compound C(AMPK inhibitor)were used to investigate if AMPK plays a key role in exercise-induced improvement of MQC and if AICAR could act as an exercise mimetic through improvement of MQC in aged hippocampus.Both exercise and AICAR improved the memory of aged mice and increased AMPK phosphorylation in the aged hippocampus.Exercise,but not AICAR,improved mitochondrial respiratory function in the aged hippocampus and increased the microtubule associated protein 1 light chain 3(LC3)-II/LC3-I ratio and the protein expression of LC3-II and autophagy related protein 7(ATG7)in the lysate of whole hippocampal tissue.Both exercise and AICAR increased the ratio of LC3-II/LC3-I and the protein expression of LC3-II in the mitochondrial fractions of the hippocampus.Regarding mitochondrial dynamics,neither exercise training nor AICAR changed the protein level of mitofusin 2(Mfn2).Exercise,but not AICAR,increased the protein level of dynamin-related protein 1(Drp1).Furthermore,both exercise training and AICAR increased the protein level of peroxisome proliferator-activated receptor γ coactivator 1α(PGC-1α),a modulator of mitochondrial biogenesis.Compound C abolished the exercise-induced effects on memory in aged mice,AMPK phosphorylation,autophagy,mitophagy,and mitochondrial fission in the aged hippocampus.However,Compound C did not reverse the exercise-induced increase in PGC-1α protein levels in the aged hippocampus.Our data provide evidence that AMPK plays an important role in the exercise-induced improvement of memory and MQC in the hippocampus of aged mice.Importantly,we demonstrated for the first time that AICAR could partially mimetic the beneficial effects of endurance exercise on memory and MQC in the hippocampus of aged mice,and thus may be a promising exercise mimetic for counteracting brain aging.
基金supported by the Youth Research Foundation of Beijing Academy of Agriculture and Forestry Sciences,China(QNJJ202420)the Beijing Science and Technology Association Youth Lifting Project,Chinathe Beijing Municipal Rural Revitalization Agricultural Science and Technology Development Project,China(NY2401020224)。
文摘Maize(Zea mays L.)is recognized as one of the most significant cereal crops worldwide,serving as a primary source of human food,animal feed,and industrial raw materials.With increasing diversification of market demands for specialty maize varieties,distinctive fresh produce cultivars characterized by unique textures have gained considerable popularity among consumers(Boyer and Shannon 1984).Notably,sweet maize is often referred to as the‘King of fruits and vegetables'due to its richness in polysaccharides,dietary fiber,trace elements,vitamins,linoleic acid,and other essential nutrients(Revilla et al.2021).
基金Project supported by the Science and Technology Research Program of Chongqing Municipal Education Commission(Grant No.KJQN202504529)the General Program of Chongqing Natural Science Foundation(Grant No.CSTB2025NSCQ-GPX0833)。
文摘Kinesin-8 motors can move with a high processivity on microtubule lattices toward the plus end.After reaching the plus end,the kinesin-8 motors can pause for a long time and promote the microtubule depolymerization.Here,using atomistic molecular dynamics simulations we studied the structural changes of the kinesin-8 head in different nucleotide states bound to the straight and curved tubulins and the corresponding interactions between them.We found that the kinesin-8 head in ATP and/or ADP–Pi state has the similar strong affinity while in ADP state has the similar weak affinity to both the straight and curved tubulins,which is strongly implicated in the mechanism of the long but very different residence times of the kinesin-8 motor on the microtubule lattice and at the end.Moreover,we found that loop-2 of the kinesin-8 head bound strongly to the curved tubulin in the stable state has a large interference with its neck linker pulled in the minusended orientation.This is contrary to the case of the head bound strongly to the straight tubulin,where loop-2 has little interference with its neck linker pulled in the minus-ended orientation.The large interference can induce a larger internal force between the two heads and thus can induce the two curved tubulins bound strongly by the two heads to be more curved relative to each other.This is strongly implicated in the mechanism of the depolymerase activity of the kinesin-8motors and explains the origin of loop-2 playing a facilitating role in the depolymerase activity.
基金supported by the National Natural Sci-ence Foundation of China(Nos.22373091,224B2305,and 22573099).
文摘In this work,we develop an extended dissipaton theory that generalizes the environmental couplings beyond the conventional linear and quadratic forms,enabling the treatment of ar-bitrary order of bath couplings.Ap-plying this theoretical framework to the condensed-phase non-Condon spectroscopy,we demonstrate the in-terplay of anharmonicity,non-Con-don and solvent effects on optical spectra,where the higher-order cou-plings arise from the anharmonicity of nuclear potential surface of the excited state.Precise simulations are carried out with high efficiency on linear absorption spectra involving the above mentioned correlated effects.We exhibit how an anharmonic potential modulates the vibronic feature,offering insights into the role of nonlinear environmental couplings in spectroscopic signatures and exemplifying the success of the extended dissipaton formalism as an exact and efficient method for higher-or-der bath couplings.
基金financially supported by the“National Natural Science Foundation of China”(No.22279082)the“Natural Science Foundation of Sichuan”(2025YFHZ0056)。
文摘Aqueous hydrogen(H_(2))gas batteries with unmatched lifespan are ideal for grid-scale energy storage,yet their deployment remains limited by the lack of low-cost,efficient,and durable hydrogen electrodes.Here,we report a high-throughput and durable gas diffusion electrode(GDE)based on a simply preparable carbon-coated nickel(Ni@C)catalyst and the design of H_(2) diffusion channels.By optimizing the carbon layer structure,a balance between the intrinsic activity and stability of the catalyst can be achieved.This Ni@C catalyst exhibits a hydrogen oxidation reaction(HOR)activity of 44 A g^(-1) as well as remarkable hydrogen evolution reaction(HER)performance.Experimental results and theoretical calculations confirm the electronic interaction between the carbon shell and Ni.In combination with a hydrophobic design,a robust and durable Ni@C-GDE has been fabricated.This electrode achieves a low HOR polarization of only 91 mV at 30 mA cm^(-2),outperforming Pt/C-GDE(154 mV),and operates stably over 4500cycles(3200 h)for HOR/HER reversing.Enabled by this electrode,a 10 Ah Ni-H_(2) battery with an energy density of 156.3 Wh kg^(-1) and cost of 62.2$kWh^(-1) is demonstrated.This work offers a viable strategy for practical and scalable hydrogen gas batteries.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82272008)The Science&Technology Development Fund of Tianjin Education Commission for Higher Education(Grant No.2021KJ194)Tianjin Key Medical Discipline(Specialty)Construction Project(Grant No.TJYXZDXK-009A).
文摘Artificial intelligence(AI)is significantly advancing precision medicine,particularly in the fields of immunogenomics,radiomics,and pathomics.In immunogenomics,AI can process vast amounts of genomic and multi-omic data to identify biomarkers associated with immunotherapy responses and disease prognosis,thus providing strong support for personalized treatments.In radiomics,AI can analyze high-dimensional features from computed tomography(CT),magnetic resonance imaging(MRI),and positron emission tomography/computed tomography(PET/CT)images to discover imaging biomarkers associated with tumor heterogeneity,treatment response,and disease progression,thereby enabling non-invasive,real-time assessments for personalized therapy.Pathomics leverages AI for deep analysis of digital pathology images,and can uncover subtle changes in tissue microenvironments,cellular characteristics,and morphological features,and offer unique insights into immunotherapy response prediction and biomarker discovery.These AI-driven technologies not only enhance the speed,accuracy,and robustness of biomarker discovery but also significantly improve the precision,personalization,and effectiveness of clinical treatments,and are driving a shift from empirical to precision medicine.Despite challenges such as data quality,model interpretability,integration of multi-modal data,and privacy protection,the ongoing advancements in AI,coupled with interdisciplinary collaboration,are poised to further enhance AI’s roles in biomarker discovery and immunotherapy response prediction.These improvements are expected to lead to more accurate,personalized treatment strategies and ultimately better patient outcomes,marking a significant step forward in the evolution of precision medicine.
文摘In order to solve the problems of high coupling and poor scalability of the traditional monomer early warning release system architecture,multi-level deployment in a complex network environment will lead to high investment in software and hardware and cannot achieve intensive multi-level deployment.This paper realizes the goal of system scalability by introducing micro service architecture and technology stack and realizes the goal of resource intensification by introducing the idea of a data forwarding agent.The designed architecture scheme has been practically applied in the“Jiangxi emergency early warning information release system software platform(phase I)project”(hereinafter referred to as“provincial emergency”),which meets the needs of flexible deployment of multi-level applications across meteorological wide area network(WAN),business private network of other commissions,offices,and bureaus,government extranet,Internet and other complex networks,and fully verifies the scientificity and rationality of the scheme.It has achieved the goal of intensive and scalable construction of provincial emergencies under the complex network environment,greatly improved the early warning capacity and communication capacity of emergencies and comprehensive disasters,provided a reliable guarantee for disaster prevention and reduction,and provided a reference for the construction of current and future early warning release system and capacity improvement project.
基金supported by grants from the National Natural Science Foundation of China(Nos.81572852 and 82104671)the Great Program of the Science Foundation of Tianjin(No.18JCZDJC33200)+1 种基金Heilongjiang Province Fund(No.LH2020H102)Tianjin Key Medical Discipline(Specialty)Construction Project(No.TJYXZDXK-032A)。
文摘This study investigated the regulatory potential of salidroside(SAL),a primary active compound in Rhodiola rosea L.,on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha(HIF-1α)pathway in osteoblasts.Luciferase reporter assay and chromatin immunoprecipitation(Ch IP)assay were employed to validate whether the receptor activator of nuclear factor-κB ligand(RANKL)is the downstream target gene of HIF-1αin osteoblasts.The study also utilized lipopolysaccharide(LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo.Furthermore,conditioned medium(CM)from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1αpathway.Hypoxic condition-induced overexpression of HIF-1αupregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells.In vivo,SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1αby downregulating the expression of RANKL,vascular endothelial growth factor(VEGF),interleukin 6(IL-6),and angiopoietin-like 4(ANGPTL4).In the paracrine experiment,conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1α/RANKL,VEGF,IL-6,and ANGPTL4 pathways.RANKL emerges as the downstream target gene regulated by HIF-1αin osteoblasts.SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1α/RANKL,VEGF,IL-6,and ANGPTL4 pathways.SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.
