Neuroserpin,a secreted protein that belongs to the serpin superfamily of serine protease inhibitors,is highly expressed in the central nervous system and plays multiple roles in brain development and pathology.As a na...Neuroserpin,a secreted protein that belongs to the serpin superfamily of serine protease inhibitors,is highly expressed in the central nervous system and plays multiple roles in brain development and pathology.As a natural inhibitor of recombinant tissue plasminogen activator,neuroserpin inhibits the increased activity of tissue plasminogen activator in ischemic conditions and extends the therapeutic windows of tissue plasminogen activator for brain ischemia.However,the neuroprotective mechanism of neuroserpin against ischemic stroke remains unclear.In this study,we used a mouse model of middle cerebral artery occlusion and oxygen-glucose deprivation/reperfusion-injured cortical neurons as in vivo and in vitro ischemia-reperfusion models,respectively.The models were used to investigate the neuroprotective effects of neuroserpin.Our findings revealed that endoplasmic reticulum stress was promptly triggered following ischemia,initially manifesting as the acute activation of endoplasmic reticulum stress transmembrane sensors and the suppression of protein synthesis,which was followed by a later apoptotic response.Notably,ischemic stroke markedly downregulated the expression of neuroserpin in cortical neurons.Exogenous neuroserpin reversed the activation of multiple endoplasmic reticulum stress signaling molecules,the reduction in protein synthesis,and the upregulation of apoptotic transcription factors.This led to a reduction in neuronal death induced by oxygen/glucose deprivation and reperfusion,as well as decreased cerebral infarction and neurological dysfunction in mice with middle cerebral artery occlusion.However,the neuroprotective effects of neuroserpin were markedly inhibited by endoplasmic reticulum stress activators thapsigargin and tunicamycin.Our findings demonstrate that neuroserpin exerts neuroprotective effects on ischemic stroke by suppressing endoplasmic reticulum stress.展开更多
Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after inju...Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.展开更多
Background:Lumbar disc degeneration(LDD)displays considerable heterogeneity in terms of clinical features and pathological changes.However,researchers have not clearly determined whether the transcriptome variations i...Background:Lumbar disc degeneration(LDD)displays considerable heterogeneity in terms of clinical features and pathological changes.However,researchers have not clearly determined whether the transcriptome variations in LDD could be used to identify or interpret the causes of heterogeneity in clinical features.This study aimed to identify the transcriptomic classification of degenerated discs in LDD patients and whether the molecular subtypes of LDD could be accurately predicted using clinical features.Methods:One hundred and twenty-two nucleus pulposus(NP)tissues from 108 patients were consecutively collected for bulk RNA sequencing(RNA-seq).An unsupervised clustering method was employed to analyze the bulk RNA matrix.Differential analysis was performed to characterize the transcriptional signatures and subtype-specific extracellular matrix(ECM)dysregulation.The cell subpopulation states of each subtype were inferred by integrating bulk and single-cell sequencing datasets.Transwell and dual-luciferase reporter gene assays were employed to investigate possible molecular mechanisms involved.Machine learning algorithm diagnostic prediction models were developed to correlate molecular classification with clinical features.Results:LDD was classified into 4 subtypes with distinct molecular signatures and ECM remodeling:C1 with collagenesis,C2 with ossification,C3 with low chondrogenesis,and C4 with fibrogenesis.Chond1-3 in C1 dominated disc collagenesis via the activation of the mechanosensors TRPV4 and PIEZO1;NP progenitor cells in C2 exhibited chondrogenic and osteogenic phenotypes;Chond1 in C3 was linked to a disrupted hypoxic microenvironment leading to reduced chondrogenesis;Macrophages in C4 played a crucial role in disc fibrogenesis via the secretion of tumor necrosis factor-α(TNF-α).Furthermore,the random forest diagnostic prediction model was proven to have a robust performance[area under the receiver operating characteristic(ROC)curve:0.9312;accuracy:0.84]in stratifying the molecular subtypes of LDD based on 12 clinical features.Conclusions:Our study delineates 4 distinct molecular subtypes of LDD that can be accurately stratified on the basis of clinical features.The identification of these subtypes would facilitate precise diagnostics and guide the development of personalized treatment strategies for LDD.展开更多
The study of target proteins is crucial for understanding molecular interactions and developing analytical platforms,therapeutic agents and functional tools.Herein,we present a novel nanoplatform activated by near-inf...The study of target proteins is crucial for understanding molecular interactions and developing analytical platforms,therapeutic agents and functional tools.Herein,we present a novel nanoplatform activated by near-infrared(NIR) light for triple-modal proteins study,which enabling target protein labeling,enrichment and visualization.Azido-naphthalimide-coated upconversion nanoparticles(UCNPs) serve as NIR light-responsive nanoplatforms,showing promising applications in studying interactions between various bioactive molecules and proteins in living systems.Under NIR light irradiation,azido-naphthalimides are activated by ultraviolet(UV) and blue light emitted from UCNPs and the resulting amino-naphthalimides intermediate not only crosslink nearby target proteins but also enable imaging performance.We demonstrate that this nanoplatform is capable of selective protein labeling and imaging in complex protein environments,achieving specific labeling and imaging of both intracellular and extracellular proteins in mammalian cells as well as bacteria.Furthermore,in vivo protein labeling has been achieved using this novel NIR light-activatable nanoplatform.This technique will open new avenues for discoveries and mechanistic interrogation in chemical biology.展开更多
Fluorinated motifs are prevalent in both pharmaceuticals and agrochemicals.The incorporation of fluorine-containing moieties to drug candidates has emerged as a potent strategy for lead optimization in pharmaceutical ...Fluorinated motifs are prevalent in both pharmaceuticals and agrochemicals.The incorporation of fluorine-containing moieties to drug candidates has emerged as a potent strategy for lead optimization in pharmaceutical research and development.While extensive research has been devoted to constructing molecules that incorporate a trifluoromethylthio(SCF_(3)−)group on a stereogenic carbon,the synthesis of trifluoromethylthiolated alkanes featuring a SCF_(3)-substituted stereogenic carbon at non-activated site remains understudied.Herein,we report a Cu-catalyzed regio-and enantioselective hydroallylation of 1-trifluoromethylthiolated alkenes.Important to the process is the regio-and enantioselective Cu-H insertion to SCF_(3)-substituted alkene to form chiralα-SCF_(3) alkyl copper intermediates,outcompeting unproductive insertion to the coupling partner,and eventually proceed to afford optically active homoallylic trifluoromethylthiolated products.展开更多
A novel trace nickel(Ni)doped tungsten(W)matrix with coated Ni on W grains was prepared by powder metallurgy method.The introduction of Ni can inhibit the reaction between W and barium-calcium aluminates(Ba-Ca alumina...A novel trace nickel(Ni)doped tungsten(W)matrix with coated Ni on W grains was prepared by powder metallurgy method.The introduction of Ni can inhibit the reaction between W and barium-calcium aluminates(Ba-Ca aluminates)during the impregnation process of the matrix.After cathode activation,the surface Ba:O molar ratio is 0.88:1.00,much higher than the Ba dispenser cathode without Ni doping.The XPS results of the cathode surface showed that the metallic Ba appeared on the activated cathode surface,forming dipoles with oxygen,and effectively reducing the cathode surface work function.The pulse electron emission current density at 1100℃_(b)(brightness temperature)was 18.26 A/cm^(2),and the calculated work function was 1.97 eV.It has a low evaporation rate and the accelerated lifetime test predict a lifetime of over 160000 h.First-principles calculations showed that the charge transfer and dipole moment in the NiW-BaO system were both increased compared to the Ba dispenser cathode,thus improving the emission performance of the Ni-W mixed matrix cathode.展开更多
In electrochemical energy storage systems,the sodium-ion battery is typically integrated in the form of a“cell-module-cluster”,but its cross-scale thermal runaway triggering risk and the propagation mechanism remain...In electrochemical energy storage systems,the sodium-ion battery is typically integrated in the form of a“cell-module-cluster”,but its cross-scale thermal runaway triggering risk and the propagation mechanism remain unclear.This study reveals the cross-scale thermal runaway triggering and propagation behavior of sodium-ion batteries of“cell-module-cluster”under overcharge conditions,and investigates the effects of key factors,including module spacing,triggering cell location,and heat dissipation condition,on the thermal runaway propagation behavior.Results demonstrate that the thermal runaway propagation in a module containing the overcharged cell follows a sequential triggering mode,while thermal runaway in the downstream module exhibits a simultaneous triggering mode with greater severity.Furthermore,increasing the module spacing or enhancing the heat dissipation capacity can effectively reduce the heat accumulation and prevent the trigger of thermal runaway.On the above basis,the multi-dimensional evaluation strategy is proposed to quantitatively assess the hazard of sodium-ion battery cluster thermal runaway.The findings serve as a foundation for the safe design of sodium-ion batteries in energy storage systems.展开更多
Persistent overcast rain was an essential limiting factor for summer maize production,of which immediate impact was the dual pressure of waterlogging and shading.However,the mechanisms underlying independent and combi...Persistent overcast rain was an essential limiting factor for summer maize production,of which immediate impact was the dual pressure of waterlogging and shading.However,the mechanisms underlying independent and combined effects of waterlogging and shading on maize yield losses remain understudied,particularly across different growth stages.Denghai 605(DH605)was selected to be subjected shading,waterlogging,and their combined stress at the 3rd leaf stage(V3),the 6th leaf stage(V6),and tasseling stage(VT).Results showed that shading,waterlogging and their combination significantly restricted leaf area expansion,reduced leaf net photosynthetic rate(P_(n))and net assimilation rate(NAR),thereby decreasing the crop growth rate(CGR)and biomass accumulation.Additionally,compared to control,the process of lignin synthesis was inhibited under stressed treatment,resulting in diminished stem mechanical strength and impaired vascular system development,which substantially reduced assimilate remobilization efficiency to the ear and ultimate grain yield.Waterlogging and combined stresses exhibited maximum impact at the V3 stage,followed by V6 and VT stages,while shading effects were most pronounced at the VT stage,followed by V6 and V3 stages.Moreover,the compound stress exacerbated the damage brought about by a single stress.As climate change is projected to increase the frequency of multiple abiotic stress occurrences,these findings provide valuable insights for future summer maize breeding research under persistent rainfall conditions.展开更多
Thermochemical sulfate reduction(TSR)is an important organic-inorganic reaction that occurs within sedimentary basins and alters the original chemical compositions and isotopic structures of hydrocarbons in natural ga...Thermochemical sulfate reduction(TSR)is an important organic-inorganic reaction that occurs within sedimentary basins and alters the original chemical compositions and isotopic structures of hydrocarbons in natural gases.We used the GC-Py-GC-IRMS method to study TSR and obtained a novel finding related to intramolecular carbon isotope fractionation in natural propane.The results show that theΔC-T(δ^(13)C_(central)-13 C_(terminal))andδ^(13)C_(central)values significantly increased to 44.7‰and 11.9‰,respectively,with increasing TSR alteration.In contrast,the 13 C_(terminal)values of propane remained largely unaltered by the TSR reaction.This difference in position-specific isotope fractionation can be attributed to the central carbon’s reactivity being higher than that of terminal carbon during TSR.In sum,the results indicate that theδ^(13)C_(terminal)values of propane can serve as robust indicators for source rock identification of natural gas altered by post-generation reactions such as TSR and anaerobic microbial oxidation.展开更多
Drought causes water shortage and consequent retardation of plants growth and development.Therefore,improving the drought tolerance of plants is necessary for expanding cultivation and resource promotion.Increasing ev...Drought causes water shortage and consequent retardation of plants growth and development.Therefore,improving the drought tolerance of plants is necessary for expanding cultivation and resource promotion.Increasing evidence indicates that phospholipase is involved in the response of plants to drought stress.The objective of this study was to create new drought-tolerant chrysanthemum germplasm,which lays a foundation for the study of the molecular mechanism of phospholipase mediated stress response in chrysanthemum.CmPLDαhas the closest relationship with sunflower HaPLDα,and belongs to the PLDαfamily.CmPLDαover-expressing plants showed a slight shrinking under 20%PEG6000 treatment.The survival rate increased significantly by 1.7−1.8 times that of the wild type.Relative water content(RWC)of CmPLDαover-expressing plants were nearly 10%higher than that of the wild type.Relative electrical conductivity and MDA content were significantly lower than those of the wild type.ABA content of the over-expression lines Z1,Z2 were 1.3 and 1.22 times that of wild type,but ABA content of antisense lines F1,F2 was approximately 0.83 and 0.81 of those of wild type.Most plants of antisense transgenic lines F1,F2 were wrinkled,with a wilting index of 5 and 6,and the survival rate was also lower than that of the wild type after recovery growth.RWC of antisense lines were lower than over-expression lines,relative electrical conductivity and MDA content were significantly higher than those of the wild type.In summary,CmPLDαcould enhance tolerance of chrysanthemum to drought conditions.展开更多
Converting CO_(2)with green hydrogen to methanol as a carbon-neutral liquid fuel is a promising route for the long-term storage and distribution of intermittent renewable energy.Nevertheless,attaining highly efficient...Converting CO_(2)with green hydrogen to methanol as a carbon-neutral liquid fuel is a promising route for the long-term storage and distribution of intermittent renewable energy.Nevertheless,attaining highly efficient methanol synthesis catalysts from the vast composition space remains a significant challenge.Here we present a machine learning framework for accelerating the development of high space-time yield(STY)methanol synthesis catalysts.A database of methanol synthesis catalysts has been compiled,consisting of catalyst composition,preparation parameters,structural characteristics,reaction conditions and their corresponding catalytic performance.A methodology for constructing catalyst features based on the intrinsic physicochemical properties of the catalyst components has been developed,which significantly reduced the data dimensionality and enhanced the efficiency of machine learning operations.Two high-precision machine learning prediction models for the activities and product selectivity of catalysts were trained and obtained.Using this machine learning framework,an efficient search was achieved within the catalyst composition space,leading to the successful identification of high STY multielement oxide methanol synthesis catalysts.Notably,the CuZnAlTi catalyst achieved high STYs of 0.49 and 0.65 g_(MeOH)/(g_(catalyst)h)for CO_(2)and CO hydrogenation to methanol at 250℃,respectively,and the STY was further increased to 2.63 g_(Me OH)/(g_(catalyst)h)in CO and CO_(2)co-hydrogenation.展开更多
Vestibular Migraine (VM) is a common neurological disorder characterized by recurrent episodes of vertigo and migraine symptoms. The pathogenesis of VM is complex and involves multiple genetic and environmental factor...Vestibular Migraine (VM) is a common neurological disorder characterized by recurrent episodes of vertigo and migraine symptoms. The pathogenesis of VM is complex and involves multiple genetic and environmental factors. Recent studies have suggested that the pathogenesis of vestibular migraine may be associated with variations in the CACNA1A gene, which is an important gene target for controlling calcium ion channels. Such variations may further affect the functions of the vestibular nervous system, thereby causing a series of vestibular nervous system-related symptoms. This article will summarize the genetic association studies of vestibular migraine, vestibular function studies, and research on how to establish relevant animal models to illustrate the possible association between CACNA1A variations and the pathogenesis of VM, providing new ideas for clarifying the pathogenesis of VM.展开更多
The efficient hydrogenolysis of esters to alkanes is the key protocol for producing advanced biofuels from renewable plant oils or fats.Due to the low reactivity of the carbonyl group in esters,a high reaction tempera...The efficient hydrogenolysis of esters to alkanes is the key protocol for producing advanced biofuels from renewable plant oils or fats.Due to the low reactivity of the carbonyl group in esters,a high reaction temperature(>250℃)is the prerequisite to ensure high conversion of esters.Here,we report a highly dispersed MoO_(x)-Ru/C bimetallic catalyst for the efficient hydrogenolysis of esters to alkanes under 150°C.The optimal catalyst exhibits>99%conversion of methyl stearate and 99%selectivity to diesel-range alkanes,reaching a high rate of up to 2.0 mmol gcat^(–1)h^(–1),5 times higher than that of Ru/C catalyst(MoO_(x)/C is inert).Integrated experimental and theoretical investigations attribute the high performance to the abundant MoO_(x)-Ru interfacial sites on the catalyst surface,which offers high activity for the C–O cleavage of esters.Furthermore,the dispersed MoO_(x)species significantly weaken the hydrocracking activity of the metallic Ru for C–C bonds,thus yielding alkane products without carbon loss.This study provides a facile and novel strategy for the design of high-performance heterogeneous catalysts for the hydrodeoxygenation of biomass-derived esters to alkane products.展开更多
To make agricultural systems sustainable in terms of their greenness and efficiency,optimizing the tillage and fertilization practices is essential.To assess the effects of tilling and fertilization practices in wheat...To make agricultural systems sustainable in terms of their greenness and efficiency,optimizing the tillage and fertilization practices is essential.To assess the effects of tilling and fertilization practices in wheat-maize cropping systems,a three-year field experiment was designed to quantify the carbon footprint(CF)and energy efficiency of the cropping systems in the North China Plain.The study parameters included four tillage practices(no tillage(NT),conventional tillage(CT),rotary tillage(RT),and subsoiling rotary tillage(SRT))and two fertilizer regimes(inorganic fertilizer(IF)and hybrid fertilizer with organic and inorganic components(HF)).The results indicated that the most prominent energy inputs and greenhouse gas(GHG)emissions could be ascribed to the use of fertilizers and fuel consumption.Under the same fertilization regime,ranking the tillage patterns with respect to the value of the crop yield,profit,CF,energy use efficiency(EUE)or energy productivity(EP)for either wheat or maize always gave the same sequence of SRT>RT>CT>NT.For the same tillage,the energy consumption associated with HF was higher than IF,but its GHG emissions and CF were lower while the yield and profit were higher.In terms of overall performance,tilling is more beneficial than NT,and reduced tillage practices(RT and SRT)are more beneficial than CT.The fertilization regime with the best overall performance was HF.Combining SRT with HF has significant potential for reducing CF and increasing EUE,thereby improving sustainability.Adopting measures that promote these optimizations can help to overcome the challenges posed by a lack of food security,energy crises and ecological stress.展开更多
Geological sequestration of CO_(2)is critical for deep decarbonization,but the geomechanical stability of coal reservoirs remains a major challenge.This study integrates nanoindentation,XRD/SEM-EDS chemo physical char...Geological sequestration of CO_(2)is critical for deep decarbonization,but the geomechanical stability of coal reservoirs remains a major challenge.This study integrates nanoindentation,XRD/SEM-EDS chemo physical characterization and 4D CT visualization to investigate the time-evolving mechanical degradation of bituminous coals with ScCO_(2)injection.The main results show that 4 d of ScCO_(2)treatment caused 50.47%–80.99%increase in load–displacement deformation and 26.92%–76.17%increase in creep depth at peak load,accompanied by 55.01%–63.38%loss in elastic modulus and 52.83%–74.81%reduction in hardness.The degradation exhibited biphasic kinetics,characterized by rapid surface-driven weakening(0–2 d),followed by stabilized matrix-scale pore homogenization(2–4 d).ScCO_(2)preferentially dissolved carbonate minerals(dolomite),driving pore network expansion and interfacial debonding,while silicate minerals resisted dissolution but promoted structural homogenization.These coupled geochemical-mechanical processes reduced the mechanical heterogeneity of the coal and altered its failure modes.The results establish a predictive framework for reservoir stability assessment and provide actionable insights for optimizing CO_(2)enhanced coalbed methane recovery.展开更多
基金supported in part by the National Key Research&Development Program of China,No.2022YFA1104900(to LS)the National Natural Science Foundation of China,Nos.82371175,82071535(both to LS),82101614(to YP)+5 种基金the International Science and Technology Cooperation Projects of Guangdong Province,No.2023A0505050121(to LS)Guangdong Basic and Applied Basic Research Foundation,Nos.2022B1515130007(to LS),2023A1515030012(to SZ),2022A1515010666(to WL)the Science and Technology Program of Guangzhou,Nos.202102070001(to LS),202201010041(to YP)Shenzhen Basic Research Grant,Nos.JCYJ20200109140414636,JCYJ20230807145103007(both to WL)awarded a Royal Society Newton Advanced Fellowship,No.AOMS-NAF0051003in collaboration with Zoltán Molnár,Department of Physiology,Anatomy and Genetics,University of Oxford(2017–2021)。
文摘Neuroserpin,a secreted protein that belongs to the serpin superfamily of serine protease inhibitors,is highly expressed in the central nervous system and plays multiple roles in brain development and pathology.As a natural inhibitor of recombinant tissue plasminogen activator,neuroserpin inhibits the increased activity of tissue plasminogen activator in ischemic conditions and extends the therapeutic windows of tissue plasminogen activator for brain ischemia.However,the neuroprotective mechanism of neuroserpin against ischemic stroke remains unclear.In this study,we used a mouse model of middle cerebral artery occlusion and oxygen-glucose deprivation/reperfusion-injured cortical neurons as in vivo and in vitro ischemia-reperfusion models,respectively.The models were used to investigate the neuroprotective effects of neuroserpin.Our findings revealed that endoplasmic reticulum stress was promptly triggered following ischemia,initially manifesting as the acute activation of endoplasmic reticulum stress transmembrane sensors and the suppression of protein synthesis,which was followed by a later apoptotic response.Notably,ischemic stroke markedly downregulated the expression of neuroserpin in cortical neurons.Exogenous neuroserpin reversed the activation of multiple endoplasmic reticulum stress signaling molecules,the reduction in protein synthesis,and the upregulation of apoptotic transcription factors.This led to a reduction in neuronal death induced by oxygen/glucose deprivation and reperfusion,as well as decreased cerebral infarction and neurological dysfunction in mice with middle cerebral artery occlusion.However,the neuroprotective effects of neuroserpin were markedly inhibited by endoplasmic reticulum stress activators thapsigargin and tunicamycin.Our findings demonstrate that neuroserpin exerts neuroprotective effects on ischemic stroke by suppressing endoplasmic reticulum stress.
文摘Exogenous neural stem cell transplantation has become one of the most promising treatment methods for chronic stroke.Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury,which limits the ability to observe long-term behavioral recovery.Here,we used a severe stroke rat model with 150 minutes of ischemia,which produced severe behavioral deficiencies that persisted at 12 weeks,to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke.Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function,reduced infarction volume,long-term human neural stem cell survival,and improved local inflammatory environment and angiogenesis.We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo,formed stable functional synaptic connections with host neurons,and exhibited the electrophysiological properties of functional mature neurons,indicating that they replaced the damaged host neurons.The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke,which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.
基金supported by the National Natural Science Foundation of China(32270887,82272507,32200654,82430079,and 82472519)the National Key Research and Development Program of China(2022YFA1103202)+7 种基金the Chongqing High-End Medical Talents for Middle-aged and Young(YXGD202408)the Army Scientific and Technological Innovation Talents Prioritized Suppor t Program(2023-124)the Natural Science Foundation of Chongqing(CSTB2023NSCQ-ZDJO008)the Postdoctoral Innovative Talent Support Program(BX20220397)the Open Project of State Key Laboratory of TraumaBurns and Combined Injury(SFLKF202201)the Project for Enhancing Innovation of Army Medical University(2023XJS39)the Talent Innovation Training Program at the Army Medical Center(ZXZYTSYS09)。
文摘Background:Lumbar disc degeneration(LDD)displays considerable heterogeneity in terms of clinical features and pathological changes.However,researchers have not clearly determined whether the transcriptome variations in LDD could be used to identify or interpret the causes of heterogeneity in clinical features.This study aimed to identify the transcriptomic classification of degenerated discs in LDD patients and whether the molecular subtypes of LDD could be accurately predicted using clinical features.Methods:One hundred and twenty-two nucleus pulposus(NP)tissues from 108 patients were consecutively collected for bulk RNA sequencing(RNA-seq).An unsupervised clustering method was employed to analyze the bulk RNA matrix.Differential analysis was performed to characterize the transcriptional signatures and subtype-specific extracellular matrix(ECM)dysregulation.The cell subpopulation states of each subtype were inferred by integrating bulk and single-cell sequencing datasets.Transwell and dual-luciferase reporter gene assays were employed to investigate possible molecular mechanisms involved.Machine learning algorithm diagnostic prediction models were developed to correlate molecular classification with clinical features.Results:LDD was classified into 4 subtypes with distinct molecular signatures and ECM remodeling:C1 with collagenesis,C2 with ossification,C3 with low chondrogenesis,and C4 with fibrogenesis.Chond1-3 in C1 dominated disc collagenesis via the activation of the mechanosensors TRPV4 and PIEZO1;NP progenitor cells in C2 exhibited chondrogenic and osteogenic phenotypes;Chond1 in C3 was linked to a disrupted hypoxic microenvironment leading to reduced chondrogenesis;Macrophages in C4 played a crucial role in disc fibrogenesis via the secretion of tumor necrosis factor-α(TNF-α).Furthermore,the random forest diagnostic prediction model was proven to have a robust performance[area under the receiver operating characteristic(ROC)curve:0.9312;accuracy:0.84]in stratifying the molecular subtypes of LDD based on 12 clinical features.Conclusions:Our study delineates 4 distinct molecular subtypes of LDD that can be accurately stratified on the basis of clinical features.The identification of these subtypes would facilitate precise diagnostics and guide the development of personalized treatment strategies for LDD.
基金supported by the National Natural Science Foundation of China (No.22007008)the LiaoNing Revitalization Talents Program (No.XLYC1907021)the Fundamental Research Funds for the Central Universities (Nos.DUT23YG120,DUT19RC(3)009)。
文摘The study of target proteins is crucial for understanding molecular interactions and developing analytical platforms,therapeutic agents and functional tools.Herein,we present a novel nanoplatform activated by near-infrared(NIR) light for triple-modal proteins study,which enabling target protein labeling,enrichment and visualization.Azido-naphthalimide-coated upconversion nanoparticles(UCNPs) serve as NIR light-responsive nanoplatforms,showing promising applications in studying interactions between various bioactive molecules and proteins in living systems.Under NIR light irradiation,azido-naphthalimides are activated by ultraviolet(UV) and blue light emitted from UCNPs and the resulting amino-naphthalimides intermediate not only crosslink nearby target proteins but also enable imaging performance.We demonstrate that this nanoplatform is capable of selective protein labeling and imaging in complex protein environments,achieving specific labeling and imaging of both intracellular and extracellular proteins in mammalian cells as well as bacteria.Furthermore,in vivo protein labeling has been achieved using this novel NIR light-activatable nanoplatform.This technique will open new avenues for discoveries and mechanistic interrogation in chemical biology.
基金the National Key R&D Program of China(No.2021YFF0701700)the National Natural Science Foundation of China(Nos.22271264 and 21971228)for financial support.
文摘Fluorinated motifs are prevalent in both pharmaceuticals and agrochemicals.The incorporation of fluorine-containing moieties to drug candidates has emerged as a potent strategy for lead optimization in pharmaceutical research and development.While extensive research has been devoted to constructing molecules that incorporate a trifluoromethylthio(SCF_(3)−)group on a stereogenic carbon,the synthesis of trifluoromethylthiolated alkanes featuring a SCF_(3)-substituted stereogenic carbon at non-activated site remains understudied.Herein,we report a Cu-catalyzed regio-and enantioselective hydroallylation of 1-trifluoromethylthiolated alkenes.Important to the process is the regio-and enantioselective Cu-H insertion to SCF_(3)-substituted alkene to form chiralα-SCF_(3) alkyl copper intermediates,outcompeting unproductive insertion to the coupling partner,and eventually proceed to afford optically active homoallylic trifluoromethylthiolated products.
基金supported by the National Natural Science Foundation of China(Nos.U2341209 and 52130407).
文摘A novel trace nickel(Ni)doped tungsten(W)matrix with coated Ni on W grains was prepared by powder metallurgy method.The introduction of Ni can inhibit the reaction between W and barium-calcium aluminates(Ba-Ca aluminates)during the impregnation process of the matrix.After cathode activation,the surface Ba:O molar ratio is 0.88:1.00,much higher than the Ba dispenser cathode without Ni doping.The XPS results of the cathode surface showed that the metallic Ba appeared on the activated cathode surface,forming dipoles with oxygen,and effectively reducing the cathode surface work function.The pulse electron emission current density at 1100℃_(b)(brightness temperature)was 18.26 A/cm^(2),and the calculated work function was 1.97 eV.It has a low evaporation rate and the accelerated lifetime test predict a lifetime of over 160000 h.First-principles calculations showed that the charge transfer and dipole moment in the NiW-BaO system were both increased compared to the Ba dispenser cathode,thus improving the emission performance of the Ni-W mixed matrix cathode.
基金supported by the Anhui Quality Infrastructure Standardization Project(Grant No.2024MKSO7)the Science and Technology Project of State Grid(SGAHDK00DJJS2310027)the Anhui Provincial Natural Science Foundation(Grant No.2208085UD03).
文摘In electrochemical energy storage systems,the sodium-ion battery is typically integrated in the form of a“cell-module-cluster”,but its cross-scale thermal runaway triggering risk and the propagation mechanism remain unclear.This study reveals the cross-scale thermal runaway triggering and propagation behavior of sodium-ion batteries of“cell-module-cluster”under overcharge conditions,and investigates the effects of key factors,including module spacing,triggering cell location,and heat dissipation condition,on the thermal runaway propagation behavior.Results demonstrate that the thermal runaway propagation in a module containing the overcharged cell follows a sequential triggering mode,while thermal runaway in the downstream module exhibits a simultaneous triggering mode with greater severity.Furthermore,increasing the module spacing or enhancing the heat dissipation capacity can effectively reduce the heat accumulation and prevent the trigger of thermal runaway.On the above basis,the multi-dimensional evaluation strategy is proposed to quantitatively assess the hazard of sodium-ion battery cluster thermal runaway.The findings serve as a foundation for the safe design of sodium-ion batteries in energy storage systems.
基金supported by the University Youth Innovation Science and Technology Support Program of Shandong Province,China(2021KJ073)the Postdoctoral Innovation Program of Shandong Province,China(202003039)+2 种基金the China Agriculture Research System(CARS-02-21)the State Key Laboratory of North China Crop Improvement and Regulation(NCCIR2023KF-8)the Key R&D Program of Shandong Province,China(2023TZXD08603)。
文摘Persistent overcast rain was an essential limiting factor for summer maize production,of which immediate impact was the dual pressure of waterlogging and shading.However,the mechanisms underlying independent and combined effects of waterlogging and shading on maize yield losses remain understudied,particularly across different growth stages.Denghai 605(DH605)was selected to be subjected shading,waterlogging,and their combined stress at the 3rd leaf stage(V3),the 6th leaf stage(V6),and tasseling stage(VT).Results showed that shading,waterlogging and their combination significantly restricted leaf area expansion,reduced leaf net photosynthetic rate(P_(n))and net assimilation rate(NAR),thereby decreasing the crop growth rate(CGR)and biomass accumulation.Additionally,compared to control,the process of lignin synthesis was inhibited under stressed treatment,resulting in diminished stem mechanical strength and impaired vascular system development,which substantially reduced assimilate remobilization efficiency to the ear and ultimate grain yield.Waterlogging and combined stresses exhibited maximum impact at the V3 stage,followed by V6 and VT stages,while shading effects were most pronounced at the VT stage,followed by V6 and V3 stages.Moreover,the compound stress exacerbated the damage brought about by a single stress.As climate change is projected to increase the frequency of multiple abiotic stress occurrences,these findings provide valuable insights for future summer maize breeding research under persistent rainfall conditions.
基金supported by the Helium Enrichment and Detection in Natural Gas Reservoirs Related to Oil and Gas Fields project(Grant No.2025ZD1010500)the Deep Earth Probe and Mineral Resources Exploration―National Science and Technology Major Project.-。
文摘Thermochemical sulfate reduction(TSR)is an important organic-inorganic reaction that occurs within sedimentary basins and alters the original chemical compositions and isotopic structures of hydrocarbons in natural gases.We used the GC-Py-GC-IRMS method to study TSR and obtained a novel finding related to intramolecular carbon isotope fractionation in natural propane.The results show that theΔC-T(δ^(13)C_(central)-13 C_(terminal))andδ^(13)C_(central)values significantly increased to 44.7‰and 11.9‰,respectively,with increasing TSR alteration.In contrast,the 13 C_(terminal)values of propane remained largely unaltered by the TSR reaction.This difference in position-specific isotope fractionation can be attributed to the central carbon’s reactivity being higher than that of terminal carbon during TSR.In sum,the results indicate that theδ^(13)C_(terminal)values of propane can serve as robust indicators for source rock identification of natural gas altered by post-generation reactions such as TSR and anaerobic microbial oxidation.
基金funded by the National Key Research and Development Program of China(2018YFD1000402)the National Natural Science Foundation of China(32030098)Jiangsu Agriculture Science and Technology Innovation Fund(CX(18)2020).
文摘Drought causes water shortage and consequent retardation of plants growth and development.Therefore,improving the drought tolerance of plants is necessary for expanding cultivation and resource promotion.Increasing evidence indicates that phospholipase is involved in the response of plants to drought stress.The objective of this study was to create new drought-tolerant chrysanthemum germplasm,which lays a foundation for the study of the molecular mechanism of phospholipase mediated stress response in chrysanthemum.CmPLDαhas the closest relationship with sunflower HaPLDα,and belongs to the PLDαfamily.CmPLDαover-expressing plants showed a slight shrinking under 20%PEG6000 treatment.The survival rate increased significantly by 1.7−1.8 times that of the wild type.Relative water content(RWC)of CmPLDαover-expressing plants were nearly 10%higher than that of the wild type.Relative electrical conductivity and MDA content were significantly lower than those of the wild type.ABA content of the over-expression lines Z1,Z2 were 1.3 and 1.22 times that of wild type,but ABA content of antisense lines F1,F2 was approximately 0.83 and 0.81 of those of wild type.Most plants of antisense transgenic lines F1,F2 were wrinkled,with a wilting index of 5 and 6,and the survival rate was also lower than that of the wild type after recovery growth.RWC of antisense lines were lower than over-expression lines,relative electrical conductivity and MDA content were significantly higher than those of the wild type.In summary,CmPLDαcould enhance tolerance of chrysanthemum to drought conditions.
基金supported by the Zhejiang Provincial Natural Science Foundation of China(LDT23E06012E06)National Key R&D Program of China(2023YFC3710800)+3 种基金the National EnergySaving and Low-Carbon Materials Production and Application Demonstration Platform Program(TC220H06N)Pioneer R&D Program of Zhejiang Province-China(2024SSYS0066,2023C03016)National Natural Science Foundation of China(42341208)Zhejiang Energy Group Research Fund(ZNKJ-2023-100)。
文摘Converting CO_(2)with green hydrogen to methanol as a carbon-neutral liquid fuel is a promising route for the long-term storage and distribution of intermittent renewable energy.Nevertheless,attaining highly efficient methanol synthesis catalysts from the vast composition space remains a significant challenge.Here we present a machine learning framework for accelerating the development of high space-time yield(STY)methanol synthesis catalysts.A database of methanol synthesis catalysts has been compiled,consisting of catalyst composition,preparation parameters,structural characteristics,reaction conditions and their corresponding catalytic performance.A methodology for constructing catalyst features based on the intrinsic physicochemical properties of the catalyst components has been developed,which significantly reduced the data dimensionality and enhanced the efficiency of machine learning operations.Two high-precision machine learning prediction models for the activities and product selectivity of catalysts were trained and obtained.Using this machine learning framework,an efficient search was achieved within the catalyst composition space,leading to the successful identification of high STY multielement oxide methanol synthesis catalysts.Notably,the CuZnAlTi catalyst achieved high STYs of 0.49 and 0.65 g_(MeOH)/(g_(catalyst)h)for CO_(2)and CO hydrogenation to methanol at 250℃,respectively,and the STY was further increased to 2.63 g_(Me OH)/(g_(catalyst)h)in CO and CO_(2)co-hydrogenation.
文摘Vestibular Migraine (VM) is a common neurological disorder characterized by recurrent episodes of vertigo and migraine symptoms. The pathogenesis of VM is complex and involves multiple genetic and environmental factors. Recent studies have suggested that the pathogenesis of vestibular migraine may be associated with variations in the CACNA1A gene, which is an important gene target for controlling calcium ion channels. Such variations may further affect the functions of the vestibular nervous system, thereby causing a series of vestibular nervous system-related symptoms. This article will summarize the genetic association studies of vestibular migraine, vestibular function studies, and research on how to establish relevant animal models to illustrate the possible association between CACNA1A variations and the pathogenesis of VM, providing new ideas for clarifying the pathogenesis of VM.
文摘The efficient hydrogenolysis of esters to alkanes is the key protocol for producing advanced biofuels from renewable plant oils or fats.Due to the low reactivity of the carbonyl group in esters,a high reaction temperature(>250℃)is the prerequisite to ensure high conversion of esters.Here,we report a highly dispersed MoO_(x)-Ru/C bimetallic catalyst for the efficient hydrogenolysis of esters to alkanes under 150°C.The optimal catalyst exhibits>99%conversion of methyl stearate and 99%selectivity to diesel-range alkanes,reaching a high rate of up to 2.0 mmol gcat^(–1)h^(–1),5 times higher than that of Ru/C catalyst(MoO_(x)/C is inert).Integrated experimental and theoretical investigations attribute the high performance to the abundant MoO_(x)-Ru interfacial sites on the catalyst surface,which offers high activity for the C–O cleavage of esters.Furthermore,the dispersed MoO_(x)species significantly weaken the hydrocracking activity of the metallic Ru for C–C bonds,thus yielding alkane products without carbon loss.This study provides a facile and novel strategy for the design of high-performance heterogeneous catalysts for the hydrodeoxygenation of biomass-derived esters to alkane products.
基金supported by research grants from the Natural Science Foundation of Shandong Province,China(ZR2020MC092)the Key Research and Development Project of Shandong Province,China(2019TSCYCX-33)the Key Research and Development Project of Shandong Province,China(LJNY202025).
文摘To make agricultural systems sustainable in terms of their greenness and efficiency,optimizing the tillage and fertilization practices is essential.To assess the effects of tilling and fertilization practices in wheat-maize cropping systems,a three-year field experiment was designed to quantify the carbon footprint(CF)and energy efficiency of the cropping systems in the North China Plain.The study parameters included four tillage practices(no tillage(NT),conventional tillage(CT),rotary tillage(RT),and subsoiling rotary tillage(SRT))and two fertilizer regimes(inorganic fertilizer(IF)and hybrid fertilizer with organic and inorganic components(HF)).The results indicated that the most prominent energy inputs and greenhouse gas(GHG)emissions could be ascribed to the use of fertilizers and fuel consumption.Under the same fertilization regime,ranking the tillage patterns with respect to the value of the crop yield,profit,CF,energy use efficiency(EUE)or energy productivity(EP)for either wheat or maize always gave the same sequence of SRT>RT>CT>NT.For the same tillage,the energy consumption associated with HF was higher than IF,but its GHG emissions and CF were lower while the yield and profit were higher.In terms of overall performance,tilling is more beneficial than NT,and reduced tillage practices(RT and SRT)are more beneficial than CT.The fertilization regime with the best overall performance was HF.Combining SRT with HF has significant potential for reducing CF and increasing EUE,thereby improving sustainability.Adopting measures that promote these optimizations can help to overcome the challenges posed by a lack of food security,energy crises and ecological stress.
基金supported by the National Natural Science Foundation of China(Nos.52204206 and U24A2090)the Fundamental Research Funds for the Central Universities of China(No.2023CDJXY-006).
文摘Geological sequestration of CO_(2)is critical for deep decarbonization,but the geomechanical stability of coal reservoirs remains a major challenge.This study integrates nanoindentation,XRD/SEM-EDS chemo physical characterization and 4D CT visualization to investigate the time-evolving mechanical degradation of bituminous coals with ScCO_(2)injection.The main results show that 4 d of ScCO_(2)treatment caused 50.47%–80.99%increase in load–displacement deformation and 26.92%–76.17%increase in creep depth at peak load,accompanied by 55.01%–63.38%loss in elastic modulus and 52.83%–74.81%reduction in hardness.The degradation exhibited biphasic kinetics,characterized by rapid surface-driven weakening(0–2 d),followed by stabilized matrix-scale pore homogenization(2–4 d).ScCO_(2)preferentially dissolved carbonate minerals(dolomite),driving pore network expansion and interfacial debonding,while silicate minerals resisted dissolution but promoted structural homogenization.These coupled geochemical-mechanical processes reduced the mechanical heterogeneity of the coal and altered its failure modes.The results establish a predictive framework for reservoir stability assessment and provide actionable insights for optimizing CO_(2)enhanced coalbed methane recovery.
