Artificial photosynthesis presents a sustainable and cost-effective approach to harnessing solar energy to produce value-added chemicals[1,2].In particular,the simultaneous photocatalytic conversion of CO_(2)and H_(2)...Artificial photosynthesis presents a sustainable and cost-effective approach to harnessing solar energy to produce value-added chemicals[1,2].In particular,the simultaneous photocatalytic conversion of CO_(2)and H_(2)O into formic acid(HCOOH)and hydrogen peroxide(H2O2)has emerged as a promising strategy to mitigate global warming driven by CO_(2)emissions.HCOOH is a versatile chemical and hydrogen carrier,offering economic and practical advantages due to its compatibility with existing industrial processes and energy storage/conversion systems.Meanwhile,H_(2)O_(2)is among the world’s top 100 essential chemicals,with a global market valued at$4.0 billion in 2020 and projected to grow to$5.2 billion by 2026.展开更多
The activation of carbon-hydrogen(C-H)bonds is of great scientific importance and offers broad applications in modern organic chemistry[1].In recent years,strategies for C-H bond activation have made notable advances,...The activation of carbon-hydrogen(C-H)bonds is of great scientific importance and offers broad applications in modern organic chemistry[1].In recent years,strategies for C-H bond activation have made notable advances,particularly in the efficient construction of complex molecular architectures.However,most existing C-H activation systems rely on expensive noble metal catalysts,including palladium,rhodium,ruthenium,and iridium.These metals not only come at a high cost but are also often associated with significant toxicity,which further limits their viability and sustainability in industrial applications.展开更多
Objective:Cytotoxic T lymphocytes(CTLs)play a crucial role in the therapeutic approach to hepatocellular carcinoma(HCC).Recent research has indicated that junctional adhesion molecule-like protein(JAML)enhances the an...Objective:Cytotoxic T lymphocytes(CTLs)play a crucial role in the therapeutic approach to hepatocellular carcinoma(HCC).Recent research has indicated that junctional adhesion molecule-like protein(JAML)enhances the antitumor activity of CD8+T cells.Our study investigates the role of JAML+CD8+T cells in HCC.Methods:We utilized time-of-flight mass cytometry and an orthotopic mouse model of HCC to examine histone modifications in tumor-infiltrating immune cells undergoing immunotherapy.Flow cytometry was used to assess CD4+T cells differentiation and JAML expression in CD8+T cells infiltrating HCC.Correlation analysis revealed a strong positive correlation between lactate dehydrogenase A+(LDHA+)CD4+T cells and JAML+CD8+T cells.Subsequently,we evaluated the therapeutic effects of an agonistic anti-JAML antibody,both alone and combined with immunotherapy.Finally,RNA sequencing was conducted to identify potential regulatory mechanisms.Results:Immunotherapy significantly increased the percentage of CD8+T cells infiltrating HCC and induced histone modifications,such as H3K18 lactylation(H3K18la)in CD4+T cells.Flow cytometry analysis revealed that lactate promotes the differentiation of CD4+T cells into Th1 cells.LDHA,an enzyme that converts pyruvate to lactate,plays a key role in this process.Correlation analysis revealed a strong positive relationship between LDHA+CD4+T cells and JAML+CD8+T cells in patients who responded to immunotherapy.Moreover,high JAML expression in CD8+T cells was associated with a more favorable prognosis.In vivo experiments demonstrated that agonistic anti-JAML antibody therapy reduced tumor volume and significantly prolonged the survival of tumor-bearing mice,independent of the effects of anti-programmed cell death protein ligand-1 antibody(αPD-L1)-mediated immunotherapy.Pathway enrichment analysis further revealed that JAML enhances CTL responses through the oxidative phosphorylation pathway.Conclusions:Activation of JAML enhances CTL responses in HCC treatment,independent ofαPD-L1-mediated immunotherapy,providing a promising strategy for advanced HCC.展开更多
With a holding capacity of up to 9,100 vehicles(conventional or electric),the Höegh Aurora holds the title of“worlds largest vehicle carrier”.Operated by Norways Höegh Autoliners,the Höegh Aurora was ...With a holding capacity of up to 9,100 vehicles(conventional or electric),the Höegh Aurora holds the title of“worlds largest vehicle carrier”.Operated by Norways Höegh Autoliners,the Höegh Aurora was built by China Merchants Heavy Industry(CMHI)in Jiangsu,China,and made its first voyage last year.Measuring 37.6 meters wide and 199.9 meters long,it is considered the worlds largest Pure Car and Truck Carrier(PCTC)vessel for transporting various types of vehicles,and thanks to strengthened decks and enhanced internal ramp systems(坡道系统),it can carry heavier electric vehicles on all 14 decks,making it future⁃proof.With a cargo capacity of 9,100 vehicles,the first Höegh Aurora class carrier beats the previous worlds largest vehicle carrier by 600 vehicles.展开更多
Dear Editor,The highly pathogenic avian influenza viruses(HPAIVs)are important epizootic and zoonotic pathogens that cause significant economic losses to the poultry industry and pose a serious risk to veterinary and ...Dear Editor,The highly pathogenic avian influenza viruses(HPAIVs)are important epizootic and zoonotic pathogens that cause significant economic losses to the poultry industry and pose a serious risk to veterinary and public health.Wild birds have been recognized as the primary reservoirs for influenza A virus,and some species show little sign of clinical disease or even can be asymptomatic during long distance carriers of the virus(Lycett et al.,2019).Since it was first discovered in 1959,the H5Nx HPAIVs have spread globally and cause outbreaks in wild birds,poultry and sporadic human and other mammalian infections(Lycett et al.,2019).Due to the reassortant events of diverse strains facilitated by migratory waterfowl,the clade 2.3.4.4 of H5Nx viruses acquiring neuraminidase(NA)gene from other low pathogenicity avian influenza viruses(LPAIVs)emerged in 2014 and gradually became the dominant sub-clade(Lee et al.,2017).展开更多
This corrigendum clarifies information in the article"PI3K/Akt/mTOR signaling orchestrates the phenotypic transition and chemo-resistance of small cell lung cancer"by Li et al.(2021).The authors regret that ...This corrigendum clarifies information in the article"PI3K/Akt/mTOR signaling orchestrates the phenotypic transition and chemo-resistance of small cell lung cancer"by Li et al.(2021).The authors regret that the image of H526 cells in the schematic illustration in Fig.4A displayed on the Webpage is wrong.The correct image for H526cells inthe schematic illustration is listed below。展开更多
The dynamics of phase separation in H–He binary systems within gas giants such as Jupiter and Saturn exhibit remarkable complexity, yet lack systematic investigation. Through large-scale machine-learning-accelerated ...The dynamics of phase separation in H–He binary systems within gas giants such as Jupiter and Saturn exhibit remarkable complexity, yet lack systematic investigation. Through large-scale machine-learning-accelerated molecular dynamics simulations spanning broad temperature-pressure-composition(2000–10000 K, 1–7 Mbar,pure H to pure He) regimes, we systematically determine self and mutual diffusion coefficients in H–He systems and establish a six-dimensional framework correlating temperature, pressure, helium abundance, phase separation degree, diffusion coefficients, and anisotropy. Key findings reveal that hydrogen exhibits active directional migration with pronounced diffusion anisotropy, whereas helium passively aggregates in response. While the conventional mixing rule underestimates mutual diffusion coefficients by neglecting velocity cross-correlations,the assumption of an ideal thermodynamic factor(Q = 1) overestimates them due to unaccounted non-ideal thermodynamic effects—both particularly pronounced in strongly phase-separated regimes. Notably, hydrogen's dual role, anisotropic diffusion and bond stabilization via helium doping, modulates demixing kinetics. Large-scale simulations(216,000 atoms) propose novel phase-separation paradigms, such as “hydrogen bubble/wisp” formation, challenging the classical “helium rain” scenario, striving to bridge atomic-scale dynamics to planetary-scale phase evolution.展开更多
Quantum spin Hall state usually emerges in non-magnetic systems,which are typically incompatible withferromagnetism.Here,we predict that two-dimensional(2D)ferrovalley semiconductor single-layer(SL)2HNbTe_(2)can be tr...Quantum spin Hall state usually emerges in non-magnetic systems,which are typically incompatible withferromagnetism.Here,we predict that two-dimensional(2D)ferrovalley semiconductor single-layer(SL)2HNbTe_(2)can be transformed into a 2D room-temperature quantum spin Hall insulator through hydrogen(H)atom adsorption.The SL 2H-NbTe_(2) is found to possess a giant spontaneous valley polarization of 274 meV,which is much larger than those of most available ferrovalley materials.Upon H atom adsorption,a transitionfrom ferromagnetism to non-magnetism emerges.More interestingly,H-adsorbed NbTe_(2) is predicted to be aquantum spin Hall insulator with a direct band gap of 110meV(equal to a working temperature of 1267 K).The predicted rich quantum effects render the 2H-NbTe_(2) a promising candidate for practical valleytronic andtopological electronics.展开更多
Preterm birth(PTB),defined as delivery before 37 weeks of gestation,is the most common adverse pregnancy outcome[1].PTB is a global health concern,with an estimated 13.4 million cases in 2020[1],accounting for more th...Preterm birth(PTB),defined as delivery before 37 weeks of gestation,is the most common adverse pregnancy outcome[1].PTB is a global health concern,with an estimated 13.4 million cases in 2020[1],accounting for more than one in 10 births worldwide.Compared to full-term births,PTBs are associated with a higher risk of short-and long-term complications,including bronchopulmonary dysplasia,necrotizing enterocolitis,visual impairment,and cerebral injuries[2].Despite substantial research efforts to prevent PTB,the global PTB rate has shown little improvement over the past decade[1].Therefore,identifying additional risk factors remains a critical goal in preventing PTB.展开更多
[Objectives]To obtain a novel cultivar of Chuanminshen violaceum with robust growth,high yield,and stable genetic traits.[Methods]A systematic selection method was employed to conduct a multi-point testing and regiona...[Objectives]To obtain a novel cultivar of Chuanminshen violaceum with robust growth,high yield,and stable genetic traits.[Methods]A systematic selection method was employed to conduct a multi-point testing and regional production trial utilizing C.violaceum strain CMS1,which was sourced from a semi-wild population in Langzhong,Sichuan Province,as the experimental material.In contrast,C.violaceum CMS2,derived from a cultivated population in Langzhong,Sichuan Province,along with a mixed population of C.violaceum cultispecies from the same region,served as the control material.Through a comparative analysis of phenological periods,agronomic traits,yield,and quality,a novel cultivar,‘Chengming No.1’,was ultimately selected and developed based on its superior comprehensive evaluation.[Results]In the phenological period survey conducted as part of a two-year comparative study,the CMS1 strain exhibited a shorter growth cycle compared to others.Furthermore,the agronomic characteristics of the CMS1 strain were superior to those of both CMS2 and CK.The average yields of CMS1,CMS2,and CK in the 2019 cultivar comparison test and yield trial were 468.88,448.52,and 422.15 kg/667 m 2,respectively.This resulted in an average yield increase of 11.07%for CMS1 compared to CK and 6.25%for CMS2 compared to CK.The average yields of CMS1,CMS2,and CK in the 2020 cultivar comparison test and yield trial were 482.69,467.54,and 436.82 kg/667 m 2,respectively.CMS1 exhibited an average yield increase of 10.50%compared to CK,while CMS2 demonstrated an average yield increase of 7.03%relative to CK.Furthermore,the average yield of CMS1 per 667 m 2 achieved a statistically significant level compared to CK in both years of the study.In multiple-point comparison and yield trials conducted in 2019 and 2020,the CMS1 strain exhibited a total ash content of 15.30%,an acid-insoluble ash content of 1.30%,a moisture content of 10.80%,and water-soluble extract amounting to 11.40%.All of the indicators conformed to the criteria established by the Sichuan Standards for Chinese Medicinal Materials(2010 Edition).[Conclusions]The CMS1 strain successfully passed the field technical appraisal for the novel cultivar of C.violaceum in 2021.This cultivar is characterized by high yield,excellent quality,and stable traits.In 2022,it received validation from the Sichuan Provincial Committee for the Certification of Non-Staple Crop Varieties and was officially named‘Chengming No.1’(CRY 2022002).This cultivar demonstrates significant potential for widespread cultivation.展开更多
Metabolic reprogramming reshapes the tumor microenvironment(TME)and facilitates metastasis,but its molecular mechanisms remain incompletely understood.Here,we identified enolase 2(ENO2),a critical glycolytic enzyme,as...Metabolic reprogramming reshapes the tumor microenvironment(TME)and facilitates metastasis,but its molecular mechanisms remain incompletely understood.Here,we identified enolase 2(ENO2),a critical glycolytic enzyme,as being associated with lymphatic metastasis in head and neck squamous cell carci-noma(HNSCC).Mechanistically,phosphoenolpyruvate(PEP),the metabolite secreted by ENO2-expressing HNSCC cells,drove histone H3 lysine 18 lactylation(H3K18la)-mediated M2 polarization in macrophages,which,in turn,enhanced the epithelial-mesenchymal transition(EMT)and invasiveness of HNSCC cells.Pharmacological inhibition of ENO2 with POMHEX effectively reversed M2 macrophage polarization and inhibited HNSCC lymphatic metastasis.Collectively,our findings underscore the prog-nostic significance of ENO2 and highlight its potential as a therapeutic target for metastatic HNSCC.Furthermore,we reveal a previously underappreciated role of PEP in modulating the tumor immune microenvironment and tumor metastasis via epigenetic modification.展开更多
Achieving room-temperature superconductivity has been an enduring scientific quest,while hydrogen-rich compounds have emerged as highly promising candidates.Here,we systematically investigated the thermodynamic stabil...Achieving room-temperature superconductivity has been an enduring scientific quest,while hydrogen-rich compounds have emerged as highly promising candidates.Here,we systematically investigated the thermodynamic stability,crystal structure,electronic properties,and superconductivity within the ternary Y-Hf-H system under high pressure.Several distinct hydrides have been revealed,in which the hydrogen atoms are present in various hydrogenic motifs.A15-type hydride P_(m)3-YHfH_(6)with isolated H−is predicted to be dynamically stabilized down to 10GPa.The H atoms form pentagonal graphene-like layered-H10 anions in the Hf plane of P6-YHfH_(19),with aT_(c)of 95K at 100GPa.There are H cages in C_(mmm)-Y_(3)HfH_(24),and attributed to the robust electron–phonon coupling and high electronic density of states of hydrogen at the Fermi level,it demonstrates near-room temperature superconductivity with a T_(c)of 275K at 250GPa.Our work makes contributions to the understanding of the fundamental properties of ternary hydrides under high pressure and provides essential references for further research in this field.展开更多
Highly pathogenic avian influenza(HPAI)H5 viruses have caused widespread mortality in wild birds and poultry,with increasing spillover risk into mammals.The recently dominant clade 2.3.4.4b has produced multiple epide...Highly pathogenic avian influenza(HPAI)H5 viruses have caused widespread mortality in wild birds and poultry,with increasing spillover risk into mammals.The recently dominant clade 2.3.4.4b has produced multiple epidemic waves,first driven by H5N8 and more recently by H5N1,which has spread more rapidly,infected a broader host range,and caused higher mortality.While earlier studies identified consistent roles of waterbird community composition in shaping HPAI outbreaks,it remains unclear whether these factors also apply to the currently circulating H5N1.We analyzed HPAI H5N1 outbreaks in European wild birds during the 2021/22epidemic,examining the influence of waterbird communities and environmental variables,and compared these patterns with earlier epidemics,including H5N1 in 2005/06 and H5N8 in 2016/17 and 2020/21.Our results showed that waterbird abundance,species richness,and the abundance of key species were positively associated with disease occurrence,whereas phylogenetic diversity was negatively associated,suggesting greater interspecific transmission among closely related hosts.Models trained on earlier epidemics accurately predicted the H5N1 occurrence in 2021/22.These findings demonstrate consistent effects of waterbird community composition across multiple epidemics and highlight their values as predictors of HPAI risk.Integrating community metrics into surveillance and early-warning systems can strengthen our capacity to anticipate future outbreaks across clades and subtypes.展开更多
Nucleosomes play a vital role in chromatin organization and gene regulation,acting as key hubs that inter-act with various chromatin-associated factors through diverse binding mechanisms.Recent research has highlighte...Nucleosomes play a vital role in chromatin organization and gene regulation,acting as key hubs that inter-act with various chromatin-associated factors through diverse binding mechanisms.Recent research has highlighted the prevalence of mutations in linker histones across different types of cancer,emphasizing their critical involvement in cancer progression.These cancer-associated mutations in linker histones have been shown to disrupt nucleosome stacking and the formation of higher-order chromatin structures,which in turn significantly affect epigenetic regulatory processes.In this review,we provide a comprehensive analysis of how cancer-associated linker histone mutations alter their physicochemical properties,influencing their binding to nucleosomes,and overall chromatin architecture.Additionally,we explore the significant impact of mutations near post-translational modification sites,which further modulate chromatin dynamics and regulatory functions,offering insights into their role in oncogenesis and potential therapeutic targets.展开更多
Solar-driven H_(2)O_(2) production through artificial photosynthesis presents a promising alternative to anthraquinone,given its lower energy consumption and eco-friendly nature[1-3].However,its catalytic performance ...Solar-driven H_(2)O_(2) production through artificial photosynthesis presents a promising alternative to anthraquinone,given its lower energy consumption and eco-friendly nature[1-3].However,its catalytic performance is severely restricted by the inefficient separation of photogenerated carriers and interface reactions[4,5].展开更多
Potassium(K)is known to enhance the catalytic performance of Fe-based catalysts in the reverse water-gas shift(rWGS)reaction,which is highly relevant during Fischer-Tropsch(FT)synthesis of CO_(2)-H_(2) mixtures.To elu...Potassium(K)is known to enhance the catalytic performance of Fe-based catalysts in the reverse water-gas shift(rWGS)reaction,which is highly relevant during Fischer-Tropsch(FT)synthesis of CO_(2)-H_(2) mixtures.To elucidate the mechanistic role of K promoter,we employed density functional theory(DFT)calculations in conjunction with microkinetic modelling for two representative surface terminations of Hägg carbide(χ-Fe_(5)C_(2)),i.e.,(010)and(510).K_(2)O results in stronger adsorption of CO_(2)and H_(2) on Hägg carbide and promotes C–O bond dissociation of adsorbed CO_(2)by increasing the electron density on Fe atoms close to the promoter oxide.The increased electron density of the surface Fe atoms results in an increased electron-electron repulsion with bonding orbitals of adsorbed CO_(2).Microkinetics simulations predict that K_(2)O increases the CO_(2)conversion during CO_(2)-FT synthesis.K_(2)O also enhances CO adsorption and dissociation,facilitating the formation of methane,used here as a proxy for hydrocarbons formation during CO_(2)-FT synthesis.CO dissociation and O removal via H_(2)O compete as the rate-controlling steps in CO_(2)-FT.展开更多
The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson’s disease (PD). Notably, the VA receives direct innervation from t...The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson’s disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K^(+) channels, or Ca^(2+)-activated K+ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.展开更多
A switch from avian-typeα-2,3 to human-typeα-2,6 receptors is an essential element for the initiation of a pandemic from an avian influenza virus.Some H9N2 viruses exhibit a preference for binding to human-typeα-2,...A switch from avian-typeα-2,3 to human-typeα-2,6 receptors is an essential element for the initiation of a pandemic from an avian influenza virus.Some H9N2 viruses exhibit a preference for binding to human-typeα-2,6 receptors.This identifies their potential threat to public health.However,our understanding of the molecular basis for the switch of receptor preference is still limited.In this study,we employed the random forest algorithm to identify the potentially key amino acid sites within hemagglutinin(HA),which are associated with the receptor binding ability of H9N2 avian influenza virus(AIV).Subsequently,these sites were further verified by receptor binding assays.A total of 12 substitutions in the HA protein(N158D,N158S,A160 N,A160D,A160T,T163I,T163V,V190T,V190A,D193 N,D193G,and N231D)were predicted to prefer binding toα-2,6 receptors.Except for the V190T substitution,the other substitutions were demonstrated to display an affinity for preferential binding toα-2,6 receptors by receptor binding assays.Especially,the A160T substitution caused a significant upregulation of immune-response genes and an increased mortality rate in mice.Our findings provide novel insights into understanding the genetic basis of receptor preference of the H9N2 AIV.展开更多
Photocatalytic hydrogen(H_(2))production using solar energy is a cutting-edge green technology that holds great potential for addressing the urgent fuel and environmental crises[1–3].To achieve high-efficiency H_(2) ...Photocatalytic hydrogen(H_(2))production using solar energy is a cutting-edge green technology that holds great potential for addressing the urgent fuel and environmental crises[1–3].To achieve high-efficiency H_(2) production,cocatalyst modification is commonly employed to provide active sites for the hydrogen evolution reaction(HER)[4,5].In this context,the kinetics of hydrogen adsorption and desorption at these active sites play a crucial role in enhancing overall photocatalytic H_(2) production efficiency.However,the H adsorption/desorption kinetics often exhibit a trade-off,presenting a significant challenge in achieving an optimal equilibrium between Hads and Hdes in many cocatalyst systems.Therefore,fine-tuning the active sites to optimize the H_(2) evolution kinetics is essential for improving photocatalytic activity[6].展开更多
文摘Artificial photosynthesis presents a sustainable and cost-effective approach to harnessing solar energy to produce value-added chemicals[1,2].In particular,the simultaneous photocatalytic conversion of CO_(2)and H_(2)O into formic acid(HCOOH)and hydrogen peroxide(H2O2)has emerged as a promising strategy to mitigate global warming driven by CO_(2)emissions.HCOOH is a versatile chemical and hydrogen carrier,offering economic and practical advantages due to its compatibility with existing industrial processes and energy storage/conversion systems.Meanwhile,H_(2)O_(2)is among the world’s top 100 essential chemicals,with a global market valued at$4.0 billion in 2020 and projected to grow to$5.2 billion by 2026.
文摘The activation of carbon-hydrogen(C-H)bonds is of great scientific importance and offers broad applications in modern organic chemistry[1].In recent years,strategies for C-H bond activation have made notable advances,particularly in the efficient construction of complex molecular architectures.However,most existing C-H activation systems rely on expensive noble metal catalysts,including palladium,rhodium,ruthenium,and iridium.These metals not only come at a high cost but are also often associated with significant toxicity,which further limits their viability and sustainability in industrial applications.
基金funded by the Major Research Plan of the National Natural Science Foundation of China(No.92159202)the National Key Research and Development Program of China(No.2021YFA1100500)+1 种基金the Leading Innovation Team Project of Hangzhou Medical College(No.CXLJ202401)the Key Research and Development Plan of Zhejiang Provincial Department of Science and Technology(No.2024C03051)。
文摘Objective:Cytotoxic T lymphocytes(CTLs)play a crucial role in the therapeutic approach to hepatocellular carcinoma(HCC).Recent research has indicated that junctional adhesion molecule-like protein(JAML)enhances the antitumor activity of CD8+T cells.Our study investigates the role of JAML+CD8+T cells in HCC.Methods:We utilized time-of-flight mass cytometry and an orthotopic mouse model of HCC to examine histone modifications in tumor-infiltrating immune cells undergoing immunotherapy.Flow cytometry was used to assess CD4+T cells differentiation and JAML expression in CD8+T cells infiltrating HCC.Correlation analysis revealed a strong positive correlation between lactate dehydrogenase A+(LDHA+)CD4+T cells and JAML+CD8+T cells.Subsequently,we evaluated the therapeutic effects of an agonistic anti-JAML antibody,both alone and combined with immunotherapy.Finally,RNA sequencing was conducted to identify potential regulatory mechanisms.Results:Immunotherapy significantly increased the percentage of CD8+T cells infiltrating HCC and induced histone modifications,such as H3K18 lactylation(H3K18la)in CD4+T cells.Flow cytometry analysis revealed that lactate promotes the differentiation of CD4+T cells into Th1 cells.LDHA,an enzyme that converts pyruvate to lactate,plays a key role in this process.Correlation analysis revealed a strong positive relationship between LDHA+CD4+T cells and JAML+CD8+T cells in patients who responded to immunotherapy.Moreover,high JAML expression in CD8+T cells was associated with a more favorable prognosis.In vivo experiments demonstrated that agonistic anti-JAML antibody therapy reduced tumor volume and significantly prolonged the survival of tumor-bearing mice,independent of the effects of anti-programmed cell death protein ligand-1 antibody(αPD-L1)-mediated immunotherapy.Pathway enrichment analysis further revealed that JAML enhances CTL responses through the oxidative phosphorylation pathway.Conclusions:Activation of JAML enhances CTL responses in HCC treatment,independent ofαPD-L1-mediated immunotherapy,providing a promising strategy for advanced HCC.
文摘With a holding capacity of up to 9,100 vehicles(conventional or electric),the Höegh Aurora holds the title of“worlds largest vehicle carrier”.Operated by Norways Höegh Autoliners,the Höegh Aurora was built by China Merchants Heavy Industry(CMHI)in Jiangsu,China,and made its first voyage last year.Measuring 37.6 meters wide and 199.9 meters long,it is considered the worlds largest Pure Car and Truck Carrier(PCTC)vessel for transporting various types of vehicles,and thanks to strengthened decks and enhanced internal ramp systems(坡道系统),it can carry heavier electric vehicles on all 14 decks,making it future⁃proof.With a cargo capacity of 9,100 vehicles,the first Höegh Aurora class carrier beats the previous worlds largest vehicle carrier by 600 vehicles.
基金supported by Zhejiang Province Science and Technology Cooperation Project of“Three Rural and Nine Parties”(grant number 2023SNJF059).
文摘Dear Editor,The highly pathogenic avian influenza viruses(HPAIVs)are important epizootic and zoonotic pathogens that cause significant economic losses to the poultry industry and pose a serious risk to veterinary and public health.Wild birds have been recognized as the primary reservoirs for influenza A virus,and some species show little sign of clinical disease or even can be asymptomatic during long distance carriers of the virus(Lycett et al.,2019).Since it was first discovered in 1959,the H5Nx HPAIVs have spread globally and cause outbreaks in wild birds,poultry and sporadic human and other mammalian infections(Lycett et al.,2019).Due to the reassortant events of diverse strains facilitated by migratory waterfowl,the clade 2.3.4.4 of H5Nx viruses acquiring neuraminidase(NA)gene from other low pathogenicity avian influenza viruses(LPAIVs)emerged in 2014 and gradually became the dominant sub-clade(Lee et al.,2017).
文摘This corrigendum clarifies information in the article"PI3K/Akt/mTOR signaling orchestrates the phenotypic transition and chemo-resistance of small cell lung cancer"by Li et al.(2021).The authors regret that the image of H526 cells in the schematic illustration in Fig.4A displayed on the Webpage is wrong.The correct image for H526cells inthe schematic illustration is listed below。
基金supported by the National University of Defense Technology Research Fund Projectthe National Natural Science Foundation of China under Grant Nos. 12047561 and 12104507+1 种基金the NSAF under Grant No. U1830206the Science and Technology Innovation Program of Hunan Province under Grant No. 2021RC4026。
文摘The dynamics of phase separation in H–He binary systems within gas giants such as Jupiter and Saturn exhibit remarkable complexity, yet lack systematic investigation. Through large-scale machine-learning-accelerated molecular dynamics simulations spanning broad temperature-pressure-composition(2000–10000 K, 1–7 Mbar,pure H to pure He) regimes, we systematically determine self and mutual diffusion coefficients in H–He systems and establish a six-dimensional framework correlating temperature, pressure, helium abundance, phase separation degree, diffusion coefficients, and anisotropy. Key findings reveal that hydrogen exhibits active directional migration with pronounced diffusion anisotropy, whereas helium passively aggregates in response. While the conventional mixing rule underestimates mutual diffusion coefficients by neglecting velocity cross-correlations,the assumption of an ideal thermodynamic factor(Q = 1) overestimates them due to unaccounted non-ideal thermodynamic effects—both particularly pronounced in strongly phase-separated regimes. Notably, hydrogen's dual role, anisotropic diffusion and bond stabilization via helium doping, modulates demixing kinetics. Large-scale simulations(216,000 atoms) propose novel phase-separation paradigms, such as “hydrogen bubble/wisp” formation, challenging the classical “helium rain” scenario, striving to bridge atomic-scale dynamics to planetary-scale phase evolution.
基金supported by the National Natural Science Foundation of China(Grant No.11874092)the Fok Ying Tong Education Foundation,China(Grant No.161005)+2 种基金the Science Fund for Distinguished Young Scholars of Hunan Province(Grant No.2021JJ10039)the Planned Science and Technology Project of Hunan Province(Grant No.2017RS3034)the Postgraduate Scientific Research Innovation Project of Hunan Province(Grant No.CX20240080)。
文摘Quantum spin Hall state usually emerges in non-magnetic systems,which are typically incompatible withferromagnetism.Here,we predict that two-dimensional(2D)ferrovalley semiconductor single-layer(SL)2HNbTe_(2)can be transformed into a 2D room-temperature quantum spin Hall insulator through hydrogen(H)atom adsorption.The SL 2H-NbTe_(2) is found to possess a giant spontaneous valley polarization of 274 meV,which is much larger than those of most available ferrovalley materials.Upon H atom adsorption,a transitionfrom ferromagnetism to non-magnetism emerges.More interestingly,H-adsorbed NbTe_(2) is predicted to be aquantum spin Hall insulator with a direct band gap of 110meV(equal to a working temperature of 1267 K).The predicted rich quantum effects render the 2H-NbTe_(2) a promising candidate for practical valleytronic andtopological electronics.
基金supported by the National Natural Science Foundation of China(8200340181972981)+1 种基金the Scientific and Technological Project of Henan Province(222102310150,China)the Open Research Fund of the National Health Commission Key Laboratory of Birth Defects Prevention(NHCKLBDP202504,China).
文摘Preterm birth(PTB),defined as delivery before 37 weeks of gestation,is the most common adverse pregnancy outcome[1].PTB is a global health concern,with an estimated 13.4 million cases in 2020[1],accounting for more than one in 10 births worldwide.Compared to full-term births,PTBs are associated with a higher risk of short-and long-term complications,including bronchopulmonary dysplasia,necrotizing enterocolitis,visual impairment,and cerebral injuries[2].Despite substantial research efforts to prevent PTB,the global PTB rate has shown little improvement over the past decade[1].Therefore,identifying additional risk factors remains a critical goal in preventing PTB.
基金Supported by Sichuan Innovation Team Project of China Agricultural Industry Research System(SCCXTD-2023-19)Key R&D Project of Sichuan Provincial Department of Science and Technology(2022YFS0592)Sichuan Provincial Science and Technology Innovation Seedling Project(MZGC20230119,MZGC20230126).
文摘[Objectives]To obtain a novel cultivar of Chuanminshen violaceum with robust growth,high yield,and stable genetic traits.[Methods]A systematic selection method was employed to conduct a multi-point testing and regional production trial utilizing C.violaceum strain CMS1,which was sourced from a semi-wild population in Langzhong,Sichuan Province,as the experimental material.In contrast,C.violaceum CMS2,derived from a cultivated population in Langzhong,Sichuan Province,along with a mixed population of C.violaceum cultispecies from the same region,served as the control material.Through a comparative analysis of phenological periods,agronomic traits,yield,and quality,a novel cultivar,‘Chengming No.1’,was ultimately selected and developed based on its superior comprehensive evaluation.[Results]In the phenological period survey conducted as part of a two-year comparative study,the CMS1 strain exhibited a shorter growth cycle compared to others.Furthermore,the agronomic characteristics of the CMS1 strain were superior to those of both CMS2 and CK.The average yields of CMS1,CMS2,and CK in the 2019 cultivar comparison test and yield trial were 468.88,448.52,and 422.15 kg/667 m 2,respectively.This resulted in an average yield increase of 11.07%for CMS1 compared to CK and 6.25%for CMS2 compared to CK.The average yields of CMS1,CMS2,and CK in the 2020 cultivar comparison test and yield trial were 482.69,467.54,and 436.82 kg/667 m 2,respectively.CMS1 exhibited an average yield increase of 10.50%compared to CK,while CMS2 demonstrated an average yield increase of 7.03%relative to CK.Furthermore,the average yield of CMS1 per 667 m 2 achieved a statistically significant level compared to CK in both years of the study.In multiple-point comparison and yield trials conducted in 2019 and 2020,the CMS1 strain exhibited a total ash content of 15.30%,an acid-insoluble ash content of 1.30%,a moisture content of 10.80%,and water-soluble extract amounting to 11.40%.All of the indicators conformed to the criteria established by the Sichuan Standards for Chinese Medicinal Materials(2010 Edition).[Conclusions]The CMS1 strain successfully passed the field technical appraisal for the novel cultivar of C.violaceum in 2021.This cultivar is characterized by high yield,excellent quality,and stable traits.In 2022,it received validation from the Sichuan Provincial Committee for the Certification of Non-Staple Crop Varieties and was officially named‘Chengming No.1’(CRY 2022002).This cultivar demonstrates significant potential for widespread cultivation.
基金supported by grants from the National Natural Science Foundation of China(82204428,U24A20815,82304526,82204427,82201001,82430108,82293681(82293680),82273941)the National High-level Personnelof Special Support Program(to Dongmei Zhang and Minfeng Chen)+5 种基金the Natural Science Foundation of Guangdong Province(2023A1515010361 and 2022A1515011813)the Guangdong Basic and Applied Basic Research Foundation(2024B1515020098)the Science and Technology Program of Guangzhou(SL2024A04J00410,SL2024A04J00374,SL2024A04J00280)the Fundamental Research Funds for The Central Universities(21624103)the Science and Technology Projects in Guangzhou(2023A03J1030,202201010173,202102070001)the Clinical Frontier Technology Program of the First Affiliated Hospital of Jinan University,China(JNU1AF-CFTP-2022-a01210).
文摘Metabolic reprogramming reshapes the tumor microenvironment(TME)and facilitates metastasis,but its molecular mechanisms remain incompletely understood.Here,we identified enolase 2(ENO2),a critical glycolytic enzyme,as being associated with lymphatic metastasis in head and neck squamous cell carci-noma(HNSCC).Mechanistically,phosphoenolpyruvate(PEP),the metabolite secreted by ENO2-expressing HNSCC cells,drove histone H3 lysine 18 lactylation(H3K18la)-mediated M2 polarization in macrophages,which,in turn,enhanced the epithelial-mesenchymal transition(EMT)and invasiveness of HNSCC cells.Pharmacological inhibition of ENO2 with POMHEX effectively reversed M2 macrophage polarization and inhibited HNSCC lymphatic metastasis.Collectively,our findings underscore the prog-nostic significance of ENO2 and highlight its potential as a therapeutic target for metastatic HNSCC.Furthermore,we reveal a previously underappreciated role of PEP in modulating the tumor immune microenvironment and tumor metastasis via epigenetic modification.
基金supported by the National Natural Science Foundation of China(Grant Nos.52072188,12122405,and 12274169)Program for Science and Technology Innovation Team in Zhejiang Province,China(Grant No.2021R01004)+2 种基金Natural Science Foundation of Zhejiang Province,China(Grant No.LQ24A040001)the Natural Science Foundation of Ningbo City,China(Grant No.2024J200)the Fundamental Research Funds for the Provincial Universities of Zhejiang(Grant No.SJLY2023003)。
文摘Achieving room-temperature superconductivity has been an enduring scientific quest,while hydrogen-rich compounds have emerged as highly promising candidates.Here,we systematically investigated the thermodynamic stability,crystal structure,electronic properties,and superconductivity within the ternary Y-Hf-H system under high pressure.Several distinct hydrides have been revealed,in which the hydrogen atoms are present in various hydrogenic motifs.A15-type hydride P_(m)3-YHfH_(6)with isolated H−is predicted to be dynamically stabilized down to 10GPa.The H atoms form pentagonal graphene-like layered-H10 anions in the Hf plane of P6-YHfH_(19),with aT_(c)of 95K at 100GPa.There are H cages in C_(mmm)-Y_(3)HfH_(24),and attributed to the robust electron–phonon coupling and high electronic density of states of hydrogen at the Fermi level,it demonstrates near-room temperature superconductivity with a T_(c)of 275K at 250GPa.Our work makes contributions to the understanding of the fundamental properties of ternary hydrides under high pressure and provides essential references for further research in this field.
基金supported by the National Natural Science Foundation of China(32271605)。
文摘Highly pathogenic avian influenza(HPAI)H5 viruses have caused widespread mortality in wild birds and poultry,with increasing spillover risk into mammals.The recently dominant clade 2.3.4.4b has produced multiple epidemic waves,first driven by H5N8 and more recently by H5N1,which has spread more rapidly,infected a broader host range,and caused higher mortality.While earlier studies identified consistent roles of waterbird community composition in shaping HPAI outbreaks,it remains unclear whether these factors also apply to the currently circulating H5N1.We analyzed HPAI H5N1 outbreaks in European wild birds during the 2021/22epidemic,examining the influence of waterbird communities and environmental variables,and compared these patterns with earlier epidemics,including H5N1 in 2005/06 and H5N8 in 2016/17 and 2020/21.Our results showed that waterbird abundance,species richness,and the abundance of key species were positively associated with disease occurrence,whereas phylogenetic diversity was negatively associated,suggesting greater interspecific transmission among closely related hosts.Models trained on earlier epidemics accurately predicted the H5N1 occurrence in 2021/22.These findings demonstrate consistent effects of waterbird community composition across multiple epidemics and highlight their values as predictors of HPAI risk.Integrating community metrics into surveillance and early-warning systems can strengthen our capacity to anticipate future outbreaks across clades and subtypes.
基金supported by the National Natural Science Foundation of China(No.12205112)financially supported by self-determined research funds of CCNU from the colleges’basic research and operation of MOE(CCNU24JC012)supported by Natural Science Foundation of Wuhan(No.2024040801020302).
文摘Nucleosomes play a vital role in chromatin organization and gene regulation,acting as key hubs that inter-act with various chromatin-associated factors through diverse binding mechanisms.Recent research has highlighted the prevalence of mutations in linker histones across different types of cancer,emphasizing their critical involvement in cancer progression.These cancer-associated mutations in linker histones have been shown to disrupt nucleosome stacking and the formation of higher-order chromatin structures,which in turn significantly affect epigenetic regulatory processes.In this review,we provide a comprehensive analysis of how cancer-associated linker histone mutations alter their physicochemical properties,influencing their binding to nucleosomes,and overall chromatin architecture.Additionally,we explore the significant impact of mutations near post-translational modification sites,which further modulate chromatin dynamics and regulatory functions,offering insights into their role in oncogenesis and potential therapeutic targets.
文摘Solar-driven H_(2)O_(2) production through artificial photosynthesis presents a promising alternative to anthraquinone,given its lower energy consumption and eco-friendly nature[1-3].However,its catalytic performance is severely restricted by the inefficient separation of photogenerated carriers and interface reactions[4,5].
文摘Potassium(K)is known to enhance the catalytic performance of Fe-based catalysts in the reverse water-gas shift(rWGS)reaction,which is highly relevant during Fischer-Tropsch(FT)synthesis of CO_(2)-H_(2) mixtures.To elucidate the mechanistic role of K promoter,we employed density functional theory(DFT)calculations in conjunction with microkinetic modelling for two representative surface terminations of Hägg carbide(χ-Fe_(5)C_(2)),i.e.,(010)and(510).K_(2)O results in stronger adsorption of CO_(2)and H_(2) on Hägg carbide and promotes C–O bond dissociation of adsorbed CO_(2)by increasing the electron density on Fe atoms close to the promoter oxide.The increased electron density of the surface Fe atoms results in an increased electron-electron repulsion with bonding orbitals of adsorbed CO_(2).Microkinetics simulations predict that K_(2)O increases the CO_(2)conversion during CO_(2)-FT synthesis.K_(2)O also enhances CO adsorption and dissociation,facilitating the formation of methane,used here as a proxy for hydrocarbons formation during CO_(2)-FT synthesis.CO dissociation and O removal via H_(2)O compete as the rate-controlling steps in CO_(2)-FT.
基金supported by grants from the National Natural Science Foundation of China(32030044,32171012,82101332,32200948,and 323B1008)the Natural Science Foundation of Jiangsu Province,China(BK20240168+3 种基金BK20190008)the grant from the State Key Laboratory of Pharmaceutical Biotechnology(LNSN-202402)the Fundamental Research Funds for the Central Universities(020814380197,020814380208)Nanjing University Integrated Research Platform of the Ministry of Education-Top Talents Program(2024300475).
文摘The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson’s disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K^(+) channels, or Ca^(2+)-activated K+ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
基金supported by the National Natural Science Foundation of China(32273037 and 32102636)the Guangdong Major Project of Basic and Applied Basic Research(2020B0301030007)+4 种基金Laboratory of Lingnan Modern Agriculture Project(NT2021007)the Guangdong Science and Technology Innovation Leading Talent Program(2019TX05N098)the 111 Center(D20008)the double first-class discipline promotion project(2023B10564003)the Department of Education of Guangdong Province(2019KZDXM004 and 2019KCXTD001).
文摘A switch from avian-typeα-2,3 to human-typeα-2,6 receptors is an essential element for the initiation of a pandemic from an avian influenza virus.Some H9N2 viruses exhibit a preference for binding to human-typeα-2,6 receptors.This identifies their potential threat to public health.However,our understanding of the molecular basis for the switch of receptor preference is still limited.In this study,we employed the random forest algorithm to identify the potentially key amino acid sites within hemagglutinin(HA),which are associated with the receptor binding ability of H9N2 avian influenza virus(AIV).Subsequently,these sites were further verified by receptor binding assays.A total of 12 substitutions in the HA protein(N158D,N158S,A160 N,A160D,A160T,T163I,T163V,V190T,V190A,D193 N,D193G,and N231D)were predicted to prefer binding toα-2,6 receptors.Except for the V190T substitution,the other substitutions were demonstrated to display an affinity for preferential binding toα-2,6 receptors by receptor binding assays.Especially,the A160T substitution caused a significant upregulation of immune-response genes and an increased mortality rate in mice.Our findings provide novel insights into understanding the genetic basis of receptor preference of the H9N2 AIV.
文摘Photocatalytic hydrogen(H_(2))production using solar energy is a cutting-edge green technology that holds great potential for addressing the urgent fuel and environmental crises[1–3].To achieve high-efficiency H_(2) production,cocatalyst modification is commonly employed to provide active sites for the hydrogen evolution reaction(HER)[4,5].In this context,the kinetics of hydrogen adsorption and desorption at these active sites play a crucial role in enhancing overall photocatalytic H_(2) production efficiency.However,the H adsorption/desorption kinetics often exhibit a trade-off,presenting a significant challenge in achieving an optimal equilibrium between Hads and Hdes in many cocatalyst systems.Therefore,fine-tuning the active sites to optimize the H_(2) evolution kinetics is essential for improving photocatalytic activity[6].
