Rheumatoid arthritis(RA)is an autoimmune disease.Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility.However,accumulating evidence demonstrates that gene...Rheumatoid arthritis(RA)is an autoimmune disease.Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility.However,accumulating evidence demonstrates that genetics also shape the gut microbiota.It is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis(CIA),while the others are resistant to CIA.Here,we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice.C57BL/6J mice and healthy human individuals have enriched B.fragilis than DBA/1J mice and RA patients.Transplantation of B.fragilis prevents CIA in DBA/1J mice.We identify that B.fragilis mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of propionate.Fibroblast-like synoviocytes(FLSs)in RA are activated to undergo tumor-like transformation.Propionate disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1,resulting in reduced FOXK1 stability,blocked interferon signaling and deactivation of RA-FLSs.We treat CIA mice with propionate and show that propionate attenuates CIA.Moreover,a combination of propionate with anti-TNF etanercept synergistically relieves CIA.These results suggest that B.fragilis or propionate could be an alternative or complementary approach to the current therapies.展开更多
Salt stress inhibits plant growth and affects the biosynthesis of its secondary metabolites.Flavonoids are natural compounds that possess many important biological activities,playing a significant role in the medicina...Salt stress inhibits plant growth and affects the biosynthesis of its secondary metabolites.Flavonoids are natural compounds that possess many important biological activities,playing a significant role in the medicinal activity of Eucommia ulmoides(E.ulmoides).To investigate the mechanism by which salt stress affects the biosynthesis of flavonoids in E.ulmoides,a comprehensive analysis of metabolomics and transcriptomics was conducted.The results indicated that salt stress led to the wilting and darkening of E.ulmoides leaves,accompanied by a decrease in chlorophyll levels,and significantly induced malondialdehyde(MDA)and relative electrical conductivity.During salt stress,most metabolites in the flavonoid biosynthesis pathway of E.ulmoides were upregulated,indicating that flavonoid biosynthesis is likely the main induced pathway under salt stress.Among them,secondary metabolites such as 6-Hydroxyluteolin and Quercetin are likely key metabolites induced by salt stress.The correlation analysis of transcriptomics and metabolomics revealed that EuSHT is a hub gene induced by salt stress,promoting the production of flavonoids such as 6-Hydroxyluteolin.The co-expression network showed a strong positive correlation between EuSHT and the biosynthesis of 6-Hydroxyluteolin and Quercetin,while it exhibited a negative correlation with Catechin biosynthesis.The branches leading to Luteolin and Dihydroquercetin are likely the main pathways for flavonoid compound biosynthesis in the plant stress response during salt stress.The results of this study provided a preliminary mechanism of secondary metabolites such as flavonoids in the medicinal plant E.ulmoides induced by salt stress and provided new theoretical support for discussing the mechanism of plant stress response.It also provided useful information for subsequent exploration of resistance genes in E.ulmoides.展开更多
Aims:Multiple genes and environmental factors are known to be involved in congenital heart disease(CHD),but epigenetic variation has received little attention.Monozygotic(MZ)twins with CHD provide a unique model for e...Aims:Multiple genes and environmental factors are known to be involved in congenital heart disease(CHD),but epigenetic variation has received little attention.Monozygotic(MZ)twins with CHD provide a unique model for exploring this phenomenon.In order to investigate the potential role of Deoxyribonucleic Acid(DNA)methyla-tion in CHD pathogenesis,the present study examined DNA methylation variation in MZ twins discordant for CHD,especially ventricular septal defect(VSD).Methods and Results:Using genome-wide DNA methylation profiles,we identified 4004 differentially methylated regions(DMRs)in 18 MZ twin pairs discordant for CHD,and 2826 genes were identified.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed a list of CHD-associated pathways.To further investigate the role of DNA methylation in VSD,data from 7 pairs of MZ twins with VSD were analyzed.We identified 1614 DMRs corresponding to 1443 genes associated with arrhythmogenic right ventricular cardiomyopathy,cyclic guanosine monopho-sphate-protein kinase G(cGMP-PKG)signaling pathway by KEGG analysis,and cell-cell adhesion,calcium ion transmembrane transport by GO analysis.A proportion of DMR-associated genes were involved in calcium signaling pathways.The methylation changes of calcium signaling genes might be related to VSD pathogenesis.Conclusion:CHD is associated with differential DNA methylation in MZ twins.CHD may be etiologically linked to DNA methylation,and methylation of calcium signaling genes may be involved in the development of VSD.展开更多
The second edition of the expert consensus on pediatric nutrition was formed based on a global update of pedia-tric nutrition guidelines or consensus worldwide,the management of congenital heart disease,and the result...The second edition of the expert consensus on pediatric nutrition was formed based on a global update of pedia-tric nutrition guidelines or consensus worldwide,the management of congenital heart disease,and the results of multi-center clinical nutrition research for congenital heart disease following thefirst Chinese consensus edition of 2016.The consensus was also shaped by the results of three discussion sessions and two questionnaires con-ducted by the 13-member collaboration group.This process was informed by both clinical guidelines and expert consensus.The quality of literature,both in English and Chinese,and the level of recommendations were evaluated using the Grading of Recommendations Assessment,Development,and Evaluations(GRADE)system.展开更多
The development of high-performance layered oxide cathodes for sodium ion batteries (SIBs) continues to facing be hindered by severe challenges to date.Herein,a single-phase P2-Na0.67Mn0.6Ni0.2Co0.1Cu0.1O2(NMNCC) comp...The development of high-performance layered oxide cathodes for sodium ion batteries (SIBs) continues to facing be hindered by severe challenges to date.Herein,a single-phase P2-Na0.67Mn0.6Ni0.2Co0.1Cu0.1O2(NMNCC) comprising multiple-layer-oriented stacked nanoflakes is designed and synthesized via a simple sol-gel method.The large lattice parameters ensure a large three-dimensional frame,which enables the diffusion of sodium ions.Owing to its optimal morphology structure modulation transition metal substitution strategy,the MNCC electrode delivers a reversible capacity of 131.3 mAh g^-1 at 0.1 C with retention of 86.7%after 200 cycles.In addition,it provides an initial capacity of 86.7 mAh g^-1,and a retention of 80.0%after 500 cycles even at a current density of up to 1 A g^-1.The stable single-phase structure and slight volume shrinkage observed after Na+extraction further delay structural degradation.High Na+mobility and low Na+diffusion resistance are also guarantee the excellent rate performance of the NMNCC electrode.Thus,we determine that the NMNCC cathode is significant in the advancement of promising novel layered oxide cathodes.展开更多
The response of agricultural productivity anomalies to drought stress plays a crucial role in the carbon cycle within terrestrial ecosystems and in ensuring food security. However, detailed analysis of how global agri...The response of agricultural productivity anomalies to drought stress plays a crucial role in the carbon cycle within terrestrial ecosystems and in ensuring food security. However, detailed analysis of how global agricultural productivity anomalies response to drought stress, particularly within irrigated and rainfed agricultural systems, remains insufficient. In this study, the impact of drought stress on agricultural productivity anomalies during the growing season(zcNDVI^(S)), across both irrigated and rainfed agriculture, were analyzed using a suite of hydro-climatic variables. Specifically, the investigation utilized the multi-scalar Standardized Precipitation Evapotranspiration Index(SPEI), the Multivariate ENSO Index(MEI), and the Madden-Julian Oscillation(MJO). Meanwhile, the relationships between hydroclimatic variables and zcNDVI^(S) were analyzed at one, two, three and four months before the ending of growing season(EOS). Results showed that(1) the percentages of significant(p<0.1) drying trends varied across the globe from 8.30% to 13.42%, 6.50% to 14.63%, 6.52% to 14.23%, and 6.47%to 14.95% at one-, two-, three-, and four-month lead times before EOS, respectively, during 2001–2020, which represented by the multiscalar SPEI. This observation highlights that most regions across the globe tend to be arid, which could significantly impact agricultural productivity;(2) the global mean correlation coefficients(rmax) for SPEI-1, SPEI-3, SPEI-6, SPEI-12(indicating SPEI at 1-, 3-, 6-, and 12-month lags), MEI, and MJO with zcNDVI^(S) ranged between 0.24–0.25, 0.27–0.28, 0.25–0.26, 0.21–0.22, –0.02–0.01 and 0.06–0.11, respectively, across both irrigated and rainfed agriculture system from 2001 to 2020.Agricultural productivity anomalies demonstrated a significant correlation with drought stress. The strongest correlations were noted for SPEI-3 and SPEI-6, suggesting a delayed response of crops to drought conditions. This indicates that agriculture ecosystem experiences prolonged disturbances due to abiotic drought stress;and(3) the percentages of regions that showed significant correlations(p<0.1) between zcNDVI^(S)and drought indices(SPEI-1, SPEI-3, SPEI-6, and SPEI-12), as well as climate indices(MEI and MJO) ranged as follows: 14.77%–20.27%, 21.51%–32.55%, 22.60%–35.68%, 21.89%–35.16%,7.93%–11.20% and 9.44%–17.94%. Quantitatively identifying how zcNDVI^(S) spatially responds to hydro-climatic variables can help us better understand the impact of drought on agricultural productivity anomalies worldwide.展开更多
Targeted protein degradation(TPD)is emerging as a strategy to overcome the limitations of traditional small-molecule inhibitors.Proteolysis-targeting chimera(PROTAC)technology can be used to target proteins by hijacki...Targeted protein degradation(TPD)is emerging as a strategy to overcome the limitations of traditional small-molecule inhibitors.Proteolysis-targeting chimera(PROTAC)technology can be used to target proteins by hijacking the ubiquitin-proteasome system.Conceptually,PROTAC aims to target the“undruggable”majority of proteins in the human proteome.Through constant exploration and optimization of PROTACs and the exploitation of other TPD strategies over two decades,TPD has expanded from theoretical studies to clinical strategies,with practical applications in oncological,immunological,and other diseases.In this review,we introduce the mechanisms,features,and molecular targets of orthodox PROTACs and summarize the PROTAC drugs under study as cancer therapeutics in clinical trials.We also discuss PROTAC derivatives and other TPD strategies,such as lysosome-targeting chimeras,autophagy-targeting chimeras,and molecular glue strategies.Collectively,the studies summarized herein support the full potential of TPD in the biomedical industry.展开更多
Herein,we define the role of ferroptosis in the pathogenesis of diabetic cardiomyopathy(DCM)by examining the expression of key regulators of ferroptosis in mice with DCM and a new ex vivo DCM model.Advanced glycation ...Herein,we define the role of ferroptosis in the pathogenesis of diabetic cardiomyopathy(DCM)by examining the expression of key regulators of ferroptosis in mice with DCM and a new ex vivo DCM model.Advanced glycation end-products(AGEs),an important pathogenic factor of DCM,were found to induce ferroptosis in engineered cardiac tissues(ECTs),as reflected through increased levels of Ptgs2 and lipid peroxides and decreased ferritin and SLC7 A11 levels.Typical morphological changes of ferroptosis in cardiomyocytes were observed using transmission electron microscopy.Inhibition of ferroptosis with ferrostatin-1 and deferoxamine prevented AGE-induced ECT remodeling and dysfunction.Ferroptosis was also evidenced in the heart of type 2 diabetic mice with DCM.Inhibition of ferroptosis by liproxstatin-1 prevented the development of diastolic dysfunction at 3 months after the onset of diabetes.Nuclear factor erythroid 2-related factor 2(NRF2)activated by sulforaphane inhibited cardiac cell ferroptosis in both AGE-treated ECTs and hearts of DCM mice by upregulating ferritin and SLC7 A11 levels.The protective effect of sulforaphane on ferroptosis was AMP-activated protein kinase(AMPK)-dependent.These findings suggest that ferroptosis plays an essential role in the pathogenesis of DCM;sulforaphane prevents ferroptosis and associated pathogenesis via AMPK-mediated NRF2 activation.This suggests a feasible therapeutic approach with sulforaphane to clinically prevent ferroptosis and DCM.展开更多
African swine fever(ASF) is a lethal hemorrhagic disease that affects wild and domestic swine. The etiological agent of ASF is African swine fever virus(ASFV). Since the first case was described in Kenya in 1921, the ...African swine fever(ASF) is a lethal hemorrhagic disease that affects wild and domestic swine. The etiological agent of ASF is African swine fever virus(ASFV). Since the first case was described in Kenya in 1921, the disease has spread to many other countries. No commercial vaccines are available to prevent ASF. In this study, we generated a recombinant Newcastle disease virus(r NDV) expressing ASFV protein 72(p72) by reverse genetics and evaluated its humoral and cellular immunogenicity in a mouse model. The recombinant virus, r NDV/p72, replicated well in embryonated chicken eggs and was safe to use in chicks and mice. The p72 gene in r NDV/p72 was stably maintained through ten passages. Mice immunized with r NDV/p72 developed high titers of ASFV p72 specific Ig G antibody, and had higher levels of Ig G1 than IgG2 a. Immunization also elicited T-cell proliferation and secretion of IFN-γ and IL-4. Taken together, these results indicate that r NDV expressing ASFV p72 might be a potential vaccine candidate for preventing ASF.展开更多
A significant gap remains between rural and urban students in the rate of admission to senior high school. One reason for this gap might be the high levels of tuition and fees for senior high school By reducing stude...A significant gap remains between rural and urban students in the rate of admission to senior high school. One reason for this gap might be the high levels of tuition and fees for senior high school By reducing students＇ expectations of attending high school, high levels of tuition and fees could be reducing student aeademic performance in junior high schools. In this paper we evaluate the impacts of a senior high tuition relief program on the test scores of poor rural seventh grade students in China. We surveyed three counties in Shaanxi Province and exploited the fact that, while the counties are adjacent to one another and share similar characteristics, only one of the three implemented a tuition relief program. Using several alternative estimation strategies, including difference-in-differences, propensity score matching and difference-in-differences matching, we find that the tuition program has a statistically significant and positive impact on the mathematics scores of seventh grade students. More importantly, this program is shown to have a statistically significant and positive effect on the poorest students in the treatment group compared to their wealthier peers.展开更多
SnSe single crystals have been demonstrated to possess excellent thermoelectric properties.In this work,we demonstrate a grain size control method in growing nanocrystalline SnSe thin films through a glancing angle pu...SnSe single crystals have been demonstrated to possess excellent thermoelectric properties.In this work,we demonstrate a grain size control method in growing nanocrystalline SnSe thin films through a glancing angle pulsed-laser deposition approach.Structural characterization reveals that the SnSe film deposited at a normal angle has a preferred orientation along a axis,while by contrast,the SnSe film deposited at an 80glancing angle develops a nanopillar structure with the growth direction towards the incident atomic flux.The glancing angle deposition greatly reduces the grain size of the thin film due to a shadowing effect to the adatoms,resulting in significantly increased power factor for more than 100%.The maximum Seebeck coefficient and power factor are 498.5 mV=K and 18.5 mWcm^(-1)K^(-2),respectively.The enhancement of thermoelectric property can be attributed to the potential barrier scattering at grain boundaries owing to the reduced grain size and increased grain boundaries in the film.Given this enhanced power factor,and considering the fact that the nanopillar structure should have much lower thermal conductivity than a plain film,the zT value of such made SnSe film could be significantly larger than the corresponding single crystal film,making it a good candidate for thin film-based thermoelectric device.展开更多
Field-based phenotyping(FBP)of crop root systemarchitecture(RSA)provides away to quantify the root growth and distribution in fieldwith a smaller scale.Studies on a better understanding of the interrelations between f...Field-based phenotyping(FBP)of crop root systemarchitecture(RSA)provides away to quantify the root growth and distribution in fieldwith a smaller scale.Studies on a better understanding of the interrelations between field crop root physiological traits,root developmental phases and environmental changes are hindered due to deficiency of in situ root system architecture testing and quantitative methods for field crop.The present study aimed to propose a protocol for field-based wheat root system architecture with technical details of key operational procedures.Phenotyping of RSA traits from root spatial coordinate data acquisition and visualization software presented scaled illustrations of wheat RSA dynamics and root developmental phases which also revealed the root topological heterogeneities,eitherwithin a plant oramong individuals.Percentage of horizontal and vertical soil coverage by root showed that root foraging capability along soil depth was better than within the horizontal dimension.In brief,our data indicated that FBP ofwheat RSA could be achieved using the protocol of datadriven model-assisted phenotyping procedure.The proposed protocol was demonstrated useful for FBP of RSAs.It was proved effective to illustrate the topological structures of the wheat root system and to quantify RSAderived parameters,this could be a useful tool for characterizing and analyzing the structural distortion,heterogeneous distribution and the soil space exploration characteristics of wheat root.展开更多
基金supported by the National Natural Science Foundation Council of China(82172386 and 81922081 to C.L.,82100943 to X.F.,82104216 to J.L.,and 82230081,82250710175 and 8226116039 to G.X.)the Department of Education of Guangdong Province(2021KTSCX104 to C.L.)+5 种基金the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab)(2020B1212030006 to A.L.)the Guangdong Provincial Science and Technology Innovation Council Grant(2017B030301018 to G.X.)the Guangdong Basic and Applied Basic Research Foundation(2022A1515012164 to C.L.,and 2023A1515012000 to X.F.)the Science,Technology and Innovation Commission of Shenzhen(JCYJ20210324104201005 to C.L.,JCYJ20220530115006014 to X.F.,JCYJ20230807095118035 to J.L.,and JCYJ20220818100617036 to G.X.)the Hong Kong General Research Fund(12102722 to A.L.)the Hong Kong RGC Themebased Research Scheme(T12-201/20-R to A.L.).
文摘Rheumatoid arthritis(RA)is an autoimmune disease.Early studies hold an opinion that gut microbiota is environmentally acquired and associated with RA susceptibility.However,accumulating evidence demonstrates that genetics also shape the gut microbiota.It is known that some strains of inbred laboratory mice are highly susceptible to collagen-induced arthritis(CIA),while the others are resistant to CIA.Here,we show that transplantation of fecal microbiota of CIA-resistant C57BL/6J mice to CIA-susceptible DBA/1J mice confer CIA resistance in DBA/1J mice.C57BL/6J mice and healthy human individuals have enriched B.fragilis than DBA/1J mice and RA patients.Transplantation of B.fragilis prevents CIA in DBA/1J mice.We identify that B.fragilis mainly produces propionate and C57BL/6J mice and healthy human individuals have higher level of propionate.Fibroblast-like synoviocytes(FLSs)in RA are activated to undergo tumor-like transformation.Propionate disrupts HDAC3-FOXK1 interaction to increase acetylation of FOXK1,resulting in reduced FOXK1 stability,blocked interferon signaling and deactivation of RA-FLSs.We treat CIA mice with propionate and show that propionate attenuates CIA.Moreover,a combination of propionate with anti-TNF etanercept synergistically relieves CIA.These results suggest that B.fragilis or propionate could be an alternative or complementary approach to the current therapies.
基金supported by the National Key Research and Development Program of China(2017YFC1600802)Henan Provincial Science and Technology Research Project,China(No.232102110134).
文摘Salt stress inhibits plant growth and affects the biosynthesis of its secondary metabolites.Flavonoids are natural compounds that possess many important biological activities,playing a significant role in the medicinal activity of Eucommia ulmoides(E.ulmoides).To investigate the mechanism by which salt stress affects the biosynthesis of flavonoids in E.ulmoides,a comprehensive analysis of metabolomics and transcriptomics was conducted.The results indicated that salt stress led to the wilting and darkening of E.ulmoides leaves,accompanied by a decrease in chlorophyll levels,and significantly induced malondialdehyde(MDA)and relative electrical conductivity.During salt stress,most metabolites in the flavonoid biosynthesis pathway of E.ulmoides were upregulated,indicating that flavonoid biosynthesis is likely the main induced pathway under salt stress.Among them,secondary metabolites such as 6-Hydroxyluteolin and Quercetin are likely key metabolites induced by salt stress.The correlation analysis of transcriptomics and metabolomics revealed that EuSHT is a hub gene induced by salt stress,promoting the production of flavonoids such as 6-Hydroxyluteolin.The co-expression network showed a strong positive correlation between EuSHT and the biosynthesis of 6-Hydroxyluteolin and Quercetin,while it exhibited a negative correlation with Catechin biosynthesis.The branches leading to Luteolin and Dihydroquercetin are likely the main pathways for flavonoid compound biosynthesis in the plant stress response during salt stress.The results of this study provided a preliminary mechanism of secondary metabolites such as flavonoids in the medicinal plant E.ulmoides induced by salt stress and provided new theoretical support for discussing the mechanism of plant stress response.It also provided useful information for subsequent exploration of resistance genes in E.ulmoides.
基金China’s National Natural Science Foundation provided funding for this study(81900222)Guangzhou Science and Technology Program(SL2022A04J01269,202201020646)Guangzhou Health Science and Technology Program(20211A010026).
文摘Aims:Multiple genes and environmental factors are known to be involved in congenital heart disease(CHD),but epigenetic variation has received little attention.Monozygotic(MZ)twins with CHD provide a unique model for exploring this phenomenon.In order to investigate the potential role of Deoxyribonucleic Acid(DNA)methyla-tion in CHD pathogenesis,the present study examined DNA methylation variation in MZ twins discordant for CHD,especially ventricular septal defect(VSD).Methods and Results:Using genome-wide DNA methylation profiles,we identified 4004 differentially methylated regions(DMRs)in 18 MZ twin pairs discordant for CHD,and 2826 genes were identified.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis revealed a list of CHD-associated pathways.To further investigate the role of DNA methylation in VSD,data from 7 pairs of MZ twins with VSD were analyzed.We identified 1614 DMRs corresponding to 1443 genes associated with arrhythmogenic right ventricular cardiomyopathy,cyclic guanosine monopho-sphate-protein kinase G(cGMP-PKG)signaling pathway by KEGG analysis,and cell-cell adhesion,calcium ion transmembrane transport by GO analysis.A proportion of DMR-associated genes were involved in calcium signaling pathways.The methylation changes of calcium signaling genes might be related to VSD pathogenesis.Conclusion:CHD is associated with differential DNA methylation in MZ twins.CHD may be etiologically linked to DNA methylation,and methylation of calcium signaling genes may be involved in the development of VSD.
基金supported by the National Natural Science Foundation of China(81970265,82270310)a Sub-Project of the National Key R&D Program“The recognition and Identification of Genetic Pathogenic Genes for Structural Birth Defects”(2021YFC2701002)+1 种基金Nanjing Science and Technology Development Project(2019060007)Jiangsu Provincial Key Research and Development Program(BE2023662).
文摘The second edition of the expert consensus on pediatric nutrition was formed based on a global update of pedia-tric nutrition guidelines or consensus worldwide,the management of congenital heart disease,and the results of multi-center clinical nutrition research for congenital heart disease following thefirst Chinese consensus edition of 2016.The consensus was also shaped by the results of three discussion sessions and two questionnaires con-ducted by the 13-member collaboration group.This process was informed by both clinical guidelines and expert consensus.The quality of literature,both in English and Chinese,and the level of recommendations were evaluated using the Grading of Recommendations Assessment,Development,and Evaluations(GRADE)system.
基金supported by the National Natural Science Foundation of China(No.21471162)the Hunan Provincial Science and Technology Plan Project(No.2017TP1001)Postgraduate Innovation project(No.502211822)。
文摘The development of high-performance layered oxide cathodes for sodium ion batteries (SIBs) continues to facing be hindered by severe challenges to date.Herein,a single-phase P2-Na0.67Mn0.6Ni0.2Co0.1Cu0.1O2(NMNCC) comprising multiple-layer-oriented stacked nanoflakes is designed and synthesized via a simple sol-gel method.The large lattice parameters ensure a large three-dimensional frame,which enables the diffusion of sodium ions.Owing to its optimal morphology structure modulation transition metal substitution strategy,the MNCC electrode delivers a reversible capacity of 131.3 mAh g^-1 at 0.1 C with retention of 86.7%after 200 cycles.In addition,it provides an initial capacity of 86.7 mAh g^-1,and a retention of 80.0%after 500 cycles even at a current density of up to 1 A g^-1.The stable single-phase structure and slight volume shrinkage observed after Na+extraction further delay structural degradation.High Na+mobility and low Na+diffusion resistance are also guarantee the excellent rate performance of the NMNCC electrode.Thus,we determine that the NMNCC cathode is significant in the advancement of promising novel layered oxide cathodes.
基金financially supported by the National Natural Science Foundation of China (Grant Nos. 41925007, 42001314, 41771360, 41975044 & 41801021)the Fundamental Research Funds for National UniversitiesChina University of Geosciences, Wuhan and China Scholarship Council。
文摘The response of agricultural productivity anomalies to drought stress plays a crucial role in the carbon cycle within terrestrial ecosystems and in ensuring food security. However, detailed analysis of how global agricultural productivity anomalies response to drought stress, particularly within irrigated and rainfed agricultural systems, remains insufficient. In this study, the impact of drought stress on agricultural productivity anomalies during the growing season(zcNDVI^(S)), across both irrigated and rainfed agriculture, were analyzed using a suite of hydro-climatic variables. Specifically, the investigation utilized the multi-scalar Standardized Precipitation Evapotranspiration Index(SPEI), the Multivariate ENSO Index(MEI), and the Madden-Julian Oscillation(MJO). Meanwhile, the relationships between hydroclimatic variables and zcNDVI^(S) were analyzed at one, two, three and four months before the ending of growing season(EOS). Results showed that(1) the percentages of significant(p<0.1) drying trends varied across the globe from 8.30% to 13.42%, 6.50% to 14.63%, 6.52% to 14.23%, and 6.47%to 14.95% at one-, two-, three-, and four-month lead times before EOS, respectively, during 2001–2020, which represented by the multiscalar SPEI. This observation highlights that most regions across the globe tend to be arid, which could significantly impact agricultural productivity;(2) the global mean correlation coefficients(rmax) for SPEI-1, SPEI-3, SPEI-6, SPEI-12(indicating SPEI at 1-, 3-, 6-, and 12-month lags), MEI, and MJO with zcNDVI^(S) ranged between 0.24–0.25, 0.27–0.28, 0.25–0.26, 0.21–0.22, –0.02–0.01 and 0.06–0.11, respectively, across both irrigated and rainfed agriculture system from 2001 to 2020.Agricultural productivity anomalies demonstrated a significant correlation with drought stress. The strongest correlations were noted for SPEI-3 and SPEI-6, suggesting a delayed response of crops to drought conditions. This indicates that agriculture ecosystem experiences prolonged disturbances due to abiotic drought stress;and(3) the percentages of regions that showed significant correlations(p<0.1) between zcNDVI^(S)and drought indices(SPEI-1, SPEI-3, SPEI-6, and SPEI-12), as well as climate indices(MEI and MJO) ranged as follows: 14.77%–20.27%, 21.51%–32.55%, 22.60%–35.68%, 21.89%–35.16%,7.93%–11.20% and 9.44%–17.94%. Quantitatively identifying how zcNDVI^(S) spatially responds to hydro-climatic variables can help us better understand the impact of drought on agricultural productivity anomalies worldwide.
基金supported by the National Natural Science Foundation of China(82172386 and 81922081 to C.L.)the Department of Education of Guangdong Province(2021KTSCX104 to C.L.)+2 种基金the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab)(2020B1212030006 to A.L.)the Guangdong Basic and Applied Basic Research Foundation(2022A1515012164 to C.L.)the Science,Technology and Innovation Commission of Shenzhen(JCYJ20210324104201005 to C.L.).
文摘Targeted protein degradation(TPD)is emerging as a strategy to overcome the limitations of traditional small-molecule inhibitors.Proteolysis-targeting chimera(PROTAC)technology can be used to target proteins by hijacking the ubiquitin-proteasome system.Conceptually,PROTAC aims to target the“undruggable”majority of proteins in the human proteome.Through constant exploration and optimization of PROTACs and the exploitation of other TPD strategies over two decades,TPD has expanded from theoretical studies to clinical strategies,with practical applications in oncological,immunological,and other diseases.In this review,we introduce the mechanisms,features,and molecular targets of orthodox PROTACs and summarize the PROTAC drugs under study as cancer therapeutics in clinical trials.We also discuss PROTAC derivatives and other TPD strategies,such as lysosome-targeting chimeras,autophagy-targeting chimeras,and molecular glue strategies.Collectively,the studies summarized herein support the full potential of TPD in the biomedical industry.
基金supported in part by American Diabetes Association(1-18-IBS-082 to LC,USA)the National Key R&D Program of China(2016YFC0900903 to YZ,China)。
文摘Herein,we define the role of ferroptosis in the pathogenesis of diabetic cardiomyopathy(DCM)by examining the expression of key regulators of ferroptosis in mice with DCM and a new ex vivo DCM model.Advanced glycation end-products(AGEs),an important pathogenic factor of DCM,were found to induce ferroptosis in engineered cardiac tissues(ECTs),as reflected through increased levels of Ptgs2 and lipid peroxides and decreased ferritin and SLC7 A11 levels.Typical morphological changes of ferroptosis in cardiomyocytes were observed using transmission electron microscopy.Inhibition of ferroptosis with ferrostatin-1 and deferoxamine prevented AGE-induced ECT remodeling and dysfunction.Ferroptosis was also evidenced in the heart of type 2 diabetic mice with DCM.Inhibition of ferroptosis by liproxstatin-1 prevented the development of diastolic dysfunction at 3 months after the onset of diabetes.Nuclear factor erythroid 2-related factor 2(NRF2)activated by sulforaphane inhibited cardiac cell ferroptosis in both AGE-treated ECTs and hearts of DCM mice by upregulating ferritin and SLC7 A11 levels.The protective effect of sulforaphane on ferroptosis was AMP-activated protein kinase(AMPK)-dependent.These findings suggest that ferroptosis plays an essential role in the pathogenesis of DCM;sulforaphane prevents ferroptosis and associated pathogenesis via AMPK-mediated NRF2 activation.This suggests a feasible therapeutic approach with sulforaphane to clinically prevent ferroptosis and DCM.
基金financially supported by the National Supporting Program(2013BAD12B05)Natural Science Foundation of China(NSFC)(no.31101839 and no.31302117)+1 种基金the key program of Gansu Province(no.1013JHTA008)Jiangsu Co-innovation Center program for Prevention and Control of Important Animal Infectious Diseases and Zoonoses
文摘African swine fever(ASF) is a lethal hemorrhagic disease that affects wild and domestic swine. The etiological agent of ASF is African swine fever virus(ASFV). Since the first case was described in Kenya in 1921, the disease has spread to many other countries. No commercial vaccines are available to prevent ASF. In this study, we generated a recombinant Newcastle disease virus(r NDV) expressing ASFV protein 72(p72) by reverse genetics and evaluated its humoral and cellular immunogenicity in a mouse model. The recombinant virus, r NDV/p72, replicated well in embryonated chicken eggs and was safe to use in chicks and mice. The p72 gene in r NDV/p72 was stably maintained through ten passages. Mice immunized with r NDV/p72 developed high titers of ASFV p72 specific Ig G antibody, and had higher levels of Ig G1 than IgG2 a. Immunization also elicited T-cell proliferation and secretion of IFN-γ and IL-4. Taken together, these results indicate that r NDV expressing ASFV p72 might be a potential vaccine candidate for preventing ASF.
基金the financial assistance of the National Natural Science Foundation of China(Grant No.71110107028,71033003,71273237 and 70803047)the grant from Poverty and Economic Policy Research Network(PEP)The generous supports of local officials and especially those from Ningshan County Government
文摘A significant gap remains between rural and urban students in the rate of admission to senior high school. One reason for this gap might be the high levels of tuition and fees for senior high school By reducing students＇ expectations of attending high school, high levels of tuition and fees could be reducing student aeademic performance in junior high schools. In this paper we evaluate the impacts of a senior high tuition relief program on the test scores of poor rural seventh grade students in China. We surveyed three counties in Shaanxi Province and exploited the fact that, while the counties are adjacent to one another and share similar characteristics, only one of the three implemented a tuition relief program. Using several alternative estimation strategies, including difference-in-differences, propensity score matching and difference-in-differences matching, we find that the tuition program has a statistically significant and positive impact on the mathematics scores of seventh grade students. More importantly, this program is shown to have a statistically significant and positive effect on the poorest students in the treatment group compared to their wealthier peers.
基金We thank support from The Hong Kong Polytechnic University(Grant Nos.1-ZVCG,1eZVGH,4eZZDC,and DD7F).
文摘SnSe single crystals have been demonstrated to possess excellent thermoelectric properties.In this work,we demonstrate a grain size control method in growing nanocrystalline SnSe thin films through a glancing angle pulsed-laser deposition approach.Structural characterization reveals that the SnSe film deposited at a normal angle has a preferred orientation along a axis,while by contrast,the SnSe film deposited at an 80glancing angle develops a nanopillar structure with the growth direction towards the incident atomic flux.The glancing angle deposition greatly reduces the grain size of the thin film due to a shadowing effect to the adatoms,resulting in significantly increased power factor for more than 100%.The maximum Seebeck coefficient and power factor are 498.5 mV=K and 18.5 mWcm^(-1)K^(-2),respectively.The enhancement of thermoelectric property can be attributed to the potential barrier scattering at grain boundaries owing to the reduced grain size and increased grain boundaries in the film.Given this enhanced power factor,and considering the fact that the nanopillar structure should have much lower thermal conductivity than a plain film,the zT value of such made SnSe film could be significantly larger than the corresponding single crystal film,making it a good candidate for thin film-based thermoelectric device.
基金Financial support from the China Postdoctoral Science Foundation(2018M632314)the State Key Program of China(2016YFD0300900)were acknowledged.
文摘Field-based phenotyping(FBP)of crop root systemarchitecture(RSA)provides away to quantify the root growth and distribution in fieldwith a smaller scale.Studies on a better understanding of the interrelations between field crop root physiological traits,root developmental phases and environmental changes are hindered due to deficiency of in situ root system architecture testing and quantitative methods for field crop.The present study aimed to propose a protocol for field-based wheat root system architecture with technical details of key operational procedures.Phenotyping of RSA traits from root spatial coordinate data acquisition and visualization software presented scaled illustrations of wheat RSA dynamics and root developmental phases which also revealed the root topological heterogeneities,eitherwithin a plant oramong individuals.Percentage of horizontal and vertical soil coverage by root showed that root foraging capability along soil depth was better than within the horizontal dimension.In brief,our data indicated that FBP ofwheat RSA could be achieved using the protocol of datadriven model-assisted phenotyping procedure.The proposed protocol was demonstrated useful for FBP of RSAs.It was proved effective to illustrate the topological structures of the wheat root system and to quantify RSAderived parameters,this could be a useful tool for characterizing and analyzing the structural distortion,heterogeneous distribution and the soil space exploration characteristics of wheat root.
