Nanosized tungsten carbide(WC)/carbon(C)catalyst was synthesized via a novel ultra-rapid confinement combustion synthesis method.The amount of activated carbon(AC)plays an important role in the morphology and structur...Nanosized tungsten carbide(WC)/carbon(C)catalyst was synthesized via a novel ultra-rapid confinement combustion synthesis method.The amount of activated carbon(AC)plays an important role in the morphology and structure,controlling both the precursor and final powder.The WC particles synthesized inside the pores of the AC had been 10-20 nm because of the confinement of the pore structure and the large specific surface area of AC.When used for oxygen reduction performance,the half-wave potential was−0.24 V,and the electron transfer number was 3.45,indicating the main reaction process was the transfer of four electrons.The detailed electrocatalytic performance and underlying mechanism were investigated in this work.Our study provides a novel approach for the design of catalysts with new compositions and new structures,which are significant for promoting the commercialization of fuel cells.展开更多
Dear Editor,Since the COVID-19 pandemic, the potential risks associated with maternal SARS-CoV-2 infection and its effect on fetal development have been a subject of considerable public concern. Previous studies have ...Dear Editor,Since the COVID-19 pandemic, the potential risks associated with maternal SARS-CoV-2 infection and its effect on fetal development have been a subject of considerable public concern. Previous studies have shown that SARS-CoV-2 infection during pregnancy may increase the incidence of adverse outcomes.展开更多
Spatial transcriptomics enables the study of localization-indexed gene expression activity in tissues,providing the transcriptional landscape that in turn indicates the potential regulatory networks of gene expression...Spatial transcriptomics enables the study of localization-indexed gene expression activity in tissues,providing the transcriptional landscape that in turn indicates the potential regulatory networks of gene expression.In situ sequencing(ISS)is a targeted spatial transcriptomic technique,based on padlock probe and rolling circle amplification combined with next-generation sequencing chemistry,for highly multiplexed in situ gene expression profiling.Here,we present improved in situ sequencing(IISS)that exploits a new probing and barcoding approach,combined with advanced image analysis pipelines for high-resolution targeted spatial gene expression profiling.We develop an improved combinatorial probe anchor ligation chemistry using a 2-base encoding strategy for barcode interrogation.The new encoding strategy results in higher signal intensity as well as improved specificity for in situ sequencing,while maintaining a streamlined analysis pipeline for targeted spatial transcriptomics.We show that IISS can be applied to both fresh frozen tissue and formalin-fixed paraffin-embedded tissue sections for single-cell level spatial gene expression analysis,based on which the developmental trajectory and cell-cell communication networks can also be constructed.展开更多
Self-organized blastoids from extended pluripotent stem(EPs)cells possess enormous potential for investigating postimplantation embryo development and related diseases.However,the limited ability of postimplantation d...Self-organized blastoids from extended pluripotent stem(EPs)cells possess enormous potential for investigating postimplantation embryo development and related diseases.However,the limited ability of postimplantation development of Eps-blastoids hinders its further application.In this study,single-cell transcriptomic analysis indicated that the“trophectoderm(TE)-like structure”of EPSblastoids was primarily composed of primitive endoderm(PrE)-related cells instead of TE-related cells.We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure.Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation.Furthermore,we demonstrated that blastocyst-like structures reconstituted by combining the EPs-derived bilineage embryo-like structure(BLEs)with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses.In summary,our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.展开更多
An intelligent liquid classification system based on 77 GHz millimeter wave radar and convolution neural network are proposed in this paper.The data are collected by the AWR1843 radar platform and processed by the neu...An intelligent liquid classification system based on 77 GHz millimeter wave radar and convolution neural network are proposed in this paper.The data are collected by the AWR1843 radar platform and processed by the neural network on the host PC in real-time.The doppler heatmap generated by radar signal processing is tried for the first time as the input of the system.The information carried by the heatmap in 2 dimensions is analyzed and the reason why the doppler heatmap could be used for classification is explained.The feasible experiment proved that the proposed method can successfully classify 8 kinds of common liquid with high accuracy.The result of the experiment is explained and the limitations of the experiment are discussed.It can be drawn that the combination of FMCW millimeter wave radar and convolution neural network is a method with great potential for liquid classification.The advantages of real time,non-invasive and unilateral measurement can also be used for the detection of dangerous liquids.展开更多
The coastal area of the East China Sea has experienced rapid urbanization and industrialization in China since 1980 s, resulting in severe pollution of its environments.Antibiotic resistance genes(ARGs) are regarded a...The coastal area of the East China Sea has experienced rapid urbanization and industrialization in China since 1980 s, resulting in severe pollution of its environments.Antibiotic resistance genes(ARGs) are regarded as a kind of emerging pollutant with potential high risk. The sediment samples were collected from Hangzhou Bay(HB),Xiangshan Bay(XB), and Taizhou Bay(TB) to investigate the spatial occurrence and distribution of 27 ARGs and class I integron–integrase gene(intI1) in the coastal area of the East China Sea. The PCR results showed the frequent presence of 11 ARGs and intI1 in the sediments of the three bays. The qPCR results further showed that sulfonamide resistance was the most prevalent ARG type and antibiotic target replacement and protection were the most important resistance mechanisms in the sediments. Regarding the subtype of ARGs, sulI, tetW, and dfrA13 were the most abundant ARGs, in which sulI was higher in TB(based on both the absolute and relative abundances) and dfrA13 was higher in HB(based on the relative abundances). The network analysis revealed that intI1 had significant correlations with tetC, sulI, sulII, and blaPSE-1. Oil was the key connected factor, which had positive connections with sulI, sulII, and blaPSE-1. In addition, the joint effect of heavy metals and nutrients & organic pollutants might be crucial for the fate of ARGs in the coastal sediments.展开更多
N^(6)-methyladenosine(m^(6)A)on chromosome-associated regulatory RNAs(carRNAs),including repeat RNAs,plays important roles in tuning the chromatin state and transcription,but the intrinsic mechanism remains unclear.He...N^(6)-methyladenosine(m^(6)A)on chromosome-associated regulatory RNAs(carRNAs),including repeat RNAs,plays important roles in tuning the chromatin state and transcription,but the intrinsic mechanism remains unclear.Here,we report that YTHDC1 plays indispensable roles in the self-renewal and differentiation potency of mouse embryonic stem cells(ESCs),which highly depends on the m^(6)A-binding ability.Ythdcl is required for sufficient rRNA synthesis and repression of the 2-cell(2C)transcriptional program in ESCs,which recapitulates the transcriptome regulation by the LINE1 scaffold.Detailed analyses revealed that YTHDC1 recognizes m^(6)A on LINE1 RNAs in the nucleus and regulates the formation of the LINE1-NCL partnership and the chromatin recruitment of KAP1.Moreover,the establishment of H3K9me3 on 2C-related retrotrans-posons is interrupted in Ythdcl-depleted ESCs and inner cell mass(ICM)cells,which consequently increases the transcriptional activities.Our study reveals a role of m^(6)A in regulating the RNA scaffold,providing a new model for the RNA-chromatin cross-talk.展开更多
Recently,metal-organic framework(MOF)-based multienzyme systems integrating different functional natural enzymes and/or nanomaterial-basedartificial enzymes are attracting increasing attention due to their high cataly...Recently,metal-organic framework(MOF)-based multienzyme systems integrating different functional natural enzymes and/or nanomaterial-basedartificial enzymes are attracting increasing attention due to their high catalytic efficiency and promising application in sensing.Simpleand controllable integration of enzymes or nanozymes within MOFs is crucial for achieving efficient cascade catalysis and high stability.Here,we report a facile electrochemical assisted biomimetic mineralization strategy to prepare an artificial multienzyme system for efficient electrochemicaldetection of biomolecules.By using the G0x@Cu-MOF/copper foam(G0x@Cu-MOF/CF)architecture as a proof of concept,efficientenzyme immobilization and cascade catalysis were achieved by in situ encapsulation of glucose oxidase(GOx)within MOFs layer grown onthree-dimensional(3D)porous conducting CF via a facile one-step electrochemical assisted biomimetic mineralization strategy.Due to thebio-electrocatalytic cascade reaction mechanism,this well-designed GOx@Cu-MOF modified electrode exhibited superior catalytic activityand thermal stability for glucose sensing.Notably,the activity of GOx@Cu-MOF/CF still remained at ca.80%after being incubated at 80℃.In sharp contrast,the activity of the unprotected electrode was reduced to the original 10%after the same treatment.The design strategypresented here may be useful in fabricating highly stable enzyme@MOF composites applied for efficient photothermal therapy and otherplatform under high temperature.展开更多
Trophoblast stem cells (TSCs), which can be derived from the trophoectoderm of a blastocyst, have the ability to sustain self-renewal and differentiate into various placental trophoblast cell types. Meanwhile, essenti...Trophoblast stem cells (TSCs), which can be derived from the trophoectoderm of a blastocyst, have the ability to sustain self-renewal and differentiate into various placental trophoblast cell types. Meanwhile, essential insights into the molecular mechanisms controlling the placental development can be gained by using TSCs as the cell model. Esrrb is a transcription factor that has been shown to play pivotal roles in both embryonic stem cell (ESC) and TSC, but the precise mechanism whereby Esrrb regulates TSC-specific transcriptome during differentiation and reprogramming is still largely unknown. In the present study, we elucidate the function of Esrrb in self-renewal and differentiation of TSCs, as well as during the induced TSC (iTSC) reprogramming. We demonstrate that the precise level of Esrrb is critical for stem state maintenance and further trophoblast differentiation of TSCs, as ectopically expressed Esrrb can partially block the rapid differentiation of TSCs in the absence of fibroblast growth factor 4. However, Esrrb depletion results in downregulation of certain key TSC-specific transcription factors, consequently causing a rapid differentiation of TSCs and these Esrrb-deficient TSCs lose the ability of hemorrhagic lesion formation in vivo. This function of Esrrb is exerted by directly binding and activating a core set of TSC-specific target genes including Cdx2, Eomes, Sox2, Fgfr4, and Bmp4. Furthermore, we show that Esrrb overexpression can facilitate the MEF-to-iTSC conversion. Moreover, Esrrb can substitute for Eomes to generate GEsTM-iTSCs. Thus, our findings provide a better understanding of the molecular mechanism of Esrrb in maintaining TSC self-renewal and during iTSC reprogramming.展开更多
Chemically defined medium is widely used for culturing mouse embryonic stem cells(mESCs),in which N2B27 works as a substitution for serum,and GSK3βand MEK inhibitors(2i)help to promote ground-state pluripo-tency.Howe...Chemically defined medium is widely used for culturing mouse embryonic stem cells(mESCs),in which N2B27 works as a substitution for serum,and GSK3βand MEK inhibitors(2i)help to promote ground-state pluripo-tency.However,recent studies suggested that MEKi might cause irreversible defects that compromise the developmental potential of mESCs.Here,we demon-strated the deficient bone morphogenetic protein(BMP)signal in the chemically defined condition is one of the main causes for the impaired pluripotency.Mechanisti-cally,activating the BMP signal pathway by BMP4 could safeguard the chromosomal integrity and proliferation capacity of mESCs through regulating downstream tar-gets Ube2s and Chmp4b.More importantly,BMP4 pro-motes a distinct in vivo developmental potential and a long-term pluripotency preservation.Besides,the pluripotent improvements driven by BMP4 are superior to those by attenuating MEK suppression.Taken together,our study shows appropriate activation of BMP signal is essential for regulating functional pluripotency and reveals that BMP4 should be applied in the serum-free culture system.展开更多
The maximum seismic response of curved bridge is significantly related to the input angle of designated earthquake. Owing to structure irregularities, bridge reactions result from the interaction between the moment an...The maximum seismic response of curved bridge is significantly related to the input angle of designated earthquake. Owing to structure irregularities, bridge reactions result from the interaction between the moment and torsion forces. Based on the solving of the seismic response of structure excited by a one-way earthquake input, a uniform expression of the unfavorable angle of the earthquake input was derived, and the corresponding maximum response of structure was determined. Considering the orthotropic and skewed dual- directional earthquake input manners, the most unfavorable angles for the two cases were also derived, respectively. Furthermore, a series finite element models were built to analyze the multi-component seismic responses by examining an example of curved girder bridge considering the variation of curvature radius and the bearings arrangement. The seismic responses of the case bridges, were excited by earthquakes at different input angles, and were calculated and analyzed using a response spectrum method. The input angles of earthquake excitation were progressively increased. From the analysis and comparison based on the calculation results mentioned above, the most unfavorable angle of earthquake excitation corresponding to the maximum seismic response of the curved bridge could be determined. It was shown that the most unfavorable angles of earthquake input resulted from the different response combination methods were essentially coherent.展开更多
Crossmodal information processing in sensory cortices has been reported in sparsely distributed neurons under normal conditions and can undergo experience-or activity-induced plasticity.Given the potential role in bra...Crossmodal information processing in sensory cortices has been reported in sparsely distributed neurons under normal conditions and can undergo experience-or activity-induced plasticity.Given the potential role in brain function as indicated by previous reports,crossmodal connectivity in the sensory cortex needs to be further explored.Using perforated whole-cell recording in anesthetized adult rats,we found that almost all neurons recorded in the primary somatosensory,auditory,and visual cortices exhibited significant membrane-potential responses to crossmodal stimulation,as recorded when brain activity states were pharmacologically down-regulated in light anesthesia.These crossmodal cortical responses were excitatory and subthreshold,and further seemed to be relayed primarily by the sensory thalamus,but not the sensory cortex,of the stimulated modality.Our experiments indicate a sensory cortical presence of widespread excitatory crossmodal inputs,which might play roles in brain functions involving crossmodal information processing or plasticity.展开更多
CORRECTION TO:PROTEIN CELL(2021)HTTPS://DOI.ORG/10.1007/S13238-021-00837-8 In the original publication of the article figure 1 is incorrectly published.The correct Figure 1 is provided in this correction.OPEN ACCESS T...CORRECTION TO:PROTEIN CELL(2021)HTTPS://DOI.ORG/10.1007/S13238-021-00837-8 In the original publication of the article figure 1 is incorrectly published.The correct Figure 1 is provided in this correction.OPEN ACCESS This article is licensed under a Creative Commons Attribution 4.0 International License,which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons licence,and indicate if changes were made.The images or other third party material in this article are included in the article's Creative Commons licence,unless indicated otherwise in a credit line to the material.If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use,you will need to obtain permission directly from the copyright holder.To view a copy of this licence,visit https://creativecommons.org/licenses/by/4.0/.展开更多
Innovation and knowledge diffusion in megaprojects is one of the most complicated issues in project management.Compared with conventional projects,megaprojects typically entail large-scale investments,long constructio...Innovation and knowledge diffusion in megaprojects is one of the most complicated issues in project management.Compared with conventional projects,megaprojects typically entail large-scale investments,long construction periods,and conflicting stakeholder interests,which result in a distinctive pattern of innovation diffusion.However,traditional investigation of innovation diffusion relies on subjective feedback from experts and frequently neglects inter-organizational knowledge creation,which frequently emerges in megaprojects.Therefore,this study adopted project network theory and modeled innovation diffusion in megaprojects as intra-and interorganizational learning processes.In addition,system dynamics and flizzy systems were combined to interpret experts9 subject options as quantitative coefficients of the project network model.This integrated model will assist in developing an insightful understanding of the mechanisms of innovation diffusion in megaprojects.Three typical network structures,namely,a traditional megaproject procurement organization(TMO),the environ megaproject organization(EMO),and an integrated megaproject organization(IMO),were examined under six management scenarios to verify the proposed analytic paradigm.Assessment of project network productivity suggested that the projectivity of the TMO was insensitive to technical and administrative innovations,the EMO could achieve substantial improvement from technical innovations,and the 1MO trended incompatibly with administrative innovations.Thus,industry practitioners and project managers can design and reform agile project coordination by using the proposed quantitative model to encourage innovation adoption and reduce productivity loss at the start of newly established collaborations.展开更多
Stroke is the most frequent cause of secondary epilepsy in the elderly.The incidence of cerebral stroke is increasing with the extension of life expectancy,and the prevalence of post-stroke epilepsy(PSE)is rising.Ther...Stroke is the most frequent cause of secondary epilepsy in the elderly.The incidence of cerebral stroke is increasing with the extension of life expectancy,and the prevalence of post-stroke epilepsy(PSE)is rising.There are various seizure types after stroke,and the occurrence of epilepsy is closely related to the type and location of stroke.Moreover,the clinical treatment of post-stroke epilepsy is difficult,which increases the risk of disability and death,and affects the prognosis and quality of life of patients.Now seizure and epilepsy after stroke is more and more get the attention of the medical profession,has been more and more researchers have devoted to seizures after stroke and PSE clinical and basic research,and hope to get a scientific and unified guideline,to give timely and effective treatment,but the exact pathophysiologic mechanism has not yet formed a unified conclusion.It has been found that ion channels,neurotransmitters,proliferation of glial cells,genetics and other factors are involved in the occurrence and development of PSE.In this review,we discuss the pathogenesis of early-onset epileptic seizures and late-onset epilepsy after stroke,in order to provide a basis for clinicians to understand the disease,and expect to provide ideas for future exploration.展开更多
Platelet-derived growth factor-BB(PDGF-BB)/platelet-derived growth factor receptor-β(PDGFR-β)pathway is conventionally considered as an important pathway to promote osteogenesis;however,recent study suggested its ro...Platelet-derived growth factor-BB(PDGF-BB)/platelet-derived growth factor receptor-β(PDGFR-β)pathway is conventionally considered as an important pathway to promote osteogenesis;however,recent study suggested its role during osteogenesis to be controversial.Regarding the differential functions of this pathway during 3 stages of bone healing,we hypothesized that temporal inhibition of PDGF-BB/PDGFR-βpathway could shift the proliferation/differentiation balance of skeletal stem and progenitor cells,toward osteogenic lineage,which leads to improved bone regeneration.We first validated that inhibition of PDGFR-βat late stage of osteogenic induction effectively enhanced differentiation toward osteoblasts.This effect was also replicated invivo by showing accelerated bone formation when block PDGFR-βpathway at late stage of critical bone defect healing mediated using biomaterials.Further,we found that such PDGFR-βinhibitor-initiated bone healing was also effective in the absence of scaffold implantation when administrated intraperitoneally.Mechanistically,timely inhibition of PDGFR-βblocked extracellular regulated protein kinase 1/2 pathway,which shift proliferation/differentiation balance of skeletal stem and progenitor cell to osteogenic lineage by upregulating osteogenesis-related products of Smad to induce osteogenesis.This study offered updated understanding of the use of PDGFR-βpathway and provides new insight routes of action and novel therapeutic methods in the field of bone repair.展开更多
基金This work was financially supported by the China Postdoctoral Science Foundation(No.2019M652169)the University Synergy Innovation Program of Anhui Province(No.GXXT-2019-016)+1 种基金the Natural Science Foundation of Anhui(No.JZ2018AKZR0063)the Fundamental Research Funds for the Central University,China(No.PA2019GDPK0044).
文摘Nanosized tungsten carbide(WC)/carbon(C)catalyst was synthesized via a novel ultra-rapid confinement combustion synthesis method.The amount of activated carbon(AC)plays an important role in the morphology and structure,controlling both the precursor and final powder.The WC particles synthesized inside the pores of the AC had been 10-20 nm because of the confinement of the pore structure and the large specific surface area of AC.When used for oxygen reduction performance,the half-wave potential was−0.24 V,and the electron transfer number was 3.45,indicating the main reaction process was the transfer of four electrons.The detailed electrocatalytic performance and underlying mechanism were investigated in this work.Our study provides a novel approach for the design of catalysts with new compositions and new structures,which are significant for promoting the commercialization of fuel cells.
基金supported by the Chinese National Program on the Key Basic Research Project(2021YFA1100300,2020YFA0112500)the National Natural Science Foundation of China(31721003,31820103009,32270856,32070857,32270858)。
文摘Dear Editor,Since the COVID-19 pandemic, the potential risks associated with maternal SARS-CoV-2 infection and its effect on fetal development have been a subject of considerable public concern. Previous studies have shown that SARS-CoV-2 infection during pregnancy may increase the incidence of adverse outcomes.
基金supported by the Natural Science Foundation of Fujian Province(2022J06022)the Quanzhou Science and Technology Plan Project(2021C040R)the Scientific Research Funds of Huaqiao University.
文摘Spatial transcriptomics enables the study of localization-indexed gene expression activity in tissues,providing the transcriptional landscape that in turn indicates the potential regulatory networks of gene expression.In situ sequencing(ISS)is a targeted spatial transcriptomic technique,based on padlock probe and rolling circle amplification combined with next-generation sequencing chemistry,for highly multiplexed in situ gene expression profiling.Here,we present improved in situ sequencing(IISS)that exploits a new probing and barcoding approach,combined with advanced image analysis pipelines for high-resolution targeted spatial gene expression profiling.We develop an improved combinatorial probe anchor ligation chemistry using a 2-base encoding strategy for barcode interrogation.The new encoding strategy results in higher signal intensity as well as improved specificity for in situ sequencing,while maintaining a streamlined analysis pipeline for targeted spatial transcriptomics.We show that IISS can be applied to both fresh frozen tissue and formalin-fixed paraffin-embedded tissue sections for single-cell level spatial gene expression analysis,based on which the developmental trajectory and cell-cell communication networks can also be constructed.
基金supported by the National Key R&D Program of China(Nos.2020YFA0112500 and 2021YFA1102900)the National Natural Science Foundation of China(Nos.31721003,81630035,82022027,31871448,32000418 and 31820103009)+2 种基金supported by the key project of the Science and Technology of Shanghai Municipality(Nos.19JC1415300 and 21JC1405500)the Shanghai municipal medical and health discipline construction projects(No.2017ZZ02015)the China Postdoctoral Science Foundation 2021M692437 and the Fundamental Research Funds for the Central Universities.
文摘Self-organized blastoids from extended pluripotent stem(EPs)cells possess enormous potential for investigating postimplantation embryo development and related diseases.However,the limited ability of postimplantation development of Eps-blastoids hinders its further application.In this study,single-cell transcriptomic analysis indicated that the“trophectoderm(TE)-like structure”of EPSblastoids was primarily composed of primitive endoderm(PrE)-related cells instead of TE-related cells.We further identified PrE-like cells in EPS cell culture that contribute to the blastoid formation with TE-like structure.Inhibition of PrE cell differentiation by inhibiting MEK signaling or knockout of Gata6 in EPS cells markedly suppressed EPS-blastoid formation.Furthermore,we demonstrated that blastocyst-like structures reconstituted by combining the EPs-derived bilineage embryo-like structure(BLEs)with either tetraploid embryos or tetraploid TE cells could implant normally and develop into live fetuses.In summary,our study reveals that TE improvement is critical for constructing a functional embryo using stem cells in vitro.
基金supported in part by the Key R&D program of Shaanxi Province(2020ZDXM5-01)in part by the Fundamental Research Funds for the Central Universities.The review of this article was coordinated by Prof.Long Li.
文摘An intelligent liquid classification system based on 77 GHz millimeter wave radar and convolution neural network are proposed in this paper.The data are collected by the AWR1843 radar platform and processed by the neural network on the host PC in real-time.The doppler heatmap generated by radar signal processing is tried for the first time as the input of the system.The information carried by the heatmap in 2 dimensions is analyzed and the reason why the doppler heatmap could be used for classification is explained.The feasible experiment proved that the proposed method can successfully classify 8 kinds of common liquid with high accuracy.The result of the experiment is explained and the limitations of the experiment are discussed.It can be drawn that the combination of FMCW millimeter wave radar and convolution neural network is a method with great potential for liquid classification.The advantages of real time,non-invasive and unilateral measurement can also be used for the detection of dangerous liquids.
基金supported by the National Natural Science Foundation of China(No.51678003)
文摘The coastal area of the East China Sea has experienced rapid urbanization and industrialization in China since 1980 s, resulting in severe pollution of its environments.Antibiotic resistance genes(ARGs) are regarded as a kind of emerging pollutant with potential high risk. The sediment samples were collected from Hangzhou Bay(HB),Xiangshan Bay(XB), and Taizhou Bay(TB) to investigate the spatial occurrence and distribution of 27 ARGs and class I integron–integrase gene(intI1) in the coastal area of the East China Sea. The PCR results showed the frequent presence of 11 ARGs and intI1 in the sediments of the three bays. The qPCR results further showed that sulfonamide resistance was the most prevalent ARG type and antibiotic target replacement and protection were the most important resistance mechanisms in the sediments. Regarding the subtype of ARGs, sulI, tetW, and dfrA13 were the most abundant ARGs, in which sulI was higher in TB(based on both the absolute and relative abundances) and dfrA13 was higher in HB(based on the relative abundances). The network analysis revealed that intI1 had significant correlations with tetC, sulI, sulII, and blaPSE-1. Oil was the key connected factor, which had positive connections with sulI, sulII, and blaPSE-1. In addition, the joint effect of heavy metals and nutrients & organic pollutants might be crucial for the fate of ARGs in the coastal sediments.
基金This work was supported by the National Key R&D Program of China(2016YFA0100400,2020YFA0113200,2018YFA0108900 and 2016YFC1000600)the National Natural Science Foundation of China(31922022,31771646,82022027,31721003,31970796,31871448 and 31871446)+3 种基金the Shanghai Rising-Star Program(19QA1409600)the Shanghai Municipal Medical and Health Discipline Construction Projects(2017ZZ02015)the Fundamental Research Funds for the Central Universities(1515219049 and 22120200410)the Major Program of the Development Fund for Shanghai Zhangjiang National Innovation Demonstration Zone(ZJ2018-ZD-004).
文摘N^(6)-methyladenosine(m^(6)A)on chromosome-associated regulatory RNAs(carRNAs),including repeat RNAs,plays important roles in tuning the chromatin state and transcription,but the intrinsic mechanism remains unclear.Here,we report that YTHDC1 plays indispensable roles in the self-renewal and differentiation potency of mouse embryonic stem cells(ESCs),which highly depends on the m^(6)A-binding ability.Ythdcl is required for sufficient rRNA synthesis and repression of the 2-cell(2C)transcriptional program in ESCs,which recapitulates the transcriptome regulation by the LINE1 scaffold.Detailed analyses revealed that YTHDC1 recognizes m^(6)A on LINE1 RNAs in the nucleus and regulates the formation of the LINE1-NCL partnership and the chromatin recruitment of KAP1.Moreover,the establishment of H3K9me3 on 2C-related retrotrans-posons is interrupted in Ythdcl-depleted ESCs and inner cell mass(ICM)cells,which consequently increases the transcriptional activities.Our study reveals a role of m^(6)A in regulating the RNA scaffold,providing a new model for the RNA-chromatin cross-talk.
基金This work was supported by the National Key Research and Development Program of China(Nos.2017YFA0206500 and 2017YFA0206801)the National Basic Research Program of China(No.2015CB932301)the National Natural Science Foundation of China(Nos.21671163,21721001,and J1310024).
文摘Recently,metal-organic framework(MOF)-based multienzyme systems integrating different functional natural enzymes and/or nanomaterial-basedartificial enzymes are attracting increasing attention due to their high catalytic efficiency and promising application in sensing.Simpleand controllable integration of enzymes or nanozymes within MOFs is crucial for achieving efficient cascade catalysis and high stability.Here,we report a facile electrochemical assisted biomimetic mineralization strategy to prepare an artificial multienzyme system for efficient electrochemicaldetection of biomolecules.By using the G0x@Cu-MOF/copper foam(G0x@Cu-MOF/CF)architecture as a proof of concept,efficientenzyme immobilization and cascade catalysis were achieved by in situ encapsulation of glucose oxidase(GOx)within MOFs layer grown onthree-dimensional(3D)porous conducting CF via a facile one-step electrochemical assisted biomimetic mineralization strategy.Due to thebio-electrocatalytic cascade reaction mechanism,this well-designed GOx@Cu-MOF modified electrode exhibited superior catalytic activityand thermal stability for glucose sensing.Notably,the activity of GOx@Cu-MOF/CF still remained at ca.80%after being incubated at 80℃.In sharp contrast,the activity of the unprotected electrode was reduced to the original 10%after the same treatment.The design strategypresented here may be useful in fabricating highly stable enzyme@MOF composites applied for efficient photothermal therapy and otherplatform under high temperature.
基金supported by the Natural Key R&D Project of China(2020YFA0113200,2018YFC1003102,and 2021YFC2700300)the National Natural Science Foundation of China(31721003,31970814,31871438,31820103009,and 82071565)+1 种基金the 2115 Talent Development Program of China Agricultural Universitythe Youth Innovation Promotion Association of Chinese Academy of Sciences(2020104)。
基金the National Key R&D Program of China (2016YFA0100400)the National Natural Science Foundation of China (31721003)+6 种基金the Ministry of Science and Technology of China (2015CB964800, 2015CB964503, and 2018YFA0108900)the National Natural Science Foundation of China (81630035, 31871446, and 31771646)the Shanghai Rising-Star Program (17QA1404200)the Shanghai Chenguang Program (16CG17)the Shanghai Municipal Medical and Health Discipline Construction Projects (2017ZZ02015)National Postdoctoral Program for Innovative Talents (BX201700307)China Postdoctoral Science Foundation (2017M621527).
文摘Trophoblast stem cells (TSCs), which can be derived from the trophoectoderm of a blastocyst, have the ability to sustain self-renewal and differentiate into various placental trophoblast cell types. Meanwhile, essential insights into the molecular mechanisms controlling the placental development can be gained by using TSCs as the cell model. Esrrb is a transcription factor that has been shown to play pivotal roles in both embryonic stem cell (ESC) and TSC, but the precise mechanism whereby Esrrb regulates TSC-specific transcriptome during differentiation and reprogramming is still largely unknown. In the present study, we elucidate the function of Esrrb in self-renewal and differentiation of TSCs, as well as during the induced TSC (iTSC) reprogramming. We demonstrate that the precise level of Esrrb is critical for stem state maintenance and further trophoblast differentiation of TSCs, as ectopically expressed Esrrb can partially block the rapid differentiation of TSCs in the absence of fibroblast growth factor 4. However, Esrrb depletion results in downregulation of certain key TSC-specific transcription factors, consequently causing a rapid differentiation of TSCs and these Esrrb-deficient TSCs lose the ability of hemorrhagic lesion formation in vivo. This function of Esrrb is exerted by directly binding and activating a core set of TSC-specific target genes including Cdx2, Eomes, Sox2, Fgfr4, and Bmp4. Furthermore, we show that Esrrb overexpression can facilitate the MEF-to-iTSC conversion. Moreover, Esrrb can substitute for Eomes to generate GEsTM-iTSCs. Thus, our findings provide a better understanding of the molecular mechanism of Esrrb in maintaining TSC self-renewal and during iTSC reprogramming.
基金This work was supported by the National Key R&D Program of China(2020YFA0112500 and 2021YFA1100300)the National Natural Science Foundation of China(31721003,31820103009,92168205,32070857 and 31871446)+3 种基金the Young Elite Scientist Sponsorship Program by CAST(2018QNRC001)the key project of the Science and Technology of Shanghai Municipality(19JC1415300)the Shanghai Rising-Star Program(19QA1409600)the Shanghai municipal medical and health discipline construction projects(no.2017ZZ02015).
文摘Chemically defined medium is widely used for culturing mouse embryonic stem cells(mESCs),in which N2B27 works as a substitution for serum,and GSK3βand MEK inhibitors(2i)help to promote ground-state pluripo-tency.However,recent studies suggested that MEKi might cause irreversible defects that compromise the developmental potential of mESCs.Here,we demon-strated the deficient bone morphogenetic protein(BMP)signal in the chemically defined condition is one of the main causes for the impaired pluripotency.Mechanisti-cally,activating the BMP signal pathway by BMP4 could safeguard the chromosomal integrity and proliferation capacity of mESCs through regulating downstream tar-gets Ube2s and Chmp4b.More importantly,BMP4 pro-motes a distinct in vivo developmental potential and a long-term pluripotency preservation.Besides,the pluripotent improvements driven by BMP4 are superior to those by attenuating MEK suppression.Taken together,our study shows appropriate activation of BMP signal is essential for regulating functional pluripotency and reveals that BMP4 should be applied in the serum-free culture system.
基金supported by the National Natural Science Foundation of China(No.51378050)China Scholarship Council(No.201307095008)
文摘The maximum seismic response of curved bridge is significantly related to the input angle of designated earthquake. Owing to structure irregularities, bridge reactions result from the interaction between the moment and torsion forces. Based on the solving of the seismic response of structure excited by a one-way earthquake input, a uniform expression of the unfavorable angle of the earthquake input was derived, and the corresponding maximum response of structure was determined. Considering the orthotropic and skewed dual- directional earthquake input manners, the most unfavorable angles for the two cases were also derived, respectively. Furthermore, a series finite element models were built to analyze the multi-component seismic responses by examining an example of curved girder bridge considering the variation of curvature radius and the bearings arrangement. The seismic responses of the case bridges, were excited by earthquakes at different input angles, and were calculated and analyzed using a response spectrum method. The input angles of earthquake excitation were progressively increased. From the analysis and comparison based on the calculation results mentioned above, the most unfavorable angle of earthquake excitation corresponding to the maximum seismic response of the curved bridge could be determined. It was shown that the most unfavorable angles of earthquake input resulted from the different response combination methods were essentially coherent.
基金This work was supported by grants from the National Natural Science Foundation of China(31970957 and 31471078)the Shanghai Science and Technology Commission(19ZR1416600)funding from 2021-JCJQ-JJ-1089.
文摘Crossmodal information processing in sensory cortices has been reported in sparsely distributed neurons under normal conditions and can undergo experience-or activity-induced plasticity.Given the potential role in brain function as indicated by previous reports,crossmodal connectivity in the sensory cortex needs to be further explored.Using perforated whole-cell recording in anesthetized adult rats,we found that almost all neurons recorded in the primary somatosensory,auditory,and visual cortices exhibited significant membrane-potential responses to crossmodal stimulation,as recorded when brain activity states were pharmacologically down-regulated in light anesthesia.These crossmodal cortical responses were excitatory and subthreshold,and further seemed to be relayed primarily by the sensory thalamus,but not the sensory cortex,of the stimulated modality.Our experiments indicate a sensory cortical presence of widespread excitatory crossmodal inputs,which might play roles in brain functions involving crossmodal information processing or plasticity.
文摘CORRECTION TO:PROTEIN CELL(2021)HTTPS://DOI.ORG/10.1007/S13238-021-00837-8 In the original publication of the article figure 1 is incorrectly published.The correct Figure 1 is provided in this correction.OPEN ACCESS This article is licensed under a Creative Commons Attribution 4.0 International License,which permits use,sharing,adaptation,distribution and reproduction in any medium or format,as long as you give appropriate credit to the original author(s)and the source,provide a link to the Creative Commons licence,and indicate if changes were made.The images or other third party material in this article are included in the article's Creative Commons licence,unless indicated otherwise in a credit line to the material.If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use,you will need to obtain permission directly from the copyright holder.To view a copy of this licence,visit https://creativecommons.org/licenses/by/4.0/.
文摘Innovation and knowledge diffusion in megaprojects is one of the most complicated issues in project management.Compared with conventional projects,megaprojects typically entail large-scale investments,long construction periods,and conflicting stakeholder interests,which result in a distinctive pattern of innovation diffusion.However,traditional investigation of innovation diffusion relies on subjective feedback from experts and frequently neglects inter-organizational knowledge creation,which frequently emerges in megaprojects.Therefore,this study adopted project network theory and modeled innovation diffusion in megaprojects as intra-and interorganizational learning processes.In addition,system dynamics and flizzy systems were combined to interpret experts9 subject options as quantitative coefficients of the project network model.This integrated model will assist in developing an insightful understanding of the mechanisms of innovation diffusion in megaprojects.Three typical network structures,namely,a traditional megaproject procurement organization(TMO),the environ megaproject organization(EMO),and an integrated megaproject organization(IMO),were examined under six management scenarios to verify the proposed analytic paradigm.Assessment of project network productivity suggested that the projectivity of the TMO was insensitive to technical and administrative innovations,the EMO could achieve substantial improvement from technical innovations,and the 1MO trended incompatibly with administrative innovations.Thus,industry practitioners and project managers can design and reform agile project coordination by using the proposed quantitative model to encourage innovation adoption and reduce productivity loss at the start of newly established collaborations.
文摘Stroke is the most frequent cause of secondary epilepsy in the elderly.The incidence of cerebral stroke is increasing with the extension of life expectancy,and the prevalence of post-stroke epilepsy(PSE)is rising.There are various seizure types after stroke,and the occurrence of epilepsy is closely related to the type and location of stroke.Moreover,the clinical treatment of post-stroke epilepsy is difficult,which increases the risk of disability and death,and affects the prognosis and quality of life of patients.Now seizure and epilepsy after stroke is more and more get the attention of the medical profession,has been more and more researchers have devoted to seizures after stroke and PSE clinical and basic research,and hope to get a scientific and unified guideline,to give timely and effective treatment,but the exact pathophysiologic mechanism has not yet formed a unified conclusion.It has been found that ion channels,neurotransmitters,proliferation of glial cells,genetics and other factors are involved in the occurrence and development of PSE.In this review,we discuss the pathogenesis of early-onset epileptic seizures and late-onset epilepsy after stroke,in order to provide a basis for clinicians to understand the disease,and expect to provide ideas for future exploration.
基金supported by the National Key Research and Development Projects(2018YFC1105400)the National Natural Science Foundation of China(81872173,82072959,and 31870959)+1 种基金the Zhejiang Provincial Natural Science Foundation(GF22H068757)the Zhejiang Undergraduate Talent Project(2021R401214).
文摘Platelet-derived growth factor-BB(PDGF-BB)/platelet-derived growth factor receptor-β(PDGFR-β)pathway is conventionally considered as an important pathway to promote osteogenesis;however,recent study suggested its role during osteogenesis to be controversial.Regarding the differential functions of this pathway during 3 stages of bone healing,we hypothesized that temporal inhibition of PDGF-BB/PDGFR-βpathway could shift the proliferation/differentiation balance of skeletal stem and progenitor cells,toward osteogenic lineage,which leads to improved bone regeneration.We first validated that inhibition of PDGFR-βat late stage of osteogenic induction effectively enhanced differentiation toward osteoblasts.This effect was also replicated invivo by showing accelerated bone formation when block PDGFR-βpathway at late stage of critical bone defect healing mediated using biomaterials.Further,we found that such PDGFR-βinhibitor-initiated bone healing was also effective in the absence of scaffold implantation when administrated intraperitoneally.Mechanistically,timely inhibition of PDGFR-βblocked extracellular regulated protein kinase 1/2 pathway,which shift proliferation/differentiation balance of skeletal stem and progenitor cell to osteogenic lineage by upregulating osteogenesis-related products of Smad to induce osteogenesis.This study offered updated understanding of the use of PDGFR-βpathway and provides new insight routes of action and novel therapeutic methods in the field of bone repair.