This cohort study was designed to explore the relationship between maternal dietary patterns(DPs)and bone health in Chinese lactating mothers and infants.We recruited 150 lactating women at 1-month postpartum.The esti...This cohort study was designed to explore the relationship between maternal dietary patterns(DPs)and bone health in Chinese lactating mothers and infants.We recruited 150 lactating women at 1-month postpartum.The estimated bone mineral density(eBMD)of subjects’calcanei and the information on dietary intake were collected.After 5-month follow-up,the eBMD of mothers and their infants were measured again.Factor analysis was applied to determine maternal DPs.General linear models were used to evaluate the association between maternal DPs and maternal eBMD loss or infants’eBMD.With all potential covariates adjusted,Factor 2(high intake of whole grains,tubers,mixed beans,soybeans and soybean products,seaweeds,and nuts)showed a positive association with the changes of maternal eBMD(β=0.16,95%CI:0.005,0.310).Factor 3(high intake of soft drinks,fried foods,and puffed foods)was inversely correlated with the changes of maternal eBMD(β=-0.22,95%CI:-0.44,0.00).The changes of maternal eBMD were positively associated with 6-month infants’eBMD(β=0.34,95%CI:0.017,0.652).In conclusion,Factor 2 might contribute to the maintenance of eBMD in lactating women,while Factor 3 could exacerbate maternal eBMD loss.Additionally,the changes of maternal eBMD presented a positive correlation with 6-month infants’eBMD.展开更多
The past few years have witnessed enormous progresses in the development of antibody-drug conjugates(ADCs).Consequently,comprehensive analysis of ADCs in biological systems is critical in supporting discovery,developm...The past few years have witnessed enormous progresses in the development of antibody-drug conjugates(ADCs).Consequently,comprehensive analysis of ADCs in biological systems is critical in supporting discovery,development and evaluation of these agents.Liquid chromatography-mass spectrometry(LC-MS)has eme rged as a promising and versatile tool for ADC analysis across a wide range of scenarios,owing to its multiplexing ability,rapid method development,as well as the capability of analyzing a variety of targets ranging from small-molecule payloads to the intact protein with a high,molecular resolution.However,despite this tremendous potential,challenges persist due to the high complexity in both the ADC molecules and the related biological systems.This review summarizes the up-to-date LC-MS-based strategies in ADC analysis and discusses the challenges and opportunities in this rapidly-evolving field.展开更多
Blood-arresting Formula on simvastatin-induced zebrafish hemorrhage model compared with that of the Heat-clearing and Blood-cooling Formula.Methods:AB strain wild type zebrafish were treated with 0.5 mM simvastatin fo...Blood-arresting Formula on simvastatin-induced zebrafish hemorrhage model compared with that of the Heat-clearing and Blood-cooling Formula.Methods:AB strain wild type zebrafish were treated with 0.5 mM simvastatin for 24 hours to establish the zebrafish hemorrhage model.Under strictly blind experimental conditions,the zebrafish were then treated with experimental agents in different concentration within the maximum non-lethal dose.The intervention effect of the Spleen-invigorating,Qi-replenishing and Blood-arresting Formula was comprehensively assessed by examining the main observational parameters such as the bleeding reduction rate and hemostatic rate while referring to the additional parameters such as blood flow,improvement rate of blood flow,velocity of movement,improvement rate of motion under spleen-qi deficiency.Results:Hemostatic effect:The bleeding rate and hemostatic rate in the zebrafish were respectively,30%,15%,45%,40%and 60%,80%,40%,47%when equal concentration of 500 mg/mL,1000 mg/mL were used.This showed that the experimental herbs B1 was superior to B2 in decreasing the bleeding rate and improving hemostatic effect in the zebrafish.Improvement of blood flow:With equal concentration,the experimental herb B1 was superior to B2 in increasing the blood flow and improvement rate of blood flow in hemorrhagic zebrafish.Promotion of the improvement of motion:With equal concentration of 500 mg/mL and 1000 mg/mL,the experimental herb B1 was superior to B2 in promoting the velocity of motion in the zebrafish and promoting the improvement rate of motion.Conclusion:The manifestations of simvastatin-induced zebrafish hemorrhage are basically similar to that of failure of the spleen to control blood in human beings.The Spleeninvigorating,Qi-replenishing and Blood-arresting Formula has good hemostatic effect on simvastatin-induced hemorrhage in the zebrafish.It also boasts the functions of improving blood flow and velocity of motion in the hemorrhagic zebrafish.Such a conclusion provides the experimental basis for the treatment of the syndrome of failure of the spleen to control blood by this formula.展开更多
Alzheimer＇s disease, the leading cause of dementia in the elderly, is a complex neurodegenerative disorder which leads to a progressive decline in cognitive functions. A rapid screening model is highly demanded for i...Alzheimer＇s disease, the leading cause of dementia in the elderly, is a complex neurodegenerative disorder which leads to a progressive decline in cognitive functions. A rapid screening model is highly demanded for identification and evaluation of novel anti-Alzheimer＇s disease drugs from a large numbers of compounds. Until now, numerous studies utilized zebrafish model for drug discovery. Since aluminum can induce a similar biological activity in zebrafish as in Alzheimer patients, in this study, we developed a novel animal model using 3 to 5 day post-fertilization larval zebrafish by optimizing the doses and duration of aluminum chloride exposure. Six anti-Alzheimer＇s disease drugs with a variety of mechanisms were tested to validate the newly developed zebrafish model. Importantly, Rivastigmine, ThT, Flurbiprofen and AM-117 could increase the value of Dyskinesia Recovery Rate by 53.4-64%, 169.4-200%, 54.5-96% and 70.9-121%, respectively. Rivastigmine, Memantine, ThT, Flurbiprofen, Rosiglitazone and AM-117 improved the value of Response Efficiency by 86.6-175.1%, 28.2-66.6%, 127.2-236.5%, 118.3-323.7%, 26.6-140.8% and 70.2-161.4%, respectively. Our results suggest that the zebrafish model developed in this study could be a useful tool for high throughput screening of potential novel anti-Alzheimer＇s disease leading compounds targeting acetylcholinesterase, N-methyl-D-aspartic acid receptor, γ-secretase, peroxisome proliferator-activated receptor-γand amyloid-β.展开更多
The emergence of new technologies such as GPS,cellphone,Bluetooth device,etc.offers opportunities for collecting high-fidelity temporal-spatial travel data in a cost-effective manner.With the vehicle trajectory data a...The emergence of new technologies such as GPS,cellphone,Bluetooth device,etc.offers opportunities for collecting high-fidelity temporal-spatial travel data in a cost-effective manner.With the vehicle trajectory data achieved from a smartphone app Metropia,this study targets on exploring the trajectory data and designing the measurements of the driving pattern.Metropia is a recently available mobile traffic app that uses prediction and coordinating technology combined with user rewards to incentivize drivers to cooperate,balance traffic load on the network,and reduce traffic congestion.Speed and celeration(acceleration and deceleration)are obtained from the Metropia platform directly and parameterized as individual and system measurements related to traffic,spatial and temporal conditions.A case study is provided in this paper to demonstrate the feasibility of this approach utilizing the trajectory data from the actual app usage.The driving behaviors at both individual and system levels are quantified from the microscopic speed and celeration records.The results from this study reveal distinct driving behavior pattern and shed lights for further opportunities to identify behavior characteristics beyond safety and environmental considerations.展开更多
Background:With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation(UCBT),the correlation between immune reconstitution(IR)after UCBT and graft-vers...Background:With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation(UCBT),the correlation between immune reconstitution(IR)after UCBT and graft-versus-host disease(GVHD)has been reported successively,but reports on double-negative T(DNT)cell reconstitution and its association with acute GVHD(aGVHD)after UCBT are lacking.Methods:A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology,the First Affiliated Hospital of USTC,between August 2018 and June 2021.IR differences were compared between the patients with and without aGVHD.Results:The absolute number of DNT cells in the healthy Chinese population was 109(70-157)/μL,accounting for 5.82(3.98-8.19)%of lymphocytes.DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation.Importantly,the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year(F=4.684,P=0.039 and F=5.583,P=0.026,respectively).In addition,the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased,and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD(HR=0.46,95%confidence interval[CI]:0.23-0.93;P=0.031).Conclusions:Compared to the number of DNT cells in Chinese healthy people,the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow.In addition,the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.展开更多
Comprehensive Summary HpnG plays a crucial role in the production of ribosylhopane,a key intermediate in the biosynthesis of bacteriohopanepolyol.Despite early extensive studies,the precise function of HpnG has remain...Comprehensive Summary HpnG plays a crucial role in the production of ribosylhopane,a key intermediate in the biosynthesis of bacteriohopanepolyol.Despite early extensive studies,the precise function of HpnG has remained elusive.Here,we report functional characterization of HpnG as a purine nucleoside phosphorylase,which converts adenosylhopane to phosphoribosylhopane in the presence of phosphate.HpnG demonstrates broad substrate specificity and impressive stability,making it a valuable enzymatic tool for applications in nucleoside processing and related biotechnology.展开更多
Organic semiconductors play a pivotal role in the development of various organic opto-electronic devices, encompassing organic light-emitting diodes (OLEDs), organic field-effect transistors(OFETs), organic solar cell...Organic semiconductors play a pivotal role in the development of various organic opto-electronic devices, encompassing organic light-emitting diodes (OLEDs), organic field-effect transistors(OFETs), organic solar cells (OSCs), organic photodetectors (OPDs),etc.[1]. Material scientists continually refine the chemical structures of organic semiconductors to optimize their opto-electronic properties and thin film morphology, thereby enhancing device performance [2]. Among the diverse array of functional groups available for modification, fluorine stands out due to its minimal atomic radius and maximal electronegativity.展开更多
In this study,driven by ERA5 reanalysis data,the Weather Research and Forecasting(WRF)version 4.0 was used to investigate the eastward propagation of the Madden-Julian oscillation(MJO)in the tropical atmosphere during...In this study,driven by ERA5 reanalysis data,the Weather Research and Forecasting(WRF)version 4.0 was used to investigate the eastward propagation of the Madden-Julian oscillation(MJO)in the tropical atmosphere during December-February(DJF)of 2007/2008.The experiment with 11 cumulus parameterization schemes respectively shows that the Grell 3D scheme is one of several worse ones in describing MJO activities.In addition,still by use of the Grell 3D scheme,four nudging assimilation experiments for water vapor in all model vertical layers(Ndg_all),lower layers(Ndg_low),middle layers(Ndg_mid),and upper layers(Ndg_upp)were conducted.It is found that when the water vapor in the model approaches to the observed value,the model performance for MJO activities is improved greatly.Among the four nudging simulations,Ndg_all certainly performs best.Although Ndg_mid is important for the MJO-filtered profiles related to moisture,Ndg_low and Ndg_upp exhibit superiority to Ndg_mid in simulating MJO eastward propagation.Ndg_low has advantages when MJO features are represented by zonal wind at 850 hPa and precipitation because the lower-level MJO-filtered moisture is conducive to the existence of lower-level condensational heating to the east of the MJO convective center.Ndg_upp performs better when describing the MJO eastward propagation features by outgoing longwave radiation(OLR)since it can capture the moisture and cloud top temperature of deep convection associated with MJO,as well as front Walker cell.These results suggest that the lower-level moisture is more important in regulating the MJO eastward propagation,and the observed maximum MJO-filtered moisture in the middle troposphere might be a phenomenon accompanying the MJO deep convection,but not a factor controlling its eastward propagation.展开更多
Hematopoietic syndrome of acute radiation syndrome(h-ARS)is an acute illness resulted from the damage of bone marrow(BM)microenvironment after exposure to radiation.Currently,the clinical management of h-ARS is limite...Hematopoietic syndrome of acute radiation syndrome(h-ARS)is an acute illness resulted from the damage of bone marrow(BM)microenvironment after exposure to radiation.Currently,the clinical management of h-ARS is limited to medication-assisted treatment,while there is still no specific therapy for the hematopoietic injury from high-dose radiation exposure.Our study aimed to assemble biomimetic three-dimensional(3D)BM microniches by co-culture of hematopoietic stem and progenitor cells(HSPCs)and mesenchymal stem cells(MSCs)in porous,injectable and viscoelastic microscaffolds in vitro.The biodegradable BM microniches were then transplanted in vivo into the BM cavity for the treatment of h-ARS.We demonstrated that the maintenance of HSPCs was prolonged by co-culture with MSCs in the porous 3D microscaffolds with 84μm in pore diameter and 11.2 kPa in Young’s modulus compared with 2D co-culture system.Besides,the minimal effective dose and therapeutic effects of the BM microniches were investigated on a murine model of h-ARS,which showed that the intramedullary cavity-injected BM microniches could adequately promote hematopoietic reconstitution and mitigate death from acute lethal radiation with a dose as low as 1000 HSPCs.Furthermore,the mRNA expression of Notch1 and its downstream target gene Hes1 of HSPCs were increased when co-cultured with MSCs,while the Jagged1 expression of the co-cultured MSCs was upregulated,indicating the significance of Notch signaling pathway in maintenance of HSPCs.Collectively,our findings provide evidence that biomimetic and injectable 3D BM microniches could maintain HSPCs,promote hematopoiesis regeneration and alleviate post-radiation injury,which provides a promising approach to renovate conventional HSPCs transplantation for clinical treatment of blood and immune disorders.展开更多
Chlorophyll （Chl） degradation is an integral process of leaf senescence, and NYE1/SGR1 has been demonstrated as a key regulator of Chl catabolism in diverse plant species. In this study, using yeast one-hybrid scree...Chlorophyll （Chl） degradation is an integral process of leaf senescence, and NYE1/SGR1 has been demonstrated as a key regulator of Chl catabolism in diverse plant species. In this study, using yeast one-hybrid screening, we identified three abscisic acid （ABA）-responsive element （ABRE）-binding transcription factors, ABF2 （AREB1）, ABF3, and ABF4 （AREB2）, as the putative binding proteins of the NYE1 promoter. Through the transactivation analysis, electrophoretic mobility shift assay, and chromatin immunoprecipitation, we demonstrated that ABF2, ABF3, and ABF4 directly bound to and activated the NYE1 promoter in vitro and in vivo. ABA is a positive regulator of leaf senescence, and exogenously applied ABA can accelerate Chl degradation. The triple mutant of the ABFs, abf2abf3abf4, as well as two ABA-insensitive mutants, abil-1 and snrk2.2/2.3/2.6, exhibited stay-green phenotypes after ABA treatment, along with decreased induction of NYE1 and NYE2 expression. In contrast, overexpression of ABF4 accelerated Chl degradation upon ABA treatment. Interestingly, ABF2/3/4 could also activate the expression of two Chl catabolic enzyme genes, PAO and NYCl, by directly binding to their promoters. In addition, abf2abf3abf4 exhibited a functional stay-green phenotype, and senescence-associated genes （SAGs）, such as SAG29 （SWEET15）, might be directly regulated by the ABFs. Taken together, our results suggest that ABF2, ABF3, and ABF4 likely act as key regulators in mediating ABA-triggered Chl degradation and leaf senescence in general in Arabidopsis.展开更多
It is confirmed that phase homogenization is very important for improving the magnetic properties of 2:17-type Sm-Co sintered magnets,In this work,the influence of solid solution process on microstructure and magnetic...It is confirmed that phase homogenization is very important for improving the magnetic properties of 2:17-type Sm-Co sintered magnets,In this work,the influence of solid solution process on microstructure and magnetic properties of the Sm(CobalFe0.233Cu0.073Zr0.024)7.6 sintered magnets was systematically studied.With the solid-solution treating duration(tS)increasing from 0 to 4 h,intrinsic coercivity(Hcj)increases from 12.83 to 36.54 kOe,magnetic field at knee-point(Hknee)increases from2.76 to 19.14 kOe,and the maximum energy product increases from 19.79 to 29.48 MGOe.The electron probe microanalyzer results reveal that there mainly exist gray and dark regions besides"white"rare earth-rich phase,and the conte nt of Sm,Fe and Cu elements for the two kinds of regions changes a lot for the specimens,Furthermore,with tS increasing up to 4 h,the elements content deviation between the gray and dark regions becomes small gradually from 3.94 at%to 0.27 at%,7.66 at%to 0.21 at%and 7.27 at%to 0.16 at%for Sm,Fe and Cu elements,respectively.Moreover,transmission electron microscopy results show that the distribution of cell size is much more concentrated for aged specimens when tS is 4 h.It is also found that the Cu concentration at cell boundaries for the 4 h solid-solution treatment case shows relatively higher values and greater concentration gradient(1.94 at%/nm).It is verified that sufficient solution treatment duration is prerequisite to form these homogeneous microstructural features,which are the key points for obtaining both high Hcj and Hknee.展开更多
The anaerobic digestion（AD）and microbial electrolysis cell（MEC）coupled system has been proved to be a promising process for biomethane production.In this paper,it was found that by co-cultivating Geobacter with Me...The anaerobic digestion（AD）and microbial electrolysis cell（MEC）coupled system has been proved to be a promising process for biomethane production.In this paper,it was found that by co-cultivating Geobacter with Methanosarcina in an AD–MEC coupled system,methane yield was further increased by 24.1%,achieving to 360.2 m L/g-COD,which was comparable to the theoretical methane yield of an anaerobic digester.With the presence of Geobacter,the maximum chemical oxygen demand（COD）removal rate（216.8 mg COD/（L·hr））and current density（304.3 A/m3）were both increased by 1.3 and 1.8 fold compared to the previous study without Geobacter,resulting in overall energy efficiency reaching up to 74.6%.Community analysis demonstrated that Geobacter and Methanosarcina could coexist together in the biofilm,and the electrochemical activities of both were confirmed by cyclic voltammetry.Our study observed that the carbon dioxide content in total gas generated from the AD reactor with Geobacter was only half of that generated from the same reactor without Geobacter,suggesting that Methanosarcina may obtain the electron transferred from Geobacter for the reduction of carbon dioxide to methane.Taken together,Geobacter not only can improve the performance of the MEC system,but also can enhance methane production.展开更多
Tocilizumab has been reported to attenuate the“cytokine storm”in COVID-19 patients.We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit ...Tocilizumab has been reported to attenuate the“cytokine storm”in COVID-19 patients.We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment.We conducted a randomized,controlled,open-label multicenter trial among COVID-19 patients.The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone.The cure rate,changes of oxygen saturation and interference,and inflammation biomarkers were observed.Thirty-three patients were randomized to the tocilizumab group,and 32 patients to the control group.The cure rate in the tocilizumab group was higher than that in the control group,but the difference was not statistically significant(94.12%vs.87.10%,rate difference 95%CI−7.19%–21.23%,P=0.4133).The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12(P=0.0359).In moderate disease patients with bilateral pulmonary lesions,the hypoxia ameliorated earlier after tocilizumab treatment,and less patients(1/12,8.33%)needed an increase of inhaled oxygen concentration compared with the controls(4/6,66.67%;rate difference 95%CI−99.17%to−17.50%,P=0.0217).No severe adverse events occurred.More mild temporary adverse events were recorded in tocilizumab recipients(20/34,58.82%)than the controls(4/31,12.90%).Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative.For patients with bilateral pulmonary lesions and elevated IL-6 levels,tocilizumab could be recommended to improve outcome.展开更多
As the pace of urbanization is accelerating, increasing amount of floodplain has been projected as the future cities. Subsequently, urban flooding is being studied by global emergency management exports due to its inc...As the pace of urbanization is accelerating, increasing amount of floodplain has been projected as the future cities. Subsequently, urban flooding is being studied by global emergency management exports due to its increasingly significant impact on us. Some existing research on flooding emergency management based on the case-based reasoning(CBR) method have made tremendous progress, but the urban flooding case with its stratified data characteristics is required a new methodology which is different from the ones applied to flash floods. So, based on the case-based reasoning(CBR) method, this paper proposed a CPIE-CBR model with four layers, classification filtration, punctiform similarity, interval similarity and entropy weight method, to calculate the case similarity among the urban flooding case with stratified data characteristics. Then we carry out the numerical simulation with the real data about China and conduct some comparison with original ways so that we observe the validity and efficiency of our model in the end.展开更多
基金NSFC and CNS for funding the projectfunded by the National Natural Science Foundation of China(NSFC,82173500)“CNS-ZD Tizhi and Health Fund”(CNS-ZD2020-163).
文摘This cohort study was designed to explore the relationship between maternal dietary patterns(DPs)and bone health in Chinese lactating mothers and infants.We recruited 150 lactating women at 1-month postpartum.The estimated bone mineral density(eBMD)of subjects’calcanei and the information on dietary intake were collected.After 5-month follow-up,the eBMD of mothers and their infants were measured again.Factor analysis was applied to determine maternal DPs.General linear models were used to evaluate the association between maternal DPs and maternal eBMD loss or infants’eBMD.With all potential covariates adjusted,Factor 2(high intake of whole grains,tubers,mixed beans,soybeans and soybean products,seaweeds,and nuts)showed a positive association with the changes of maternal eBMD(β=0.16,95%CI:0.005,0.310).Factor 3(high intake of soft drinks,fried foods,and puffed foods)was inversely correlated with the changes of maternal eBMD(β=-0.22,95%CI:-0.44,0.00).The changes of maternal eBMD were positively associated with 6-month infants’eBMD(β=0.34,95%CI:0.017,0.652).In conclusion,Factor 2 might contribute to the maintenance of eBMD in lactating women,while Factor 3 could exacerbate maternal eBMD loss.Additionally,the changes of maternal eBMD presented a positive correlation with 6-month infants’eBMD.
文摘The past few years have witnessed enormous progresses in the development of antibody-drug conjugates(ADCs).Consequently,comprehensive analysis of ADCs in biological systems is critical in supporting discovery,development and evaluation of these agents.Liquid chromatography-mass spectrometry(LC-MS)has eme rged as a promising and versatile tool for ADC analysis across a wide range of scenarios,owing to its multiplexing ability,rapid method development,as well as the capability of analyzing a variety of targets ranging from small-molecule payloads to the intact protein with a high,molecular resolution.However,despite this tremendous potential,challenges persist due to the high complexity in both the ADC molecules and the related biological systems.This review summarizes the up-to-date LC-MS-based strategies in ADC analysis and discusses the challenges and opportunities in this rapidly-evolving field.
基金National Key Basic Research and Development Program(973 Program)(2013CB531705).
文摘Blood-arresting Formula on simvastatin-induced zebrafish hemorrhage model compared with that of the Heat-clearing and Blood-cooling Formula.Methods:AB strain wild type zebrafish were treated with 0.5 mM simvastatin for 24 hours to establish the zebrafish hemorrhage model.Under strictly blind experimental conditions,the zebrafish were then treated with experimental agents in different concentration within the maximum non-lethal dose.The intervention effect of the Spleen-invigorating,Qi-replenishing and Blood-arresting Formula was comprehensively assessed by examining the main observational parameters such as the bleeding reduction rate and hemostatic rate while referring to the additional parameters such as blood flow,improvement rate of blood flow,velocity of movement,improvement rate of motion under spleen-qi deficiency.Results:Hemostatic effect:The bleeding rate and hemostatic rate in the zebrafish were respectively,30%,15%,45%,40%and 60%,80%,40%,47%when equal concentration of 500 mg/mL,1000 mg/mL were used.This showed that the experimental herbs B1 was superior to B2 in decreasing the bleeding rate and improving hemostatic effect in the zebrafish.Improvement of blood flow:With equal concentration,the experimental herb B1 was superior to B2 in increasing the blood flow and improvement rate of blood flow in hemorrhagic zebrafish.Promotion of the improvement of motion:With equal concentration of 500 mg/mL and 1000 mg/mL,the experimental herb B1 was superior to B2 in promoting the velocity of motion in the zebrafish and promoting the improvement rate of motion.Conclusion:The manifestations of simvastatin-induced zebrafish hemorrhage are basically similar to that of failure of the spleen to control blood in human beings.The Spleeninvigorating,Qi-replenishing and Blood-arresting Formula has good hemostatic effect on simvastatin-induced hemorrhage in the zebrafish.It also boasts the functions of improving blood flow and velocity of motion in the hemorrhagic zebrafish.Such a conclusion provides the experimental basis for the treatment of the syndrome of failure of the spleen to control blood by this formula.
基金Acknowledgments The authors thank the National Natural Science Foundation of China （81302646）, Natural Science Foundation of Zhejiang Province （LQ13H300002）, Science Technology Department of Zhejiang Province （2015F50015） and Health and Family Planning commission of Zhejiang Province （XKQ-010-001 and 2013KYB070） for financial support.
文摘Alzheimer＇s disease, the leading cause of dementia in the elderly, is a complex neurodegenerative disorder which leads to a progressive decline in cognitive functions. A rapid screening model is highly demanded for identification and evaluation of novel anti-Alzheimer＇s disease drugs from a large numbers of compounds. Until now, numerous studies utilized zebrafish model for drug discovery. Since aluminum can induce a similar biological activity in zebrafish as in Alzheimer patients, in this study, we developed a novel animal model using 3 to 5 day post-fertilization larval zebrafish by optimizing the doses and duration of aluminum chloride exposure. Six anti-Alzheimer＇s disease drugs with a variety of mechanisms were tested to validate the newly developed zebrafish model. Importantly, Rivastigmine, ThT, Flurbiprofen and AM-117 could increase the value of Dyskinesia Recovery Rate by 53.4-64%, 169.4-200%, 54.5-96% and 70.9-121%, respectively. Rivastigmine, Memantine, ThT, Flurbiprofen, Rosiglitazone and AM-117 improved the value of Response Efficiency by 86.6-175.1%, 28.2-66.6%, 127.2-236.5%, 118.3-323.7%, 26.6-140.8% and 70.2-161.4%, respectively. Our results suggest that the zebrafish model developed in this study could be a useful tool for high throughput screening of potential novel anti-Alzheimer＇s disease leading compounds targeting acetylcholinesterase, N-methyl-D-aspartic acid receptor, γ-secretase, peroxisome proliferator-activated receptor-γand amyloid-β.
文摘The emergence of new technologies such as GPS,cellphone,Bluetooth device,etc.offers opportunities for collecting high-fidelity temporal-spatial travel data in a cost-effective manner.With the vehicle trajectory data achieved from a smartphone app Metropia,this study targets on exploring the trajectory data and designing the measurements of the driving pattern.Metropia is a recently available mobile traffic app that uses prediction and coordinating technology combined with user rewards to incentivize drivers to cooperate,balance traffic load on the network,and reduce traffic congestion.Speed and celeration(acceleration and deceleration)are obtained from the Metropia platform directly and parameterized as individual and system measurements related to traffic,spatial and temporal conditions.A case study is provided in this paper to demonstrate the feasibility of this approach utilizing the trajectory data from the actual app usage.The driving behaviors at both individual and system levels are quantified from the microscopic speed and celeration records.The results from this study reveal distinct driving behavior pattern and shed lights for further opportunities to identify behavior characteristics beyond safety and environmental considerations.
基金National Natural Science Foundation of China(Nos.82270223,82170209,and 82100230)Anhui Provincial Key Research and Development Project(No.2022e07020015)+1 种基金Anhui Health Research Project(No.AHWJ2022a 011)Fundamental Research Funds for the Central Universities(Nos.WK9110000204,and WK9110000168)
文摘Background:With an increasing number of patients with hematological malignancies being treated with umbilical cord blood transplantation(UCBT),the correlation between immune reconstitution(IR)after UCBT and graft-versus-host disease(GVHD)has been reported successively,but reports on double-negative T(DNT)cell reconstitution and its association with acute GVHD(aGVHD)after UCBT are lacking.Methods:A population-based observational study was conducted among 131 patients with hematological malignancies who underwent single-unit UCBT as their first transplant at the Department of Hematology,the First Affiliated Hospital of USTC,between August 2018 and June 2021.IR differences were compared between the patients with and without aGVHD.Results:The absolute number of DNT cells in the healthy Chinese population was 109(70-157)/μL,accounting for 5.82(3.98-8.19)%of lymphocytes.DNT cells showed delayed recovery and could not reach their normal levels even one year after transplantation.Importantly,the absolute number and percentage of DNT cells were significantly higher in UCBT patients without aGVHD than in those with aGVHD within one year(F=4.684,P=0.039 and F=5.583,P=0.026,respectively).In addition,the number of DNT cells in the first month after transplantation decreased significantly with the degree of aGVHD increased,and faster DNT cell reconstitution in the first month after UCBT was an independent protective factor for aGVHD(HR=0.46,95%confidence interval[CI]:0.23-0.93;P=0.031).Conclusions:Compared to the number of DNT cells in Chinese healthy people,the reconstitution of DNT cells in adults with hematological malignancies after UCBT was slow.In addition,the faster reconstitution of DNT cells in the early stage after transplantation was associated with a lower incidence of aGVHD.
基金supported by grants from the National Key Research andDevelopmenttProgram(2018YFA0900402,2021YFA0910501)the National Natural Science Foundation of China(21921003,32270070,32270050,U22A20451)+1 种基金the Funding of Innovative Research Team of High-Level Local Universities in Shanghai and a key laboratory program of the Education Commission of Shanghai Municipality(ZDSYS14005)West Light Foundation of The Chinese Academy of Sciences(xbzg-zdsys-202105).
文摘Comprehensive Summary HpnG plays a crucial role in the production of ribosylhopane,a key intermediate in the biosynthesis of bacteriohopanepolyol.Despite early extensive studies,the precise function of HpnG has remained elusive.Here,we report functional characterization of HpnG as a purine nucleoside phosphorylase,which converts adenosylhopane to phosphoribosylhopane in the presence of phosphate.HpnG demonstrates broad substrate specificity and impressive stability,making it a valuable enzymatic tool for applications in nucleoside processing and related biotechnology.
基金National Natural Science Foundation of China (22135007 and 22361132545)National Key Research and Development Program of China funded by MOST (2019YFA0705900)Sichuan Science and Technology Program (2023NSFSC0990)。
文摘Organic semiconductors play a pivotal role in the development of various organic opto-electronic devices, encompassing organic light-emitting diodes (OLEDs), organic field-effect transistors(OFETs), organic solar cells (OSCs), organic photodetectors (OPDs),etc.[1]. Material scientists continually refine the chemical structures of organic semiconductors to optimize their opto-electronic properties and thin film morphology, thereby enhancing device performance [2]. Among the diverse array of functional groups available for modification, fluorine stands out due to its minimal atomic radius and maximal electronegativity.
基金Supported by the National Natural Science Foundation of China(41975090 and 42075077)Natural Science Foundation of Hunan Province,China(2022JJ20043).
文摘In this study,driven by ERA5 reanalysis data,the Weather Research and Forecasting(WRF)version 4.0 was used to investigate the eastward propagation of the Madden-Julian oscillation(MJO)in the tropical atmosphere during December-February(DJF)of 2007/2008.The experiment with 11 cumulus parameterization schemes respectively shows that the Grell 3D scheme is one of several worse ones in describing MJO activities.In addition,still by use of the Grell 3D scheme,four nudging assimilation experiments for water vapor in all model vertical layers(Ndg_all),lower layers(Ndg_low),middle layers(Ndg_mid),and upper layers(Ndg_upp)were conducted.It is found that when the water vapor in the model approaches to the observed value,the model performance for MJO activities is improved greatly.Among the four nudging simulations,Ndg_all certainly performs best.Although Ndg_mid is important for the MJO-filtered profiles related to moisture,Ndg_low and Ndg_upp exhibit superiority to Ndg_mid in simulating MJO eastward propagation.Ndg_low has advantages when MJO features are represented by zonal wind at 850 hPa and precipitation because the lower-level MJO-filtered moisture is conducive to the existence of lower-level condensational heating to the east of the MJO convective center.Ndg_upp performs better when describing the MJO eastward propagation features by outgoing longwave radiation(OLR)since it can capture the moisture and cloud top temperature of deep convection associated with MJO,as well as front Walker cell.These results suggest that the lower-level moisture is more important in regulating the MJO eastward propagation,and the observed maximum MJO-filtered moisture in the middle troposphere might be a phenomenon accompanying the MJO deep convection,but not a factor controlling its eastward propagation.
文摘Hematopoietic syndrome of acute radiation syndrome(h-ARS)is an acute illness resulted from the damage of bone marrow(BM)microenvironment after exposure to radiation.Currently,the clinical management of h-ARS is limited to medication-assisted treatment,while there is still no specific therapy for the hematopoietic injury from high-dose radiation exposure.Our study aimed to assemble biomimetic three-dimensional(3D)BM microniches by co-culture of hematopoietic stem and progenitor cells(HSPCs)and mesenchymal stem cells(MSCs)in porous,injectable and viscoelastic microscaffolds in vitro.The biodegradable BM microniches were then transplanted in vivo into the BM cavity for the treatment of h-ARS.We demonstrated that the maintenance of HSPCs was prolonged by co-culture with MSCs in the porous 3D microscaffolds with 84μm in pore diameter and 11.2 kPa in Young’s modulus compared with 2D co-culture system.Besides,the minimal effective dose and therapeutic effects of the BM microniches were investigated on a murine model of h-ARS,which showed that the intramedullary cavity-injected BM microniches could adequately promote hematopoietic reconstitution and mitigate death from acute lethal radiation with a dose as low as 1000 HSPCs.Furthermore,the mRNA expression of Notch1 and its downstream target gene Hes1 of HSPCs were increased when co-cultured with MSCs,while the Jagged1 expression of the co-cultured MSCs was upregulated,indicating the significance of Notch signaling pathway in maintenance of HSPCs.Collectively,our findings provide evidence that biomimetic and injectable 3D BM microniches could maintain HSPCs,promote hematopoiesis regeneration and alleviate post-radiation injury,which provides a promising approach to renovate conventional HSPCs transplantation for clinical treatment of blood and immune disorders.
文摘Chlorophyll （Chl） degradation is an integral process of leaf senescence, and NYE1/SGR1 has been demonstrated as a key regulator of Chl catabolism in diverse plant species. In this study, using yeast one-hybrid screening, we identified three abscisic acid （ABA）-responsive element （ABRE）-binding transcription factors, ABF2 （AREB1）, ABF3, and ABF4 （AREB2）, as the putative binding proteins of the NYE1 promoter. Through the transactivation analysis, electrophoretic mobility shift assay, and chromatin immunoprecipitation, we demonstrated that ABF2, ABF3, and ABF4 directly bound to and activated the NYE1 promoter in vitro and in vivo. ABA is a positive regulator of leaf senescence, and exogenously applied ABA can accelerate Chl degradation. The triple mutant of the ABFs, abf2abf3abf4, as well as two ABA-insensitive mutants, abil-1 and snrk2.2/2.3/2.6, exhibited stay-green phenotypes after ABA treatment, along with decreased induction of NYE1 and NYE2 expression. In contrast, overexpression of ABF4 accelerated Chl degradation upon ABA treatment. Interestingly, ABF2/3/4 could also activate the expression of two Chl catabolic enzyme genes, PAO and NYCl, by directly binding to their promoters. In addition, abf2abf3abf4 exhibited a functional stay-green phenotype, and senescence-associated genes （SAGs）, such as SAG29 （SWEET15）, might be directly regulated by the ABFs. Taken together, our results suggest that ABF2, ABF3, and ABF4 likely act as key regulators in mediating ABA-triggered Chl degradation and leaf senescence in general in Arabidopsis.
基金Project supported by the National Key Research and Development Program of China(2016YFB0700903)the National Natural Science Foundation of China(5159088251401054)。
文摘It is confirmed that phase homogenization is very important for improving the magnetic properties of 2:17-type Sm-Co sintered magnets,In this work,the influence of solid solution process on microstructure and magnetic properties of the Sm(CobalFe0.233Cu0.073Zr0.024)7.6 sintered magnets was systematically studied.With the solid-solution treating duration(tS)increasing from 0 to 4 h,intrinsic coercivity(Hcj)increases from 12.83 to 36.54 kOe,magnetic field at knee-point(Hknee)increases from2.76 to 19.14 kOe,and the maximum energy product increases from 19.79 to 29.48 MGOe.The electron probe microanalyzer results reveal that there mainly exist gray and dark regions besides"white"rare earth-rich phase,and the conte nt of Sm,Fe and Cu elements for the two kinds of regions changes a lot for the specimens,Furthermore,with tS increasing up to 4 h,the elements content deviation between the gray and dark regions becomes small gradually from 3.94 at%to 0.27 at%,7.66 at%to 0.21 at%and 7.27 at%to 0.16 at%for Sm,Fe and Cu elements,respectively.Moreover,transmission electron microscopy results show that the distribution of cell size is much more concentrated for aged specimens when tS is 4 h.It is also found that the Cu concentration at cell boundaries for the 4 h solid-solution treatment case shows relatively higher values and greater concentration gradient(1.94 at%/nm).It is verified that sufficient solution treatment duration is prerequisite to form these homogeneous microstructural features,which are the key points for obtaining both high Hcj and Hknee.
基金supported by the National Natural Science Foundation of China(Nos.31270166,31300116 and 51408580)the Chinese Academy of Sciences foundation(Nos.Y4C5011100 and KLCAS-2013-03)
文摘The anaerobic digestion（AD）and microbial electrolysis cell（MEC）coupled system has been proved to be a promising process for biomethane production.In this paper,it was found that by co-cultivating Geobacter with Methanosarcina in an AD–MEC coupled system,methane yield was further increased by 24.1%,achieving to 360.2 m L/g-COD,which was comparable to the theoretical methane yield of an anaerobic digester.With the presence of Geobacter,the maximum chemical oxygen demand（COD）removal rate（216.8 mg COD/（L·hr））and current density（304.3 A/m3）were both increased by 1.3 and 1.8 fold compared to the previous study without Geobacter,resulting in overall energy efficiency reaching up to 74.6%.Community analysis demonstrated that Geobacter and Methanosarcina could coexist together in the biofilm,and the electrochemical activities of both were confirmed by cyclic voltammetry.Our study observed that the carbon dioxide content in total gas generated from the AD reactor with Geobacter was only half of that generated from the same reactor without Geobacter,suggesting that Methanosarcina may obtain the electron transferred from Geobacter for the reduction of carbon dioxide to methane.Taken together,Geobacter not only can improve the performance of the MEC system,but also can enhance methane production.
基金This work was supported by the Department of Science and Technology of Anhui Province and Health Commission of Anhui Province(No.202004a07020001)the China National Center for Biotechnology Development(No.2020YFC0843800).
文摘Tocilizumab has been reported to attenuate the“cytokine storm”in COVID-19 patients.We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment.We conducted a randomized,controlled,open-label multicenter trial among COVID-19 patients.The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone.The cure rate,changes of oxygen saturation and interference,and inflammation biomarkers were observed.Thirty-three patients were randomized to the tocilizumab group,and 32 patients to the control group.The cure rate in the tocilizumab group was higher than that in the control group,but the difference was not statistically significant(94.12%vs.87.10%,rate difference 95%CI−7.19%–21.23%,P=0.4133).The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12(P=0.0359).In moderate disease patients with bilateral pulmonary lesions,the hypoxia ameliorated earlier after tocilizumab treatment,and less patients(1/12,8.33%)needed an increase of inhaled oxygen concentration compared with the controls(4/6,66.67%;rate difference 95%CI−99.17%to−17.50%,P=0.0217).No severe adverse events occurred.More mild temporary adverse events were recorded in tocilizumab recipients(20/34,58.82%)than the controls(4/31,12.90%).Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative.For patients with bilateral pulmonary lesions and elevated IL-6 levels,tocilizumab could be recommended to improve outcome.
基金Supported by Beijing Natural Science Foundation(9162003)
文摘As the pace of urbanization is accelerating, increasing amount of floodplain has been projected as the future cities. Subsequently, urban flooding is being studied by global emergency management exports due to its increasingly significant impact on us. Some existing research on flooding emergency management based on the case-based reasoning(CBR) method have made tremendous progress, but the urban flooding case with its stratified data characteristics is required a new methodology which is different from the ones applied to flash floods. So, based on the case-based reasoning(CBR) method, this paper proposed a CPIE-CBR model with four layers, classification filtration, punctiform similarity, interval similarity and entropy weight method, to calculate the case similarity among the urban flooding case with stratified data characteristics. Then we carry out the numerical simulation with the real data about China and conduct some comparison with original ways so that we observe the validity and efficiency of our model in the end.
