In the selective oxidation of biomass-based 1,2-propanediol(PDO)with oxygen as the terminal oxidant,it is challenging to improve the lactic acid(LA)selectivity for nonnoble metal nanoparticles(NPs)due to their limited...In the selective oxidation of biomass-based 1,2-propanediol(PDO)with oxygen as the terminal oxidant,it is challenging to improve the lactic acid(LA)selectivity for nonnoble metal nanoparticles(NPs)due to their limited oxygen reduction rate and easy C-C cleavage.Given the high economic feasibility of nonnoble metals,i.e.,Cu,in this work,copper and nitrogen codoped porous carbon nanosheets encapsulating ultrafine Cu nanoparticles(Cu@Cu-N-C)were developed to realize highly selective of PDO oxidation to LA.The carbon-encapsulated ultrasmall Cu^(0)NPs in Cu@Cu-N-C have high PDO dehydrogenation activity while N-coordinated Cu(Cu-N)sites are responsible for the high oxygen reduction efficacy.Therefore,the performance of catalytic PDO conversion to LA is optimized by a proposed pathway of PDO→hydroxylacetone→lactaldehyde→LA.Specifically,the enhanced LA selectivity is 88.5%,and the PDO conversion is up to 75.1%in an O_(2)-pressurized reaction system(1.0 MPa O_(2)),superior to other Cu-based catalysts,while in a milder nonpressurized system(O_(2)flow rate of 100 mL min-1),a remarkable LA selectivity(94.2%)is obtained with 39.8%PDO conversion,2.2 times higher than that of supported Au nanoparticles(1%Au/C).Moreover,carbon encapsulation offers Cu@Cu-N-C with strong leaching resistance for better recycling.展开更多
Active suspension systems(ASSs)have been proposed and developed for a few decades,and have now once again become a thriving topic in both academia and industry,due to the high demand for driving comfort and safety and...Active suspension systems(ASSs)have been proposed and developed for a few decades,and have now once again become a thriving topic in both academia and industry,due to the high demand for driving comfort and safety and the compatibility of ASSs with vehicle electrification and autonomy.Existing review papers on ASSs mainly cover dynamics modeling and robust control;however,the gap between academic research outcomes and industrial application requirements has not yet been bridged,hindering most ASS research knowledge from being transferred to vehicle companies.This paper comprehensively reviews advances in ASSs for road vehicles,with a focus on hardware structures and control strategies.In particular,state-of-the-art ASSs that have been recently adopted in production cars are discussed in detail,including the representative solutions of Mercedes active body control(ABC)and Audi predictive active suspension;novel concepts that could become alternative candidates are also introduced,including series active variable geometry suspension,and the active wheel-alignment system.ASSs with compact structure,small mass increment,low power consumption,high-frequency response,acceptable economic costs,and high reliability are more likely to be adopted by car manufacturers.In terms of control strategies,the development of future ASSs aims not only to stabilize the chassis attitude and attenuate the chassis vibration,but also to enable ASSs to cooperate with other modules(e.g.,steering and braking)and sensors(e.g.,cameras)within a car,and even with high-level decision-making(e.g.,reference driving speed)in the overall transportation system-strategies that will be compatible with the rapidly developing electric and autonomous vehicles.展开更多
Cardiovascular disease is the leading cause of global mortality,with anticoagulant therapy being the main prevention and treatment strategy.Recombinant hirudin(r-hirudin)is a direct thrombin inhibitor that can potenti...Cardiovascular disease is the leading cause of global mortality,with anticoagulant therapy being the main prevention and treatment strategy.Recombinant hirudin(r-hirudin)is a direct thrombin inhibitor that can potentially prevent thrombosis via subcutaneous(SC)and intravenous(IV)administration,but there is a risk of haemorrhage via SC and IV.Thus,microneedle(MN)provides painless and sanitary alternatives to syringes and oral administration.However,the current technological process for the micro mould is complicated and expensive.The micro mould obtained via three-dimensional(3D)printing is expected to save time and cost,as well as provide a diverse range of MNs.Therefore,we explored a method for MNs array model production based on 3D printing and translate it to micro mould that can be used for fabrication of dissolving MNs patch.The results show that r-hirudin-loaded and hyaluronic acid(HA)-based MNs can achieve transdermal drug delivery and exhibit significant potential in the prevention of thromboembolic disease without bleeding in animal models.These results indicate that based on 3D printing technology,MNs combined with r-hirudin are expected to achieve diverse customizableMNs and thus realize personalized transdermal anticoagulant delivery for minimally invasive and long-term treatment of thrombotic disease.展开更多
[Objectives] This study was conducted to investigate the effects of different treatments on rooting and germination of Paeonia rockii T. Hong et J.J.Li seeds. [Methods] Different stratification time and temperatures a...[Objectives] This study was conducted to investigate the effects of different treatments on rooting and germination of Paeonia rockii T. Hong et J.J.Li seeds. [Methods] Different stratification time and temperatures and different GA_3 concentrations and treatment time were set to screen the optimum treatment method for promoting seed rooting and germination. [Results] The rooting rate was the highest when the seeds were subjected to 30 d of stratification treatment in an incubator at 25℃, and treated with 300 mg/L GA_3 for 24 h. Soaking the seeds with 300 mg/L GA_3 for 24 h combined with 30 d of stratification treatment was most beneficial to germination, and the germination rate was over 90%. [Conclusions] This study provides technical guidance and basic information for the rooting and germination of P. rockii seeds.展开更多
[Objective] This study aimed to identify a maunanase-producing strain isolated from soil. [Method] With kanjac powder as the substrate, a man- nanase-producing dominant strain was iselated from the soil samples collec...[Objective] This study aimed to identify a maunanase-producing strain isolated from soil. [Method] With kanjac powder as the substrate, a man- nanase-producing dominant strain was iselated from the soil samples collected from Kunyu Mountain by using plate selection method. Sequence analysis of the 16SrDNA fragment of the strain was conducted, and the strain was identified as Bacillus subtilis. Fermentation conditions and enzymatic characteristics were studied preliminarily. [ Result] Experimental result showed that enzyme yield of this strain was different in different medium and in the same medium at different tempera- ture. Enzyme yield of this strain in LB medium was higher when incubated at 27 ℃ than at 30 ℃ ; however, incubation at 30 ℃ was more conducive to the enzyme production than incubation at 27 ℃ in SOC medium. The optimal reaction pH was 7.0 and the optimal reaction temperature was 55 ℃ for enzyme production of this strain. When the temperature was above 55 ℃, enzyme activity declined sharply with the raise of temperature. Under the optimum conditions, enzyme activity could achieve 95.3 U. [ Conclusion] This study provided reference for the industrial application of degradation products of mannan.展开更多
The tremendous public health and economic impact of coronavirus disease 2019(COVID-19), caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2), has become a huge challenge globally. There is increasing e...The tremendous public health and economic impact of coronavirus disease 2019(COVID-19), caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2), has become a huge challenge globally. There is increasing evidence that SARS-CoV-2 induces intestinal infections. Type Ⅲ interferon(IFN-λ) has an antiviral role in intestinal infection, with focused, long-lasting, and non-inflammatory characteristics. This review presents a summary of the structure of SARSCoV-2, including its invasion and immune escape mechanisms. Emphasis was placed on the gastrointestinal impact of SARS-CoV-2, including changes to the intestinal microbiome, activation of immune cells, and inflammatory responses.We also describe the comprehensive functions of IFN-λ in anti-enteric SARS-CoV-2 infection, and discuss the potential application of IFN-λ as a therapeutic agent for COVID-19 with intestinal symptoms.展开更多
Aiming at the problem that the existing models have a poor segmentation effect on imbalanced data sets with small-scale samples,a bilateral U-Net network model with a spatial attention mechanism is designed.The model ...Aiming at the problem that the existing models have a poor segmentation effect on imbalanced data sets with small-scale samples,a bilateral U-Net network model with a spatial attention mechanism is designed.The model uses the lightweight MobileNetV2 as the backbone network for feature hierarchical extraction and proposes an Attentive Pyramid Spatial Attention(APSA)module compared to the Attenuated Spatial Pyramid module,which can increase the receptive field and enhance the information,and finally adds the context fusion prediction branch that fuses high-semantic and low-semantic prediction results,and the model effectively improves the segmentation accuracy of small data sets.The experimental results on the CamVid data set show that compared with some existing semantic segmentation networks,the algorithm has a better segmentation effect and segmentation accuracy,and its mIOU reaches 75.85%.Moreover,to verify the generality of the model and the effectiveness of the APSA module,experiments were conducted on the VOC 2012 data set,and the APSA module improved mIOU by about 12.2%.展开更多
Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with ...Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.展开更多
7-Ketophytosterols are the major oxidation products of phytosterols in foods, which have been associated with atherosclerosis. However, their absorption mechanism remains unclear. The aim of our work was to investigat...7-Ketophytosterols are the major oxidation products of phytosterols in foods, which have been associated with atherosclerosis. However, their absorption mechanism remains unclear. The aim of our work was to investigate the absorption mechanism of 7-ketophytosterols and their effects on the cholesterol transport using Caco-2 cell model. The absorption percentage of 7-ketositosterol and 7-ketocampesterol was 1.16%-1.68% and 1.18%-2.23% respectively in the Caco-2 model, which is higher than that of their parent phytosterols, but lower than cholesterol-d7. The apparent permeability of 7-ketositosterol and 7-ketocampesterol at 30 μmol/L in the basolateral(BL)-to-apical(AP)direction were 0.42-and 0.55-fold of that in the AP-to-BL direction, indicating an active intake in the permeation mechanism of 7-ketophytosterols. Ezetimibe could significantly inhibit the transport of 7-ketophytosterols(P < 0.05), which means that their transport depends on niemann-pick c1-like 1(NPC1L1)protein. The transport of cholesterol-d7 was significantly inhibited by 7-ketophytosterols(P < 0.05). Taken together, this study deepened our understanding of the absorption mechanism of common food-born 7-ketophytosterols and provides useful information on the inhibition of 7-ketophytosterols absorption.展开更多
In the rice-wheat rotation system,biochar(BC)can be applied at the initiation of the rice or wheat season.Here,we compared the effects of BC that were applied at two different crop seasons on wheat production,quality,...In the rice-wheat rotation system,biochar(BC)can be applied at the initiation of the rice or wheat season.Here,we compared the effects of BC that were applied at two different crop seasons on wheat production,quality,and soil profile properties in a rice-wheat rotation system with nitrogen(N)fertilizer applied at 280 kg/ha rate.Results showed that both wheat grain production and N recovery use efficiency were influenced by BC applied at two crop seasons.Biochar application did not affect the total non-essential amino-acid,but when applied during wheat season,BC significantly(p<0.05)increased total essential amino acid in grain by 12.3%,particularly for the valine(+48.2%),methionine(+43.8%),and isoleucine(+10.3%).We found that BC significantly(p<0.05)decreased the pH of soil at 0–6 cm and 20–30 cm by 0.14–0.18 and 0.05–0.08 units,respectively.The NH4+-N content of the whole observed soil profile were reduced by BC application,however,the effect of BC on NO3–-N content varied with the application season and profile depth.Interestingly,BC applied at wheat and rice season significantly(p<0.05)improved topsoil N contents by 48.4%and 19.7%,respectively.In addition,data suggested that BC applied during wheat season performed better in enhancing soil available phosphorus,potassium,and organic matter contents.In conclusion,we suggest that the optimum application time of BC for enhancing crop production and quality(take amino-acid content for example)and improving soil fertility is at the initiation of the wheat season.展开更多
Adult tendon stem/progenitor cells(TSPCs)are essential for tendon maintenance,regeneration,and repair,yet they become susceptible to senescence with age,impairing the self-healing capacity of tendons.In this study,we ...Adult tendon stem/progenitor cells(TSPCs)are essential for tendon maintenance,regeneration,and repair,yet they become susceptible to senescence with age,impairing the self-healing capacity of tendons.In this study,we employ a recently developed deep-learning-based efficacy prediction system to screen potential stemness-promoting and senescence-inhibiting drugs from natural products using the transcriptional signatures of stemness.The top-ranked candidate,prim-O-glucosylcimifugin(POG),a saposhnikovia root extract,could ameliorate TPSC senescent phenotypes caused by long-term passage and natural aging in rats and humans,as well as restore the self-renewal and proliferative capacities and tenogenic potential of aged TSPCs.In vivo,the systematic administration of POG or the local delivery of POG nanoparticles functionally rescued endogenous tendon regeneration and repair in aged rats to levels similar to those of normal animals.Mechanistically,POG protects TSPCs against functional impairment during both passage-induced and natural aging by simultaneously suppressing nuclear factor-κB and decreasing mTOR signaling with the induction of autophagy.Thus,the strategy of pharmacological intervention with the deep learning-predicted compound POG could rejuvenate aged TSPCs and improve the regenerative capacity of aged tendons.展开更多
In order to effectively solve the problems of low accuracy,large amount of computation and complex logic of deep learning algorithms in behavior recognition,a kind of behavior recognition based on the fusion of 3 dime...In order to effectively solve the problems of low accuracy,large amount of computation and complex logic of deep learning algorithms in behavior recognition,a kind of behavior recognition based on the fusion of 3 dimensional batch normalization visual geometry group(3D-BN-VGG)and long short-term memory(LSTM)network is designed.In this network,3D convolutional layer is used to extract the spatial domain features and time domain features of video sequence at the same time,multiple small convolution kernels are stacked to replace large convolution kernels,thus the depth of neural network is deepened and the number of network parameters is reduced.In addition,the latest batch normalization algorithm is added to the 3-dimensional convolutional network to improve the training speed.Then the output of the full connection layer is sent to LSTM network as the feature vectors to extract the sequence information.This method,which directly uses the output of the whole base level without passing through the full connection layer,reduces the parameters of the whole fusion network to 15324485,nearly twice as much as those of 3D-BN-VGG.Finally,it reveals that the proposed network achieves 96.5%and 74.9%accuracy in the UCF-101 and HMDB-51 respectively,and the algorithm has a calculation speed of 1066 fps and an acceleration ratio of 1,which has a significant predominance in velocity.展开更多
基金supported by the National Natural Science Foundation of China(32371407,82160421)the Natural Science Foundation of Jiangsu Province(BK20211322)。
文摘In the selective oxidation of biomass-based 1,2-propanediol(PDO)with oxygen as the terminal oxidant,it is challenging to improve the lactic acid(LA)selectivity for nonnoble metal nanoparticles(NPs)due to their limited oxygen reduction rate and easy C-C cleavage.Given the high economic feasibility of nonnoble metals,i.e.,Cu,in this work,copper and nitrogen codoped porous carbon nanosheets encapsulating ultrafine Cu nanoparticles(Cu@Cu-N-C)were developed to realize highly selective of PDO oxidation to LA.The carbon-encapsulated ultrasmall Cu^(0)NPs in Cu@Cu-N-C have high PDO dehydrogenation activity while N-coordinated Cu(Cu-N)sites are responsible for the high oxygen reduction efficacy.Therefore,the performance of catalytic PDO conversion to LA is optimized by a proposed pathway of PDO→hydroxylacetone→lactaldehyde→LA.Specifically,the enhanced LA selectivity is 88.5%,and the PDO conversion is up to 75.1%in an O_(2)-pressurized reaction system(1.0 MPa O_(2)),superior to other Cu-based catalysts,while in a milder nonpressurized system(O_(2)flow rate of 100 mL min-1),a remarkable LA selectivity(94.2%)is obtained with 39.8%PDO conversion,2.2 times higher than that of supported Au nanoparticles(1%Au/C).Moreover,carbon encapsulation offers Cu@Cu-N-C with strong leaching resistance for better recycling.
基金supported by the Imperial College Research Fellowship(ICRF 2022-2026)。
文摘Active suspension systems(ASSs)have been proposed and developed for a few decades,and have now once again become a thriving topic in both academia and industry,due to the high demand for driving comfort and safety and the compatibility of ASSs with vehicle electrification and autonomy.Existing review papers on ASSs mainly cover dynamics modeling and robust control;however,the gap between academic research outcomes and industrial application requirements has not yet been bridged,hindering most ASS research knowledge from being transferred to vehicle companies.This paper comprehensively reviews advances in ASSs for road vehicles,with a focus on hardware structures and control strategies.In particular,state-of-the-art ASSs that have been recently adopted in production cars are discussed in detail,including the representative solutions of Mercedes active body control(ABC)and Audi predictive active suspension;novel concepts that could become alternative candidates are also introduced,including series active variable geometry suspension,and the active wheel-alignment system.ASSs with compact structure,small mass increment,low power consumption,high-frequency response,acceptable economic costs,and high reliability are more likely to be adopted by car manufacturers.In terms of control strategies,the development of future ASSs aims not only to stabilize the chassis attitude and attenuate the chassis vibration,but also to enable ASSs to cooperate with other modules(e.g.,steering and braking)and sensors(e.g.,cameras)within a car,and even with high-level decision-making(e.g.,reference driving speed)in the overall transportation system-strategies that will be compatible with the rapidly developing electric and autonomous vehicles.
基金supported by the National Natural Science Foundation of China (NSFC 81902995)the project funded by China Postdoctoral Science Foundation (2018M641936)
文摘Cardiovascular disease is the leading cause of global mortality,with anticoagulant therapy being the main prevention and treatment strategy.Recombinant hirudin(r-hirudin)is a direct thrombin inhibitor that can potentially prevent thrombosis via subcutaneous(SC)and intravenous(IV)administration,but there is a risk of haemorrhage via SC and IV.Thus,microneedle(MN)provides painless and sanitary alternatives to syringes and oral administration.However,the current technological process for the micro mould is complicated and expensive.The micro mould obtained via three-dimensional(3D)printing is expected to save time and cost,as well as provide a diverse range of MNs.Therefore,we explored a method for MNs array model production based on 3D printing and translate it to micro mould that can be used for fabrication of dissolving MNs patch.The results show that r-hirudin-loaded and hyaluronic acid(HA)-based MNs can achieve transdermal drug delivery and exhibit significant potential in the prevention of thromboembolic disease without bleeding in animal models.These results indicate that based on 3D printing technology,MNs combined with r-hirudin are expected to achieve diverse customizableMNs and thus realize personalized transdermal anticoagulant delivery for minimally invasive and long-term treatment of thrombotic disease.
基金Supported by the Cooperative Project Between the People's Republic of China and the Republic of Korea
文摘[Objectives] This study was conducted to investigate the effects of different treatments on rooting and germination of Paeonia rockii T. Hong et J.J.Li seeds. [Methods] Different stratification time and temperatures and different GA_3 concentrations and treatment time were set to screen the optimum treatment method for promoting seed rooting and germination. [Results] The rooting rate was the highest when the seeds were subjected to 30 d of stratification treatment in an incubator at 25℃, and treated with 300 mg/L GA_3 for 24 h. Soaking the seeds with 300 mg/L GA_3 for 24 h combined with 30 d of stratification treatment was most beneficial to germination, and the germination rate was over 90%. [Conclusions] This study provides technical guidance and basic information for the rooting and germination of P. rockii seeds.
基金Supported by Science and Technology Project from Binzhou Medical College(BY2007KJ14)
文摘[Objective] This study aimed to identify a maunanase-producing strain isolated from soil. [Method] With kanjac powder as the substrate, a man- nanase-producing dominant strain was iselated from the soil samples collected from Kunyu Mountain by using plate selection method. Sequence analysis of the 16SrDNA fragment of the strain was conducted, and the strain was identified as Bacillus subtilis. Fermentation conditions and enzymatic characteristics were studied preliminarily. [ Result] Experimental result showed that enzyme yield of this strain was different in different medium and in the same medium at different tempera- ture. Enzyme yield of this strain in LB medium was higher when incubated at 27 ℃ than at 30 ℃ ; however, incubation at 30 ℃ was more conducive to the enzyme production than incubation at 27 ℃ in SOC medium. The optimal reaction pH was 7.0 and the optimal reaction temperature was 55 ℃ for enzyme production of this strain. When the temperature was above 55 ℃, enzyme activity declined sharply with the raise of temperature. Under the optimum conditions, enzyme activity could achieve 95.3 U. [ Conclusion] This study provided reference for the industrial application of degradation products of mannan.
基金Supported by National Natural Science Foundation of China(to M.Y.),No.81970468.
文摘The tremendous public health and economic impact of coronavirus disease 2019(COVID-19), caused by severe acute respiratory syndrome coronavirus 2(SARSCoV-2), has become a huge challenge globally. There is increasing evidence that SARS-CoV-2 induces intestinal infections. Type Ⅲ interferon(IFN-λ) has an antiviral role in intestinal infection, with focused, long-lasting, and non-inflammatory characteristics. This review presents a summary of the structure of SARSCoV-2, including its invasion and immune escape mechanisms. Emphasis was placed on the gastrointestinal impact of SARS-CoV-2, including changes to the intestinal microbiome, activation of immune cells, and inflammatory responses.We also describe the comprehensive functions of IFN-λ in anti-enteric SARS-CoV-2 infection, and discuss the potential application of IFN-λ as a therapeutic agent for COVID-19 with intestinal symptoms.
基金Ministry of Science and Technology Basic Resources Survey Special Project,Grant/Award Number:2019FY100900High-level Hospital Construction Project,Grant/Award Number:DFJH2019015+2 种基金National Natural Science Foundation of China,Grant/Award Number:61871021Guangdong Natural Science Foundation,Grant/Award Number:2019A1515011676Beijing Key Laboratory of Robotics Bionic and Functional Research。
文摘Aiming at the problem that the existing models have a poor segmentation effect on imbalanced data sets with small-scale samples,a bilateral U-Net network model with a spatial attention mechanism is designed.The model uses the lightweight MobileNetV2 as the backbone network for feature hierarchical extraction and proposes an Attentive Pyramid Spatial Attention(APSA)module compared to the Attenuated Spatial Pyramid module,which can increase the receptive field and enhance the information,and finally adds the context fusion prediction branch that fuses high-semantic and low-semantic prediction results,and the model effectively improves the segmentation accuracy of small data sets.The experimental results on the CamVid data set show that compared with some existing semantic segmentation networks,the algorithm has a better segmentation effect and segmentation accuracy,and its mIOU reaches 75.85%.Moreover,to verify the generality of the model and the effectiveness of the APSA module,experiments were conducted on the VOC 2012 data set,and the APSA module improved mIOU by about 12.2%.
基金the National Natural Science Foundation of China(No.81960043 and No.81600180)Natural Science Foundation of Jiangxi Province(No.20192ACB20030 and No.20203BBGL73197)Science and Technology Innovation Base Construction Project of Jiangxi Province(No.20212BCG74001 and No.20211ZDG02006).
文摘Objective Preclinical evidence and clinical trials have suggested synergistic effects of epigenetic modifiers in combination with cytotoxic agents for the treatment of leukemia.However,their efficacy in patients with relapsed/refractory acute myeloid leukemia(R/R AML)remains unclear.Methods Clinical data of R/R AML patients who received a CDCAG regimen(chidamide,decitabine,cytarabine,aclarubicin,and granulocyte colony-stimulating factor)from July 1,2018 to October 31,2021 at our center were retrospectively assessed,and the safety and efficacy of the CDCAG regimen were evaluated.Patients were followed up until November 30,2021,with a median follow-up of 21.6 months(95%CI:10.0–33.2 months).Results A total of 67 patients were enrolled.Two patients died within 3 weeks after the initiation,and therefore only 65 patients underwent the assement for clinical response and survival.It was found that 56.9%patients achieved complete remission with a median overall survival(OS)of 9.6 months.The median OS of responders was 25.9 months,while that of non-responders was 5.0 months(P<0.0001).Patients with gene mutations had a superior overall response rate(ORR)(80.4%vs.45.5%,P=0.043)compared to those without gene mutations.The presence of DNA methyltransferase 3 A(DNMT3A),ten-eleven translocation-2(TET2),and isocitrate dehydrogenase 1/2(IDH1/2)mutations did not affect the response rate(88.2%vs.68.9%,P=0.220)and reflected a better OS(not attained vs.9.0 months,P=0.05).The most common non-hematologic adverse events were pulmonary infection(73.1%),followed by febrile neutropenia(23.9%)and sepsis(19.4%).Conclusions The CDCAG regimen was effective and well-tolerated in R/R AML patients,increasing the potential for allogeneic hematopoietic stem cell transplantation.Moreover,patients with DNMT3A,TET2,and IDH1/2 mutations might benefit from this regimen.
基金supported by the National Natural Science Foundation of China (32072179)Zhejiang Provincial Natural Science Foundation of China (LD21C200001)。
文摘7-Ketophytosterols are the major oxidation products of phytosterols in foods, which have been associated with atherosclerosis. However, their absorption mechanism remains unclear. The aim of our work was to investigate the absorption mechanism of 7-ketophytosterols and their effects on the cholesterol transport using Caco-2 cell model. The absorption percentage of 7-ketositosterol and 7-ketocampesterol was 1.16%-1.68% and 1.18%-2.23% respectively in the Caco-2 model, which is higher than that of their parent phytosterols, but lower than cholesterol-d7. The apparent permeability of 7-ketositosterol and 7-ketocampesterol at 30 μmol/L in the basolateral(BL)-to-apical(AP)direction were 0.42-and 0.55-fold of that in the AP-to-BL direction, indicating an active intake in the permeation mechanism of 7-ketophytosterols. Ezetimibe could significantly inhibit the transport of 7-ketophytosterols(P < 0.05), which means that their transport depends on niemann-pick c1-like 1(NPC1L1)protein. The transport of cholesterol-d7 was significantly inhibited by 7-ketophytosterols(P < 0.05). Taken together, this study deepened our understanding of the absorption mechanism of common food-born 7-ketophytosterols and provides useful information on the inhibition of 7-ketophytosterols absorption.
基金financially supported by the Higher Education Department of Guangdong Province (No.2020KCXTD025)the National Key Research and Development Program of China (No.2017YFD0800404).
文摘In the rice-wheat rotation system,biochar(BC)can be applied at the initiation of the rice or wheat season.Here,we compared the effects of BC that were applied at two different crop seasons on wheat production,quality,and soil profile properties in a rice-wheat rotation system with nitrogen(N)fertilizer applied at 280 kg/ha rate.Results showed that both wheat grain production and N recovery use efficiency were influenced by BC applied at two crop seasons.Biochar application did not affect the total non-essential amino-acid,but when applied during wheat season,BC significantly(p<0.05)increased total essential amino acid in grain by 12.3%,particularly for the valine(+48.2%),methionine(+43.8%),and isoleucine(+10.3%).We found that BC significantly(p<0.05)decreased the pH of soil at 0–6 cm and 20–30 cm by 0.14–0.18 and 0.05–0.08 units,respectively.The NH4+-N content of the whole observed soil profile were reduced by BC application,however,the effect of BC on NO3–-N content varied with the application season and profile depth.Interestingly,BC applied at wheat and rice season significantly(p<0.05)improved topsoil N contents by 48.4%and 19.7%,respectively.In addition,data suggested that BC applied during wheat season performed better in enhancing soil available phosphorus,potassium,and organic matter contents.In conclusion,we suggest that the optimum application time of BC for enhancing crop production and quality(take amino-acid content for example)and improving soil fertility is at the initiation of the wheat season.
基金supported by the National Natural Science Foundations of China 82230030 and 81871492(Y.L.),82201020(Y.W),and 82100980(S.S.J)the Beijing Natural Science Foundation JL23002(Y.L.)and 7214305(S.S.J)+6 种基金the Beijing International Science and Technology Cooperation Project Z221100002722003(Y.L.)the Innovative Research Team of High-level Local Universities in Shanghai SHSMU-ZLCX20212402(Y.L.)Ten-Thousand Talents Program QNBJ2019-2(Y.L.)the Key R&D Plan of Ningxia Hui Autonomous Region 2020BCG01001(Y.L.)Beijing Nova Program Z211100002121043(Y.W.)China National Postdoctoral Program for Innovative Talents BX2021022(Y.W.),BX20200020(S.S.J)China Postdoctoral Science Foundation 2021M700281(Y.W.)。
文摘Adult tendon stem/progenitor cells(TSPCs)are essential for tendon maintenance,regeneration,and repair,yet they become susceptible to senescence with age,impairing the self-healing capacity of tendons.In this study,we employ a recently developed deep-learning-based efficacy prediction system to screen potential stemness-promoting and senescence-inhibiting drugs from natural products using the transcriptional signatures of stemness.The top-ranked candidate,prim-O-glucosylcimifugin(POG),a saposhnikovia root extract,could ameliorate TPSC senescent phenotypes caused by long-term passage and natural aging in rats and humans,as well as restore the self-renewal and proliferative capacities and tenogenic potential of aged TSPCs.In vivo,the systematic administration of POG or the local delivery of POG nanoparticles functionally rescued endogenous tendon regeneration and repair in aged rats to levels similar to those of normal animals.Mechanistically,POG protects TSPCs against functional impairment during both passage-induced and natural aging by simultaneously suppressing nuclear factor-κB and decreasing mTOR signaling with the induction of autophagy.Thus,the strategy of pharmacological intervention with the deep learning-predicted compound POG could rejuvenate aged TSPCs and improve the regenerative capacity of aged tendons.
基金the National Natural Science Foundation of China(No.61772417,61634004,61602377)Key R&D Program Projects in Shaanxi Province(No.2017GY-060)Shaanxi Natural Science Basic Research Project(No.2018JM4018).
文摘In order to effectively solve the problems of low accuracy,large amount of computation and complex logic of deep learning algorithms in behavior recognition,a kind of behavior recognition based on the fusion of 3 dimensional batch normalization visual geometry group(3D-BN-VGG)and long short-term memory(LSTM)network is designed.In this network,3D convolutional layer is used to extract the spatial domain features and time domain features of video sequence at the same time,multiple small convolution kernels are stacked to replace large convolution kernels,thus the depth of neural network is deepened and the number of network parameters is reduced.In addition,the latest batch normalization algorithm is added to the 3-dimensional convolutional network to improve the training speed.Then the output of the full connection layer is sent to LSTM network as the feature vectors to extract the sequence information.This method,which directly uses the output of the whole base level without passing through the full connection layer,reduces the parameters of the whole fusion network to 15324485,nearly twice as much as those of 3D-BN-VGG.Finally,it reveals that the proposed network achieves 96.5%and 74.9%accuracy in the UCF-101 and HMDB-51 respectively,and the algorithm has a calculation speed of 1066 fps and an acceleration ratio of 1,which has a significant predominance in velocity.
