The ongoing development of small molecule drugs underscores the urgent need for novel excipients to formulate poorly soluble drug candidates.Cucurbit[7]uril(CB[7])possesses high binding affinities for a variety of mol...The ongoing development of small molecule drugs underscores the urgent need for novel excipients to formulate poorly soluble drug candidates.Cucurbit[7]uril(CB[7])possesses high binding affinities for a variety of molecular vips.However,its moderate water solubility limits broader application.Here we report the synthesis of three CB[7]derivatives M1-M3 by modifying an average of 4.2,5.5,and 5.9 sulfonatopropoxy groups onto their"equator"carbons.Compared to CB[7],their water-solubility increased by at least 26.6-,23.6-,and 19.2-fold,respectively,while the maximum tolerated doses(MTD)of M1 and M2 improved by 2.5-and 2.3-fold.Phase solubility diagram studies demonstrate that M1 and M2 significantly enhance the water-solubility of eighteen poorly soluble drugs.In vivo experiments in rat complete Freund's arthritis reveal that M1 not only improves the anti-inflammatory efficacy of indomethacin by up to 52%,but also substantially reduces its side effect of gastric ulcer.展开更多
Achieving intrinsic strengthening of boron nitride nanosheets(BNNSs)in Ti matrix composites was still an unsettled issue due to its severe and uncontrollable interface reaction.In the present study,high-performance BN...Achieving intrinsic strengthening of boron nitride nanosheets(BNNSs)in Ti matrix composites was still an unsettled issue due to its severe and uncontrollable interface reaction.In the present study,high-performance BNNSs/Ti composites were fabricated by using the warm compaction(WC)technique and rapid heat treatment(HT)strategy on the basis of interfacial nano-TiBw design.The intrinsic structure of BNNSs was well-retained and nano-TiBw on partially reacted BNNSs led to a brilliant interface bond-ing and BNNSs intrinsic strengthening.Tensile tests revealed that 0.1 wt.%BNNSs/Ti composites exhibited the tensile strength(UTS)of 876 MPa(61%higher than pure Ti)and the fracture elongation of 22.6%,demonstrating the well-balanced property.By employing the insitu TEM experiment,we solve an existing debate,uncovering the synergistic toughening effect from BNNSs and interfacial nano-TiBw which effectively inhibited the micro-cracks propagation on BNNSs and heterogeneous interface.This work paves a new way for developing high-performance BNNSs/Ti composites by reaction interface manipulation and underscores the importance of maintaining BNNSs intrinsic structure in the Ti matrix.展开更多
BACKGROUND:This study aimed to establish an eff ective nomogram to predict the survival of heat stroke(HS)based on risk factors.METHODS:This was a retrospective,observational multicenter cohort study.We analyzed patie...BACKGROUND:This study aimed to establish an eff ective nomogram to predict the survival of heat stroke(HS)based on risk factors.METHODS:This was a retrospective,observational multicenter cohort study.We analyzed patients diagnosed with HS,who were treated between May 1 and September 30,2018 at 15 tertiary hospitals from 11 cities in Northern China.RESULTS:Among the 175 patients,32 patients(18.29%)died before hospital discharge.After the univariate analysis,mechanical ventilation,initial mean arterial pressure<70 mmHg,maximum heart rate,lab results on day 1(white blood cell count,alanine aminotransferase,creatinine),and Glasgow admission prediction score were included in multivariate analysis.Multivariate Cox regression showed that invasive ventilation,initial mean arterial pressure<70 mmHg(1 mmHg=0.133 kPa),and Glasgow admission prediction score were independent risk factors for HS.The nomogram was established for predicting 7-d and 14-d survival in the training cohort.The nomogram exhibited a concordance index(C-index)of 0.880(95%confidence interval[95%CI]0.831-0.930)by bootstrapping validation(B=1,000).Furthermore,the nomogram performed better when predicting 14-d survival,compared to 7-d survival.The prognostic index cut-off value was set at 2.085,according to the operating characteristic curve for overall survival prediction.The model showed good calibration ability in the internal and external validation datasets.CONCLUSION:A novel nomogram,integrated with prognostic factors,was proposed;it was highly predictive of the survival in HS patients.展开更多
In this paper,promising but simple schemes are investigated to enhance the micro-bunching of relativistic electron beams for coherent harmonic generation(CHG)by using phase merging effects.In contrast to the standard ...In this paper,promising but simple schemes are investigated to enhance the micro-bunching of relativistic electron beams for coherent harmonic generation(CHG)by using phase merging effects.In contrast to the standard CHG scheme,two specially designed dispersion sections(DSs)are adopted with the DS-modulator–DS configuration.The phase space of the e beam is appropriately coupled in the first DS,and the electrons within one seed wavelength can merge to the same phase with a matched second DS.Micro-bunching of the e beam can thus be enhanced by a large margin with much higher-harmonic components.Taking e beams from laser wakefield accelerators(LWFAs)as an example,start-to-end simulations are performed to show the effectiveness and robustness of the proposed schemes with several configurations.The beam current can be optimized to several tens to hundreds of kiloamperes,and the radiation power reaches hundreds of megawatts in the extreme ultraviolet regime within a 3.5 m-long beamline.The proposed schemes offer new opportunities for future compact free-electron lasers driven by LWFAs and provides prospects for truly compact and widely applicable systems.展开更多
针对软件定义网络(Software Defined Network,SDN)的负载均衡问题,为使网络的资源分配更加合理,防止网络拥塞,设计了一种基于Q-学习的负载均衡(Q-learning Load Balance,QLLB)算法,可根据网络环境自行作出决策,避免网络拥塞,实现网络资...针对软件定义网络(Software Defined Network,SDN)的负载均衡问题,为使网络的资源分配更加合理,防止网络拥塞,设计了一种基于Q-学习的负载均衡(Q-learning Load Balance,QLLB)算法,可根据网络环境自行作出决策,避免网络拥塞,实现网络资源的合理分配。与最短路径算法Dijkstra、蚁群算法进行的性能对比结果表明,QLLB算法有效实现了负载均衡,使得各个链路的带宽利用率更加平均,吞吐量分别提升了约8%和2%,可有效提升网络性能。展开更多
In the present study,the effects of process parameters(output voltage x,nitrogen flux l and specific strengthening time s)on the microstructure and wear resistance properties of TiN coatings prepared by electrospark d...In the present study,the effects of process parameters(output voltage x,nitrogen flux l and specific strengthening time s)on the microstructure and wear resistance properties of TiN coatings prepared by electrospark deposition(ESD)were investigatedsystematically.The microstructure of the coatings was characterized for thickness(TOC),content of TiN(CON)and porosity(POC).A statistical model was developed to identify the significant factors affecting the microstructure and wear resistance of the coatings.The results show that the output voltage x and nitrogen flux l present significant effects on majority of the evaluation indexes such asTOC,friction coefficient(COF)and wear mass loss(Id),while the specific strengthening time s has a significant effect on POC and asmall effect on the other indexes.The optimal process parameters were obtained as follows:output voltage(x,60V),nitrogen flux(l,15L/min)and specific strengthening time(s,3min/cm2).The variation of wear mass loss(Id)by the variation of the outputvoltage(x)and nitrogen flux(l)is attributed to the change of wear mechanisms of TiN coatings.The main wear mechanism of TiNcoating prepared under optimal process parameters is micro-cutting wear accompanied by micro-fracture wear.展开更多
为探究现代工艺酿造的浓香型白酒不同馏分中各风味组分以及对应酒精度的馏出特性和相关性,以机械化酿造的34个不同馏分的浓香型原酒为研究对象,采用液液萃取-气相色谱-质谱联用(liquid-liquid-extraction gas chromatography-mass,LLE-G...为探究现代工艺酿造的浓香型白酒不同馏分中各风味组分以及对应酒精度的馏出特性和相关性,以机械化酿造的34个不同馏分的浓香型原酒为研究对象,采用液液萃取-气相色谱-质谱联用(liquid-liquid-extraction gas chromatography-mass,LLE-GC-MS)对样品风味物质进行定性定量分析,结合感官品评分析结果,进行了层次聚类热图分析,Pearson相关性分析以及正交偏最小二乘判别分析(orthogonal projections to latent structures-discriminant analysis,OPLS-DA),建立了不同馏分酒精度变化的数学模型:C t=73.373-0.012e 0.007t,其中决定系数以及均方根误差均为0.997,表示模型拟合的效果非常好。通过总结馏出规律,可以很好地把34个馏分分为4个大类,其中馏分0~2为酒头,馏分3~12为头段酒,馏分13~26为中段酒,馏分27~33为酒尾。16种主要风味物质按照相关性分成了A、B两个大类,且2个类别之间存在着显著的负相关,A类物质随着馏分的馏出,含量逐渐降低,B类物质的趋势则完全相反。感官评定结果显示,头段酒的综合评价最好,酯香浓郁,窖香突出,糟味明显,口感谐调,而没有明显的尾味。该研究分别基于风味物质和酒精度建立了不同时间段馏分的分类模型,为浓香型白酒现代工艺的量质摘酒、分段摘酒提供了参考依据。展开更多
基金National Natural Science Foundation of China(Nos.21921003 and 22201293)the National Key R&D Program of China(No.2023YFC3503400)for financial support。
文摘The ongoing development of small molecule drugs underscores the urgent need for novel excipients to formulate poorly soluble drug candidates.Cucurbit[7]uril(CB[7])possesses high binding affinities for a variety of molecular vips.However,its moderate water solubility limits broader application.Here we report the synthesis of three CB[7]derivatives M1-M3 by modifying an average of 4.2,5.5,and 5.9 sulfonatopropoxy groups onto their"equator"carbons.Compared to CB[7],their water-solubility increased by at least 26.6-,23.6-,and 19.2-fold,respectively,while the maximum tolerated doses(MTD)of M1 and M2 improved by 2.5-and 2.3-fold.Phase solubility diagram studies demonstrate that M1 and M2 significantly enhance the water-solubility of eighteen poorly soluble drugs.In vivo experiments in rat complete Freund's arthritis reveal that M1 not only improves the anti-inflammatory efficacy of indomethacin by up to 52%,but also substantially reduces its side effect of gastric ulcer.
基金the National Natural Science Foundation of China(No.52301186)the Fundamental Research Funds for the Central Universitiesthe Young Elite Scientists Sponsorship Program by CAST(Grant No.2022QNRC001).
文摘Achieving intrinsic strengthening of boron nitride nanosheets(BNNSs)in Ti matrix composites was still an unsettled issue due to its severe and uncontrollable interface reaction.In the present study,high-performance BNNSs/Ti composites were fabricated by using the warm compaction(WC)technique and rapid heat treatment(HT)strategy on the basis of interfacial nano-TiBw design.The intrinsic structure of BNNSs was well-retained and nano-TiBw on partially reacted BNNSs led to a brilliant interface bond-ing and BNNSs intrinsic strengthening.Tensile tests revealed that 0.1 wt.%BNNSs/Ti composites exhibited the tensile strength(UTS)of 876 MPa(61%higher than pure Ti)and the fracture elongation of 22.6%,demonstrating the well-balanced property.By employing the insitu TEM experiment,we solve an existing debate,uncovering the synergistic toughening effect from BNNSs and interfacial nano-TiBw which effectively inhibited the micro-cracks propagation on BNNSs and heterogeneous interface.This work paves a new way for developing high-performance BNNSs/Ti composites by reaction interface manipulation and underscores the importance of maintaining BNNSs intrinsic structure in the Ti matrix.
文摘BACKGROUND:This study aimed to establish an eff ective nomogram to predict the survival of heat stroke(HS)based on risk factors.METHODS:This was a retrospective,observational multicenter cohort study.We analyzed patients diagnosed with HS,who were treated between May 1 and September 30,2018 at 15 tertiary hospitals from 11 cities in Northern China.RESULTS:Among the 175 patients,32 patients(18.29%)died before hospital discharge.After the univariate analysis,mechanical ventilation,initial mean arterial pressure<70 mmHg,maximum heart rate,lab results on day 1(white blood cell count,alanine aminotransferase,creatinine),and Glasgow admission prediction score were included in multivariate analysis.Multivariate Cox regression showed that invasive ventilation,initial mean arterial pressure<70 mmHg(1 mmHg=0.133 kPa),and Glasgow admission prediction score were independent risk factors for HS.The nomogram was established for predicting 7-d and 14-d survival in the training cohort.The nomogram exhibited a concordance index(C-index)of 0.880(95%confidence interval[95%CI]0.831-0.930)by bootstrapping validation(B=1,000).Furthermore,the nomogram performed better when predicting 14-d survival,compared to 7-d survival.The prognostic index cut-off value was set at 2.085,according to the operating characteristic curve for overall survival prediction.The model showed good calibration ability in the internal and external validation datasets.CONCLUSION:A novel nomogram,integrated with prognostic factors,was proposed;it was highly predictive of the survival in HS patients.
基金supported by the National Natural Science Foundation of China(Grant Nos.12388102,12225411,12105353,11991072,and 12174410)the CAS Project for Young Scientists in Basic Research(Grant No.YSBR060)+1 种基金the Program of Shanghai Academic Research Leader(Grant No.22XD1424200)the State Key Laboratory Program of the Chinese Ministry of Science and Technology and CAS Youth Innovation Promotion Association(Y201952 and 2022242).
文摘In this paper,promising but simple schemes are investigated to enhance the micro-bunching of relativistic electron beams for coherent harmonic generation(CHG)by using phase merging effects.In contrast to the standard CHG scheme,two specially designed dispersion sections(DSs)are adopted with the DS-modulator–DS configuration.The phase space of the e beam is appropriately coupled in the first DS,and the electrons within one seed wavelength can merge to the same phase with a matched second DS.Micro-bunching of the e beam can thus be enhanced by a large margin with much higher-harmonic components.Taking e beams from laser wakefield accelerators(LWFAs)as an example,start-to-end simulations are performed to show the effectiveness and robustness of the proposed schemes with several configurations.The beam current can be optimized to several tens to hundreds of kiloamperes,and the radiation power reaches hundreds of megawatts in the extreme ultraviolet regime within a 3.5 m-long beamline.The proposed schemes offer new opportunities for future compact free-electron lasers driven by LWFAs and provides prospects for truly compact and widely applicable systems.
文摘针对软件定义网络(Software Defined Network,SDN)的负载均衡问题,为使网络的资源分配更加合理,防止网络拥塞,设计了一种基于Q-学习的负载均衡(Q-learning Load Balance,QLLB)算法,可根据网络环境自行作出决策,避免网络拥塞,实现网络资源的合理分配。与最短路径算法Dijkstra、蚁群算法进行的性能对比结果表明,QLLB算法有效实现了负载均衡,使得各个链路的带宽利用率更加平均,吞吐量分别提升了约8%和2%,可有效提升网络性能。
文摘In the present study,the effects of process parameters(output voltage x,nitrogen flux l and specific strengthening time s)on the microstructure and wear resistance properties of TiN coatings prepared by electrospark deposition(ESD)were investigatedsystematically.The microstructure of the coatings was characterized for thickness(TOC),content of TiN(CON)and porosity(POC).A statistical model was developed to identify the significant factors affecting the microstructure and wear resistance of the coatings.The results show that the output voltage x and nitrogen flux l present significant effects on majority of the evaluation indexes such asTOC,friction coefficient(COF)and wear mass loss(Id),while the specific strengthening time s has a significant effect on POC and asmall effect on the other indexes.The optimal process parameters were obtained as follows:output voltage(x,60V),nitrogen flux(l,15L/min)and specific strengthening time(s,3min/cm2).The variation of wear mass loss(Id)by the variation of the outputvoltage(x)and nitrogen flux(l)is attributed to the change of wear mechanisms of TiN coatings.The main wear mechanism of TiNcoating prepared under optimal process parameters is micro-cutting wear accompanied by micro-fracture wear.
文摘为探究现代工艺酿造的浓香型白酒不同馏分中各风味组分以及对应酒精度的馏出特性和相关性,以机械化酿造的34个不同馏分的浓香型原酒为研究对象,采用液液萃取-气相色谱-质谱联用(liquid-liquid-extraction gas chromatography-mass,LLE-GC-MS)对样品风味物质进行定性定量分析,结合感官品评分析结果,进行了层次聚类热图分析,Pearson相关性分析以及正交偏最小二乘判别分析(orthogonal projections to latent structures-discriminant analysis,OPLS-DA),建立了不同馏分酒精度变化的数学模型:C t=73.373-0.012e 0.007t,其中决定系数以及均方根误差均为0.997,表示模型拟合的效果非常好。通过总结馏出规律,可以很好地把34个馏分分为4个大类,其中馏分0~2为酒头,馏分3~12为头段酒,馏分13~26为中段酒,馏分27~33为酒尾。16种主要风味物质按照相关性分成了A、B两个大类,且2个类别之间存在着显著的负相关,A类物质随着馏分的馏出,含量逐渐降低,B类物质的趋势则完全相反。感官评定结果显示,头段酒的综合评价最好,酯香浓郁,窖香突出,糟味明显,口感谐调,而没有明显的尾味。该研究分别基于风味物质和酒精度建立了不同时间段馏分的分类模型,为浓香型白酒现代工艺的量质摘酒、分段摘酒提供了参考依据。
