Neural stem cells(NSCs)have the potential for self-renewal and multidirectional differentiation,and their transplantation has achieved good efficacy in a variety of diseases.However,only 1%-10%of transplanted NSCs sur...Neural stem cells(NSCs)have the potential for self-renewal and multidirectional differentiation,and their transplantation has achieved good efficacy in a variety of diseases.However,only 1%-10%of transplanted NSCs survive in the ischemic and hypoxic microenvironment of posthemorrhagic hydrocephalus.^(Sox2)is an important factor for NSCs to maintain proliferation.Therefore,^(Sox2)-overexpressing NSCs(NSC^(Sox2))may be more successful in improving neurological dysfunction after posthemorrhagic hydrocephalus.In this study,human NSC^(Sox2)was transplanted into a posthemorrhagic hydrocephalus mouse model,and retinoic acid was administered to further promote NSC differentiation.The results showed that NSC^(Sox2)attenuated the ventricular enlargement caused by posthemorrhagic hydrocephalus and improved neurological function.NSC^(Sox2)also promoted nerve regeneration,inhibited neuroinflammation and promoted M2 polarization(anti-inflammatory phenotype),thereby reducing cerebrospinal fluid secretion in choroid plexus.These findings suggest that NSC^(Sox2)rescued ventricular enlargement and neurological dysfunction induced by posthemorrhagic hydrocephalus through neural regeneration and modulation of inflammation.展开更多
Ischemic stroke is the leading cause of death in the Chinese population.The incidence of cerebral infarction is higher in high-altitude regions,particularly those above 3,500 m,than in populations residing at lower al...Ischemic stroke is the leading cause of death in the Chinese population.The incidence of cerebral infarction is higher in high-altitude regions,particularly those above 3,500 m,than in populations residing at lower altitudes[1].There are various speculations regarding the mechanisms behind this phenomenon,one of which is that the low oxygen content and cold climate at high altitudes may increase the occurrence of vascular diseases[2].The multifactorial effect of high-altitude environments on residential populations makes it challenging for researchers to determine the specific pathways through which these diseases occur.展开更多
Workpiece rotational grinding is widely used in the ultra-precision machining of hard and brittle semiconductor materials,including single-crystal silicon,silicon carbide,and gallium arsenide.Surface roughness and sub...Workpiece rotational grinding is widely used in the ultra-precision machining of hard and brittle semiconductor materials,including single-crystal silicon,silicon carbide,and gallium arsenide.Surface roughness and subsurface damage depth(SDD)are crucial indicators for evaluating the surface quality of these materials after grinding.Existing prediction models lack general applicability and do not accurately account for the complex material behavior under grinding conditions.This paper introduces novel models for predicting both surface roughness and SDD in hard and brittle semiconductor materials.The surface roughness model uniquely incorporates the material’s elastic recovery properties,revealing the significant impact of these properties on prediction accuracy.The SDD model is distinguished by its analysis of the interactions between abrasive grits and the workpiece,as well as the mechanisms governing stress-induced damage evolution.The surface roughness model and SDD model both establish a stable relationship with the grit depth of cut(GDC).Additionally,we have developed an analytical relationship between the GDC and grinding process parameters.This,in turn,enables the establishment of an analytical framework for predicting surface roughness and SDD based on grinding process parameters,which cannot be achieved by previous models.The models were validated through systematic experiments on three different semiconductor materials,demonstrating excellent agreement with experimental data,with prediction errors of 6.3%for surface roughness and6.9%for SDD.Additionally,this study identifies variations in elastic recovery and material plasticity as critical factors influencing surface roughness and SDD across different materials.These findings significantly advance the accuracy of predictive models and broaden their applicability for grinding hard and brittle semiconductor materials.展开更多
Hybrid manufacturing(HM)uses additive manufacturing(AM)techniques to prepare complex or fine structures on traditional processing parts,which can fully utilize the advantages of AM to form complex parts,and the high e...Hybrid manufacturing(HM)uses additive manufacturing(AM)techniques to prepare complex or fine structures on traditional processing parts,which can fully utilize the advantages of AM to form complex parts,and the high efficiency and low cost of conventional processing methods in manufacturing regular components.A bimetal material was produced by selective laser melting(SLM)of AlSi10Mg on the deformed Al6061 alloy substrate in this study.Firstly,the interface characteristics of the two alloys were studied.The results show that a metallurgical interface with a thickness of 100–200μm was formed as the result of the Marangoni convection during SLM preparation.In detail,the circular flow in the melt pool at the interface led to the dilution of alloying elements and the change of microstructure.Moreover,a suitable first-layer thickness can eff ectively suppress the hot cracks at the interfacial region.Based on the optimized results,the hybrid manufactured samples with diff erent SLM processed volume ratios(SLM-part)to the substrate were prepared to study the mechanical properties and the deformation behavior of hybrid parts.The results show that the volume ratio of the SLM-part to the substrate had an influence on the strength and the elasto-plastic behavior by aff ecting the distribution of plastic deformation.展开更多
Lift-to-drag ratio (L/D) is nearly the most important index in determining the aerodynamic performance of a hypersonic flight vehicle,because the flight distance is linearly proportional to the L/D according to Bregue...Lift-to-drag ratio (L/D) is nearly the most important index in determining the aerodynamic performance of a hypersonic flight vehicle,because the flight distance is linearly proportional to the L/D according to Breguet's equation.In general,the higher the L/D of a vehicle,the greater the flight range if the specific impulse,structural mass ratio,and flight velocity are given.Naturally,the pursuit of a high L/D for hypersonic vehicles has never ceased [1,2].展开更多
This paper proposes a co-optimal strategy using line hardening,mobile devices(mobile ice-melting device,mobile emergency generator,mobile energy storage system),and repair crew dispatching to improve distribution syst...This paper proposes a co-optimal strategy using line hardening,mobile devices(mobile ice-melting device,mobile emergency generator,mobile energy storage system),and repair crew dispatching to improve distribution system resilience during ice storms.A multi-stage defender-attacker-defender model is established to take into account interactions and coupling relationships between different measures.In our proposed model,ice storms will attack the distribution and transportation system in a worst-case scenario,affecting system performance from various perspectives.Corresponding to the different operating states in the distribution system affected by ice storms,aiming at minimizing the weighted load shedding value,this paper applies various measures to different stages to improve the response and defense capabilities to ice storms and realize restoration of the distribution system ultimately.The nested column-and-constraint generation algorithm is used to solve the model efficiently.The effectiveness of the proposed model and solution method for enhancing the distribution system resilience is verified on the modified IEEE 33-bus distribution system and modified realworld zone of Caracas 141-bus distribution system.展开更多
Currently,the efficacy of albumin-bound paclitaxel(PTX@Alb)is still limited due to theimpaired PTX@Alb accumulation in tumors partly mediated by the dense collagen distribution.Meanwhile,acquired immune resistance alw...Currently,the efficacy of albumin-bound paclitaxel(PTX@Alb)is still limited due to theimpaired PTX@Alb accumulation in tumors partly mediated by the dense collagen distribution.Meanwhile,acquired immune resistance always occurs due to the enhanced programmed cell death-ligand 1(PD-L1)expression after PTX@Alb treatment,which then leads to immune tolerance.To fill these gaps,we newly revealed that tamoxifen(TAM),a clinically widely used adjuvant therapy for breast cancer withmitochondrial metabolism blockade capacity,could also be used as a novel effective PD-L1 and TGF-bdual-inhibitor via inducing the phosphorylation of adenosine 5ʹ-monophosphate-activated protein kinase(AMPK)protein.Following this,to obtain a more significant effect,TPP-TAM was prepared by conjugatingmitochondria-targeted triphenylphosphine(TPP)with TAM,which then further self-assembledwith albumin(Alb)to form TPP-TAM@Alb nanoparticles.By doing this,TPP-TAM@Alb nanoparticleseffectively decreased the expression of collagen in vitro,which then led to the enhanced accumulation ofPTX@Alb in 4T1 tumors.Besides,TPP-TAM@Alb also effectively decreased the expression of PD-L1 and TGF-b in tumors to better sensitize PTX@Alb-mediated chemo-immunotherapy by enhancing T cellinfiltration.All in all,we newly put forward a novel mitochondrial metabolism blockade strategy toinhibit PTX@Alb-resistant tumors,further supporting its better clinical application。展开更多
A full account of semisyntheses of polychlorinated marine steroids clionastatins A and B is described.We have developed a unique two-stage chlorination-oxidation strategy that enabled concise and divergent semisynthes...A full account of semisyntheses of polychlorinated marine steroids clionastatins A and B is described.We have developed a unique two-stage chlorination-oxidation strategy that enabled concise and divergent semisyntheses of clionastatins A and B in 16 steps from inexpensive testosterone.Key transformations in chlorination stage include(a)conformationally controlled,stereospecific dichlorination through an unusualβ-chloronium intermediate to install the diequatorial C1,C2-dichloride;(b)C4-OH directed C19–H oxygenation followed by challenging neopentyl chlorination to install the C19–Cl.The high oxidation level was constructed through(a)the desaturation at C6–C7 through one-pot photochemical dibromination–reductive debromination;(b)regioselective anti-Markovnikov oxidation of the C6–C7 double bond by photoredox-metal dual catalysis to forge the B ring enone;(c)late-stage desaturation with SeO_(2)to introduce C8–C9 double bond.Wharton transposition was used to forge the D-ring enone,and thermodynamically driven epimerization secured the cis-fused C/D ring system.Furthermore,we also provided a 14-step approach to clionastatin A by optimizing the construction of the D-ring enone with a dehydration-oxidation sequence.展开更多
基金supported by the National Natural Science Foundation of China,Nos.82473334(to LZ),82401629(to XL)the Major Scientific and Technological Achievements Transformation Project of Ningxia Hui Autonomous Region,No.2022CJE09013(to LZ)+4 种基金Mianyang Science and Technology Bureau(Mianyang Science and Technology Program),No.2023ZYDF097(to LZ)NHC Key Laboratory of Nuclear Technology Medical Transformation(Mianyang Central Hospital),No.2023HYX001(to LZ)Spinal Cord Diseases Clinical Medical Center of Yunnan Province,No.2024JSKFKT-16(to BG)the Natural Science Foundation of Sichuan Province,No.2024NSFSC1646(to XL)the China Postdoctoral Science Foundation,Nos.GZC20231811(to XL),2024T170601(to XL)and 2024M76228(to XL).
文摘Neural stem cells(NSCs)have the potential for self-renewal and multidirectional differentiation,and their transplantation has achieved good efficacy in a variety of diseases.However,only 1%-10%of transplanted NSCs survive in the ischemic and hypoxic microenvironment of posthemorrhagic hydrocephalus.^(Sox2)is an important factor for NSCs to maintain proliferation.Therefore,^(Sox2)-overexpressing NSCs(NSC^(Sox2))may be more successful in improving neurological dysfunction after posthemorrhagic hydrocephalus.In this study,human NSC^(Sox2)was transplanted into a posthemorrhagic hydrocephalus mouse model,and retinoic acid was administered to further promote NSC differentiation.The results showed that NSC^(Sox2)attenuated the ventricular enlargement caused by posthemorrhagic hydrocephalus and improved neurological function.NSC^(Sox2)also promoted nerve regeneration,inhibited neuroinflammation and promoted M2 polarization(anti-inflammatory phenotype),thereby reducing cerebrospinal fluid secretion in choroid plexus.These findings suggest that NSC^(Sox2)rescued ventricular enlargement and neurological dysfunction induced by posthemorrhagic hydrocephalus through neural regeneration and modulation of inflammation.
基金supported by the National Natural Science Foundation of Chongqing,China(CSTB2022NSCQ-MSX1100)National Natural Science Foundation of China(grant no.82101499).
文摘Ischemic stroke is the leading cause of death in the Chinese population.The incidence of cerebral infarction is higher in high-altitude regions,particularly those above 3,500 m,than in populations residing at lower altitudes[1].There are various speculations regarding the mechanisms behind this phenomenon,one of which is that the low oxygen content and cold climate at high altitudes may increase the occurrence of vascular diseases[2].The multifactorial effect of high-altitude environments on residential populations makes it challenging for researchers to determine the specific pathways through which these diseases occur.
基金supported by the National Key Research and Development Program of China(2022YFB3605902)the National Natural Science Foundation of China(52375411,52293402)。
文摘Workpiece rotational grinding is widely used in the ultra-precision machining of hard and brittle semiconductor materials,including single-crystal silicon,silicon carbide,and gallium arsenide.Surface roughness and subsurface damage depth(SDD)are crucial indicators for evaluating the surface quality of these materials after grinding.Existing prediction models lack general applicability and do not accurately account for the complex material behavior under grinding conditions.This paper introduces novel models for predicting both surface roughness and SDD in hard and brittle semiconductor materials.The surface roughness model uniquely incorporates the material’s elastic recovery properties,revealing the significant impact of these properties on prediction accuracy.The SDD model is distinguished by its analysis of the interactions between abrasive grits and the workpiece,as well as the mechanisms governing stress-induced damage evolution.The surface roughness model and SDD model both establish a stable relationship with the grit depth of cut(GDC).Additionally,we have developed an analytical relationship between the GDC and grinding process parameters.This,in turn,enables the establishment of an analytical framework for predicting surface roughness and SDD based on grinding process parameters,which cannot be achieved by previous models.The models were validated through systematic experiments on three different semiconductor materials,demonstrating excellent agreement with experimental data,with prediction errors of 6.3%for surface roughness and6.9%for SDD.Additionally,this study identifies variations in elastic recovery and material plasticity as critical factors influencing surface roughness and SDD across different materials.These findings significantly advance the accuracy of predictive models and broaden their applicability for grinding hard and brittle semiconductor materials.
文摘Hybrid manufacturing(HM)uses additive manufacturing(AM)techniques to prepare complex or fine structures on traditional processing parts,which can fully utilize the advantages of AM to form complex parts,and the high efficiency and low cost of conventional processing methods in manufacturing regular components.A bimetal material was produced by selective laser melting(SLM)of AlSi10Mg on the deformed Al6061 alloy substrate in this study.Firstly,the interface characteristics of the two alloys were studied.The results show that a metallurgical interface with a thickness of 100–200μm was formed as the result of the Marangoni convection during SLM preparation.In detail,the circular flow in the melt pool at the interface led to the dilution of alloying elements and the change of microstructure.Moreover,a suitable first-layer thickness can eff ectively suppress the hot cracks at the interfacial region.Based on the optimized results,the hybrid manufactured samples with diff erent SLM processed volume ratios(SLM-part)to the substrate were prepared to study the mechanical properties and the deformation behavior of hybrid parts.The results show that the volume ratio of the SLM-part to the substrate had an influence on the strength and the elasto-plastic behavior by aff ecting the distribution of plastic deformation.
基金supported by the National Natural Science Foundation of China(Grant No.11572333)the State Key Laboratory of High Temperature Gas Dynamics,Institute of Mechanics,Chinese Academy of Sciences(Grant No.LHD2017TC01)the Chinese Academy of Sciences Foundation Frontier Scientific Research Program(Grant No.ZDBS-LY-JSC005)。
文摘Lift-to-drag ratio (L/D) is nearly the most important index in determining the aerodynamic performance of a hypersonic flight vehicle,because the flight distance is linearly proportional to the L/D according to Breguet's equation.In general,the higher the L/D of a vehicle,the greater the flight range if the specific impulse,structural mass ratio,and flight velocity are given.Naturally,the pursuit of a high L/D for hypersonic vehicles has never ceased [1,2].
文摘This paper proposes a co-optimal strategy using line hardening,mobile devices(mobile ice-melting device,mobile emergency generator,mobile energy storage system),and repair crew dispatching to improve distribution system resilience during ice storms.A multi-stage defender-attacker-defender model is established to take into account interactions and coupling relationships between different measures.In our proposed model,ice storms will attack the distribution and transportation system in a worst-case scenario,affecting system performance from various perspectives.Corresponding to the different operating states in the distribution system affected by ice storms,aiming at minimizing the weighted load shedding value,this paper applies various measures to different stages to improve the response and defense capabilities to ice storms and realize restoration of the distribution system ultimately.The nested column-and-constraint generation algorithm is used to solve the model efficiently.The effectiveness of the proposed model and solution method for enhancing the distribution system resilience is verified on the modified IEEE 33-bus distribution system and modified realworld zone of Caracas 141-bus distribution system.
基金the National Natural Science Foundation of China(22377093)the Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholar(LR23C100001,China)the Zhejiang Qianjiang Talent Plan(QJD20020224,China).
文摘Currently,the efficacy of albumin-bound paclitaxel(PTX@Alb)is still limited due to theimpaired PTX@Alb accumulation in tumors partly mediated by the dense collagen distribution.Meanwhile,acquired immune resistance always occurs due to the enhanced programmed cell death-ligand 1(PD-L1)expression after PTX@Alb treatment,which then leads to immune tolerance.To fill these gaps,we newly revealed that tamoxifen(TAM),a clinically widely used adjuvant therapy for breast cancer withmitochondrial metabolism blockade capacity,could also be used as a novel effective PD-L1 and TGF-bdual-inhibitor via inducing the phosphorylation of adenosine 5ʹ-monophosphate-activated protein kinase(AMPK)protein.Following this,to obtain a more significant effect,TPP-TAM was prepared by conjugatingmitochondria-targeted triphenylphosphine(TPP)with TAM,which then further self-assembledwith albumin(Alb)to form TPP-TAM@Alb nanoparticles.By doing this,TPP-TAM@Alb nanoparticleseffectively decreased the expression of collagen in vitro,which then led to the enhanced accumulation ofPTX@Alb in 4T1 tumors.Besides,TPP-TAM@Alb also effectively decreased the expression of PD-L1 and TGF-b in tumors to better sensitize PTX@Alb-mediated chemo-immunotherapy by enhancing T cellinfiltration.All in all,we newly put forward a novel mitochondrial metabolism blockade strategy toinhibit PTX@Alb-resistant tumors,further supporting its better clinical application。
基金Financial support from the National Natural Science Foundation of China(Nos.22071205 and 21772164)NFFTBS(J1310024)+1 种基金NCETFJ,and PCSIRT is acknowledged.The authors are also grateful for the financial support(LMDBKF-2019-03)the Laboratory for Marine Drugs and Bioproducts,Pilot National Laboratory for Marine Science and Technology.
文摘A full account of semisyntheses of polychlorinated marine steroids clionastatins A and B is described.We have developed a unique two-stage chlorination-oxidation strategy that enabled concise and divergent semisyntheses of clionastatins A and B in 16 steps from inexpensive testosterone.Key transformations in chlorination stage include(a)conformationally controlled,stereospecific dichlorination through an unusualβ-chloronium intermediate to install the diequatorial C1,C2-dichloride;(b)C4-OH directed C19–H oxygenation followed by challenging neopentyl chlorination to install the C19–Cl.The high oxidation level was constructed through(a)the desaturation at C6–C7 through one-pot photochemical dibromination–reductive debromination;(b)regioselective anti-Markovnikov oxidation of the C6–C7 double bond by photoredox-metal dual catalysis to forge the B ring enone;(c)late-stage desaturation with SeO_(2)to introduce C8–C9 double bond.Wharton transposition was used to forge the D-ring enone,and thermodynamically driven epimerization secured the cis-fused C/D ring system.Furthermore,we also provided a 14-step approach to clionastatin A by optimizing the construction of the D-ring enone with a dehydration-oxidation sequence.
