Drying experiments of two paper mill sludge were carried using hot air with a temperature range of 50?C - 80?C and an air velocity of 0.96 m/son a laboratory convective dryer. The drying characteristics were discussed...Drying experiments of two paper mill sludge were carried using hot air with a temperature range of 50?C - 80?C and an air velocity of 0.96 m/son a laboratory convective dryer. The drying characteristics were discussed and the drying kinetic equation was solved. The dependence of the reaction rate constant on the drying temperature was given by Arrhenius equation, and the activation energies for moisture diffusion in paper mill sludge sample A and B were found to be 21.53 kJ/mol and 15.38 kJ/mol, respectively.展开更多
Ducted fans have been extensively used in Unmanned Aerial Vehicles(UAVs)for a variety of missions because of high efficiency,high safety and low noise.Wind,as a kind of typical meteorological condition,brings signific...Ducted fans have been extensively used in Unmanned Aerial Vehicles(UAVs)for a variety of missions because of high efficiency,high safety and low noise.Wind,as a kind of typical meteorological condition,brings significant aerodynamic interference to the ducted fan,which seriously threatens flight stability and safety.In this work,the numerical simulation with the Unsteady Reynolds Averaged Navier-Stokes(URANS)method and the sliding mesh technique is performed to evaluate the steady wind effect.The results show that the wind will lead to serious unsteady effects in the flow field,and the thrust fluctuates at the blade passing frequency of 200 Hz.As the wind speed increases,the rotor thrust increases,the duct thrust decreases,and the total thrust changes little.Flow instability may occur when the wind speed exceeds 8 m/s.As the angle of low-speed wind increases,the rotor thrust changes little,the duct thrust increases,and the total thrust increases.In addition,we figure out that cases with the same crosswind ratio are similar in results,and increasing the rotating speed or fan radius is beneficial to performance improvement in wind.The findings are essential to the ducted fan design and UAV flight control design for stable and safe operations in wind conditions.展开更多
Exploiting novel endogenous glyphosate-tolerant alleles is highly desirable and has promising potential for weed control in rice breeding. Here,through fusions of different effective cytosine and adenine deaminases wi...Exploiting novel endogenous glyphosate-tolerant alleles is highly desirable and has promising potential for weed control in rice breeding. Here,through fusions of different effective cytosine and adenine deaminases with nCas9-NG, we engineered an effective surrogate two-component composite base editing system, STCBE-2, with improved C-to-T and A-to-G base editing efficiency and expanded the editing window. Furthermore,we targeted a rice endogenous OsEPSPS gene for artificial evolution through STCBE-2-mediated near-saturated mutagenesis. After hygromycin and glyphosate selection, we identified a novel OsEPSPS allele with an Asp-213-Asn(D213N)mutation(OsEPSPS-D213N) in the predicted glyphosate-binding domain, which conferred rice plants reliable glyphosate tolerance and had not been reported or applied in rice breeding. Collectively, we developed a novel dual base editor which will be valuable for artificial evolution of important genes in crops. And the novel glyphosate-tolerant rice germplasm generated in this study will benefit weeds management in rice paddy fields.展开更多
Dear Editor,Base editors(BEs)are promising tools that enable single-nucleotide substitutions in specific target genes,generating loss-offunction or gain-of-function mutations,which can greatly accelerate plant functio...Dear Editor,Base editors(BEs)are promising tools that enable single-nucleotide substitutions in specific target genes,generating loss-offunction or gain-of-function mutations,which can greatly accelerate plant functional genomics and crop improvement(Ren et al.,2018;Zeng et al.,2020;Xu et al.,2021;Yan et al.,2021;Li et al.,2023).To date,three major classes of BEs have been engineered:cytosine BEs(CBEs)for C-to-T transitions(Komor et al.,2016),adenine BEs(ABEs)for A-to-G transitions(Gaudelli et al.,2017).展开更多
Ducted fans are widely used in various applications of Unmanned Aerial Vehicles(UAVs)due to the high efficiency,low noise and high safety.The unsteady characteristics of ducted fans flying near the ground are signific...Ducted fans are widely used in various applications of Unmanned Aerial Vehicles(UAVs)due to the high efficiency,low noise and high safety.The unsteady characteristics of ducted fans flying near the ground are significant,which may bring stability problems.In this paper,the sliding mesh technology is applied and the Unsteady Reynolds Averaged Navier-Stokes(URANS)method is adopted to evaluate the influence of ground on the aerodynamic performance of ducted fans.The time-averaged results show that the ground leads to the decrease of duct thrust,the increase of rotor thrust and the decrease of total thrust.The transient results show that there exist small-scale stall cells with circumferential movements in ground effect.The stall cells start to appear at the blade root when the height is 0.8 rotor radius distance,and arise at both the blade root and tip when the height drops to 0.2.It is found that the unsteady cells rotate between blade passages with an approximate relative speed of 30%-80%of the fan speed,and lead to thrust fluctuations up to 37%of the total thrust.The results are essential to the flight control design of the ducted fan flying vehicle,to ensure its stability in ground effect.展开更多
The cell surface membrane proteome is a class of proteins encoded by ~25% of all protein-coding genes in living organisms and plays a key role in mediating communication between the cells and their surrounding environ...The cell surface membrane proteome is a class of proteins encoded by ~25% of all protein-coding genes in living organisms and plays a key role in mediating communication between the cells and their surrounding environment. However, most cell surface membrane proteins(CSMPs) are naturally expressed at very low levels compared with intracellular proteins. The difficulties in their purification with high specificity further hinder the understanding of their structure and function. In this study, we developed a new photolabeling probe to achieve efficient tagging and facile enrichment of the CSMPs. The probe is composed of a lipid tail for cell surface localization, a polyethylene glycol(PEG) spacer for increased water solubility, two 4-(N-maleimido)benzophenone(MBP) groups for UV-active tagging of the CSMPs, and a biotin tag for subsequent isolation. Application of this photolabeling probe resulted in the successful enrichment and identification of 3098 annotated CSMPs in HT22 cells with close to 70% selectivity. The proposed photolabeling probe and enrichment strategy were demonstrated to be a powerful method for deep cell surface proteome profiling, representing one of the largest groups of current drug targets.展开更多
Loss of function of the von Hippel-Lindau(VHL)tumor suppressor gene is a hallmark of clear cell renal cell carcinoma(ccRCC).The importance of heterogeneity in the loss of this tumor suppressor has been under reported....Loss of function of the von Hippel-Lindau(VHL)tumor suppressor gene is a hallmark of clear cell renal cell carcinoma(ccRCC).The importance of heterogeneity in the loss of this tumor suppressor has been under reported.To study the impact of intratumoral VHL heterogeneity observed in human ccRCC,we engineered VHL gene deletion in four RCC models,including a new primary tumor cell line derived from an aggressive metastatic case.The VHL gene-deleted(VHL-KO)cells underwent epithelial-to-mesenchymal transition(EMT)and exhibited increased motility but diminished proliferation and tumorigenicity compared to the parental VHL-expressing(VHL+)cells.Renal tumors with either VHL+or VHL-KO cells alone exhibit minimal metastatic potential.Combined tumors displayed rampant lung metastases,highlighting a novel cooperative metastatic mechanism.The poorly proliferative VHL-KO cells stimulated the proliferation,EMT,and motility of neighboring VHL+cells.Periostin(POSTN),a soluble protein overexpressed and secreted by VHL non-expressing(VHL−)cells,promoted metastasis by enhancing the motility of VHL-WT cells and facilitating tumor cell vascular escape.Genetic deletion or antibody blockade of POSTN dramatically suppressed lung metastases in our preclinical models.This work supports a new strategy to halt the progression of ccRCC by disrupting the critical metastatic crosstalk between heterogeneous cell populations within a tumor.展开更多
温度是影响动力电池性能的关键因素.高效热管理技术可有效控制动力电池温度和温差.本研究采用微通道热管阵列作为电池热管理系统的热传导元件,分析了其在高热功率密度下的传热性能,理论计算了其等效导热系数,优化分析了其槽道尺寸对流...温度是影响动力电池性能的关键因素.高效热管理技术可有效控制动力电池温度和温差.本研究采用微通道热管阵列作为电池热管理系统的热传导元件,分析了其在高热功率密度下的传热性能,理论计算了其等效导热系数,优化分析了其槽道尺寸对流动传热的影响,对比了其与主流散热技术的性能差异.研究发现,热功率密度为0.3658 W cm^-2时,强制风冷散热条件下,采用微通道热管阵列技术可维持热源处表面温度45℃以下,温差1.3℃以下,低于无微通道热管阵列导热情况下的温升15℃,温差3.8℃.随着热功率密度增大至0.9176 W cm^-2,微通道热管阵列的等效导热系数增大为6027 W m^-1K^-1,其热源处表面最大瞬态温差约2.75℃.增大槽道尺寸参数可进一步改善微通道热管阵列的导热系数,改善其传热性能,但对液体回流驱动力有一定影响.该阵列具有较好的动态工况热稳定性和低温快速加热能力.与烧结热管组的温度性能相比,微通道热管阵列组最大温度可降低15.1℃,表面温差降低14℃,具有显著降温和均温优势,表明微通道热管阵列在动力电池热管理系统中具有广泛应用前景.展开更多
In this review,the evolution of high strain Na_(0.5)Bi_(0.5)TiO_(3)-based lead-free piezoceramics and their multilayer actuators has been explored.First,in terms of Na_(0.5)Bi_(0.5)TiO_(3)-based ceramic materials,the ...In this review,the evolution of high strain Na_(0.5)Bi_(0.5)TiO_(3)-based lead-free piezoceramics and their multilayer actuators has been explored.First,in terms of Na_(0.5)Bi_(0.5)TiO_(3)-based ceramic materials,the origin of high strain,the typical chemical modification methods of obtaining large strain and extrinsic factors affecting the large strain are discussed.Then it briefly summarizes the problems existing in Na_(0.5)Bi_(0.5)TiO_(3)-based ceramics for multilayer actuator applications.Strategies to optimize strain performance by means of microstructure control and phase structure design are also discussed.Thereafter,in terms of multilayer actuator,we describe its characteristics,applications and preparation process systematically,as well as the recent development of Na_(0.5)Bi_(0.5)TiO_(3)-based multilayer actuator.At last,perspectives on directions of following work and promising fields for the applications of the materials and their devices are presented.展开更多
Background:Increased hypoxia-inducible factor 2α(HIF2α)activation is a common event in clear cell renal cell carcinoma(ccRCC)progression.However,the function and underlying mechanism of HIF2α in ccRCC remains uninv...Background:Increased hypoxia-inducible factor 2α(HIF2α)activation is a common event in clear cell renal cell carcinoma(ccRCC)progression.However,the function and underlying mechanism of HIF2α in ccRCC remains uninvestigated.We conducted this study to access the potential link between junction plakoglobin(JUP)and HIF2αin ccRCC.Methods:Affinity purification and mass spectrometry(AP-MS)screening,glutathione-s-transferase(GST)pull-down and co-immunoprecipitation(Co-IP)assays were performed to detect the interacting proteins of HIF2α.Quantitative PCR(qPCR)and Western blotting were used to detect the expression of JUP in human ccRCC samples.Luciferase reporter assays,chromatin immunoprecipitation(ChIP),cycloheximide chase assays,and ubiquitination assays were conducted to explore the regulation of JUP on the activity of HIF2α.Cell Counting Kit-8(CCK-8)assays,colony formation assays,transwell assays,and xenograft tumor assays were performed to investigate the effect of JUP knockdown or overexpression on the tumorigenicity of renal cancer cells.Results:We identified JUP as a novel HIF2α-binding partner and revealed an important role of JUP in recruiting von Hippel-Lindau(VHL)and histone deacetylases 1/2(HDAC1/2)to HIF2α to regulate its stability and transactivation.JUP knockdown promoted and overexpression suppressed the tumorigenicity of renal cell carcinoma in vitro and in vivo.Importantly,the low expression of JUP was found in clinical ccRCC samples and correlated with enhanced hypoxia scores and poor treatment outcomes.Conclusion:Taken together,these data support a role of JUP in modulating HIF2α signaling during ccRCC progression and identify JUP as a potential therapeutic target.展开更多
The thermal management of battery systems is critical for maintaining the energy storage capacity,life span,and thermal safety of batteries used in electric vehicles,because the operating temperature is a key factor a...The thermal management of battery systems is critical for maintaining the energy storage capacity,life span,and thermal safety of batteries used in electric vehicles,because the operating temperature is a key factor affecting battery performance.Excessive temperature rises and large temperature differences accelerate the degradation rate of such batteries.Currently,the increasing demand for fast charging and special on-vehicle scenarios has increased the heat dissipation requirements of battery thermal management systems.To address this demand,this work proposes a novel micro heat pipe array(MHPA)for thermal management under a broadened research scope,including high heat generation rates,large tilt angles,mild vibration,and distributed heat generation conditions.The experimental results indicate that the temperature difference is maintained 3.44°C at a large heat generation of 50 W for a limited range of tilt angles.Furthermore,a mild vehicle vibra-tion condition was found to improve temperature uniformity by 3.3°C at a heat generation of 10 W.However,the use of distributed heat sources results in a temperature variation of 3.88°C,suggesting that the heat generation distribution needs to be considered in thermal analyses.Understanding the effects of these special battery-operating conditions on the MHPA could significantly contribute to the enhancement of heat transfer capability and temperature uniformity improvement of battery thermal management systems based on heat pipe technologies.This would facilitate the realization of meeting the higher requirements of future battery systems.展开更多
文摘Drying experiments of two paper mill sludge were carried using hot air with a temperature range of 50?C - 80?C and an air velocity of 0.96 m/son a laboratory convective dryer. The drying characteristics were discussed and the drying kinetic equation was solved. The dependence of the reaction rate constant on the drying temperature was given by Arrhenius equation, and the activation energies for moisture diffusion in paper mill sludge sample A and B were found to be 21.53 kJ/mol and 15.38 kJ/mol, respectively.
基金This study was co-supported by the National Key Research and Development Program of China(No.2020YFC1512500),The Advanced Aviation Power Innovation institution,The Aero Engine Academy of China,and Tsinghua University Initiative Scientific Research Program,China.
文摘Ducted fans have been extensively used in Unmanned Aerial Vehicles(UAVs)for a variety of missions because of high efficiency,high safety and low noise.Wind,as a kind of typical meteorological condition,brings significant aerodynamic interference to the ducted fan,which seriously threatens flight stability and safety.In this work,the numerical simulation with the Unsteady Reynolds Averaged Navier-Stokes(URANS)method and the sliding mesh technique is performed to evaluate the steady wind effect.The results show that the wind will lead to serious unsteady effects in the flow field,and the thrust fluctuates at the blade passing frequency of 200 Hz.As the wind speed increases,the rotor thrust increases,the duct thrust decreases,and the total thrust changes little.Flow instability may occur when the wind speed exceeds 8 m/s.As the angle of low-speed wind increases,the rotor thrust changes little,the duct thrust increases,and the total thrust increases.In addition,we figure out that cases with the same crosswind ratio are similar in results,and increasing the rotating speed or fan radius is beneficial to performance improvement in wind.The findings are essential to the ducted fan design and UAV flight control design for stable and safe operations in wind conditions.
基金partly funded by the National Natural Science Foundation of China (32188102 to LX)Hainan Yazhou Bay Seed Lab (B21HJ0215 to LX)+2 种基金the Central Public-Interest Scientific Institution-Based Research Fund (S2023ZD03 to LX)Key Laboratory of Gene Editing Technologies (Hainan), ChinaNational Engineering Research Center of Crop Molecular Breeding。
文摘Exploiting novel endogenous glyphosate-tolerant alleles is highly desirable and has promising potential for weed control in rice breeding. Here,through fusions of different effective cytosine and adenine deaminases with nCas9-NG, we engineered an effective surrogate two-component composite base editing system, STCBE-2, with improved C-to-T and A-to-G base editing efficiency and expanded the editing window. Furthermore,we targeted a rice endogenous OsEPSPS gene for artificial evolution through STCBE-2-mediated near-saturated mutagenesis. After hygromycin and glyphosate selection, we identified a novel OsEPSPS allele with an Asp-213-Asn(D213N)mutation(OsEPSPS-D213N) in the predicted glyphosate-binding domain, which conferred rice plants reliable glyphosate tolerance and had not been reported or applied in rice breeding. Collectively, we developed a novel dual base editor which will be valuable for artificial evolution of important genes in crops. And the novel glyphosate-tolerant rice germplasm generated in this study will benefit weeds management in rice paddy fields.
基金funded by the National Natural Science Foundation of China(grant no.32188102 to L.X.)the Hainan Yazhou Bay Seed Lab(grant no.B23CJ0208 to L.X.)+1 种基金the Central Publicinterest Scientific Institution-Based Research Fund(grant no.ZDXM2308 to L.X.)the National Engineering Research Centre of Crop Molecular Breeding.
文摘Dear Editor,Base editors(BEs)are promising tools that enable single-nucleotide substitutions in specific target genes,generating loss-offunction or gain-of-function mutations,which can greatly accelerate plant functional genomics and crop improvement(Ren et al.,2018;Zeng et al.,2020;Xu et al.,2021;Yan et al.,2021;Li et al.,2023).To date,three major classes of BEs have been engineered:cytosine BEs(CBEs)for C-to-T transitions(Komor et al.,2016),adenine BEs(ABEs)for A-to-G transitions(Gaudelli et al.,2017).
基金co-supported by the National Key Research and Development Program of China(No.2020YFC1512500)The Advanced Aviation Power Innovation institution,The Aero Engine Academy of ChinaTsinghua University Initiative Scientific Research Program.
文摘Ducted fans are widely used in various applications of Unmanned Aerial Vehicles(UAVs)due to the high efficiency,low noise and high safety.The unsteady characteristics of ducted fans flying near the ground are significant,which may bring stability problems.In this paper,the sliding mesh technology is applied and the Unsteady Reynolds Averaged Navier-Stokes(URANS)method is adopted to evaluate the influence of ground on the aerodynamic performance of ducted fans.The time-averaged results show that the ground leads to the decrease of duct thrust,the increase of rotor thrust and the decrease of total thrust.The transient results show that there exist small-scale stall cells with circumferential movements in ground effect.The stall cells start to appear at the blade root when the height is 0.8 rotor radius distance,and arise at both the blade root and tip when the height drops to 0.2.It is found that the unsteady cells rotate between blade passages with an approximate relative speed of 30%-80%of the fan speed,and lead to thrust fluctuations up to 37%of the total thrust.The results are essential to the flight control design of the ducted fan flying vehicle,to ensure its stability in ground effect.
基金supported by National Natural Science Foundation of China (Nos. 32088101, 22074158, 21904008)National Key R&D Program of China (Nos. 2021YFA1302604, 2021YFA1301601, 2017YFA0505002)National Key Laboratory of Proteomics (Nos. SKLP-K201706, 2021-NCPSB-003)。
文摘The cell surface membrane proteome is a class of proteins encoded by ~25% of all protein-coding genes in living organisms and plays a key role in mediating communication between the cells and their surrounding environment. However, most cell surface membrane proteins(CSMPs) are naturally expressed at very low levels compared with intracellular proteins. The difficulties in their purification with high specificity further hinder the understanding of their structure and function. In this study, we developed a new photolabeling probe to achieve efficient tagging and facile enrichment of the CSMPs. The probe is composed of a lipid tail for cell surface localization, a polyethylene glycol(PEG) spacer for increased water solubility, two 4-(N-maleimido)benzophenone(MBP) groups for UV-active tagging of the CSMPs, and a biotin tag for subsequent isolation. Application of this photolabeling probe resulted in the successful enrichment and identification of 3098 annotated CSMPs in HT22 cells with close to 70% selectivity. The proposed photolabeling probe and enrichment strategy were demonstrated to be a powerful method for deep cell surface proteome profiling, representing one of the largest groups of current drug targets.
基金supported by the NCI/NIH (grant number 1R21CA216770)Tobacco-Related Disease Research Program (grant number 27IR-0016)+5 种基金CDMRP Kidney Cancer Research Program (grant number W81XWH-20-1-0918)Cancer Research Coordinating Committee (grant number CRC15-380768)2021 Kure It Cancer Research Grant (www.kureit.org) to L.W.UCLA institutional support grants included the UCLA Jonsson Comprehensive Cancer Center (grant number P30CA016042)the UCLA Clinical and Translational Science Institute (grant number UL1TR001881)UCLA 3 R grant (Office of Vice Chancellor of Research) to L.W.UCLA Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Research Award Program.
文摘Loss of function of the von Hippel-Lindau(VHL)tumor suppressor gene is a hallmark of clear cell renal cell carcinoma(ccRCC).The importance of heterogeneity in the loss of this tumor suppressor has been under reported.To study the impact of intratumoral VHL heterogeneity observed in human ccRCC,we engineered VHL gene deletion in four RCC models,including a new primary tumor cell line derived from an aggressive metastatic case.The VHL gene-deleted(VHL-KO)cells underwent epithelial-to-mesenchymal transition(EMT)and exhibited increased motility but diminished proliferation and tumorigenicity compared to the parental VHL-expressing(VHL+)cells.Renal tumors with either VHL+or VHL-KO cells alone exhibit minimal metastatic potential.Combined tumors displayed rampant lung metastases,highlighting a novel cooperative metastatic mechanism.The poorly proliferative VHL-KO cells stimulated the proliferation,EMT,and motility of neighboring VHL+cells.Periostin(POSTN),a soluble protein overexpressed and secreted by VHL non-expressing(VHL−)cells,promoted metastasis by enhancing the motility of VHL-WT cells and facilitating tumor cell vascular escape.Genetic deletion or antibody blockade of POSTN dramatically suppressed lung metastases in our preclinical models.This work supports a new strategy to halt the progression of ccRCC by disrupting the critical metastatic crosstalk between heterogeneous cell populations within a tumor.
文摘温度是影响动力电池性能的关键因素.高效热管理技术可有效控制动力电池温度和温差.本研究采用微通道热管阵列作为电池热管理系统的热传导元件,分析了其在高热功率密度下的传热性能,理论计算了其等效导热系数,优化分析了其槽道尺寸对流动传热的影响,对比了其与主流散热技术的性能差异.研究发现,热功率密度为0.3658 W cm^-2时,强制风冷散热条件下,采用微通道热管阵列技术可维持热源处表面温度45℃以下,温差1.3℃以下,低于无微通道热管阵列导热情况下的温升15℃,温差3.8℃.随着热功率密度增大至0.9176 W cm^-2,微通道热管阵列的等效导热系数增大为6027 W m^-1K^-1,其热源处表面最大瞬态温差约2.75℃.增大槽道尺寸参数可进一步改善微通道热管阵列的导热系数,改善其传热性能,但对液体回流驱动力有一定影响.该阵列具有较好的动态工况热稳定性和低温快速加热能力.与烧结热管组的温度性能相比,微通道热管阵列组最大温度可降低15.1℃,表面温差降低14℃,具有显著降温和均温优势,表明微通道热管阵列在动力电池热管理系统中具有广泛应用前景.
基金the support by the National Natural Science Foundation of China(No.U1732117,51902111 and 51672092)the China Postdoctoral Science Foundation(No.2019M662602)+1 种基金the Open Fund of Guangxi Key Laboratory of Information Materials(No.191015-K)the Donguan Innovative Research Team Program.
文摘In this review,the evolution of high strain Na_(0.5)Bi_(0.5)TiO_(3)-based lead-free piezoceramics and their multilayer actuators has been explored.First,in terms of Na_(0.5)Bi_(0.5)TiO_(3)-based ceramic materials,the origin of high strain,the typical chemical modification methods of obtaining large strain and extrinsic factors affecting the large strain are discussed.Then it briefly summarizes the problems existing in Na_(0.5)Bi_(0.5)TiO_(3)-based ceramics for multilayer actuator applications.Strategies to optimize strain performance by means of microstructure control and phase structure design are also discussed.Thereafter,in terms of multilayer actuator,we describe its characteristics,applications and preparation process systematically,as well as the recent development of Na_(0.5)Bi_(0.5)TiO_(3)-based multilayer actuator.At last,perspectives on directions of following work and promising fields for the applications of the materials and their devices are presented.
基金supported by National Natural Science Foundation of China(grant number 81772721,81874089,81602236,81702522)Natural Science Foundation of Jiangxi Province of China(20202BABL216060)National Major Scientific and Technological Special Project for“Significant New Drugs Development”(2017ZX09304022).
文摘Background:Increased hypoxia-inducible factor 2α(HIF2α)activation is a common event in clear cell renal cell carcinoma(ccRCC)progression.However,the function and underlying mechanism of HIF2α in ccRCC remains uninvestigated.We conducted this study to access the potential link between junction plakoglobin(JUP)and HIF2αin ccRCC.Methods:Affinity purification and mass spectrometry(AP-MS)screening,glutathione-s-transferase(GST)pull-down and co-immunoprecipitation(Co-IP)assays were performed to detect the interacting proteins of HIF2α.Quantitative PCR(qPCR)and Western blotting were used to detect the expression of JUP in human ccRCC samples.Luciferase reporter assays,chromatin immunoprecipitation(ChIP),cycloheximide chase assays,and ubiquitination assays were conducted to explore the regulation of JUP on the activity of HIF2α.Cell Counting Kit-8(CCK-8)assays,colony formation assays,transwell assays,and xenograft tumor assays were performed to investigate the effect of JUP knockdown or overexpression on the tumorigenicity of renal cancer cells.Results:We identified JUP as a novel HIF2α-binding partner and revealed an important role of JUP in recruiting von Hippel-Lindau(VHL)and histone deacetylases 1/2(HDAC1/2)to HIF2α to regulate its stability and transactivation.JUP knockdown promoted and overexpression suppressed the tumorigenicity of renal cell carcinoma in vitro and in vivo.Importantly,the low expression of JUP was found in clinical ccRCC samples and correlated with enhanced hypoxia scores and poor treatment outcomes.Conclusion:Taken together,these data support a role of JUP in modulating HIF2α signaling during ccRCC progression and identify JUP as a potential therapeutic target.
基金This work was supported by the National Natural Science Foundation of China(No.U1864212)by the State Key Laboratory of Automotive Safety and Energy(No.ZZ2019-051).
文摘The thermal management of battery systems is critical for maintaining the energy storage capacity,life span,and thermal safety of batteries used in electric vehicles,because the operating temperature is a key factor affecting battery performance.Excessive temperature rises and large temperature differences accelerate the degradation rate of such batteries.Currently,the increasing demand for fast charging and special on-vehicle scenarios has increased the heat dissipation requirements of battery thermal management systems.To address this demand,this work proposes a novel micro heat pipe array(MHPA)for thermal management under a broadened research scope,including high heat generation rates,large tilt angles,mild vibration,and distributed heat generation conditions.The experimental results indicate that the temperature difference is maintained 3.44°C at a large heat generation of 50 W for a limited range of tilt angles.Furthermore,a mild vehicle vibra-tion condition was found to improve temperature uniformity by 3.3°C at a heat generation of 10 W.However,the use of distributed heat sources results in a temperature variation of 3.88°C,suggesting that the heat generation distribution needs to be considered in thermal analyses.Understanding the effects of these special battery-operating conditions on the MHPA could significantly contribute to the enhancement of heat transfer capability and temperature uniformity improvement of battery thermal management systems based on heat pipe technologies.This would facilitate the realization of meeting the higher requirements of future battery systems.
