Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen r...Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.展开更多
Network updates have become increasingly prevalent since the broad adoption of software-defined networks(SDNs)in data centers.Modern TCP designs,including cutting-edge TCP variants DCTCP,CUBIC,and BBR,however,are not ...Network updates have become increasingly prevalent since the broad adoption of software-defined networks(SDNs)in data centers.Modern TCP designs,including cutting-edge TCP variants DCTCP,CUBIC,and BBR,however,are not resilient to network updates that provoke flow rerouting.In this paper,we first demonstrate that popular TCP implementations perform inadequately in the presence of frequent and inconsistent network updates,because inconsistent and frequent network updates result in out-of-order packets and packet drops induced via transitory congestion and lead to serious performance deterioration.We look into the causes and propose a network update-friendly TCP(NUFTCP),which is an extension of the DCTCP variant,as a solution.Simulations are used to assess the proposed NUFTCP.Our findings reveal that NUFTCP can more effectively manage the problems of out-of-order packets and packet drops triggered in network updates,and it outperforms DCTCP considerably.展开更多
Neoantigen-targeted immunotherapy is a rapidly advancing field that holds great promise for treating cancer.The recognition of antigens by immune cells is a crucial step in tumor-specific killing,and neoantigens gener...Neoantigen-targeted immunotherapy is a rapidly advancing field that holds great promise for treating cancer.The recognition of antigens by immune cells is a crucial step in tumor-specific killing,and neoantigens generated by mutations in cancer cells possess high immunogenicity and are selectively expressed in tumor cells,making them an attractive therapeutic target.Currently,neoantigens find utility in various domains,primarily in the realm of neoantigen vaccines such as DC vaccines,nucleic acid vaccines,and synthetic long peptide vaccines.Additionally,they hold promise in adoptive cell therapy,encompassing tumor-infiltrating cells,T cell receptors,and chimeric antigen receptors which are expressed by genetically modified T cells.In this review,we summarized recent progress in the clinical use of tumor vaccines and adoptive cell therapy targeting neoantigens,discussed the potential of neoantigen burden as an immune checkpoint in clinical settings.With the aid of state-of-the-art sequencing and bioinformatics technologies,together with significant advancements in artificial intelligence,we anticipated that neoantigens will be fully exploited for personalized tumor immunotherapy,from screening to clinical application.展开更多
Weather forecasting for the Zhangjiakou competition zone of the Beijing 2022 Winter Olympic Games is a challenging task due to its complex terrain.Numerical weather prediction models generally perform poorly for cold ...Weather forecasting for the Zhangjiakou competition zone of the Beijing 2022 Winter Olympic Games is a challenging task due to its complex terrain.Numerical weather prediction models generally perform poorly for cold air pools and winds over complex terrains,due to their low spatiotemporal resolution and limitations in the description of dynamics,thermodynamics,and microphysics in mountainous areas.This study proposes an ensemble-learning model,named ENSL,for surface temperature and wind forecasts at the venues of the Zhangjiakou competition zone,by integrating five individual models—linear regression,random forest,gradient boosting decision tree,support vector machine,and artificial neural network(ANN),with a ridge regression as meta model.The ENSL employs predictors from the high-resolution ECMWF model forecast(ECMWF-HRES) data and topography data,and targets from automatic weather station observations.Four categories of predictors(synoptic-pattern related fields,surface element fields,terrain,and temporal features) are fed into ENSL.The results demonstrate that ENSL achieves better performance and generalization than individual models.The root-mean-square error(RMSE) for the temperature and wind speed predictions is reduced by 48.2% and 28.5%,respectively,relative to ECMWF-HRES.For the gust speed,the performance of ENSL is consistent with ANN(best individual model) in the whole dataset,whereas ENSL outperforms on extreme gust samples(42.7% compared with 38.7% obtained by ECMWF-HRES in terms of RMSE reduction).Sensitivity analysis of predictors in the four categories shows that ENSL fits their feature importance rankings and physical explanations effectively.展开更多
A great deal of oil contaminated the shoreline by the Qingdao oil pipeline explosion in 2013. The four oildegrading consortia were enriched from sediment samples with crude oil as sole carbon and energy sources. The b...A great deal of oil contaminated the shoreline by the Qingdao oil pipeline explosion in 2013. The four oildegrading consortia were enriched from sediment samples with crude oil as sole carbon and energy sources. The biodiversity and community analysis showed that the Luteibacter, Parvibaculum and a genus belonging to Alcanivoracaceae were found predominant bacteria in the four consortia, which belonged to Proteobacteria. Nine strains exhibiting distinct 16S rRNA gene sequences were isolated from the consortia. These strains were identified to eight genera based on 16S rRNA gene sequences. Five of the nine strains degraded more than 30% of the crude oil in two weeks by gravimetric method. From the analysis of GC-MS, most of the isolated strains tended to degrade n-alkanes rather than PAHs. Five strains showed high degrading ability of the total n-alkanes. Only Strain D2 showed great PAHs degrading ability and the degrading rates ranged from 34.9% to 77.5%. The sequencing analysis of the oil-degrading consortia confirmed that the genus of Alcanivorax was one of the dominant bacteria in Consortia A and E and Strain E4 might be one of the dominant bacteria. The strains obtained in this study demonstrated the potential for oil bioremediation in oil-contaminated beach ecosystems.展开更多
Power analysis is a key component for planning prospective studies such as clinical trials. However, some journals in biomedical and psychosocial sciences ask for power analysis for data already collected and analysed...Power analysis is a key component for planning prospective studies such as clinical trials. However, some journals in biomedical and psychosocial sciences ask for power analysis for data already collected and analysed before accepting manuscripts for publication. In this report, post hoc power analysis for retrospective studies is examined and the informativeness of understanding the power for detecting significant effects of the results analysed, using the same data on which the power analysis is based, is scrutinised. Monte Carlo simulation is used to investigate the performance of posthoc power analysis.展开更多
The sieving and enrichment of rare tumor cells from large-volume pleural effusion(PE)samples is a promising technique for cell-based lung tumor diagnosis and drug tests,which features high throughput and recovery,puri...The sieving and enrichment of rare tumor cells from large-volume pleural effusion(PE)samples is a promising technique for cell-based lung tumor diagnosis and drug tests,which features high throughput and recovery,purification,as well as viability rates of rare target cells as the prerequisites for high sensitivity,specificity,and accuracy of tumor cell analysis.In this paper,we propose a three-dimensional(3 D)sieving method for rare tumor cell enrichment,which effectively eliminates the"dead zones"in traditional two-dimensional(2 D)cell filters with a dimension-raising strategy to satisfy the requirements mentioned above.The prototype device was combined with a funnel-shaped holder,a flexible micropore membrane in the middle,and a3 D spiral fluid channel covered on the membrane as a three-layer ice-creaming cone composite structure.Driven by gravity alone,the device performed as follows:(1)20-fold throughput compared with the 2 D commercial planee hich was up to 20 mL/min for a threefold dilution of whole blood sample;(2)high recovery rates of 84.5%±21%,86%±25%,83%±14%for 100,1000,and 10000 cells/mL,respectively,in 30 mL phosphate buffer saline(PBS)sample,and a 100%positive detection rate in the case of≤5 A549 cells in 1 mL PBS;(3)a typical purification rate of 85.5%±9.1%;and(4)a viability rate of>93%.In the demonstration application,this device effectively enriched rare target cells from large volumes(>25 mL)of clinical pleural effusions.The following results indicated that tumor cells were easy-to-discover in the enriched PE samples,and the proliferation capability of purified cells was(>4.6 times)significantly stronger than that of unprocessed cells in the subsequent 6-day culture.The above evaluation indicates that the proposed easily reproducible method for the effective execution of rare cell enrichments and assays is expected to become a practical technique for clinical cell-based tumor diagnosis.展开更多
The source region of the Yellow River has experienced obvious climate and discharge changes in recent decades due to global warming, which largely affects the water resources and ecological and environmental security ...The source region of the Yellow River has experienced obvious climate and discharge changes in recent decades due to global warming, which largely affects the water resources and ecological and environmental security in the Yellow River basin. This study analyzed the changes in runoff and several climate factors in the source region of the Yellow River based on the observed discharges at the Tangnag hydrological station, routine meteorological data from China Meteorological Administration(CMA) stations within and near this source region, and several evaporation datasets. The results indicate that the runoff in the source region was relatively abundant from 1960 to 1989 and then declined sharply afterward. It recovered slightly after 2005 but was still below normal—10% less than that during 1960–1989. Similarly, the precipitation amounts in the source region were relatively low in the 1990s, but they increased significantly after 2003, with an average increase of 31.4 mm or 6% more when compared to that in 1960–1989. In addition, the temperatures in the source region continued to rise from 1960 to 2017, and the evaporation levels also showed an upward trend after 1990. The influences of the spatial and temporal variations in climatic factors on runoff in the source region were then further analyzed. The results indicate that the decreases in precipitation and the number of days of heavy rainfall in the source region from 1990 to 2002 were important reasons for the lower runoff during this period. After 2003, the precipitation in the southeastern part of the source region, which is a key area for runoff generation,increased only to a limited extent, but the evaporation in the entire source region generally increased with increasing temperature,which might have led to the low capacity for actual runoff production in each subbasin and persistent low runoff in the source region. Therefore, such a climate response to global warming in the source region might be unfavorable for increased runoff in the future. The above analysis provides a valuable reference for the future planning and management of water resources in the source region of the Yellow River and the entire Yellow River Basin in the context of warming.展开更多
Traumatic brain injury(TBI)accelerates fracture healing,but the underlying mechanism remains largely unknown.Accumulating evidence indicates that the central nervous system(CNS)plays a pivotal role in regulating immun...Traumatic brain injury(TBI)accelerates fracture healing,but the underlying mechanism remains largely unknown.Accumulating evidence indicates that the central nervous system(CNS)plays a pivotal role in regulating immune system and skeletal homeostasis.However,the impact of CNS injury on hematopoiesis commitment was overlooked.Here,we found that the dramatically elevated sympathetic tone accompanied with TBI-accelerated fracture healing;chemical sympathectomy blocks TBIinduced fracture healing.TBI-induced hypersensitivity of adrenergic signaling promotes the proliferation of bone marrow hematopoietic stem cells(HSCs)and swiftly skews HSCs toward anti-inflammation myeloid cells within 14 days,which favor fracture healing.Knockout ofβ3-orβ2-adrenergic receptor(AR)eliminate TBI-mediated anti-inflammation macrophage expansion and TBIaccelerated fracture healing.RNA sequencing of bone marrow cells revealed that Adrb2 and Adrb3 maintain proliferation and commitment of immune cells.Importantly,flow cytometry confirmed that deletion ofβ2-AR inhibits M2 polarization of macrophages at 7th day and 14th day;and TBI-induced HSCs proliferation was impaired inβ3-AR knockout mice.Moreover,β3-andβ2-AR agonists synergistically promote infiltration of M2 macrophages in callus and accelerate bone healing process.Thus,we conclude that TBI accelerates bone formation during early stage of fracture healing process by shaping the anti-inflammation environment in the bone marrow.These results implicate that the adrenergic signals could serve as potential targets for fracture management.展开更多
Drug-eluting stent(DES)is a promising strategy for esophageal cancer.However,full-covered drug-loaded stents cause damage to non-tumor tissue in the esophagus,and the development controlled-release system to prevent n...Drug-eluting stent(DES)is a promising strategy for esophageal cancer.However,full-covered drug-loaded stents cause damage to non-tumor tissue in the esophagus,and the development controlled-release system to prevent non-tumor tissue injure is currently a major challenge.Here,in situ mineralized manganese dioxide coating on Ce6 embedded electrospun fibers covered stent was developed for effective tumor therapy via intraluminal photodynamic therapy(PDT),which could reduce phototoxicity to normal esophageal tissue.Oxidation of manganese ions,which was previously swelled between fibers,was used to accomplish mineralization.After implantation,the manganese dioxide coating in situ reacts with tumor endogenous H^(+) and H_(2)O_(2),which,on the one hand,could effectively alleviate the hypoxic microenvironment which leads to resistance to PDT,and on the other hand,could expose the Ce6-fibers below the coating for intraluminal PDT.In addition,due to the slow degradation of the coating,this stent could own sustained photodynamic performance for up to one month.Notably,the PDT efficiency of the stent was investigated on orthotopic rabbit esophageal cancer models.Overall,this work suggests that in situ mineralized manganese dioxide coated electrospun fibers covered stent may provide a new strategy for advanced esophageal cancer patients as a functional drug delivery platform.展开更多
To address the driving conflicts of connected automated vehicles(CAVs)at unsignalized roundabouts,a cooperative decision-making framework is proposed.The personalized driving preferences of CAVs are considered in the ...To address the driving conflicts of connected automated vehicles(CAVs)at unsignalized roundabouts,a cooperative decision-making framework is proposed.The personalized driving preferences of CAVs are considered in the decision-making algorithm,which are reflected by different driving styles.A motion prediction algorithm is used to improve the decision-making performance.The effect of the motion prediction algorithm on the decisionmaking performance is evaluated,including the advancement of driving safety and the computational load for the hardware.The cooperative game theoretic approach is applied to the interaction modelling and collaborative decision making of CAVs.Finally,hardware-in-the-loop(HIL)tests are carried out to evaluate the feasibility and real-time performance of the proposed algorithm.展开更多
基金supported by the National Key R&D Program of China,No.2021YFA0805200(to SY)the National Natural Science Foundation of China,No.31970954(to SY)two grants from the Department of Science and Technology of Guangdong Province,Nos.2021ZT09Y007,2020B121201006(both to XJL)。
文摘Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto r.The mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy patients.These aggregates alter protein-protein interactions and compromise transcriptional activity.In this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic factor.Overexpressio n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor aggregation.Conversely.knocking down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor aggregation.Our findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.
基金supportted by the King Khalid University through the Large Group Project(No.RGP.2/312/44).
文摘Network updates have become increasingly prevalent since the broad adoption of software-defined networks(SDNs)in data centers.Modern TCP designs,including cutting-edge TCP variants DCTCP,CUBIC,and BBR,however,are not resilient to network updates that provoke flow rerouting.In this paper,we first demonstrate that popular TCP implementations perform inadequately in the presence of frequent and inconsistent network updates,because inconsistent and frequent network updates result in out-of-order packets and packet drops induced via transitory congestion and lead to serious performance deterioration.We look into the causes and propose a network update-friendly TCP(NUFTCP),which is an extension of the DCTCP variant,as a solution.Simulations are used to assess the proposed NUFTCP.Our findings reveal that NUFTCP can more effectively manage the problems of out-of-order packets and packet drops triggered in network updates,and it outperforms DCTCP considerably.
基金This research was supported by the Clinical Frontier Technology Program of the First Affiliated Hospital of Jinan University,China(No.JNU1AF-CFTP-2022-a01223)Natural Science Foundation of Guangdong Province(2019A1515011763,2020A1515110639,2021A1515010994,2022A1515011695)Guangzhou Science and Technology Plan City-School Joint Funding Project(202201020084,202201020065).
文摘Neoantigen-targeted immunotherapy is a rapidly advancing field that holds great promise for treating cancer.The recognition of antigens by immune cells is a crucial step in tumor-specific killing,and neoantigens generated by mutations in cancer cells possess high immunogenicity and are selectively expressed in tumor cells,making them an attractive therapeutic target.Currently,neoantigens find utility in various domains,primarily in the realm of neoantigen vaccines such as DC vaccines,nucleic acid vaccines,and synthetic long peptide vaccines.Additionally,they hold promise in adoptive cell therapy,encompassing tumor-infiltrating cells,T cell receptors,and chimeric antigen receptors which are expressed by genetically modified T cells.In this review,we summarized recent progress in the clinical use of tumor vaccines and adoptive cell therapy targeting neoantigens,discussed the potential of neoantigen burden as an immune checkpoint in clinical settings.With the aid of state-of-the-art sequencing and bioinformatics technologies,together with significant advancements in artificial intelligence,we anticipated that neoantigens will be fully exploited for personalized tumor immunotherapy,from screening to clinical application.
基金Supported by the National Key Research and Development Program of China (2018YDD0300104)Key Research and Development Program of Hebei Province of China (21375404D)After-Action-Review Project of China Meteorological Administration(FPZJ2023-014)。
文摘Weather forecasting for the Zhangjiakou competition zone of the Beijing 2022 Winter Olympic Games is a challenging task due to its complex terrain.Numerical weather prediction models generally perform poorly for cold air pools and winds over complex terrains,due to their low spatiotemporal resolution and limitations in the description of dynamics,thermodynamics,and microphysics in mountainous areas.This study proposes an ensemble-learning model,named ENSL,for surface temperature and wind forecasts at the venues of the Zhangjiakou competition zone,by integrating five individual models—linear regression,random forest,gradient boosting decision tree,support vector machine,and artificial neural network(ANN),with a ridge regression as meta model.The ENSL employs predictors from the high-resolution ECMWF model forecast(ECMWF-HRES) data and topography data,and targets from automatic weather station observations.Four categories of predictors(synoptic-pattern related fields,surface element fields,terrain,and temporal features) are fed into ENSL.The results demonstrate that ENSL achieves better performance and generalization than individual models.The root-mean-square error(RMSE) for the temperature and wind speed predictions is reduced by 48.2% and 28.5%,respectively,relative to ECMWF-HRES.For the gust speed,the performance of ENSL is consistent with ANN(best individual model) in the whole dataset,whereas ENSL outperforms on extreme gust samples(42.7% compared with 38.7% obtained by ECMWF-HRES in terms of RMSE reduction).Sensitivity analysis of predictors in the four categories shows that ENSL fits their feature importance rankings and physical explanations effectively.
基金The National Natural Science Foundation of China under contract Nos 41406127 and 41476103the Basic Scientific Fund for National Public Research Institutes of China under contract No.2015T05+2 种基金the National Natural Science Foundation of ChinaShandong Joint Funded Project under contract No.U1406403the Marine Science and Technology Project of Huangdao District under contract No.2014-4-20the 2012 Taishan Scholar Award and China-ASEAN Maritime Cooperation Fund East Asia Marine Cooperation Platform
文摘A great deal of oil contaminated the shoreline by the Qingdao oil pipeline explosion in 2013. The four oildegrading consortia were enriched from sediment samples with crude oil as sole carbon and energy sources. The biodiversity and community analysis showed that the Luteibacter, Parvibaculum and a genus belonging to Alcanivoracaceae were found predominant bacteria in the four consortia, which belonged to Proteobacteria. Nine strains exhibiting distinct 16S rRNA gene sequences were isolated from the consortia. These strains were identified to eight genera based on 16S rRNA gene sequences. Five of the nine strains degraded more than 30% of the crude oil in two weeks by gravimetric method. From the analysis of GC-MS, most of the isolated strains tended to degrade n-alkanes rather than PAHs. Five strains showed high degrading ability of the total n-alkanes. Only Strain D2 showed great PAHs degrading ability and the degrading rates ranged from 34.9% to 77.5%. The sequencing analysis of the oil-degrading consortia confirmed that the genus of Alcanivorax was one of the dominant bacteria in Consortia A and E and Strain E4 might be one of the dominant bacteria. The strains obtained in this study demonstrated the potential for oil bioremediation in oil-contaminated beach ecosystems.
文摘Power analysis is a key component for planning prospective studies such as clinical trials. However, some journals in biomedical and psychosocial sciences ask for power analysis for data already collected and analysed before accepting manuscripts for publication. In this report, post hoc power analysis for retrospective studies is examined and the informativeness of understanding the power for detecting significant effects of the results analysed, using the same data on which the power analysis is based, is scrutinised. Monte Carlo simulation is used to investigate the performance of posthoc power analysis.
基金supported by the National Key Research and Development Program of China(No.2018YFC2001100)the National Natural Science Foundation of China(Nos.61774167 and 61801477)+2 种基金the Instrument Development Program of the Chinese Academy of Sciences,Beijing Municipal Natural Science Foundation(Nos.4192062 and 4182072)Beijing Municipal Administration of Hospitals Incubating Program(No.PX2017050)Youth Innovation Promotion Association of Chinese Academy of Sciences。
文摘The sieving and enrichment of rare tumor cells from large-volume pleural effusion(PE)samples is a promising technique for cell-based lung tumor diagnosis and drug tests,which features high throughput and recovery,purification,as well as viability rates of rare target cells as the prerequisites for high sensitivity,specificity,and accuracy of tumor cell analysis.In this paper,we propose a three-dimensional(3 D)sieving method for rare tumor cell enrichment,which effectively eliminates the"dead zones"in traditional two-dimensional(2 D)cell filters with a dimension-raising strategy to satisfy the requirements mentioned above.The prototype device was combined with a funnel-shaped holder,a flexible micropore membrane in the middle,and a3 D spiral fluid channel covered on the membrane as a three-layer ice-creaming cone composite structure.Driven by gravity alone,the device performed as follows:(1)20-fold throughput compared with the 2 D commercial planee hich was up to 20 mL/min for a threefold dilution of whole blood sample;(2)high recovery rates of 84.5%±21%,86%±25%,83%±14%for 100,1000,and 10000 cells/mL,respectively,in 30 mL phosphate buffer saline(PBS)sample,and a 100%positive detection rate in the case of≤5 A549 cells in 1 mL PBS;(3)a typical purification rate of 85.5%±9.1%;and(4)a viability rate of>93%.In the demonstration application,this device effectively enriched rare target cells from large volumes(>25 mL)of clinical pleural effusions.The following results indicated that tumor cells were easy-to-discover in the enriched PE samples,and the proliferation capability of purified cells was(>4.6 times)significantly stronger than that of unprocessed cells in the subsequent 6-day culture.The above evaluation indicates that the proposed easily reproducible method for the effective execution of rare cell enrichments and assays is expected to become a practical technique for clinical cell-based tumor diagnosis.
基金supported by the Second Tibetan Plateau Scientific Expedition and Research Program(STEP)(Grant No.2019QZKK0103)the National Natural Science Foundation of China(Grant No.42150205)。
文摘The source region of the Yellow River has experienced obvious climate and discharge changes in recent decades due to global warming, which largely affects the water resources and ecological and environmental security in the Yellow River basin. This study analyzed the changes in runoff and several climate factors in the source region of the Yellow River based on the observed discharges at the Tangnag hydrological station, routine meteorological data from China Meteorological Administration(CMA) stations within and near this source region, and several evaporation datasets. The results indicate that the runoff in the source region was relatively abundant from 1960 to 1989 and then declined sharply afterward. It recovered slightly after 2005 but was still below normal—10% less than that during 1960–1989. Similarly, the precipitation amounts in the source region were relatively low in the 1990s, but they increased significantly after 2003, with an average increase of 31.4 mm or 6% more when compared to that in 1960–1989. In addition, the temperatures in the source region continued to rise from 1960 to 2017, and the evaporation levels also showed an upward trend after 1990. The influences of the spatial and temporal variations in climatic factors on runoff in the source region were then further analyzed. The results indicate that the decreases in precipitation and the number of days of heavy rainfall in the source region from 1990 to 2002 were important reasons for the lower runoff during this period. After 2003, the precipitation in the southeastern part of the source region, which is a key area for runoff generation,increased only to a limited extent, but the evaporation in the entire source region generally increased with increasing temperature,which might have led to the low capacity for actual runoff production in each subbasin and persistent low runoff in the source region. Therefore, such a climate response to global warming in the source region might be unfavorable for increased runoff in the future. The above analysis provides a valuable reference for the future planning and management of water resources in the source region of the Yellow River and the entire Yellow River Basin in the context of warming.
基金This study was partly supported by the National Natural Science Foundation of China(91949203 to Zhang Y.Z.,82102627 to Lv X.)Key Project of Hebei Provincial Natural Fund(H2020206456)+1 种基金Hubei Provincial Natural Science Foundation of China(2021CFB095)Wuhan Knowledge Innovation Project 2022020801020468.
文摘Traumatic brain injury(TBI)accelerates fracture healing,but the underlying mechanism remains largely unknown.Accumulating evidence indicates that the central nervous system(CNS)plays a pivotal role in regulating immune system and skeletal homeostasis.However,the impact of CNS injury on hematopoiesis commitment was overlooked.Here,we found that the dramatically elevated sympathetic tone accompanied with TBI-accelerated fracture healing;chemical sympathectomy blocks TBIinduced fracture healing.TBI-induced hypersensitivity of adrenergic signaling promotes the proliferation of bone marrow hematopoietic stem cells(HSCs)and swiftly skews HSCs toward anti-inflammation myeloid cells within 14 days,which favor fracture healing.Knockout ofβ3-orβ2-adrenergic receptor(AR)eliminate TBI-mediated anti-inflammation macrophage expansion and TBIaccelerated fracture healing.RNA sequencing of bone marrow cells revealed that Adrb2 and Adrb3 maintain proliferation and commitment of immune cells.Importantly,flow cytometry confirmed that deletion ofβ2-AR inhibits M2 polarization of macrophages at 7th day and 14th day;and TBI-induced HSCs proliferation was impaired inβ3-AR knockout mice.Moreover,β3-andβ2-AR agonists synergistically promote infiltration of M2 macrophages in callus and accelerate bone healing process.Thus,we conclude that TBI accelerates bone formation during early stage of fracture healing process by shaping the anti-inflammation environment in the bone marrow.These results implicate that the adrenergic signals could serve as potential targets for fracture management.
基金This research was funded by the National Natural Science Foundation of China(Nos.81971714,81771943,and 51873107)Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grants(Nos.20152528 and 20171906)+3 种基金Shanghai Jiao Tong University“Medical and Research”Program(Nos.ZH2018ZDA04 and ZH2018ZDA19)Shanghai Talent Development Fund(No.2018099)the Collaborative Innovation Center of Suzhou Nano Science and TechnologyL.Cheng was supported by the Tang Scholar of Soochow University。
文摘Drug-eluting stent(DES)is a promising strategy for esophageal cancer.However,full-covered drug-loaded stents cause damage to non-tumor tissue in the esophagus,and the development controlled-release system to prevent non-tumor tissue injure is currently a major challenge.Here,in situ mineralized manganese dioxide coating on Ce6 embedded electrospun fibers covered stent was developed for effective tumor therapy via intraluminal photodynamic therapy(PDT),which could reduce phototoxicity to normal esophageal tissue.Oxidation of manganese ions,which was previously swelled between fibers,was used to accomplish mineralization.After implantation,the manganese dioxide coating in situ reacts with tumor endogenous H^(+) and H_(2)O_(2),which,on the one hand,could effectively alleviate the hypoxic microenvironment which leads to resistance to PDT,and on the other hand,could expose the Ce6-fibers below the coating for intraluminal PDT.In addition,due to the slow degradation of the coating,this stent could own sustained photodynamic performance for up to one month.Notably,the PDT efficiency of the stent was investigated on orthotopic rabbit esophageal cancer models.Overall,this work suggests that in situ mineralized manganese dioxide coated electrospun fibers covered stent may provide a new strategy for advanced esophageal cancer patients as a functional drug delivery platform.
基金A*STAR,Singapore,under Grant SERC 1922500046 and Grant A2084c0156the SUG-NAP,Nanyang Technological University,under Grant M4082268.050.
文摘To address the driving conflicts of connected automated vehicles(CAVs)at unsignalized roundabouts,a cooperative decision-making framework is proposed.The personalized driving preferences of CAVs are considered in the decision-making algorithm,which are reflected by different driving styles.A motion prediction algorithm is used to improve the decision-making performance.The effect of the motion prediction algorithm on the decisionmaking performance is evaluated,including the advancement of driving safety and the computational load for the hardware.The cooperative game theoretic approach is applied to the interaction modelling and collaborative decision making of CAVs.Finally,hardware-in-the-loop(HIL)tests are carried out to evaluate the feasibility and real-time performance of the proposed algorithm.
