The remodeling of axonal connections following injury is an important feature driving functional recovery.The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory ...The remodeling of axonal connections following injury is an important feature driving functional recovery.The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory fibers.While the reticulospinal tract has been shown to be particularly prone to axonal growth and plasticity following injuries of the spinal cord,the differential capacities of excitatory and inhibitory fibers for plasticity remain unclear.As adaptive axonal plasticity involves a sophisticated interplay between excitatory and inhibitory input,we investigated in this study the plastic potential of glutamatergic(vGlut2)and GABAergic(vGat)fibers originating from the gigantocellular nucleus and the lateral paragigantocellular nucleus,two nuclei important for locomotor function.Using a combination of viral tracing,chemogenetic silencing,and AI-based kinematic analysis,we investigated plasticity and its impact on functional recovery within the first 3 weeks following injury,a period prone to neuronal remodeling.We demonstrate that,in this time frame,while vGlut2-positive fibers within the gigantocellular and lateral paragigantocellular nuclei rewire significantly following cervical spinal cord injury,vGat-positive fibers are rather unresponsive to injury.We also show that the acute silencing of excitatory axonal fibers which rewire in response to lesions of the spinal cord triggers a worsening of the functional recovery.Using kinematic analysis,we also pinpoint the locomotion features associated with the gigantocellular nucleus or lateral paragigantocellular nucleus during functional recovery.Overall,our study increases the understanding of the role of the gigantocellular and lateral paragigantocellular nuclei during functional recovery following spinal cord injury.展开更多
Background:Although light-intensity physical activity(LPA)has been suggested to be associated with a lower risk of mortality,the minimal and optimal volumes of LPA remain unclear.We aimed to examine the minimal and op...Background:Although light-intensity physical activity(LPA)has been suggested to be associated with a lower risk of mortality,the minimal and optimal volumes of LPA remain unclear.We aimed to examine the minimal and optimal volumes of LPA associated with the risks of mortality and disease incidence(i.e.,cardiovascular diseases and cancer).Methods:Data were derived from the population-based UK Biobank cohort study,including 69,492 adults aged 43-78 years.Accelerometermeasured LPA was defined using a validated,published machine learning-based Random Forest activity method,which was categorized into 4 quartile groups.All-cause and cause-specific mortality(cardiovascular disease-and cancer-specific)were determined according to the International Classification of Diseases,10th version codes.Disease incidence was defined based on primary care,hospitalization,or death records.Results:During a median follow-up period of 8.04 years,2024 adults died from all causes,539 from cardiovascular disease,and 1175 from cancer.For all-cause mortality,compared with participants in the lowest quartile of LPA(<3.9 h/day),the hazard ratios(HRs)and 95%confidence intervals(95%CIs)were 0.82(95%CI:0.73-0.93)for those with 3.9 to<5.0 h/day,0.75(95%CI:0.66-0.85)for those with 5.0 to<6.1 h/day,and 0.77(95%CI:0.68-0.88)for those with≥6.1 h/day,respectively.There was an inverse non-linear dose-response association between LPA and all-cause mortality,with an optimal dose of 5.72 h/day(95%CI:5.45-6.41;HR=0.63,95%CI:0.56-0.71)and a minimal dose of 3.59 h/day(95%CI:3.53-8.56;HR=0.81,95%CI:0.78-0.86),with the 5th percentile as the reference.Similar patterns were observed for cause-specific mortality and disease incidence(cardiovascular disease and cancer).Conclusion:Engaging in LPA for~3.5 h/day was conservatively associated with lower risk of mortality and disease incidence,with further risk reductions observed up to an optimal dose of~6.0 h/day.These findings suggest that sufficient LPA offers important health benefits,which can inform the development of future PA guidelines.展开更多
Although the combination of chemotherapy and immunotherapy can improve the treatment of breast cancer,traditional drugs are highly toxic because they do not specifically target tumors.In this study,we developed a self...Although the combination of chemotherapy and immunotherapy can improve the treatment of breast cancer,traditional drugs are highly toxic because they do not specifically target tumors.In this study,we developed a self-driving bacteria/nanoparticle biohybrid called Bif@PDA-aPD1/DOX-Lip by attaching polydopamine(PDA)coated doxorubicin(DOX)liposomes and the immune checkpoint inhibitor anti-programmed cell death protein 1 antibody(aPD-1)to Bifidobacterium infantis(B.infantis,Bif).Using the homing abilities of bacteria,Bif@PDA-aPD1/DOX-Lip could actively accumulate in tumor tissue,releasing DOX and aPD-1 in the acidic environment to have a synergistic anti-tumor effect.Results show that the concentration of DOX in tumors of the Bif@PDA-aPD1/DOX-Lip group was 6.31 times higher than in the free DOX group.The combination of DOX and aPD-1 not only killed tumor cells but also promoted immune normalization by maturing dendritic cells(DCs),increasing M1 macrophage ratio,and enhancing infiltration of CD8+and CD4+T cells in tumors and spleen.Therefore,Bif@PDA-aPD1/DOX-Lip therapy significantly inhibited tumor growth and increased the average survival time of mice to over 80 days.The Bif@PDA-aPD1/DOX-Lip biomotors offer a highly effective method for enhancing chemo-immunotherapy in solid tumors.展开更多
This paper develops a semi-analytical solution for pile penetration in natural soft clays using the strain path method(SPM).The stress-strain behavior of soils is characterized by the S-CLAY1S model,which can capture ...This paper develops a semi-analytical solution for pile penetration in natural soft clays using the strain path method(SPM).The stress-strain behavior of soils is characterized by the S-CLAY1S model,which can capture the anisotropic evolution and destructuring nature of soft clays.By integrating the S-CLAY1S model into the theoretical framework of the SPM,a set of ordinary differential equations is formulated with respect to the vertical coordinate of soil particles.The distribution of excess pore water pressure(EPWP)following pile installation is approximated through one-dimensional(1D)radial integration around the pile shaft.The distribution of stresses and EPWP,along with the evolution of fabric anisotropy within the soil surrounding the pile,is presented to illustrate the response of pile penetration in natural soft clays.The proposed solution is validated against existing theoretical solutions using the SPM and cavity expansion method(CEM),along with experimental data.The findings demonstrate that the SPM reveals lower radial effective stresses and EPWP at the pile shaft than that of CEM.Pile penetration alters the soil's anisotropic properties,inducing rotational hardening and affecting post-installation stress distribution.Soil destructuration eliminates bonding among particles near the pile,resulting in a complete disruption of soil structure at the pile surface,which is particularly pronounced for higher initial soil structure ratios.Minimal variation was observed in the three principal stresses and shear stress on the cone side surface as the angle increased from 18°to 60°,except for a slight reduction in EPWP.展开更多
Due to water conflicts and allocation in the Lancang-Mekong River Basin(LMRB),the spatio-temporal differentiation of total water resources and the natural-human influence need to be clarified.This work investigated LM...Due to water conflicts and allocation in the Lancang-Mekong River Basin(LMRB),the spatio-temporal differentiation of total water resources and the natural-human influence need to be clarified.This work investigated LMRB's terrestrial water storage anomaly(TWSA)and its spatio-temporal dynamics during 2002–2020.Considering the effects of natural factors and human activities,the respective contributions of climate variability and human activities to terrestrial water storage change(TWSC)were separated.Results showed that:(1)LMRB's TWSA decreased by 0.3158 cm/a.(2)TWSA showed a gradual increase in distribution from southwest of MRB to middle LMRB and from northeast of LRB to middle LMRB.TWSA positively changed in Myanmar while slightly changed in Laos and China.It negatively changed in Vietnam,Thailand and Cambodia.(3)TWSA components decreased in a descending order of soil moisture,groundwater and precipitation.(4)Natural factors had a substantial and spatial differentiated influence on TWSA over the LMRB.(5)Climate variability contributed 79%of TWSC in the LMRB while human activities contributed 21%with an increasing impact after 2008.The TWSC of upstream basin countries was found to be controlled by climate variability while Vietnam and Cambodia's TWSC has been controlled by human activities since 2012.展开更多
Incremental Nonlinear Dynamic Inversion(INDI)is a control approach that has gained popularity in flight control over the past decade.Besides the INDI law,several common additional components complement an INDI-based c...Incremental Nonlinear Dynamic Inversion(INDI)is a control approach that has gained popularity in flight control over the past decade.Besides the INDI law,several common additional components complement an INDI-based controller.This paper,the second part of a two-part series of surveys on INDI,aims to summarize the modern trends in INDI and its related components.Besides a comprehensive components specification,it addresses their most common challenges,compares different variants,and discusses proposed advances.Further important aspects of INDI are gain design,stability,and robustness.This paper also provides an overview of research conducted concerning these aspects.This paper is written in a tutorial style to familiarize researchers with the essential specifics and pitfalls of INDI and its components.At the same time,it can also serve as a reference for readers already familiar with INDI.展开更多
基金supported by the Deutsche Forschungsgemeinschaft(DFG),TRR274(Project ID 408885537,Sy Nergy,EXC 2145/ID 390857198,to FMB)。
文摘The remodeling of axonal connections following injury is an important feature driving functional recovery.The reticulospinal tract is an interesting descending motor tract that contains both excitatory and inhibitory fibers.While the reticulospinal tract has been shown to be particularly prone to axonal growth and plasticity following injuries of the spinal cord,the differential capacities of excitatory and inhibitory fibers for plasticity remain unclear.As adaptive axonal plasticity involves a sophisticated interplay between excitatory and inhibitory input,we investigated in this study the plastic potential of glutamatergic(vGlut2)and GABAergic(vGat)fibers originating from the gigantocellular nucleus and the lateral paragigantocellular nucleus,two nuclei important for locomotor function.Using a combination of viral tracing,chemogenetic silencing,and AI-based kinematic analysis,we investigated plasticity and its impact on functional recovery within the first 3 weeks following injury,a period prone to neuronal remodeling.We demonstrate that,in this time frame,while vGlut2-positive fibers within the gigantocellular and lateral paragigantocellular nuclei rewire significantly following cervical spinal cord injury,vGat-positive fibers are rather unresponsive to injury.We also show that the acute silencing of excitatory axonal fibers which rewire in response to lesions of the spinal cord triggers a worsening of the functional recovery.Using kinematic analysis,we also pinpoint the locomotion features associated with the gigantocellular nucleus or lateral paragigantocellular nucleus during functional recovery.Overall,our study increases the understanding of the role of the gigantocellular and lateral paragigantocellular nuclei during functional recovery following spinal cord injury.
基金supported by the National Key Research and Development Plan:Real-Time Intelligent Active Intervention on Integration of Ten Important Chronic Diseases(2020YFC2003504-2,to BX)。
文摘Background:Although light-intensity physical activity(LPA)has been suggested to be associated with a lower risk of mortality,the minimal and optimal volumes of LPA remain unclear.We aimed to examine the minimal and optimal volumes of LPA associated with the risks of mortality and disease incidence(i.e.,cardiovascular diseases and cancer).Methods:Data were derived from the population-based UK Biobank cohort study,including 69,492 adults aged 43-78 years.Accelerometermeasured LPA was defined using a validated,published machine learning-based Random Forest activity method,which was categorized into 4 quartile groups.All-cause and cause-specific mortality(cardiovascular disease-and cancer-specific)were determined according to the International Classification of Diseases,10th version codes.Disease incidence was defined based on primary care,hospitalization,or death records.Results:During a median follow-up period of 8.04 years,2024 adults died from all causes,539 from cardiovascular disease,and 1175 from cancer.For all-cause mortality,compared with participants in the lowest quartile of LPA(<3.9 h/day),the hazard ratios(HRs)and 95%confidence intervals(95%CIs)were 0.82(95%CI:0.73-0.93)for those with 3.9 to<5.0 h/day,0.75(95%CI:0.66-0.85)for those with 5.0 to<6.1 h/day,and 0.77(95%CI:0.68-0.88)for those with≥6.1 h/day,respectively.There was an inverse non-linear dose-response association between LPA and all-cause mortality,with an optimal dose of 5.72 h/day(95%CI:5.45-6.41;HR=0.63,95%CI:0.56-0.71)and a minimal dose of 3.59 h/day(95%CI:3.53-8.56;HR=0.81,95%CI:0.78-0.86),with the 5th percentile as the reference.Similar patterns were observed for cause-specific mortality and disease incidence(cardiovascular disease and cancer).Conclusion:Engaging in LPA for~3.5 h/day was conservatively associated with lower risk of mortality and disease incidence,with further risk reductions observed up to an optimal dose of~6.0 h/day.These findings suggest that sufficient LPA offers important health benefits,which can inform the development of future PA guidelines.
基金supported by the Science and Technology Strategic Cooperation Programs of Luzhou Municipal People's Government and Southwest Medical University(No.2024LZXNYDJ017)the Project Program of the Science and Technology Department of Sichuan Province(No.2025zNSFSC0679)the Project Program of Chongqing Science and Technology Bureau(No.cstc2020jcyjmsxmX1037).
文摘Although the combination of chemotherapy and immunotherapy can improve the treatment of breast cancer,traditional drugs are highly toxic because they do not specifically target tumors.In this study,we developed a self-driving bacteria/nanoparticle biohybrid called Bif@PDA-aPD1/DOX-Lip by attaching polydopamine(PDA)coated doxorubicin(DOX)liposomes and the immune checkpoint inhibitor anti-programmed cell death protein 1 antibody(aPD-1)to Bifidobacterium infantis(B.infantis,Bif).Using the homing abilities of bacteria,Bif@PDA-aPD1/DOX-Lip could actively accumulate in tumor tissue,releasing DOX and aPD-1 in the acidic environment to have a synergistic anti-tumor effect.Results show that the concentration of DOX in tumors of the Bif@PDA-aPD1/DOX-Lip group was 6.31 times higher than in the free DOX group.The combination of DOX and aPD-1 not only killed tumor cells but also promoted immune normalization by maturing dendritic cells(DCs),increasing M1 macrophage ratio,and enhancing infiltration of CD8+and CD4+T cells in tumors and spleen.Therefore,Bif@PDA-aPD1/DOX-Lip therapy significantly inhibited tumor growth and increased the average survival time of mice to over 80 days.The Bif@PDA-aPD1/DOX-Lip biomotors offer a highly effective method for enhancing chemo-immunotherapy in solid tumors.
基金support from the National Natural Science Foundation of China(Grant No.42407256)the State Key Laboratory of Hydraulics and Mountain River Engineering,China(Grant No.SKHL2113)the Sichuan Science and Technology Program(Grant No.2024YFHZ0341).
文摘This paper develops a semi-analytical solution for pile penetration in natural soft clays using the strain path method(SPM).The stress-strain behavior of soils is characterized by the S-CLAY1S model,which can capture the anisotropic evolution and destructuring nature of soft clays.By integrating the S-CLAY1S model into the theoretical framework of the SPM,a set of ordinary differential equations is formulated with respect to the vertical coordinate of soil particles.The distribution of excess pore water pressure(EPWP)following pile installation is approximated through one-dimensional(1D)radial integration around the pile shaft.The distribution of stresses and EPWP,along with the evolution of fabric anisotropy within the soil surrounding the pile,is presented to illustrate the response of pile penetration in natural soft clays.The proposed solution is validated against existing theoretical solutions using the SPM and cavity expansion method(CEM),along with experimental data.The findings demonstrate that the SPM reveals lower radial effective stresses and EPWP at the pile shaft than that of CEM.Pile penetration alters the soil's anisotropic properties,inducing rotational hardening and affecting post-installation stress distribution.Soil destructuration eliminates bonding among particles near the pile,resulting in a complete disruption of soil structure at the pile surface,which is particularly pronounced for higher initial soil structure ratios.Minimal variation was observed in the three principal stresses and shear stress on the cone side surface as the angle increased from 18°to 60°,except for a slight reduction in EPWP.
基金National Natural Science Foundation of China,No.42161006Yunnan Fundamental Research Projects No.202201AT070094,No.202301BF070001-004+1 种基金Special Project for High-level Talents of Yunnan Province for Young Top Talents,No.C6213001159European Research Council(ERC)Starting-Grant STORIES,No.101040939。
文摘Due to water conflicts and allocation in the Lancang-Mekong River Basin(LMRB),the spatio-temporal differentiation of total water resources and the natural-human influence need to be clarified.This work investigated LMRB's terrestrial water storage anomaly(TWSA)and its spatio-temporal dynamics during 2002–2020.Considering the effects of natural factors and human activities,the respective contributions of climate variability and human activities to terrestrial water storage change(TWSC)were separated.Results showed that:(1)LMRB's TWSA decreased by 0.3158 cm/a.(2)TWSA showed a gradual increase in distribution from southwest of MRB to middle LMRB and from northeast of LRB to middle LMRB.TWSA positively changed in Myanmar while slightly changed in Laos and China.It negatively changed in Vietnam,Thailand and Cambodia.(3)TWSA components decreased in a descending order of soil moisture,groundwater and precipitation.(4)Natural factors had a substantial and spatial differentiated influence on TWSA over the LMRB.(5)Climate variability contributed 79%of TWSC in the LMRB while human activities contributed 21%with an increasing impact after 2008.The TWSC of upstream basin countries was found to be controlled by climate variability while Vietnam and Cambodia's TWSC has been controlled by human activities since 2012.
文摘Incremental Nonlinear Dynamic Inversion(INDI)is a control approach that has gained popularity in flight control over the past decade.Besides the INDI law,several common additional components complement an INDI-based controller.This paper,the second part of a two-part series of surveys on INDI,aims to summarize the modern trends in INDI and its related components.Besides a comprehensive components specification,it addresses their most common challenges,compares different variants,and discusses proposed advances.Further important aspects of INDI are gain design,stability,and robustness.This paper also provides an overview of research conducted concerning these aspects.This paper is written in a tutorial style to familiarize researchers with the essential specifics and pitfalls of INDI and its components.At the same time,it can also serve as a reference for readers already familiar with INDI.
