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
Amyotrophic lateral sclerosis(ALS)is a rapidly progressing neurodegenerative disease,leading to muscle weakness,paralysis and ultimately death due to respiratory failure.Currently licensed drugs have only very limited...Amyotrophic lateral sclerosis(ALS)is a rapidly progressing neurodegenerative disease,leading to muscle weakness,paralysis and ultimately death due to respiratory failure.Currently licensed drugs have only very limited effects on slowing down disease progression or biomarkers.Despite numerous successful preclinical analyses,most new drugs fail when translated to clinical trials(Petrov et al.,2017).This is believed to be,in part,due to the multilayer heterogeneity of ALS(e.g.,clinical,genetic,and molecular;Tzeplaeff et al.,2024).Studies integrating multi-omic data are still limited,making it difficult to fully understand the biological complexity that characterizes the disease.展开更多
Extreme rainfall events(EREs)frequently hit the middle and lower reaches of the Yellow River basin(YRB)during boreal summer.Recent observations have indicated that EREs exhibit teleconnection patterns across long spat...Extreme rainfall events(EREs)frequently hit the middle and lower reaches of the Yellow River basin(YRB)during boreal summer.Recent observations have indicated that EREs exhibit teleconnection patterns across long spatial distances.This study investigated ERE teleconnections in the YRB using the Event Synchronization(ES)method in combination with Complex Network(CN)theory.EREs in the YRB are significantly synchronized with other regions from regional to global scales.Additionally,high-resolution CMIP6 models in general show better skill in capturing these characteristics compared to low-resolution models.A further examination shows that the spatial synchronization patterns exhibit pronounced timescale dependence.Significant ERE synchronizations between the YRB and Europe were uncovered,where the YRB lags Eastern Europe by 3-5 days and Western Europe by 5-7 days,with Rossby wave propagation playing a key role.Wave trains from Europe propagate downstream along the Eurasian jet,inducing anomalous circulations over the YRB that enhance vertical upward motion and moisture transport,ultimately triggering EREs.Two distinct wave trains are observed:one is associated with Eastern Europe-YRB synchronization,occurring in the midlatitude region;the other is linked to Western Europe-YRB synchronization,positioned at higher latitudes.Notably,17.5%of Eastern Europe-YRB synchronization cases and 17.0%of Western Europe-YRB cases overlap.Quantitative analysis indicates that the synchronized events between Eastern(Western)Europe and the YRB account for roughly 28%(30%)of EREs in the YRB.These findings are critical for better understanding ERE mechanisms,offering guidance for forecasting and early warning capabilities for EREs in the YRB.展开更多
Humans can learn complex and dexterous manipulation tasks by observing videos,imitating and exploring.Multiple endeffectors manipulation of free micron-sized deformable cells is one of the challenging tasks in robotic...Humans can learn complex and dexterous manipulation tasks by observing videos,imitating and exploring.Multiple endeffectors manipulation of free micron-sized deformable cells is one of the challenging tasks in robotic micromanipulation.We propose an imitation-enhanced reinforcement learning method inspired by the human learning process that enables robots to learn cell micromanipulation skills from videos.Firstly,for the microscopic robot micromanipulation videos,a multi-task observation(MTO)network is designed to identify the two end-effectors and the manipulated objects to obtain the spatiotemporal trajectories.The spatiotemporal constraints of the robot's actions are obtained by the task-parameterised hidden Markov model(THMM).To simultaneously address the safety and dexterity of robot micromanipulation,an imitation learning optimisation-based soft actor-critic(ILOSAC)algorithm is proposed in which the robot can perform skill learning by demonstration and exploration.The proposed method is capable of performing complex cell manipulation tasks in a realistic physical environment.Experiments indicated that compared with current methods and manual remote manipulation,the proposed framework achieved a shorter operation time and less deformation of cells,which is expected to facilitate the development of robot skill learning.展开更多
This study evaluates the stabilizing effect of lignin, extracted from Eucalyptus globulus, on an energetic composite of nitrated cellulose carbamate (NCC) plasticized with diethylene glycol dinitrate (DEGDN), compared...This study evaluates the stabilizing effect of lignin, extracted from Eucalyptus globulus, on an energetic composite of nitrated cellulose carbamate (NCC) plasticized with diethylene glycol dinitrate (DEGDN), compared to conventional stabilizers 2-nitrodiphenylamine (2-NDPA) and 1,3-dimethyl-1,3-diphenylurea (C-II). FTIR analysis confirms lignin's capacity to scavenge nitroxyl radicals formed during thermolysis of nitrocarbamate and nitrate ester bonds, thereby inhibiting decomposition. Moreover, the incorporation of C-II, 2-NDPA, and lignin significantly raised the peak temperature of the main thermolysis, as confirmed by DSC and TGA, indicating a progressive stability enhancement in the order: NCC/DEGDN < NCC/DEGDN/C-II < NCC/DEGDN/lignin < NCC/DEGDN/2-NDPA. Additionally, the effect of each stabilizer on the decomposition pathway was characterized by TGA-FTIR. The findings show that stabilizer type significantly affects the intensity of gaseous products released during decomposition without altering their nature. Notably, NH2 groups formed during NCC degradation play a key role in nitrogen conversion, particularly by reducing toxic NO emissions.展开更多
Spinal cord injury(SCI)causes severe trauma to the central nervous system(CNS),involving complex pathological processes such as oxidative stress,inflammation,demyelination,and scar formation.During SCI progression,ong...Spinal cord injury(SCI)causes severe trauma to the central nervous system(CNS),involving complex pathological processes such as oxidative stress,inflammation,demyelination,and scar formation.During SCI progression,ongoing myelin degeneration leads to the release of myelin debris,which directly inhibits neural regeneration and impairs functional recovery following the injury.Moreover,bone marrow-derived macrophages(BMDMs)infiltrate the injured site and extensively phagocytose myelin debris,transforming into lipid-laden foam cells.These foam cells accumulate at the lesion core,significantly promoting fibrotic scar formation.To address these challenges,we developed a composite scaffold consisting of a foam cell membrane-coated polycaprolactone(PCL)nanofiber membrane that was integrated with a dual-matrix human acellular amniotic membrane(HAAM)hydrogel.A comprehensive evaluation combining material characterization,in vitro assays,and in vivo assessment using a Sprague-Dawley rat spinal cord defect model demonstrated that the scaffold retains the bioactive properties of HAAM,effectively clearing myelin debris and mitigating foam cell accumulation while concurrently promoting neural regeneration following SCI.The proposed novel biomaterial-based strategy offers a promising approach to addressing the persistent accumulation of myelin debris after SCI.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
Many insects and their relatives are renowned for sophisticated compound eyes,which are also preserved in the fossil record.Yet there are other types of eyes,notably the so-called stemmata of holometabolans,such as be...Many insects and their relatives are renowned for sophisticated compound eyes,which are also preserved in the fossil record.Yet there are other types of eyes,notably the so-called stemmata of holometabolans,such as beetles,bees,and butterflies.Stemmata are not as effective as compound eyes,except in some predatory larvae.Here we report three lacewing larvae with large forward-directed stemmata from Cretaceous Kachin amber,Myanmar.The stemmata are large relative to those of other fossil lacewing larvae,comparable to the simple eyes of modern larvae capable of image formation.The head is very wide in one larva,representing a new type of morphology as demonstrated by a quantitative comparison of the head and stylets of over 400 fossil and extant lacewing larvae.The arrangement of the exceptionally large stemmata of the larvae reported here provides stereoscopic vision.These new specimens demonstrate the convergent evolution of highly developed simple eyes in at least two additional lineages of lacewings,showcasing the enormous diversity of lacewing larvae in the Cretaceous.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
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.
文摘Amyotrophic lateral sclerosis(ALS)is a rapidly progressing neurodegenerative disease,leading to muscle weakness,paralysis and ultimately death due to respiratory failure.Currently licensed drugs have only very limited effects on slowing down disease progression or biomarkers.Despite numerous successful preclinical analyses,most new drugs fail when translated to clinical trials(Petrov et al.,2017).This is believed to be,in part,due to the multilayer heterogeneity of ALS(e.g.,clinical,genetic,and molecular;Tzeplaeff et al.,2024).Studies integrating multi-omic data are still limited,making it difficult to fully understand the biological complexity that characterizes the disease.
基金the Guangdong Basic and Applied Basic Research Foundation (Grant No. 2023B1515020084)the National Natural Science Foundation of China (Grant Nos.42175068, 42475057, and 42261144687)
文摘Extreme rainfall events(EREs)frequently hit the middle and lower reaches of the Yellow River basin(YRB)during boreal summer.Recent observations have indicated that EREs exhibit teleconnection patterns across long spatial distances.This study investigated ERE teleconnections in the YRB using the Event Synchronization(ES)method in combination with Complex Network(CN)theory.EREs in the YRB are significantly synchronized with other regions from regional to global scales.Additionally,high-resolution CMIP6 models in general show better skill in capturing these characteristics compared to low-resolution models.A further examination shows that the spatial synchronization patterns exhibit pronounced timescale dependence.Significant ERE synchronizations between the YRB and Europe were uncovered,where the YRB lags Eastern Europe by 3-5 days and Western Europe by 5-7 days,with Rossby wave propagation playing a key role.Wave trains from Europe propagate downstream along the Eurasian jet,inducing anomalous circulations over the YRB that enhance vertical upward motion and moisture transport,ultimately triggering EREs.Two distinct wave trains are observed:one is associated with Eastern Europe-YRB synchronization,occurring in the midlatitude region;the other is linked to Western Europe-YRB synchronization,positioned at higher latitudes.Notably,17.5%of Eastern Europe-YRB synchronization cases and 17.0%of Western Europe-YRB cases overlap.Quantitative analysis indicates that the synchronized events between Eastern(Western)Europe and the YRB account for roughly 28%(30%)of EREs in the YRB.These findings are critical for better understanding ERE mechanisms,offering guidance for forecasting and early warning capabilities for EREs in the YRB.
基金supported in part with the General Programme of the National Natural Science Foundation of China(Grant 62576312)the Key Research and Development Program of Zhejiang Province(Grant 2025C01132)the Shandong Province Key R&D Plan Project(Grant 2022LZGC020).
文摘Humans can learn complex and dexterous manipulation tasks by observing videos,imitating and exploring.Multiple endeffectors manipulation of free micron-sized deformable cells is one of the challenging tasks in robotic micromanipulation.We propose an imitation-enhanced reinforcement learning method inspired by the human learning process that enables robots to learn cell micromanipulation skills from videos.Firstly,for the microscopic robot micromanipulation videos,a multi-task observation(MTO)network is designed to identify the two end-effectors and the manipulated objects to obtain the spatiotemporal trajectories.The spatiotemporal constraints of the robot's actions are obtained by the task-parameterised hidden Markov model(THMM).To simultaneously address the safety and dexterity of robot micromanipulation,an imitation learning optimisation-based soft actor-critic(ILOSAC)algorithm is proposed in which the robot can perform skill learning by demonstration and exploration.The proposed method is capable of performing complex cell manipulation tasks in a realistic physical environment.Experiments indicated that compared with current methods and manual remote manipulation,the proposed framework achieved a shorter operation time and less deformation of cells,which is expected to facilitate the development of robot skill learning.
文摘This study evaluates the stabilizing effect of lignin, extracted from Eucalyptus globulus, on an energetic composite of nitrated cellulose carbamate (NCC) plasticized with diethylene glycol dinitrate (DEGDN), compared to conventional stabilizers 2-nitrodiphenylamine (2-NDPA) and 1,3-dimethyl-1,3-diphenylurea (C-II). FTIR analysis confirms lignin's capacity to scavenge nitroxyl radicals formed during thermolysis of nitrocarbamate and nitrate ester bonds, thereby inhibiting decomposition. Moreover, the incorporation of C-II, 2-NDPA, and lignin significantly raised the peak temperature of the main thermolysis, as confirmed by DSC and TGA, indicating a progressive stability enhancement in the order: NCC/DEGDN < NCC/DEGDN/C-II < NCC/DEGDN/lignin < NCC/DEGDN/2-NDPA. Additionally, the effect of each stabilizer on the decomposition pathway was characterized by TGA-FTIR. The findings show that stabilizer type significantly affects the intensity of gaseous products released during decomposition without altering their nature. Notably, NH2 groups formed during NCC degradation play a key role in nitrogen conversion, particularly by reducing toxic NO emissions.
基金supported by the National N atural Science Foundation of China(Nos.82371383 and 32371400)the Medical Research Projects of the Health Commission of Jiangsu Province(No.K2023006)+1 种基金the Clinical Special Research Project of Nantong University(No.2024JZ052)the Key Research Project of School-Land Collaboration at Jiangsu Vocational College of Medicine(No.202490401).
文摘Spinal cord injury(SCI)causes severe trauma to the central nervous system(CNS),involving complex pathological processes such as oxidative stress,inflammation,demyelination,and scar formation.During SCI progression,ongoing myelin degeneration leads to the release of myelin debris,which directly inhibits neural regeneration and impairs functional recovery following the injury.Moreover,bone marrow-derived macrophages(BMDMs)infiltrate the injured site and extensively phagocytose myelin debris,transforming into lipid-laden foam cells.These foam cells accumulate at the lesion core,significantly promoting fibrotic scar formation.To address these challenges,we developed a composite scaffold consisting of a foam cell membrane-coated polycaprolactone(PCL)nanofiber membrane that was integrated with a dual-matrix human acellular amniotic membrane(HAAM)hydrogel.A comprehensive evaluation combining material characterization,in vitro assays,and in vivo assessment using a Sprague-Dawley rat spinal cord defect model demonstrated that the scaffold retains the bioactive properties of HAAM,effectively clearing myelin debris and mitigating foam cell accumulation while concurrently promoting neural regeneration following SCI.The proposed novel biomaterial-based strategy offers a promising approach to addressing the persistent accumulation of myelin debris after SCI.
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supported by a Volkswagen Foundation Lichtenberg professorship,the German Research Foundation(DFG Ha 6300/6-1)LMUexcellent+1 种基金the Imaging Center of the Department of Biology,University of Greifswald and the German Research Foundation(DFG INST 292/119-1 FUGGDFG INST 292/120-1 FUGG)for funding imaging there.
文摘Many insects and their relatives are renowned for sophisticated compound eyes,which are also preserved in the fossil record.Yet there are other types of eyes,notably the so-called stemmata of holometabolans,such as beetles,bees,and butterflies.Stemmata are not as effective as compound eyes,except in some predatory larvae.Here we report three lacewing larvae with large forward-directed stemmata from Cretaceous Kachin amber,Myanmar.The stemmata are large relative to those of other fossil lacewing larvae,comparable to the simple eyes of modern larvae capable of image formation.The head is very wide in one larva,representing a new type of morphology as demonstrated by a quantitative comparison of the head and stylets of over 400 fossil and extant lacewing larvae.The arrangement of the exceptionally large stemmata of the larvae reported here provides stereoscopic vision.These new specimens demonstrate the convergent evolution of highly developed simple eyes in at least two additional lineages of lacewings,showcasing the enormous diversity of lacewing larvae in the Cretaceous.
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.
