Angiogenesis,the expansion of pre-existing vascular networks,is crucial for normal organ growth and tissue repair,but is also involved in various pathologies,including inflammation,ischemia,diabetes,and cancer.In soli...Angiogenesis,the expansion of pre-existing vascular networks,is crucial for normal organ growth and tissue repair,but is also involved in various pathologies,including inflammation,ischemia,diabetes,and cancer.In solid tumors,angiogenesis supports growth,nutrient delivery,waste removal,and metastasis.Tumors can induce angiogenesis through proangiogenic factors including VEGF,FGF-2,PDGF,angiopoietins,HGF,TNF,IL-6,SCF,tryptase,and chymase.This balance is disrupted in tumors,and extracellular vesicles(EVs)contribute to this by transferring proangiogenic factors and increasing their expression in endothelial cells(ECs).Malignant melanoma,a particular type of skin cancer,accounts for only 1%of skin cancer cases but more than 75%of deaths.Its incidence has risen significantly,with a 40%increase between 2012 and 2022,especially in fair-skinned populations.Advanced metastatic stages have a high mortality due to delayed diagnosis.This review examines the molecular basis of angiogenesis in melanoma,focusing on melanoma-derived EVs and their possible use in new antiangiogenic therapies.展开更多
In addition to its recognized role in providing structural support, bone plays a crucial role in maintaining the functionality and balance of various organs by secreting specific cytokines(also known as osteokines). T...In addition to its recognized role in providing structural support, bone plays a crucial role in maintaining the functionality and balance of various organs by secreting specific cytokines(also known as osteokines). This reciprocal influence extends to these organs modulating bone homeostasis and development, although this aspect has yet to be systematically reviewed. This review aims to elucidate this bidirectional crosstalk, with a particular focus on the role of osteokines. Additionally, it presents a unique compilation of evidence highlighting the critical function of extracellular vesicles(EVs) within bone-organ axes for the first time. Moreover, it explores the implications of this crosstalk for designing and implementing bone-on-chips and assembloids, underscoring the importance of comprehending these interactions for advancing physiologically relevant in vitro models. Consequently, this review establishes a robust theoretical foundation for preventing, diagnosing, and treating diseases related to the bone-organ axis from the perspective of cytokines, EVs, hormones, and metabolites.展开更多
Milk-derived extracellular vesicles(EVs)are promising for oral drug delivery,yet different loading methods exhibit distinct impacts on drug encapsulation and membrane integrity.This study demonstrated that sonication ...Milk-derived extracellular vesicles(EVs)are promising for oral drug delivery,yet different loading methods exhibit distinct impacts on drug encapsulation and membrane integrity.This study demonstrated that sonication method achieved high drug encapsulation in commercial milk-derived EVs(S-CM EVs),but impaired EV structure,compromising transcytosis.Incubation method(I-CM EVs)preserved EVs delivery ability,but had low drug loading.Further proteomic and transmembrane studies showed that sonication greatly damaged membrane proteins involved in trans-epithelial transportation,especially endoplasmic reticulum-Golgi pathway.To overcome this dilemma,we generated a hybrid CM EVs(H-CM EVs)by fusing I-CM EVs and S-CM EVs.H-CM EVs demonstrated comparable drug encapsulation to S-CM EVs(56.14%),significantly higher than I-CM EVs(11.92%).Importantly,H-CM EVs could maintain efficient drug delivery capability by restoring membrane fluidity,repairing damaged proteins,and enhancing enzyme resistance of SCM EVs.H-CM EVs exhibited excellent absorption characteristics with 1.85-fold higher of area under the curve and 2.50-fold higher of max plasma concentration than those of SCM EVs.On typeⅠdiabetic mice,orally delivery of insulin loaded H-CM EVs and I-CM EVs showed improved hypoglycemic effects with pharmacological availabilities of 5.15%and 5.31%,which was 1.7-fold higher than that of S-CM EVs(3.00%).This H-CM EVs platform not only achieved high drug loading and maintained functionality for effective oral delivery but also highlighted the significant translational potential for improved clinical outcomes.展开更多
The event-based vision sensor(EVS),which can generate efficient spiking data streams by exclusively detecting motion,exemplifies neuromorphic vision methodologies.Generally,its inherent lack of texture features limits...The event-based vision sensor(EVS),which can generate efficient spiking data streams by exclusively detecting motion,exemplifies neuromorphic vision methodologies.Generally,its inherent lack of texture features limits effectiveness in complex vision processing tasks,necessitating supplementary visual information.However,to date,no event-based hybrid vision solution has been developed that preserves the characteristics of complete spike data streams to support synchronous computation architectures based on spiking neural network(SNN).In this paper,we present a novel spike-based sensor with digitized pixels,which integrates the event detection structure with the pulse frequency modulation(PFM)circuit.This design enables the simultaneous output of spiking data that encodes both temporal changes and texture information.Fabricated in 180 nm process,the proposed sensor achieves a resolution of 128×128,a maximum event rate of 960 Meps,a grayscale frame rate of 117.1 kfps,and a measured power consumption of 60.1 mW,which is suited for high-speed,low-latency,edge SNNbased vision computing systems.展开更多
Ephemeroviruses(EVs)are arthropod-borne rhabdoviruses and were isolated exclusively from cattle and haematophagous arthropods until two new ephemeroviruses were first identified from domestic pigs most recently.Here w...Ephemeroviruses(EVs)are arthropod-borne rhabdoviruses and were isolated exclusively from cattle and haematophagous arthropods until two new ephemeroviruses were first identified from domestic pigs most recently.Here we report the identification of newer EVs in wild boar by meta-transcriptomic(MTT)sequencing.Further screening by specific RT-nPCR of tissue samples of 459 free-ranging wild boars collected between 2018 and 2023 from 26 provinces across China confirmed five positive wild boars in four provinces.Interestingly,two ticks especially collected from two positive wild boars were also EV positive.Finally,four complete genome sequences of wild boar ephemeroviruses(WbEVs)were obtained with two strains belonging to a new EV species,and the rest two falling into porcine ephemerovirus 2(PoEV2)species identified from domestic pigs.Our study has further extended EV host range and demonstrated natural circulations of divergent EVs in wild boars,in which ticks may play roles.Biological implications of EV infection in wild boars should be interesting topics for future investigations.展开更多
Imagine a city that seems to hum rather than roar-a place where innovation moves at the pace of everyday life instead of like the flashy glamor of high-end tech hubs.This is Liuzhou,a city in southern China that is qu...Imagine a city that seems to hum rather than roar-a place where innovation moves at the pace of everyday life instead of like the flashy glamor of high-end tech hubs.This is Liuzhou,a city in southern China that is quietly shaping the future of electric vehicles(EVs).It has become an unlikely yet powerful engine of change in the world of clean mobility.展开更多
The global automotive sector is moving towards zero-emission transportation,which has led to the rapid growthof the electric vehidles(EVs)market,projected to reach USD1,318 billion in 2028.However,behind the booming d...The global automotive sector is moving towards zero-emission transportation,which has led to the rapid growthof the electric vehidles(EVs)market,projected to reach USD1,318 billion in 2028.However,behind the booming develop-ment of the electric vehicle market,its safety issues havealways been the focal point of consumers'concern and alsothe cornerstone for the sustained and healthy developmentof the new energy vehicle industry.展开更多
Recycling electric vehicle batteries has become a priority in China.NEW stationary power storage cabinets have been set up beside the parking lots of the Green Eco Manufacture(GEM)Industrial Park in Wuhan,Hubei Provin...Recycling electric vehicle batteries has become a priority in China.NEW stationary power storage cabinets have been set up beside the parking lots of the Green Eco Manufacture(GEM)Industrial Park in Wuhan,Hubei Province,to charge electric vehicles(EVs).展开更多
Chronic diabetic wounds result from a disrupted microenvironment where oxidative stress,impaired angiogenesis,and persistent infection create a vicious cycle that delays healing.Unfortunately,existing treatments often...Chronic diabetic wounds result from a disrupted microenvironment where oxidative stress,impaired angiogenesis,and persistent infection create a vicious cycle that delays healing.Unfortunately,existing treatments often fail to address these interrelated issues,resulting in suboptimal healing.Here,we propose a base-tip dual-component hydrogel microneedle(MN)system(GBEVs-pVEGF/AgNPs@MNs),consisting of a tip loaded with plant-bacterial hybrid extracellular vesicles(GBEVs-pVEGF)and a base containing silver nanoparticles(AgNPs).Upon penetrating the necrotic tissue of diabetic wounds,our multifunctional MNs could effectively deliver GBEVs-pVEGF,thereby alleviating oxidative stress,promoting cell migration,and facilitating angiogenesis.Additionally,the physical barrier formed by the basal layer synergistically mitigates persistent bacterial infections during wound healing in conjunction with the antimicrobial agent AgNPs.This multifunctional MN system,integrating antioxidant,angiogenic,and antimicrobial properties,effectively restores the disrupted wound microenvironment,offering significant potential for accelerating diabetic wound healing.展开更多
Background:Patients with gastric cancer(GC)are prone to lymph node metastasis(LNM),which is an important factor for recurrence and poor prognosis of GC.Nowadays,more and more studies have confirmed that exosomes can p...Background:Patients with gastric cancer(GC)are prone to lymph node metastasis(LNM),which is an important factor for recurrence and poor prognosis of GC.Nowadays,more and more studies have confirmed that exosomes can participate in tumor lymphangiogenesis.An in-depth exploration of the pathological mechanism in the process of LNM in GC may provide effective targets and improve the diagnosis and treatment effect.Materials and Methods:We used sequencing analysis of collected serum to screen out exo-miRNA related to LNM in GC.ELISA,qRT-PCR,Western Blot,RNA pull-down assay,Transwell assay,animal experiments,and other experiments were used to verify the results.Results:In this study,we screened out miR-224-3p related to GC progression and LNM in a vascular endothelial growth Factor C(VEGFC)-independent manner.We found that exo-miR-224-3p derived from GC cells could enter human lymphatic endothelial cells(HLECs)and promote the tube formation and migration of HLECs.In addition,it was revealed that miR-224-3p could bind to the 3′UTR region of GSK3B mRNA.Then,we proved that inhibiting the expression of GSK3B could suppress the phosphorylation ofβ-catenin and promote the transcription of PROX1,thus leading to tumor lymphangiogenesis.Furthermore,it was also found that hnRNPA1 mediated the sorting of miR-224-3p into exosomes,and the high expression of PKM2 promoted the secretion of exomiR-224-3p.Conclusions:Our discovery of the exo-miR-224-3p/GSK3B/β-catenin/PROX1 axis may provide a new direction for the clinical treatment of GC.展开更多
Electric vehicle(EV) drive trains are constantly subjected to an imbalance between demanded torque and generated electromagnetic torque due to unpredictable terrain, traffic, and other external factors. This imbalance...Electric vehicle(EV) drive trains are constantly subjected to an imbalance between demanded torque and generated electromagnetic torque due to unpredictable terrain, traffic, and other external factors. This imbalance leads to significant torsional vibrations and speed fluctuations, which not only compromise passenger comfort but also exert additional mechanical stress on the EVs. Conventional sensorless methods offer speed estimation and control;however, they provide suboptimal performance with sudden load torque disturbances and operational uncertainties, especially at low speeds and across diverse real-world driving cycles. To address these challenges and improve system robustness, this work proposes an advanced sensorless integral sliding mode control(ASISMC) that enhances performance under diverse operating conditions. The proposed ASISMC methodology shows robust performance across a wide speed range, effectively mitigating abrupt load torque disturbances while minimizing the effect of uncertainties within the system dynamics. The approach is experimentally validated for a wide range of speeds and periodic/non-periodic load torque disturbances. Additional validation through the new European driving cycle(NEDC) and urban dynamometer driving schedule(UDDS) demonstrates the method's effectiveness and reliability in real-world driving conditions.展开更多
基金supported by grants from the Jagiellonian University,Poland(N18/DBS/000007)the Polish National Science Centre(2018/31/N/NZ4/03787).
文摘Angiogenesis,the expansion of pre-existing vascular networks,is crucial for normal organ growth and tissue repair,but is also involved in various pathologies,including inflammation,ischemia,diabetes,and cancer.In solid tumors,angiogenesis supports growth,nutrient delivery,waste removal,and metastasis.Tumors can induce angiogenesis through proangiogenic factors including VEGF,FGF-2,PDGF,angiopoietins,HGF,TNF,IL-6,SCF,tryptase,and chymase.This balance is disrupted in tumors,and extracellular vesicles(EVs)contribute to this by transferring proangiogenic factors and increasing their expression in endothelial cells(ECs).Malignant melanoma,a particular type of skin cancer,accounts for only 1%of skin cancer cases but more than 75%of deaths.Its incidence has risen significantly,with a 40%increase between 2012 and 2022,especially in fair-skinned populations.Advanced metastatic stages have a high mortality due to delayed diagnosis.This review examines the molecular basis of angiogenesis in melanoma,focusing on melanoma-derived EVs and their possible use in new antiangiogenic therapies.
基金supported by the National Natural Science Foundation of China (82230071, 82172098)the Integrated Project of Major Research Plan of National Natural Science Foundation of China (92249303)+2 种基金the Laboratory Animal Research Project of Shanghai Committee of Science and Technology (23141900600)the Shanghai Clinical Research Plan (SHDC2023CRT01)the Young Elite Scientist Sponsorship Program by China Association for Science and Technology (YESS20230049)。
文摘In addition to its recognized role in providing structural support, bone plays a crucial role in maintaining the functionality and balance of various organs by secreting specific cytokines(also known as osteokines). This reciprocal influence extends to these organs modulating bone homeostasis and development, although this aspect has yet to be systematically reviewed. This review aims to elucidate this bidirectional crosstalk, with a particular focus on the role of osteokines. Additionally, it presents a unique compilation of evidence highlighting the critical function of extracellular vesicles(EVs) within bone-organ axes for the first time. Moreover, it explores the implications of this crosstalk for designing and implementing bone-on-chips and assembloids, underscoring the importance of comprehending these interactions for advancing physiologically relevant in vitro models. Consequently, this review establishes a robust theoretical foundation for preventing, diagnosing, and treating diseases related to the bone-organ axis from the perspective of cytokines, EVs, hormones, and metabolites.
基金financial support from the the Regional Innovation and Development Joint Fund of National Natural Science Foundation of China(grant numbers:U22A20356)the National Key R&D Program of China(No.2021YFE0115200)the National Natural Science Foundation of China(No.81872818).
文摘Milk-derived extracellular vesicles(EVs)are promising for oral drug delivery,yet different loading methods exhibit distinct impacts on drug encapsulation and membrane integrity.This study demonstrated that sonication method achieved high drug encapsulation in commercial milk-derived EVs(S-CM EVs),but impaired EV structure,compromising transcytosis.Incubation method(I-CM EVs)preserved EVs delivery ability,but had low drug loading.Further proteomic and transmembrane studies showed that sonication greatly damaged membrane proteins involved in trans-epithelial transportation,especially endoplasmic reticulum-Golgi pathway.To overcome this dilemma,we generated a hybrid CM EVs(H-CM EVs)by fusing I-CM EVs and S-CM EVs.H-CM EVs demonstrated comparable drug encapsulation to S-CM EVs(56.14%),significantly higher than I-CM EVs(11.92%).Importantly,H-CM EVs could maintain efficient drug delivery capability by restoring membrane fluidity,repairing damaged proteins,and enhancing enzyme resistance of SCM EVs.H-CM EVs exhibited excellent absorption characteristics with 1.85-fold higher of area under the curve and 2.50-fold higher of max plasma concentration than those of SCM EVs.On typeⅠdiabetic mice,orally delivery of insulin loaded H-CM EVs and I-CM EVs showed improved hypoglycemic effects with pharmacological availabilities of 5.15%and 5.31%,which was 1.7-fold higher than that of S-CM EVs(3.00%).This H-CM EVs platform not only achieved high drug loading and maintained functionality for effective oral delivery but also highlighted the significant translational potential for improved clinical outcomes.
基金supported in part by the National Key Research and Development Program of China(Grant No.2022YFB2804401)the National Natural Science Foundation of China(Grant Nos.62334008,62134004,62404218)+1 种基金the Beijing Natural Science Foundation(Grant No.Z220005)Chinese Academy of Sciences(Grant No.ZDBS-LY-JSC008).
文摘The event-based vision sensor(EVS),which can generate efficient spiking data streams by exclusively detecting motion,exemplifies neuromorphic vision methodologies.Generally,its inherent lack of texture features limits effectiveness in complex vision processing tasks,necessitating supplementary visual information.However,to date,no event-based hybrid vision solution has been developed that preserves the characteristics of complete spike data streams to support synchronous computation architectures based on spiking neural network(SNN).In this paper,we present a novel spike-based sensor with digitized pixels,which integrates the event detection structure with the pulse frequency modulation(PFM)circuit.This design enables the simultaneous output of spiking data that encodes both temporal changes and texture information.Fabricated in 180 nm process,the proposed sensor achieves a resolution of 128×128,a maximum event rate of 960 Meps,a grayscale frame rate of 117.1 kfps,and a measured power consumption of 60.1 mW,which is suited for high-speed,low-latency,edge SNNbased vision computing systems.
基金supported by Wildlife Borne Infectious Diseases Monitoring Project of the State Forestry and Grassland Administration of China to Zhongzhong Tu(2020076060)the National Key Research and Development Program of China to Changchun Tu(32130104).
文摘Ephemeroviruses(EVs)are arthropod-borne rhabdoviruses and were isolated exclusively from cattle and haematophagous arthropods until two new ephemeroviruses were first identified from domestic pigs most recently.Here we report the identification of newer EVs in wild boar by meta-transcriptomic(MTT)sequencing.Further screening by specific RT-nPCR of tissue samples of 459 free-ranging wild boars collected between 2018 and 2023 from 26 provinces across China confirmed five positive wild boars in four provinces.Interestingly,two ticks especially collected from two positive wild boars were also EV positive.Finally,four complete genome sequences of wild boar ephemeroviruses(WbEVs)were obtained with two strains belonging to a new EV species,and the rest two falling into porcine ephemerovirus 2(PoEV2)species identified from domestic pigs.Our study has further extended EV host range and demonstrated natural circulations of divergent EVs in wild boars,in which ticks may play roles.Biological implications of EV infection in wild boars should be interesting topics for future investigations.
文摘Imagine a city that seems to hum rather than roar-a place where innovation moves at the pace of everyday life instead of like the flashy glamor of high-end tech hubs.This is Liuzhou,a city in southern China that is quietly shaping the future of electric vehicles(EVs).It has become an unlikely yet powerful engine of change in the world of clean mobility.
文摘The global automotive sector is moving towards zero-emission transportation,which has led to the rapid growthof the electric vehidles(EVs)market,projected to reach USD1,318 billion in 2028.However,behind the booming develop-ment of the electric vehicle market,its safety issues havealways been the focal point of consumers'concern and alsothe cornerstone for the sustained and healthy developmentof the new energy vehicle industry.
文摘Recycling electric vehicle batteries has become a priority in China.NEW stationary power storage cabinets have been set up beside the parking lots of the Green Eco Manufacture(GEM)Industrial Park in Wuhan,Hubei Province,to charge electric vehicles(EVs).
基金support from the National Natural Science Foundation of China(No.82472444).
文摘Chronic diabetic wounds result from a disrupted microenvironment where oxidative stress,impaired angiogenesis,and persistent infection create a vicious cycle that delays healing.Unfortunately,existing treatments often fail to address these interrelated issues,resulting in suboptimal healing.Here,we propose a base-tip dual-component hydrogel microneedle(MN)system(GBEVs-pVEGF/AgNPs@MNs),consisting of a tip loaded with plant-bacterial hybrid extracellular vesicles(GBEVs-pVEGF)and a base containing silver nanoparticles(AgNPs).Upon penetrating the necrotic tissue of diabetic wounds,our multifunctional MNs could effectively deliver GBEVs-pVEGF,thereby alleviating oxidative stress,promoting cell migration,and facilitating angiogenesis.Additionally,the physical barrier formed by the basal layer synergistically mitigates persistent bacterial infections during wound healing in conjunction with the antimicrobial agent AgNPs.This multifunctional MN system,integrating antioxidant,angiogenic,and antimicrobial properties,effectively restores the disrupted wound microenvironment,offering significant potential for accelerating diabetic wound healing.
基金supported by grants from the National Natural Science Foundation of China(Nos.82072664,81974374,82173125,82103677).
文摘Background:Patients with gastric cancer(GC)are prone to lymph node metastasis(LNM),which is an important factor for recurrence and poor prognosis of GC.Nowadays,more and more studies have confirmed that exosomes can participate in tumor lymphangiogenesis.An in-depth exploration of the pathological mechanism in the process of LNM in GC may provide effective targets and improve the diagnosis and treatment effect.Materials and Methods:We used sequencing analysis of collected serum to screen out exo-miRNA related to LNM in GC.ELISA,qRT-PCR,Western Blot,RNA pull-down assay,Transwell assay,animal experiments,and other experiments were used to verify the results.Results:In this study,we screened out miR-224-3p related to GC progression and LNM in a vascular endothelial growth Factor C(VEGFC)-independent manner.We found that exo-miR-224-3p derived from GC cells could enter human lymphatic endothelial cells(HLECs)and promote the tube formation and migration of HLECs.In addition,it was revealed that miR-224-3p could bind to the 3′UTR region of GSK3B mRNA.Then,we proved that inhibiting the expression of GSK3B could suppress the phosphorylation ofβ-catenin and promote the transcription of PROX1,thus leading to tumor lymphangiogenesis.Furthermore,it was also found that hnRNPA1 mediated the sorting of miR-224-3p into exosomes,and the high expression of PKM2 promoted the secretion of exomiR-224-3p.Conclusions:Our discovery of the exo-miR-224-3p/GSK3B/β-catenin/PROX1 axis may provide a new direction for the clinical treatment of GC.
文摘Electric vehicle(EV) drive trains are constantly subjected to an imbalance between demanded torque and generated electromagnetic torque due to unpredictable terrain, traffic, and other external factors. This imbalance leads to significant torsional vibrations and speed fluctuations, which not only compromise passenger comfort but also exert additional mechanical stress on the EVs. Conventional sensorless methods offer speed estimation and control;however, they provide suboptimal performance with sudden load torque disturbances and operational uncertainties, especially at low speeds and across diverse real-world driving cycles. To address these challenges and improve system robustness, this work proposes an advanced sensorless integral sliding mode control(ASISMC) that enhances performance under diverse operating conditions. The proposed ASISMC methodology shows robust performance across a wide speed range, effectively mitigating abrupt load torque disturbances while minimizing the effect of uncertainties within the system dynamics. The approach is experimentally validated for a wide range of speeds and periodic/non-periodic load torque disturbances. Additional validation through the new European driving cycle(NEDC) and urban dynamometer driving schedule(UDDS) demonstrates the method's effectiveness and reliability in real-world driving conditions.
