Background Depressive symptoms are established risk factors for various health outcomes.However,previous studies assessed depressive symptoms at a single time point,neglecting individual variations over time.Aims To i...Background Depressive symptoms are established risk factors for various health outcomes.However,previous studies assessed depressive symptoms at a single time point,neglecting individual variations over time.Aims To identify depressive symptoms trajectories through repeated measures and examine their associations with cardiovascular disease(CVD),cancer and mortality.Methods This study included 20634 UK Biobank participants free of CVD and cancer at baseline with two or more assessments of depressive symptoms during 2006-2016.Group-based trajectory modelling identified depressive symptoms trajectories.Incident CVD,cancer and mortality were followed up until 2021 through linked registries.Results Six depressive symptoms trajectories were identified:no symptoms(n=6407),mild-stable(n=11539),moderate-stable(n=2183),severe-decreasing(n=206),moderate-increasing(n=177)and severe-stable(n=122).During a median follow-up of 5.5 years,1471 CVD cases,1275 cancer cases and 503 deaths were documented.Compared with the no symptoms trajectory,the mildstable,moderate-stable and severe-stable trajectories exhibited higher CVD risk,with hazard ratios(HRs)(95%CIs)of 1.19(1.06 to 1.34),1.32(1.08 to 1.34)and 2.99(1.85 to 4.84),respectively.Moderate-increasing and severe-stable trajectories were associated with higher mortality risks,with HRs(95%CIs)of 2.27(1.04 to 4.93)and 3.26(1.55 to 6.88),respectively.However,the severedecreasing trajectory was not associated with higher risks of adverse outcomes.We did not find significant associations between any trajectory and cancer.Conclusions Trajectories related to stable and increasing depressive symptoms,but not the trajectory associated with severe depressive symptoms at the initial assessment but decreasing at the follow-up,were associated with higher risks of CVD and mortality.Alleviating severe depressive symptoms at the initial onset may mitigate CVD and mortality risks.展开更多
The focus of drug delivery is shifting toward smart drug carriers that release the cargo in response to a change in the microenvironment due to an internal or external trigger. As the most clinically successful nanosy...The focus of drug delivery is shifting toward smart drug carriers that release the cargo in response to a change in the microenvironment due to an internal or external trigger. As the most clinically successful nanosystem, liposomes naturally come under the spotlight of this trend. This review summarizes the latest development about the design and construction of photo-responsive liposomes with gold nanoparticles for the controlled drug release. Alongside, we overview the mechanism involved in this process and the representative applications.展开更多
Background The evidence regarding the association between leucocyte telomere length(LTL)and brain health is sparse and inconclusive.Aims To investigate the associations of LTL with brain structure and the risk of deme...Background The evidence regarding the association between leucocyte telomere length(LTL)and brain health is sparse and inconclusive.Aims To investigate the associations of LTL with brain structure and the risk of dementia based on a large-scale prospective study.Methods LTL in the peripheral blood was measured by the quantitative polymerase chain reaction(qPCR)assay from 439961 individuals in the UK Biobank recruited between 2006 and 2010 and followed up until 2020.Electronic health records were used to record the incidence of dementia,including Alzheimer’s disease(AD)and vascular dementia(VD).The brain structure,including total and regional brain volume,of 38740 participants was then assessed by magnetic resonance imaging(MRI).Results During a median follow-up of 11.6 years,a total of 5820(1.3%)dementia cases were documented.The restricted cubic spline model showed significant overall associations between LTL and the risk of dementia and AD(p for overall<0.05).The multivariable adjusted hazard ratios(HRs)for the lowest LTL tertile compared with the highest LTL tertile were 1.14(95%confidence interval(CI):1.06 to 1.21)for dementia,1.28(95%CI:1.12 to 1.46)for AD and 1.18(95%CI:0.98 to 1.42)for VD.Furthermore,we found that shorter LTL was associated with smaller total brain volume(β=−0.0128,p=0.003),white matter volume(β=−0.0224,p<0.001),hippocampus volume(β=−0.0172,p<0.001),thalamus volume(β=−0.0239,p<0.001)and accumbens(β=−0.0155,p=0.001).Conclusions Shorter LTL is associated with total and regional brain structure and a higher risk of incident dementia and AD,implying the potential of telomere length as a predictive biomarker of brain health.展开更多
Developing an effective method to synthesize high-performance high-voltage LiCoO_(2) is essential for its industrialization in lithium batteries(LIBs).This work proposes a simple mass-produced strategy for the first t...Developing an effective method to synthesize high-performance high-voltage LiCoO_(2) is essential for its industrialization in lithium batteries(LIBs).This work proposes a simple mass-produced strategy for the first time,that is,negative temperature coefficient thermosensitive Pr_(6)O_(11) nanoparticles are uniformly modified on LiCoO_(2) to prepare LiCoO_(2)@Pr_(6)O_(11)(LCO@PrO)via a liquid-phase mixing combined with annealing method.Tested at 274 mA g−1,the modified LCO@PrO electrodes deliver excellent 4.5 V high-voltage cycling performance with capacity retention ratios of 90.8%and 80.5%at 25 and 60℃,being much larger than those of 22.8%and 63.2%for bare LCO electrodes.Several effective strategies were used to clearly unveil the performance enhancement mechanism induced by Pr_(6)O_(11) modification.It is discovered that Pr_(6)O_(11) can improve interface compatibility,exhibit improved conductivity at elevated temperature,thus enhance the Li^(+)diffusion kinetics,and suppress the phase transformation of LCO and its resulting mechanical stresses.The 450 mAh LCO@PrO‖graphite pouch cells show excellent LIB performance and improved thermal safety characteristics.Importantly,the energy density of such pouch cell was increased even by~42%at 5 C.This extremely convenient technology is feasible for producing high-energy density LIBs with negligible cost increase,undoubtedly providing important academic inspiration for industrialization.展开更多
Exosomes,nanoscopic extracellular vesicles produced by cells,are pivotal in mediating intracellular communication by transporting nucleic acids,proteins,lipids,and other bioactive molecules,thereby influencing physiol...Exosomes,nanoscopic extracellular vesicles produced by cells,are pivotal in mediating intracellular communication by transporting nucleic acids,proteins,lipids,and other bioactive molecules,thereby influencing physiological and pathological states.Their endogenous origin and inherent diversity confer distinct advantages over synthetic vehicles like liposomes and nanoparticles in diagnostic and therapeutic applications.Despite their potential,the clinical utility of exosomes is hampered by challenges such as limited storage stability,yield,purity,and targeting efficiency.This review focuses on exosomes as targeted therapeutic agents,examining their biogenesis,classification,isolation,and characterisation,while also addressing the current limitations in yield,purity,and targeting.We delve into the literature to propose optimisation strategies that can enhance their therapeutic efficacy and accelerate the translation of exosome-based therapies into clinical practice.展开更多
Sustainable travel behavior intervention is an essential strategy to promote the development of urban transportation.The interventions offer personalized strategies based on certain scenario and participants to promot...Sustainable travel behavior intervention is an essential strategy to promote the development of urban transportation.The interventions offer personalized strategies based on certain scenario and participants to promote its effectiveness over hard travel restrictions.However,personalized strategies may also bring about difficulties to identify the actual effect of the measures.Furthermore,based on current practice,to make full use of travel behavior interventions,it is necessary to construct a unified methodological evidencebased framework to assess the reliability and effectiveness of travel behavior intervention studies.In response to these issues,we applied evidence-based knowledge graph to the field of sustainable travel behavior interventions to help decision supporters design sustainable travel behavior interventions wisely and in turn avoid excessive use of hard travel restrictions.We introduced concept of evidence-based practice to conduct a systematic analysis concerning reliability and validity of current full volume empirical studies by dimensions of scenarios,types of interventions and targets.In addition,we took advantage of high extensivity and integrability of knowledge graph to organize evidence-based related elements.Result of the systematic analysis shows that in terms of reliability of evidence,school intervention is the best scenario,knowledge incentive is the best intervention type and promoting public transit and walking proportion are the best targets.Oppositely,the reliability of interventions in workplace,belonging to reward and threat along with aiming at changing travel patterns generally and lowering travel carbon emission need to be enhanced.From the study,various research prospects are raised to promote evidence quality in the field of travel behavior intervention implementation.As a pioneer study,our research contributes to the field of urban transportation in introducing concepts of evidence-based practice and enabling optimization and extension of our achievement via the usage of knowledge graph,enhancing reliability and objectivity in urban transportation decision-making.展开更多
A composite scaffold composed of a porous scaffold and hydrogel filling can facilitate engraftment,survival,and retention in cell transplantation processes.This study presents a composite scaffold made of poly(ε-capr...A composite scaffold composed of a porous scaffold and hydrogel filling can facilitate engraftment,survival,and retention in cell transplantation processes.This study presents a composite scaffold made of poly(ε-caprolactone)(PCL)and methacrylated hyaluronic acid(MeHA)hydrogel and describes the corresponding physical properties(surface area,porosity,and mechanical strength)and host response(angiogenesis and fibrosis)after subcutaneous transplantation.Specifically,we synthesise MeHA with different degrees of substitution and fabricate a PCL scaffold with different porosities.Subsequently,we construct a series of PCL/MeHA composite scaffolds by combining these hydrogels and scaffolds.In experiments with mice,the scaffold composed of 3%PCL and 10-100 kDa,degree of substitution 70%MeHA results in the least fibrosis and a higher degree of angiogenesis.This study highlights the potential of PCL/MeHA composite scaffolds for subcutaneous cell transplantation,given their desirable physical properties and host response.展开更多
The initiation and development of major infammatory diseases,i.e.,cancer,vascular infammation,and some autoimmune diseases are closely linked to the immune system.Biologics-based immunotherapy is exerting a critical r...The initiation and development of major infammatory diseases,i.e.,cancer,vascular infammation,and some autoimmune diseases are closely linked to the immune system.Biologics-based immunotherapy is exerting a critical role against these diseases,whereas the usage of the immunomodulators is always limited by various factors such as susceptibility to digestion by enzymes in vivo,poor penetration across biological barriers,and rapid clearance by the reticuloendothelial system.Drug delivery strategies are potent to promote their delivery.Herein,we reviewed the potential targets for immunotherapy against the major infammatory diseases,discussed the biologics and drug delivery systems involved in the immunotherapy,particularly highlighted the approved therapy tactics,and finally offer perspectives in this feld.展开更多
Co-delivery of chemotherapeutics and immunostimulant or chemoimmunotherapy is an emerging strategy in cancer therapy.The precise control of the targeting and release of agents is critical in this methodology.This arti...Co-delivery of chemotherapeutics and immunostimulant or chemoimmunotherapy is an emerging strategy in cancer therapy.The precise control of the targeting and release of agents is critical in this methodology.This article proposes the asynchronous release of the chemotherapeutic agents and immunostimulants to realize the synergistic effect between chemotherapy and immunotherapy.To obtain a proof-of-concept,a co-delivery system was prepared via a drug-delivering-drug(DDD)strategy for cytosolic co-delivery of Poly I:C,a synthetic ds RNA analog to activate RIG-I signaling,and PTX,a commonly used chemotherapeutics,in which pure PTX nanorods were sequentially coated with Poly I:C and mannuronic acid via stimulating the RIG-I signaling axis.The co-delivery system with a diameter of 200 nm enables profound immunogenicity of cancer cells,exhibiting increased secretion of cytokines and chemokines,pronounced immune response in vivo,and significant inhibition of tumor growth.Also,we found that intracellularly sustained release of cytotoxic agents could elicit the immunogenicity of cancer cells.Overall,the intracellular asynchronous release of chemotherapeutics and immunomodulators is a promising strategy to promote the immunogenicity of cancer cells and augment the antitumor immune response.展开更多
Hypertrophic scars are unfavorable skin diseases characterized by excessive collagen deposition.Although systemic treatments exist in clinic to manage hypertrophic scars,they pose significant side effects and tend to ...Hypertrophic scars are unfavorable skin diseases characterized by excessive collagen deposition.Although systemic treatments exist in clinic to manage hypertrophic scars,they pose significant side effects and tend to lose efficacy over prolonged applications.Traditional Chinese medicine(TCM)offers as a promising candidate to treat pathological scars.A large number of TCMs have been studied to show anti-scarring effect,however,the natural barrier of the skin impedes their penetration,lowering its therapeutic efficacy.Herein,we reported the use of dissolvable hyaluronic acid(HA)microneedles(MNs)as a vehicle to aid the transdermal delivery of therapeutic agent,a model TCM called shikonin for the treatment of hypertrophic scars.Here,shikonin was mixed with HA to make MNs with adequate mechanical strength for skin penetration,making its dosage controllable during the fabrication process.The therapeutic effect of the shikonin MNs was studied in vira using HSFs and then further verified with quantitative reverse transcriptase polymerase chain reaction.Our data suggest that the shikonin HA MNs significantly reduce the viability and proliferation of the HSFs and downregulate the fibrotic-related genes(i.e.,TGFβ1,FAP-αand COL1 A1).Furthermore,we observed a localized therapeutic effect of the shikonin HA MNs that is beneficial for site-specific treatment.展开更多
Atherosclerosis(AS) is a lipid-driven chronic inflammatory disease occurring at the arterial subendothelial space. Macrophages play a critical role in the initiation and development of AS. Herein,targeted codelivery o...Atherosclerosis(AS) is a lipid-driven chronic inflammatory disease occurring at the arterial subendothelial space. Macrophages play a critical role in the initiation and development of AS. Herein,targeted codelivery of anti-miR 155 and anti-inflammatory baicalein is exploited to polarize macrophages toward M2 phenotype, inhibit inflammation and treat AS. The codelivery system consists of a carrier-free strategy(drug-delivering-drug, DDD), fabricated by loading anti-miR155 on baicalein nanocrystals,named as baicalein nanorods(BNRs), followed by sialic acid coating to target macrophages. The codelivery system, with a diameter of 150 nm, enables efficient intracellular delivery of anti-miR155 and polarizes M1 to M2, while markedly lowers the level of inflammatory factors in vitro and in vivo. In particular, intracellular fate assay reveals that the codelivery system allows for sustained drug release over time after internalization. Moreover, due to prolonged blood circulation and improved accumulation at the AS plaque, the codelivery system significantly alleviates AS in animal model by increasing the artery lumen diameter, reducing blood pressure, promoting M2 polarization, inhibiting secretion of inflammatory factors and decreasing blood lipids. Taken together, the codelivery could potentially be used to treat vascular inflammation.展开更多
Transdermal drug delivery systems(TDDs) avoid gastrointestinal degradation and hepatic first-pass metabolism, providing good drug bioavailability and patient compliance. One emerging type of TDDs is the wearable patch...Transdermal drug delivery systems(TDDs) avoid gastrointestinal degradation and hepatic first-pass metabolism, providing good drug bioavailability and patient compliance. One emerging type of TDDs is the wearable patch worn on the skin surface to deliver medication through the skin. They can generally be grouped into passive and active types, depending on the properties of materials,design principles and integrated devices. This review describes the latest advancement in the development of wearable patches, focusing on the integration of stimulus-responsive materials and electronics.This development is deemed to provide a dosage, temporal, and spatial control of therapeutics delivery.展开更多
Silica nanoparticles have been studied extensively in biomedical field due to their high biocompatibility,controllable morphology and so on.They can be used both as the drug carrier and imaging vehicle.Here,an aminate...Silica nanoparticles have been studied extensively in biomedical field due to their high biocompatibility,controllable morphology and so on.They can be used both as the drug carrier and imaging vehicle.Here,an aminated ultra-small silica nanoparticle based system is developed with various functionalities.Multiple molecules including fluorophore,folic acid,and antibody are coupled to this system to achieve specific applications such as bacterial/cell labelling and recognition.展开更多
Our immune system has a vital role,and any variation because of either heritable or non-heritable stimuli might cause health disorders such as cancer,diabetes,and cardiovascular diseases1.In addition,the complexity of...Our immune system has a vital role,and any variation because of either heritable or non-heritable stimuli might cause health disorders such as cancer,diabetes,and cardiovascular diseases1.In addition,the complexity of the anatomical barriers,such as the blood brain barrier,challenges the therapy of central nervous system(CNS)diseases.The goal of nano-dimensional drugs(nanomedicines)is to improve the efficacy of treatments while minimizing systemic toxicity and side effects.展开更多
Low back pain associated with degenerative disc diseases has been a major health concern that brings suffering to the patients physically and economically.Many existing therapeutic strategies provide shortterm relief ...Low back pain associated with degenerative disc diseases has been a major health concern that brings suffering to the patients physically and economically.Many existing therapeutic strategies provide shortterm relief of symptoms rather than treatment of the underlying cause.Development of an engineered tissue for disc regeneration is still in its infancy due to the limited autologous healthy disc cell source from the patients.It is also challenging to mimic the complexity of micro-architecture in the native disc tissue that determine their unique structural properties.To date,simple tissue models that mimic the annulus fibrosus(AF)micro-environment for understanding the potential of mesenchymal stem cells(MSCs)in AF tissue engineering are still lacking.In this study,the assembly of a coiled hydrogel microfiber has shown its capability to encapsulate MSCs and create an engineered tissue model that mimics the multiple lamellae of native AF.Using this model,we investigated the potential of MSCs that were previously induced by ascorbic acid(AA).Compared to non-induced MSCs,AA-induced MSCs exhibited significant increase in AF-associated biomarkers during later development in the engineered AF tissue model and also encouraged collagen accumulation through the down-regulated catabolic gene MMP1 and upregulated anti-catabolic gene TIMP1.Furthermore,AA-induced MSCs exhibited a Col2/Col1 ratio closer to that of a native AF tissue.These results suggested that AA-induced MSCs could be a potential cell source for AF tissue engineering and this established tissue model may provide a simple tool for successful AF tissue engineering strategies in the future.展开更多
基金supported by the Zhejiang Provincial Natural Science Foundation of China(grant number LY23G030005)the National Natural Science Foundation of China(grant number 72204071)the Scientific Research Foundation for Scholars of HZNU(grant number 4265C50221204119).
文摘Background Depressive symptoms are established risk factors for various health outcomes.However,previous studies assessed depressive symptoms at a single time point,neglecting individual variations over time.Aims To identify depressive symptoms trajectories through repeated measures and examine their associations with cardiovascular disease(CVD),cancer and mortality.Methods This study included 20634 UK Biobank participants free of CVD and cancer at baseline with two or more assessments of depressive symptoms during 2006-2016.Group-based trajectory modelling identified depressive symptoms trajectories.Incident CVD,cancer and mortality were followed up until 2021 through linked registries.Results Six depressive symptoms trajectories were identified:no symptoms(n=6407),mild-stable(n=11539),moderate-stable(n=2183),severe-decreasing(n=206),moderate-increasing(n=177)and severe-stable(n=122).During a median follow-up of 5.5 years,1471 CVD cases,1275 cancer cases and 503 deaths were documented.Compared with the no symptoms trajectory,the mildstable,moderate-stable and severe-stable trajectories exhibited higher CVD risk,with hazard ratios(HRs)(95%CIs)of 1.19(1.06 to 1.34),1.32(1.08 to 1.34)and 2.99(1.85 to 4.84),respectively.Moderate-increasing and severe-stable trajectories were associated with higher mortality risks,with HRs(95%CIs)of 2.27(1.04 to 4.93)and 3.26(1.55 to 6.88),respectively.However,the severedecreasing trajectory was not associated with higher risks of adverse outcomes.We did not find significant associations between any trajectory and cancer.Conclusions Trajectories related to stable and increasing depressive symptoms,but not the trajectory associated with severe depressive symptoms at the initial assessment but decreasing at the follow-up,were associated with higher risks of CVD and mortality.Alleviating severe depressive symptoms at the initial onset may mitigate CVD and mortality risks.
文摘The focus of drug delivery is shifting toward smart drug carriers that release the cargo in response to a change in the microenvironment due to an internal or external trigger. As the most clinically successful nanosystem, liposomes naturally come under the spotlight of this trend. This review summarizes the latest development about the design and construction of photo-responsive liposomes with gold nanoparticles for the controlled drug release. Alongside, we overview the mechanism involved in this process and the representative applications.
基金This work was supported by the National Natural Science Foundation of China(grant number 72204071)Zhejiang Provincial Natural Science Foundation of China(grant number LY23G030005)Scientific Research Foundation for Scholars of HZNU(grant number 4265C50221204119)。
文摘Background The evidence regarding the association between leucocyte telomere length(LTL)and brain health is sparse and inconclusive.Aims To investigate the associations of LTL with brain structure and the risk of dementia based on a large-scale prospective study.Methods LTL in the peripheral blood was measured by the quantitative polymerase chain reaction(qPCR)assay from 439961 individuals in the UK Biobank recruited between 2006 and 2010 and followed up until 2020.Electronic health records were used to record the incidence of dementia,including Alzheimer’s disease(AD)and vascular dementia(VD).The brain structure,including total and regional brain volume,of 38740 participants was then assessed by magnetic resonance imaging(MRI).Results During a median follow-up of 11.6 years,a total of 5820(1.3%)dementia cases were documented.The restricted cubic spline model showed significant overall associations between LTL and the risk of dementia and AD(p for overall<0.05).The multivariable adjusted hazard ratios(HRs)for the lowest LTL tertile compared with the highest LTL tertile were 1.14(95%confidence interval(CI):1.06 to 1.21)for dementia,1.28(95%CI:1.12 to 1.46)for AD and 1.18(95%CI:0.98 to 1.42)for VD.Furthermore,we found that shorter LTL was associated with smaller total brain volume(β=−0.0128,p=0.003),white matter volume(β=−0.0224,p<0.001),hippocampus volume(β=−0.0172,p<0.001),thalamus volume(β=−0.0239,p<0.001)and accumbens(β=−0.0155,p=0.001).Conclusions Shorter LTL is associated with total and regional brain structure and a higher risk of incident dementia and AD,implying the potential of telomere length as a predictive biomarker of brain health.
基金jointly supported by the Natural Science Foundations of China(Nos.22179020,12174057)Fujian Natural Science Foundation for Distinguished Young Scholars(Grant No.2020J06042)+2 种基金Foreign science and technology cooperation project of Fuzhou Science and Technology Bureau(No.2021-Y-086)Natural Science Foundation of Fujian Province(Grant No.2018J01660)Cultivation plan of outstanding young scientific research talents of Fujian Education Department(Grant No.J1-1323).
文摘Developing an effective method to synthesize high-performance high-voltage LiCoO_(2) is essential for its industrialization in lithium batteries(LIBs).This work proposes a simple mass-produced strategy for the first time,that is,negative temperature coefficient thermosensitive Pr_(6)O_(11) nanoparticles are uniformly modified on LiCoO_(2) to prepare LiCoO_(2)@Pr_(6)O_(11)(LCO@PrO)via a liquid-phase mixing combined with annealing method.Tested at 274 mA g−1,the modified LCO@PrO electrodes deliver excellent 4.5 V high-voltage cycling performance with capacity retention ratios of 90.8%and 80.5%at 25 and 60℃,being much larger than those of 22.8%and 63.2%for bare LCO electrodes.Several effective strategies were used to clearly unveil the performance enhancement mechanism induced by Pr_(6)O_(11) modification.It is discovered that Pr_(6)O_(11) can improve interface compatibility,exhibit improved conductivity at elevated temperature,thus enhance the Li^(+)diffusion kinetics,and suppress the phase transformation of LCO and its resulting mechanical stresses.The 450 mAh LCO@PrO‖graphite pouch cells show excellent LIB performance and improved thermal safety characteristics.Importantly,the energy density of such pouch cell was increased even by~42%at 5 C.This extremely convenient technology is feasible for producing high-energy density LIBs with negligible cost increase,undoubtedly providing important academic inspiration for industrialization.
基金supported by the Shanghai Rising-Star Program Yangfan Project,No.22YF1414000National Natural Science Foundation of China,Nos.82202335,82230071,82172098.
文摘Exosomes,nanoscopic extracellular vesicles produced by cells,are pivotal in mediating intracellular communication by transporting nucleic acids,proteins,lipids,and other bioactive molecules,thereby influencing physiological and pathological states.Their endogenous origin and inherent diversity confer distinct advantages over synthetic vehicles like liposomes and nanoparticles in diagnostic and therapeutic applications.Despite their potential,the clinical utility of exosomes is hampered by challenges such as limited storage stability,yield,purity,and targeting efficiency.This review focuses on exosomes as targeted therapeutic agents,examining their biogenesis,classification,isolation,and characterisation,while also addressing the current limitations in yield,purity,and targeting.We delve into the literature to propose optimisation strategies that can enhance their therapeutic efficacy and accelerate the translation of exosome-based therapies into clinical practice.
基金supported by the Science and Technology Commission of Shanghai Municipal under Grant 22511104200the Fundamental Research Funds for the Central Universities under No.2022-5-YB-02.
文摘Sustainable travel behavior intervention is an essential strategy to promote the development of urban transportation.The interventions offer personalized strategies based on certain scenario and participants to promote its effectiveness over hard travel restrictions.However,personalized strategies may also bring about difficulties to identify the actual effect of the measures.Furthermore,based on current practice,to make full use of travel behavior interventions,it is necessary to construct a unified methodological evidencebased framework to assess the reliability and effectiveness of travel behavior intervention studies.In response to these issues,we applied evidence-based knowledge graph to the field of sustainable travel behavior interventions to help decision supporters design sustainable travel behavior interventions wisely and in turn avoid excessive use of hard travel restrictions.We introduced concept of evidence-based practice to conduct a systematic analysis concerning reliability and validity of current full volume empirical studies by dimensions of scenarios,types of interventions and targets.In addition,we took advantage of high extensivity and integrability of knowledge graph to organize evidence-based related elements.Result of the systematic analysis shows that in terms of reliability of evidence,school intervention is the best scenario,knowledge incentive is the best intervention type and promoting public transit and walking proportion are the best targets.Oppositely,the reliability of interventions in workplace,belonging to reward and threat along with aiming at changing travel patterns generally and lowering travel carbon emission need to be enhanced.From the study,various research prospects are raised to promote evidence quality in the field of travel behavior intervention implementation.As a pioneer study,our research contributes to the field of urban transportation in introducing concepts of evidence-based practice and enabling optimization and extension of our achievement via the usage of knowledge graph,enhancing reliability and objectivity in urban transportation decision-making.
基金supported by Collaborative Research Fund from the Research Grants Council(RGC)of the Hong Kong Special Administrative Region China,No.C5044-21GResearch Institute of Tsinghua at Pearl River Delta,No.9239094(both to CX).
文摘A composite scaffold composed of a porous scaffold and hydrogel filling can facilitate engraftment,survival,and retention in cell transplantation processes.This study presents a composite scaffold made of poly(ε-caprolactone)(PCL)and methacrylated hyaluronic acid(MeHA)hydrogel and describes the corresponding physical properties(surface area,porosity,and mechanical strength)and host response(angiogenesis and fibrosis)after subcutaneous transplantation.Specifically,we synthesise MeHA with different degrees of substitution and fabricate a PCL scaffold with different porosities.Subsequently,we construct a series of PCL/MeHA composite scaffolds by combining these hydrogels and scaffolds.In experiments with mice,the scaffold composed of 3%PCL and 10-100 kDa,degree of substitution 70%MeHA results in the least fibrosis and a higher degree of angiogenesis.This study highlights the potential of PCL/MeHA composite scaffolds for subcutaneous cell transplantation,given their desirable physical properties and host response.
基金supported by the National Natural Science Foundation of China(Nos.81872823 and 82073782)the Double FirstClass(CPU2018PZQ13,China)of the China Pharmaceutical University,the Shanghai Science and Technology Committee(No.19430741500,China)+1 种基金the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine(TCM-201905,China)the Start-up Grant from City University of Hong Kong(No.9610472,China)。
文摘The initiation and development of major infammatory diseases,i.e.,cancer,vascular infammation,and some autoimmune diseases are closely linked to the immune system.Biologics-based immunotherapy is exerting a critical role against these diseases,whereas the usage of the immunomodulators is always limited by various factors such as susceptibility to digestion by enzymes in vivo,poor penetration across biological barriers,and rapid clearance by the reticuloendothelial system.Drug delivery strategies are potent to promote their delivery.Herein,we reviewed the potential targets for immunotherapy against the major infammatory diseases,discussed the biologics and drug delivery systems involved in the immunotherapy,particularly highlighted the approved therapy tactics,and finally offer perspectives in this feld.
基金supported by the National Natural Science Foundation of China(Nos.81872823,81871477 and 82073782)the Double First-Class(CPU2018PZQ13,China)of the CPU+1 种基金the Shanghai Science and Technology Committee(19430741500,China)the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of Traditional Chinese Medicine(TCM-201905,China)。
文摘Co-delivery of chemotherapeutics and immunostimulant or chemoimmunotherapy is an emerging strategy in cancer therapy.The precise control of the targeting and release of agents is critical in this methodology.This article proposes the asynchronous release of the chemotherapeutic agents and immunostimulants to realize the synergistic effect between chemotherapy and immunotherapy.To obtain a proof-of-concept,a co-delivery system was prepared via a drug-delivering-drug(DDD)strategy for cytosolic co-delivery of Poly I:C,a synthetic ds RNA analog to activate RIG-I signaling,and PTX,a commonly used chemotherapeutics,in which pure PTX nanorods were sequentially coated with Poly I:C and mannuronic acid via stimulating the RIG-I signaling axis.The co-delivery system with a diameter of 200 nm enables profound immunogenicity of cancer cells,exhibiting increased secretion of cytokines and chemokines,pronounced immune response in vivo,and significant inhibition of tumor growth.Also,we found that intracellularly sustained release of cytotoxic agents could elicit the immunogenicity of cancer cells.Overall,the intracellular asynchronous release of chemotherapeutics and immunomodulators is a promising strategy to promote the immunogenicity of cancer cells and augment the antitumor immune response.
基金support from Singapore Agency for Science,Technology and Research(A*STAR)Science and Engineering Research Council Additive Manufacturing for Biological Materials(AMBM)program(A18A8b0059,Singapore)City University of Hong Kong(#9610472,China)+1 种基金General Research Fund(GRF)from University Grant Committee of Hong Kong(UGC)Research Grant Council(RGC)(#9042951,China)NSFC/RGC Joint Research Scheme(N_City U118/20,China)
文摘Hypertrophic scars are unfavorable skin diseases characterized by excessive collagen deposition.Although systemic treatments exist in clinic to manage hypertrophic scars,they pose significant side effects and tend to lose efficacy over prolonged applications.Traditional Chinese medicine(TCM)offers as a promising candidate to treat pathological scars.A large number of TCMs have been studied to show anti-scarring effect,however,the natural barrier of the skin impedes their penetration,lowering its therapeutic efficacy.Herein,we reported the use of dissolvable hyaluronic acid(HA)microneedles(MNs)as a vehicle to aid the transdermal delivery of therapeutic agent,a model TCM called shikonin for the treatment of hypertrophic scars.Here,shikonin was mixed with HA to make MNs with adequate mechanical strength for skin penetration,making its dosage controllable during the fabrication process.The therapeutic effect of the shikonin MNs was studied in vira using HSFs and then further verified with quantitative reverse transcriptase polymerase chain reaction.Our data suggest that the shikonin HA MNs significantly reduce the viability and proliferation of the HSFs and downregulate the fibrotic-related genes(i.e.,TGFβ1,FAP-αand COL1 A1).Furthermore,we observed a localized therapeutic effect of the shikonin HA MNs that is beneficial for site-specific treatment.
基金supported by the National Natural Science Foundation of China(Nos.81872823 and 81773826)the Double First-Class(CPU2018PZQ13,China)of the China Pharmeutical University+2 种基金the Ministry of Science and Technology of China(2018ZX09711001)the Shanghai Science and Technology Committee(19430741500,China)the Key Laboratory of Modern Chinese Medicine Preparation of Ministry of Education of Jiangxi University of traditional Chinese Medicine(TCM201905,China)
文摘Atherosclerosis(AS) is a lipid-driven chronic inflammatory disease occurring at the arterial subendothelial space. Macrophages play a critical role in the initiation and development of AS. Herein,targeted codelivery of anti-miR 155 and anti-inflammatory baicalein is exploited to polarize macrophages toward M2 phenotype, inhibit inflammation and treat AS. The codelivery system consists of a carrier-free strategy(drug-delivering-drug, DDD), fabricated by loading anti-miR155 on baicalein nanocrystals,named as baicalein nanorods(BNRs), followed by sialic acid coating to target macrophages. The codelivery system, with a diameter of 150 nm, enables efficient intracellular delivery of anti-miR155 and polarizes M1 to M2, while markedly lowers the level of inflammatory factors in vitro and in vivo. In particular, intracellular fate assay reveals that the codelivery system allows for sustained drug release over time after internalization. Moreover, due to prolonged blood circulation and improved accumulation at the AS plaque, the codelivery system significantly alleviates AS in animal model by increasing the artery lumen diameter, reducing blood pressure, promoting M2 polarization, inhibiting secretion of inflammatory factors and decreasing blood lipids. Taken together, the codelivery could potentially be used to treat vascular inflammation.
基金support by Strategic Interdisciplinary Research Grant (7020029) from City University of Hong KongGeneral Research Fund (GRF) grant from the Research Grants Council (RGC) of the Hong Kong Special Administrative Region, China (City U 11200820, 11202222)+2 种基金the Mainland/Hong Kong Joint Research Scheme sponsored by the RGC Hong Kongthe National Natural Science Foundation of China (N_City U118/20)the Inno HK funding support from the Hong Kong Centre for Cerebro-cardiovascular Health Engineering (COCHE)。
文摘Transdermal drug delivery systems(TDDs) avoid gastrointestinal degradation and hepatic first-pass metabolism, providing good drug bioavailability and patient compliance. One emerging type of TDDs is the wearable patch worn on the skin surface to deliver medication through the skin. They can generally be grouped into passive and active types, depending on the properties of materials,design principles and integrated devices. This review describes the latest advancement in the development of wearable patches, focusing on the integration of stimulus-responsive materials and electronics.This development is deemed to provide a dosage, temporal, and spatial control of therapeutics delivery.
基金This work was supported by Singapore MOE Academic Research Fund(AcRF)Tier 1 grant(RG49/18)Additive Manufacturing for Biological Materials(AMBM)program from Singapore A*STAR Science and Engineering Research Council(A18A8b0059).
文摘Silica nanoparticles have been studied extensively in biomedical field due to their high biocompatibility,controllable morphology and so on.They can be used both as the drug carrier and imaging vehicle.Here,an aminated ultra-small silica nanoparticle based system is developed with various functionalities.Multiple molecules including fluorophore,folic acid,and antibody are coupled to this system to achieve specific applications such as bacterial/cell labelling and recognition.
文摘Our immune system has a vital role,and any variation because of either heritable or non-heritable stimuli might cause health disorders such as cancer,diabetes,and cardiovascular diseases1.In addition,the complexity of the anatomical barriers,such as the blood brain barrier,challenges the therapy of central nervous system(CNS)diseases.The goal of nano-dimensional drugs(nanomedicines)is to improve the efficacy of treatments while minimizing systemic toxicity and side effects.
基金supported by Singapore Agency for Science,Technology and Research(A^(*)STAR)Science and Engineering Research Council Additive Manufacturing for Biological Materials(AMBM)Program(A18A8b0059 to Chenjie Xu)Start-up Grant for Professor from City University of Hong Kong(SGP9380099 and SRG7005212 to Dong-An WangSGP9610472 to Chenjie Xu)。
文摘Low back pain associated with degenerative disc diseases has been a major health concern that brings suffering to the patients physically and economically.Many existing therapeutic strategies provide shortterm relief of symptoms rather than treatment of the underlying cause.Development of an engineered tissue for disc regeneration is still in its infancy due to the limited autologous healthy disc cell source from the patients.It is also challenging to mimic the complexity of micro-architecture in the native disc tissue that determine their unique structural properties.To date,simple tissue models that mimic the annulus fibrosus(AF)micro-environment for understanding the potential of mesenchymal stem cells(MSCs)in AF tissue engineering are still lacking.In this study,the assembly of a coiled hydrogel microfiber has shown its capability to encapsulate MSCs and create an engineered tissue model that mimics the multiple lamellae of native AF.Using this model,we investigated the potential of MSCs that were previously induced by ascorbic acid(AA).Compared to non-induced MSCs,AA-induced MSCs exhibited significant increase in AF-associated biomarkers during later development in the engineered AF tissue model and also encouraged collagen accumulation through the down-regulated catabolic gene MMP1 and upregulated anti-catabolic gene TIMP1.Furthermore,AA-induced MSCs exhibited a Col2/Col1 ratio closer to that of a native AF tissue.These results suggested that AA-induced MSCs could be a potential cell source for AF tissue engineering and this established tissue model may provide a simple tool for successful AF tissue engineering strategies in the future.
