Herpes zoster(HZ)is a painful condition resulting from reactivation of dormant varicella-zoster virus(VZV)in a previously VZV-infected person[1].Typical clinical manifestation of HZ are unilateral radicular pain and a...Herpes zoster(HZ)is a painful condition resulting from reactivation of dormant varicella-zoster virus(VZV)in a previously VZV-infected person[1].Typical clinical manifestation of HZ are unilateral radicular pain and a vesicular rash limited to one side of the body in the distribution of a nerve[2].The most common complication of HZ postherpetic neuralgia(PHN).展开更多
Small interfering RNAs （siRNA） have enormous potential as therapeutics to target and treat various bone disor- ders such as osteoporosis and cancer bone metastases. However, effective and specific delivery of siRNA ...Small interfering RNAs （siRNA） have enormous potential as therapeutics to target and treat various bone disor- ders such as osteoporosis and cancer bone metastases. However, effective and specific delivery of siRNA therapeu- tics to bone and bone-specific cells in vivo is very challenging. To realize the full therapeutic potential of siRNA in treating bone disorders, a safe and efficient, tissue- and cell-specific delivery system must be developed. This review focuses on recent advances in bone site-specific delivery of siRNA at the tissue or cellular level. Bone-targeted nanoparticulate siRNA carriers and various bone-targeted moieties such as bisphosphonates, oligopeptides （Asp）8 and （AspSerSer）6, and aptamers are highlighted. Incorporation of these bone-seeking targeting moieties into siRNA carriers allows for recognition of different sub-tissue functional domains of bone and also specific cell types residing in bone tissue. It also provides a means for bone-formation surface-, bone-resorption surface-, or osteoblast- specific targeting and transportation of siRNA therapeutics. The discussion mainly focuses on systemic and local bone-specific delivery of siRNA in osteoporosis and bone metastasis preclinical models.展开更多
Peptide-drug conjugates(PDCs)are the next generation of targeted therapeutics drug after antibody-drug conjugates(ADCs),with the core benefits of enhanced cellular permeability and improved drug selectivity.Two drugs ...Peptide-drug conjugates(PDCs)are the next generation of targeted therapeutics drug after antibody-drug conjugates(ADCs),with the core benefits of enhanced cellular permeability and improved drug selectivity.Two drugs are now approved for market by US Food and Drug Administration(FDA),and in the last two years,the pharmaceutical companies have been developing PDCs as targeted therapeutic candidates for cancer,coronavirus disease 2019(COVID-19),metabolic diseases,and so on.The therapeutic benefits of PDCs are significant,but poor stability,low bioactivity,long research and development time,and slow clinical development process as therapeutic agents of PDC,how can we design PDCs more effectively and what is the future direction of PDCs?This review summarises the components and functions of PDCs for therapeutic,from drug target screening and PDC design improvement strategies to clinical applications to improve the permeability,targeting,and stability of the various components of PDCs.This holds great promise for the future of PDCs,such as bicyclic peptide-toxin coupling or supramolecular nanostructures for peptide-conjugated drugs.The mode of drug delivery is determined according to the PDC design and current clinical trials are summarised.The way is shown for future PDC development.展开更多
Understanding the heterogeneous preferences of individuals for disaster insurance attributes is critical for product improvement and policy design.In an era of global environmental change,the Qinghai-Tibet Plateau is ...Understanding the heterogeneous preferences of individuals for disaster insurance attributes is critical for product improvement and policy design.In an era of global environmental change,the Qinghai-Tibet Plateau is a hotspot of natural hazards.Improving the capability of rural housing disaster insurance to foster local residents’disaster resilience is of great signifcance but remains under addressed.We used a discrete choice experiment approach to provide the frst estimates of rural residents’preferences for rural housing disaster insurance attributes in central and western Tibet.We estimated residents’preferences and willingness-to-pay for the sum insured,subsidy rate,insured object,and perils covered.The potential impacts of increasing the sum insured,expanding the insured object,and lowering subsidy rates were evaluated.Our results suggest that residents prefer products with a high sum insured,high subsidy rate,and a complete list of insured objects.Residents who have experienced specifc hazards tend to prefer the corresponding perils covered.Females and residents who have a closer social network are more likely to purchase insurance.Product improvement and policy simulation results suggest that,while lowering the subsidy rate,increasing the sum insured and expanding the insured object could promote participation and improve residents’welfare.Our results could improve the understanding of the preferences of households in remote regions and support policy implementations.展开更多
The microneedle(MN), a highly efficient and versatile device, has attracted extensive scientific and industrial interests in the past decades due to prominent properties including painless penetration, low cost, excel...The microneedle(MN), a highly efficient and versatile device, has attracted extensive scientific and industrial interests in the past decades due to prominent properties including painless penetration, low cost, excellent therapeutic efficacy, and relative safety. The robust microneedle enabling transdermal delivery has a paramount potential to create advanced functional devices with superior nature for biomedical applications. In this review, a great effort has been made to summarize the advance of microneedles including their materials and latest fabrication method, such as three-dimensional printing(3DP). Importantly, a variety of representative biomedical applications of microneedles such as disease treatment, immunobiological administration, disease diagnosis and cosmetic field, are highlighted in detail. At last, conclusions and future perspectives for development of advanced microneedles in biomedical fields have been discussed systematically. Taken together, as an emerging tool, microneedles have showed profound promise for biomedical applications.展开更多
We report gold nanoparticles(AuNPs)doped iron-based metal-organic frameworks(GIM)which displays near-infrared light(NIR)-enhanced cascade nanozyme against hypoxic tumors.Due to the strong protein adsorption-induced su...We report gold nanoparticles(AuNPs)doped iron-based metal-organic frameworks(GIM)which displays near-infrared light(NIR)-enhanced cascade nanozyme against hypoxic tumors.Due to the strong protein adsorption-induced surface passivation,AuNPs suffer from the loss of glucose oxidase(GOx)activity.However,GIM could protect the GOx-like activity of AuNPs with the satisfactory shield capability.In addition,GIM exhibited excellent photothermal conversion ability and unique NIR light-enhanced GOx-like activity,which could efficiently increase the endogenous H2O2 production.Meanwhile,as the produced H2O2 is converted by GIM into O2 and highly toxic OH.Thus,GIM-catalyzed cascade reactions with NIR light irradiation not only offer the O2 but also promote the reactive oxygen species(ROS)generation at tumor sites.The produced O2 could be further applied to AuNPs catalytic oxidation of glucose and relieve hypoxic condition of tumor microenvironment(TME).As a proof-of-concept study,GIM demonstrates the admirable tumor ablation under NIR irradiation in vivo.展开更多
Inflammatory leukocytes infiltration is orchestrated by mechanisms involving chemokines,selectins,addressins and other adhesion molecules derived from endothelial cells(ECs),but how they respond to inflammatory cues a...Inflammatory leukocytes infiltration is orchestrated by mechanisms involving chemokines,selectins,addressins and other adhesion molecules derived from endothelial cells(ECs),but how they respond to inflammatory cues and coordinate leukocyte transmigration remain elusive.In this study,using hepatic ischemia/reperfusion injury(HIRI)as a model,we identified that endothelial Notch activation was rapidly and dynamically induced in liver sinusoidal endothelial cells(LSECs)in acute inflammation.In mice with EC-specific Notch activation(NICeCA),HIRI induced exacerbated liver damage.Consistently,endothelial Notch activation enhanced neutrophil infiltration and tumor necrosis factor(TNF)-αexpression in HIRI.Transcriptome analysis and further qRT-PCR as well as immunofluorescence indicated that endomucin(EMCN),a negative regulator of leukocyte adhesion,was downregulated in LSECs from NICeCA mice.EMCN was downregulated during HIRI in wild-type mice and in vitro cultured ECs insulted by hypoxia/re-oxygenation injury.Notch activation in ECs led to increased neutrophil adhesion and transendothelial migration,which was abrogated by EMCN overexpression in vitro.In mice deficient of RBPj,the integrative transcription factor of canonical Notch signaling,although overwhelming sinusoidal malformation aggravated HIRI,the expression of EMCN was upregulated;and pharmaceutical Notch blockade in vitro also upregulated EMCN and inhibited transendothelial migration of neutrophils.The Notch activation-exaggerated HIRI was compromised by blocking LFA-1,which mediated leukocyte adherence by associating with EMCN.Therefore,endothelial Notch signaling controls neutrophil transmigration via EMCN to modulate acute inflammation in HIRI.展开更多
基金supported by the Operation of Public Health Emergency Response Mechanism of the Chinese Center for Disease Control and Prevention(10239322002001,0000017)Research on Vaccine Evaluation Strategy and capacity Building Project(09207).
文摘Herpes zoster(HZ)is a painful condition resulting from reactivation of dormant varicella-zoster virus(VZV)in a previously VZV-infected person[1].Typical clinical manifestation of HZ are unilateral radicular pain and a vesicular rash limited to one side of the body in the distribution of a nerve[2].The most common complication of HZ postherpetic neuralgia(PHN).
基金supported by the Cancer Prevention Research Institute of Texas(CPRIT,RP 150656,X.L.)National Institute of Health(NIH/NCI,R15CA182769, X.L.)
文摘Small interfering RNAs （siRNA） have enormous potential as therapeutics to target and treat various bone disor- ders such as osteoporosis and cancer bone metastases. However, effective and specific delivery of siRNA therapeu- tics to bone and bone-specific cells in vivo is very challenging. To realize the full therapeutic potential of siRNA in treating bone disorders, a safe and efficient, tissue- and cell-specific delivery system must be developed. This review focuses on recent advances in bone site-specific delivery of siRNA at the tissue or cellular level. Bone-targeted nanoparticulate siRNA carriers and various bone-targeted moieties such as bisphosphonates, oligopeptides （Asp）8 and （AspSerSer）6, and aptamers are highlighted. Incorporation of these bone-seeking targeting moieties into siRNA carriers allows for recognition of different sub-tissue functional domains of bone and also specific cell types residing in bone tissue. It also provides a means for bone-formation surface-, bone-resorption surface-, or osteoblast- specific targeting and transportation of siRNA therapeutics. The discussion mainly focuses on systemic and local bone-specific delivery of siRNA in osteoporosis and bone metastasis preclinical models.
基金supported by the National Natural Science Foundation of China(NSFC,No.82073884,China)NSFC-Liaoning joint fund key program(No.U20A20413,China)+1 种基金Postdoctoral Research Startup Project(No.3110211220,China)Postdoctoral Research Startup Project(No.3110210640,China)。
文摘Peptide-drug conjugates(PDCs)are the next generation of targeted therapeutics drug after antibody-drug conjugates(ADCs),with the core benefits of enhanced cellular permeability and improved drug selectivity.Two drugs are now approved for market by US Food and Drug Administration(FDA),and in the last two years,the pharmaceutical companies have been developing PDCs as targeted therapeutic candidates for cancer,coronavirus disease 2019(COVID-19),metabolic diseases,and so on.The therapeutic benefits of PDCs are significant,but poor stability,low bioactivity,long research and development time,and slow clinical development process as therapeutic agents of PDC,how can we design PDCs more effectively and what is the future direction of PDCs?This review summarises the components and functions of PDCs for therapeutic,from drug target screening and PDC design improvement strategies to clinical applications to improve the permeability,targeting,and stability of the various components of PDCs.This holds great promise for the future of PDCs,such as bicyclic peptide-toxin coupling or supramolecular nanostructures for peptide-conjugated drugs.The mode of drug delivery is determined according to the PDC design and current clinical trials are summarised.The way is shown for future PDC development.
基金supported by the Second Tibetan Plateau Scientifc Expedition and Research Program(STEP No.2019QZKK0906)the joint project of National Natural Science Foundation of China(NSFC)and Bill Melinda Gates Foundation(BMGF)under Grant No.72261147759。
文摘Understanding the heterogeneous preferences of individuals for disaster insurance attributes is critical for product improvement and policy design.In an era of global environmental change,the Qinghai-Tibet Plateau is a hotspot of natural hazards.Improving the capability of rural housing disaster insurance to foster local residents’disaster resilience is of great signifcance but remains under addressed.We used a discrete choice experiment approach to provide the frst estimates of rural residents’preferences for rural housing disaster insurance attributes in central and western Tibet.We estimated residents’preferences and willingness-to-pay for the sum insured,subsidy rate,insured object,and perils covered.The potential impacts of increasing the sum insured,expanding the insured object,and lowering subsidy rates were evaluated.Our results suggest that residents prefer products with a high sum insured,high subsidy rate,and a complete list of insured objects.Residents who have experienced specifc hazards tend to prefer the corresponding perils covered.Females and residents who have a closer social network are more likely to purchase insurance.Product improvement and policy simulation results suggest that,while lowering the subsidy rate,increasing the sum insured and expanding the insured object could promote participation and improve residents’welfare.Our results could improve the understanding of the preferences of households in remote regions and support policy implementations.
基金financially supported by the National Natural Science Foundation of China (Grants Nos. 21874066, 81601632 and 21563009, China)the Natural Science Foundation of Jiangsu Province (BK20160616, China)+2 种基金the Fundamental Research Funds for Central Universities (China)the Shuangchuang Program of Jiangsu Province (China)Thousand Talents Program for Young Researchers (China)
文摘The microneedle(MN), a highly efficient and versatile device, has attracted extensive scientific and industrial interests in the past decades due to prominent properties including painless penetration, low cost, excellent therapeutic efficacy, and relative safety. The robust microneedle enabling transdermal delivery has a paramount potential to create advanced functional devices with superior nature for biomedical applications. In this review, a great effort has been made to summarize the advance of microneedles including their materials and latest fabrication method, such as three-dimensional printing(3DP). Importantly, a variety of representative biomedical applications of microneedles such as disease treatment, immunobiological administration, disease diagnosis and cosmetic field, are highlighted in detail. At last, conclusions and future perspectives for development of advanced microneedles in biomedical fields have been discussed systematically. Taken together, as an emerging tool, microneedles have showed profound promise for biomedical applications.
基金This work was financially supported by the National Natural Science Foundation of China(Nos.21874066,81601632 and 61804076)the Natural Science Foundation of Jiangsu Province(Nos.BK20160616 and BK20180700)the Fundamental Research Funds for Central Universities,the Shuangchuang Program of Jiangsu Province,and the Thousand Talents Program for Young Researchers.
文摘We report gold nanoparticles(AuNPs)doped iron-based metal-organic frameworks(GIM)which displays near-infrared light(NIR)-enhanced cascade nanozyme against hypoxic tumors.Due to the strong protein adsorption-induced surface passivation,AuNPs suffer from the loss of glucose oxidase(GOx)activity.However,GIM could protect the GOx-like activity of AuNPs with the satisfactory shield capability.In addition,GIM exhibited excellent photothermal conversion ability and unique NIR light-enhanced GOx-like activity,which could efficiently increase the endogenous H2O2 production.Meanwhile,as the produced H2O2 is converted by GIM into O2 and highly toxic OH.Thus,GIM-catalyzed cascade reactions with NIR light irradiation not only offer the O2 but also promote the reactive oxygen species(ROS)generation at tumor sites.The produced O2 could be further applied to AuNPs catalytic oxidation of glucose and relieve hypoxic condition of tumor microenvironment(TME).As a proof-of-concept study,GIM demonstrates the admirable tumor ablation under NIR irradiation in vivo.
基金This work was supported by grants from the National Natural Science Foundation of China(31730041,31671523,and 81470416).
文摘Inflammatory leukocytes infiltration is orchestrated by mechanisms involving chemokines,selectins,addressins and other adhesion molecules derived from endothelial cells(ECs),but how they respond to inflammatory cues and coordinate leukocyte transmigration remain elusive.In this study,using hepatic ischemia/reperfusion injury(HIRI)as a model,we identified that endothelial Notch activation was rapidly and dynamically induced in liver sinusoidal endothelial cells(LSECs)in acute inflammation.In mice with EC-specific Notch activation(NICeCA),HIRI induced exacerbated liver damage.Consistently,endothelial Notch activation enhanced neutrophil infiltration and tumor necrosis factor(TNF)-αexpression in HIRI.Transcriptome analysis and further qRT-PCR as well as immunofluorescence indicated that endomucin(EMCN),a negative regulator of leukocyte adhesion,was downregulated in LSECs from NICeCA mice.EMCN was downregulated during HIRI in wild-type mice and in vitro cultured ECs insulted by hypoxia/re-oxygenation injury.Notch activation in ECs led to increased neutrophil adhesion and transendothelial migration,which was abrogated by EMCN overexpression in vitro.In mice deficient of RBPj,the integrative transcription factor of canonical Notch signaling,although overwhelming sinusoidal malformation aggravated HIRI,the expression of EMCN was upregulated;and pharmaceutical Notch blockade in vitro also upregulated EMCN and inhibited transendothelial migration of neutrophils.The Notch activation-exaggerated HIRI was compromised by blocking LFA-1,which mediated leukocyte adherence by associating with EMCN.Therefore,endothelial Notch signaling controls neutrophil transmigration via EMCN to modulate acute inflammation in HIRI.
