In this work, a facile strategy is proposed to construct stretchable electronics based on agarose hydrogels. The hot agarose solution is casted onto a template with patterned Ag nanowires, endowing agarose hydrogel wi...In this work, a facile strategy is proposed to construct stretchable electronics based on agarose hydrogels. The hot agarose solution is casted onto a template with patterned Ag nanowires, endowing agarose hydrogel with patterned conductive surface. After further heating treatment, Ag nanowires can be embedded into the agarose hydrogel, which improves the stability of Ag pattern and has no obvious e ffect on the conductivity of hydrogels. The agarose hydrogel with patterned Ag nanowires is certi fied to be an e ffective stretchable electrode to record the motion of joints, which has great potential applications in the field of wearable devices.展开更多
Three-dimensional (3D) bioprinting is a computer-assisted technology which precisely controls spatial position of biomaterials, growth factors and living cells, offering unprecedented possibility to bridge the gap b...Three-dimensional (3D) bioprinting is a computer-assisted technology which precisely controls spatial position of biomaterials, growth factors and living cells, offering unprecedented possibility to bridge the gap between structurally mimic tissue constructs and functional tissues or organoids. We briefly focus on diverse bioinks used in the recent progresses of biofabrication and 3D bioprinting of various tissue architectures including blood vessel, bone, cartilage, skin, heart, liver and nerve systems. This paper provides readers a guideline with the conjunction between bioinks and the targeted tissue or organ types in structuration and final functionalization of these tissue analogues. The challenges and perspectives in 3D bioprinting field are also illustrated.展开更多
Hepatocellular carcinoma is a common and fatal malignancy for which there is no effective systemic therapeutic strategy.Dihydroartemisinin(DHA),a derivative of artemisinin,has been shown to exert anti-tumor effects th...Hepatocellular carcinoma is a common and fatal malignancy for which there is no effective systemic therapeutic strategy.Dihydroartemisinin(DHA),a derivative of artemisinin,has been shown to exert anti-tumor effects through the production of reactive oxygen species(ROS)and resultant mitochondrial damage.However,clinical translation is limited by several drawbacks,such as insolubility,instability and low bioavailability.Here,based on a nanomedicine-based delivery strategy,we fabricated mitochondria-targeted carrier-free nanoparticles coupling DHA and triphenylphosphonium(TPP),aiming to improve bioavailability and mitochondrial targeting.DHA-TPP nanoparticles can be passively delivered to the tumor site by enhanced penetration and retention and then internalized.Flow cytometry and Western blot analysis showed that DHA-TPP nanoparticles increased intracellular ROS,which increased mitochondrial stress and in turn upregulated the downstream Bcl-2 pathway,leading to apoptosis.In vivo experiments showed that DHA-TPP nanoparticles exhibited anti-tumor effects in a mouse model of hepatocellular carcinoma.These findings suggest carrier-free DHA-TPP nanoparticles as a potential therapeutic strategy for hepatocellular carcinoma.展开更多
Recently,the utilization of nonsteroidal anti-inflammatory drugs(NSAIDs)to sensitize cisplatin(CDDP)has gained substantial traction in the treatment of ovarian cancer(OC).However,even widely employed NSAIDs such as ce...Recently,the utilization of nonsteroidal anti-inflammatory drugs(NSAIDs)to sensitize cisplatin(CDDP)has gained substantial traction in the treatment of ovarian cancer(OC).However,even widely employed NSAIDs such as celecoxib and naproxen carry an elevated risk of cardiovascular events,notably throm-bosis.Furthermore,the diminished sensitivity to CDDP therapy in OC is multifactorial,rendering the ap-plication of NSAIDs only partially effective due to their cyclooxygenase-2(COX-2)inhibiting mechanism.Hence,in this study,reactive oxygen species(ROS)-responsive composite nano-hydrangeas loaded with the Chinese medicine small molecule allicin and platinum(IV)prodrug(DTP@AP NPs)were prepared to achieve comprehensive chemosensitization.On one front,allicin achieved COX-2 blocking therapy,en-compassing the inhibition of proliferation,angiogenesis and endothelial mesenchymal transition(EMT),thereby mitigating the adverse impacts of CDDP chemotherapy.Simultaneously,synergistic chemosensi-tization was achieved from multifaceted mechanisms by decreasing CDDP inactivation,damaging mito-chondria and inhibiting DNA repair.In essence,these findings provided an optimized approach for syner-gizing CDDP with COX-2 inhibitors,offering a promising avenue for enhancing OC treatment outcomes.展开更多
This study aims to determine the effects of nanoscale pores system characteristics on CH4 adsorption capacity in anthracite.A total of 24 coal samples from the southern Sichuan Basin,China,were examined systemically u...This study aims to determine the effects of nanoscale pores system characteristics on CH4 adsorption capacity in anthracite.A total of 24 coal samples from the southern Sichuan Basin,China,were examined systemically using coal maceral analysis,vitrinite reflectance tests, proximate analysis,ultimate analysis,low-temperature N2 adsorption-desorption experiments,nuclear magnetic resonance (NMR)analysis,and CH4 isotherm adsorption experiments.Results show that nano-pores are divided into four types on the basis of pore size ranges:super micropores (<4 nm),micropores (4-10 nm),mesopores (10-100 nm),and macropores (>100 nm).Super micropores,micropores,and mesopores make up the bulk of coal porosity,providing extremely large adsorption space with large intemal surface area.This leads us to the conclusion that the threshold of pore diameter between adsorption pores and seepage pores is 100 nm.The "ink bottle"pores have the largest CH4 adsorption capacity, followed by semi-opened pores,whereas opened pores have the smallest CH4 adsorption capacity which indicates that anthracite pores with more irregular shapes possess higher CH4 adsorption capacity.CH4 adsorption capacity increased with the increase in NMR porosity and the bound water saturation.Moreover,CH4 adsorption capacity is positively correlated with NMR permeability when NMR permeability is less than 8 ×10^-3 md.By contrast,the two factors are negatively correlated when NMR permeability is greater than 8 × 10^-3 md.展开更多
Prodrug self-delivery carriers with targeting that specifically responded to tumor microenvironments have good potential to improve the application dilemma of approved clinical therapeutic drugs(systemic distribution ...Prodrug self-delivery carriers with targeting that specifically responded to tumor microenvironments have good potential to improve the application dilemma of approved clinical therapeutic drugs(systemic distribution and side effects).It's noted the conversion of gemcitabine(GEM)to inactive ingredients under the action of cytidine deaminase(CDA)during metabolism in vivo limits its clinical effect.A high level of reactive oxygen species(ROS)results in a high level of oxidative stress in tumor cells,which changes the expression of CDA and optimizes the metabolism of GEM in vivo and overcome drug resistance.In this study,the ROS responsive and ROS self-supplied prodrug of artemisia(ART)-thioacetal bond(TK)-GEM was synthesized and self-vectors based on ART-TK-GEM(TK@FA NPs)was prepared by using nano precipitation.ROS responsive characteristics ensure specific release of prodrugs in tumor cells with high level of ROS thereby reducing side effects on normal cells and tissues.The endogenous ROS and newly generated ROS by ART can reduce the expression of CDA and optimizes the metabolism of GEM,and the accumulated ROS can also induce apoptosis of tumor cells,realizing synergistic anti-tumor effect of chemical drugs and traditional Chinese medicines.This paper proposes a simple method by using clinically approved drugs to improve the insufficient effect of existing chemotherapy and overcome resistance,which has potential to appropriately shorten the drug development cycle and accelerate the clinical investigation of drugs.展开更多
Photodynamic therapy(PDT)has shown great application potential in cancer treatment and the important manifestation of PDT in the inhibition of tumors is the activation of immunogenic cell death(ICD)effects.However,the...Photodynamic therapy(PDT)has shown great application potential in cancer treatment and the important manifestation of PDT in the inhibition of tumors is the activation of immunogenic cell death(ICD)effects.However,the strategy is limited in the innate hypoxic tumor microenvironment.There are two key elements for the realization of enhanced PDT:specific cellular uptake and release of the photosensitizer in the tumor,and a sufficient amount of oxygen to ensure photodynamic efficiency.Herein,self-oxygenated biomimetic nanoparticles(CS@M NPs)co-assembled by photosensitizer prodrug(Ce6-S-S-LA)and squalene(SQ)were engineered.In the treatment of triple negative breast cancer(TNBC),the oxygen carried by SQ can be converted to reactive oxygen species(ROS).Meanwhile,glutathione(GSH)consumption during transformation from Ce6-S-S-LA to chlorin e6(Ce6)avoided the depletion of ROS.The co-assembled(CS NPs)were encapsulated by homologous tumor cell membrane to improve the tumor targeting.The results showed that the ICD effect of CS@M NPs was confirmed by the significant release of calreticulin(CRT)and high mobility group protein B1(HMGB1),and it significantly activated the immune system by inhibiting the hypoxia inducible factor-1alpha(HIF-1α)-CD39-CD73-adenosine a2a receptor(A2AR)pathway,which not only promoted the maturation of dendritic cells(DC)and the presentation of tumor specific antigens,but also induced effective immune infiltration of tumors.Overall,the integrated nanoplatform implements the concept of multiple advantages of tumor targeting,reactive drug release,and synergistic photodynamic therapy-immunotherapy,which can achieve nearly 90%tumor suppression rate in orthotopic TNBC models.展开更多
基金The authors acknowledge financial support from the National Natural Science Foundation of China(Project No.21774132,21703253,21877052,31700706)Natural Science Foundation for Distinguished Young Scholars of Jiangsu Province(BK20180030)the Fundamental Research Funds for the Central Universities(JUSRP51712B)and Open Funding Project of the State Key Laboratory of Biochemical Engineering(No.2019KF-02).
文摘In this work, a facile strategy is proposed to construct stretchable electronics based on agarose hydrogels. The hot agarose solution is casted onto a template with patterned Ag nanowires, endowing agarose hydrogel with patterned conductive surface. After further heating treatment, Ag nanowires can be embedded into the agarose hydrogel, which improves the stability of Ag pattern and has no obvious e ffect on the conductivity of hydrogels. The agarose hydrogel with patterned Ag nanowires is certi fied to be an e ffective stretchable electrode to record the motion of joints, which has great potential applications in the field of wearable devices.
基金The authors acknowledge financial support from the National Natural Science Foundation of China (Project No. 21703253, 21774132, 21644007) and the Talent Fund of the Recruit- ment Program of Global Youth Experts.
文摘Three-dimensional (3D) bioprinting is a computer-assisted technology which precisely controls spatial position of biomaterials, growth factors and living cells, offering unprecedented possibility to bridge the gap between structurally mimic tissue constructs and functional tissues or organoids. We briefly focus on diverse bioinks used in the recent progresses of biofabrication and 3D bioprinting of various tissue architectures including blood vessel, bone, cartilage, skin, heart, liver and nerve systems. This paper provides readers a guideline with the conjunction between bioinks and the targeted tissue or organ types in structuration and final functionalization of these tissue analogues. The challenges and perspectives in 3D bioprinting field are also illustrated.
基金funded and supported by the Department of Science and Technology of Guangdong Province(No.2022B1111020005)Key Laboratory of Guangdong Provincial Food and Drug Administration(No.2021ZDB03)+3 种基金the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab,No.2020B1212030006)Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme(No.Guochao Liao,2019)Guangdong Basic and Applied Basic Research Foundation(Nos.2020B1515130005,2022A1515110270,202201011563)The Bureau of Science and Technology of Guangzhou City(No.HMJH_(2)019000)。
文摘Hepatocellular carcinoma is a common and fatal malignancy for which there is no effective systemic therapeutic strategy.Dihydroartemisinin(DHA),a derivative of artemisinin,has been shown to exert anti-tumor effects through the production of reactive oxygen species(ROS)and resultant mitochondrial damage.However,clinical translation is limited by several drawbacks,such as insolubility,instability and low bioavailability.Here,based on a nanomedicine-based delivery strategy,we fabricated mitochondria-targeted carrier-free nanoparticles coupling DHA and triphenylphosphonium(TPP),aiming to improve bioavailability and mitochondrial targeting.DHA-TPP nanoparticles can be passively delivered to the tumor site by enhanced penetration and retention and then internalized.Flow cytometry and Western blot analysis showed that DHA-TPP nanoparticles increased intracellular ROS,which increased mitochondrial stress and in turn upregulated the downstream Bcl-2 pathway,leading to apoptosis.In vivo experiments showed that DHA-TPP nanoparticles exhibited anti-tumor effects in a mouse model of hepatocellular carcinoma.These findings suggest carrier-free DHA-TPP nanoparticles as a potential therapeutic strategy for hepatocellular carcinoma.
基金supported by the Guangdong Basic and Applied Basic Research Foundation of China(No.2021A1515011050)President Foundation of the Third Affiliated Hospital of Southern Medical University(No.YM202202)+1 种基金the Health Economics Association Research Program of Guangdong Province(No.2022-WJZD-20)the Higher Education Teaching Management Association Curriculum Thinking and Administration Program of Guangdong Province(No.X-KCSZ2021082).
文摘Recently,the utilization of nonsteroidal anti-inflammatory drugs(NSAIDs)to sensitize cisplatin(CDDP)has gained substantial traction in the treatment of ovarian cancer(OC).However,even widely employed NSAIDs such as celecoxib and naproxen carry an elevated risk of cardiovascular events,notably throm-bosis.Furthermore,the diminished sensitivity to CDDP therapy in OC is multifactorial,rendering the ap-plication of NSAIDs only partially effective due to their cyclooxygenase-2(COX-2)inhibiting mechanism.Hence,in this study,reactive oxygen species(ROS)-responsive composite nano-hydrangeas loaded with the Chinese medicine small molecule allicin and platinum(IV)prodrug(DTP@AP NPs)were prepared to achieve comprehensive chemosensitization.On one front,allicin achieved COX-2 blocking therapy,en-compassing the inhibition of proliferation,angiogenesis and endothelial mesenchymal transition(EMT),thereby mitigating the adverse impacts of CDDP chemotherapy.Simultaneously,synergistic chemosensi-tization was achieved from multifaceted mechanisms by decreasing CDDP inactivation,damaging mito-chondria and inhibiting DNA repair.In essence,these findings provided an optimized approach for syner-gizing CDDP with COX-2 inhibitors,offering a promising avenue for enhancing OC treatment outcomes.
基金This research was funded by the Open Foundation of Key Laboratory of Tectonics and Petroleum Resources (China University of Geosciences)(No.TPR-2016-04)the Open Foundation of Shandong Provincial Key Laboratory of Depositional Mineralization & Sedimentary Mineral,(Shandong University of Science and Technology)(No. DMSM2017031)+3 种基金the Youth Science and Technology Innovation Fund Project (Xi'an Shiyou University)(No.290088259)the National Science and Technology Major Project (No.2017ZX05039001-002)the National Natural Science Foundation of China (Grant Nos.41702127 and 41772150)the Scientific Research Program Funded by Shaanxi Provincial Education Department (No.17JK0617).
文摘This study aims to determine the effects of nanoscale pores system characteristics on CH4 adsorption capacity in anthracite.A total of 24 coal samples from the southern Sichuan Basin,China,were examined systemically using coal maceral analysis,vitrinite reflectance tests, proximate analysis,ultimate analysis,low-temperature N2 adsorption-desorption experiments,nuclear magnetic resonance (NMR)analysis,and CH4 isotherm adsorption experiments.Results show that nano-pores are divided into four types on the basis of pore size ranges:super micropores (<4 nm),micropores (4-10 nm),mesopores (10-100 nm),and macropores (>100 nm).Super micropores,micropores,and mesopores make up the bulk of coal porosity,providing extremely large adsorption space with large intemal surface area.This leads us to the conclusion that the threshold of pore diameter between adsorption pores and seepage pores is 100 nm.The "ink bottle"pores have the largest CH4 adsorption capacity, followed by semi-opened pores,whereas opened pores have the smallest CH4 adsorption capacity which indicates that anthracite pores with more irregular shapes possess higher CH4 adsorption capacity.CH4 adsorption capacity increased with the increase in NMR porosity and the bound water saturation.Moreover,CH4 adsorption capacity is positively correlated with NMR permeability when NMR permeability is less than 8 ×10^-3 md.By contrast,the two factors are negatively correlated when NMR permeability is greater than 8 × 10^-3 md.
基金financial support from Guangdong Nature Resource Center(GDNRC,No.(2020)037)Natural Science Foundation of Guangdong Province(Nos.22019A1515011498,2019A1515011619)。
文摘Prodrug self-delivery carriers with targeting that specifically responded to tumor microenvironments have good potential to improve the application dilemma of approved clinical therapeutic drugs(systemic distribution and side effects).It's noted the conversion of gemcitabine(GEM)to inactive ingredients under the action of cytidine deaminase(CDA)during metabolism in vivo limits its clinical effect.A high level of reactive oxygen species(ROS)results in a high level of oxidative stress in tumor cells,which changes the expression of CDA and optimizes the metabolism of GEM in vivo and overcome drug resistance.In this study,the ROS responsive and ROS self-supplied prodrug of artemisia(ART)-thioacetal bond(TK)-GEM was synthesized and self-vectors based on ART-TK-GEM(TK@FA NPs)was prepared by using nano precipitation.ROS responsive characteristics ensure specific release of prodrugs in tumor cells with high level of ROS thereby reducing side effects on normal cells and tissues.The endogenous ROS and newly generated ROS by ART can reduce the expression of CDA and optimizes the metabolism of GEM,and the accumulated ROS can also induce apoptosis of tumor cells,realizing synergistic anti-tumor effect of chemical drugs and traditional Chinese medicines.This paper proposes a simple method by using clinically approved drugs to improve the insufficient effect of existing chemotherapy and overcome resistance,which has potential to appropriately shorten the drug development cycle and accelerate the clinical investigation of drugs.
基金supported by the Guangdong Nature Resource Center(No.(2020)037)Natural Science Foundation of Guangdong Province(Nos.22019A1515011498 and 2019A1515011619)+2 种基金Basic and Applied Basic Research Foundation of Guangdong Province(No.2020B1515120063)National Natural Science Foundation of China(No.81803877)supported by the China Postdoctoral Science Foundation(No.2022M721535)。
文摘Photodynamic therapy(PDT)has shown great application potential in cancer treatment and the important manifestation of PDT in the inhibition of tumors is the activation of immunogenic cell death(ICD)effects.However,the strategy is limited in the innate hypoxic tumor microenvironment.There are two key elements for the realization of enhanced PDT:specific cellular uptake and release of the photosensitizer in the tumor,and a sufficient amount of oxygen to ensure photodynamic efficiency.Herein,self-oxygenated biomimetic nanoparticles(CS@M NPs)co-assembled by photosensitizer prodrug(Ce6-S-S-LA)and squalene(SQ)were engineered.In the treatment of triple negative breast cancer(TNBC),the oxygen carried by SQ can be converted to reactive oxygen species(ROS).Meanwhile,glutathione(GSH)consumption during transformation from Ce6-S-S-LA to chlorin e6(Ce6)avoided the depletion of ROS.The co-assembled(CS NPs)were encapsulated by homologous tumor cell membrane to improve the tumor targeting.The results showed that the ICD effect of CS@M NPs was confirmed by the significant release of calreticulin(CRT)and high mobility group protein B1(HMGB1),and it significantly activated the immune system by inhibiting the hypoxia inducible factor-1alpha(HIF-1α)-CD39-CD73-adenosine a2a receptor(A2AR)pathway,which not only promoted the maturation of dendritic cells(DC)and the presentation of tumor specific antigens,but also induced effective immune infiltration of tumors.Overall,the integrated nanoplatform implements the concept of multiple advantages of tumor targeting,reactive drug release,and synergistic photodynamic therapy-immunotherapy,which can achieve nearly 90%tumor suppression rate in orthotopic TNBC models.