Chlorine-rich argyrodite electrolytes,despite their exceptional ionic conductivity,face critical challenges in industrial utilization of all-solid-state lithium batteries(ASSLBs)due to inherent air instability and uns...Chlorine-rich argyrodite electrolytes,despite their exceptional ionic conductivity,face critical challenges in industrial utilization of all-solid-state lithium batteries(ASSLBs)due to inherent air instability and unsatisfactory compatibility with lithium metal anodes.To solve this problem,this work doped the P unit in Li_(5.5)PS_(4.5)Cl_(1.5),yielding a modified electrolyte LPSC-5%Li_(3)PO_(4)with significantly enhanced chemical/electrochemical stability.The integration of P units within the bulk structure reinforces lattice stability through robust P-O bonding while inhibiting reactive sulfur species responsible for moisture-triggered H_(2)S generation,resulting in enhanced air/moisture stability.Moreover,the electrolyte demonstrates an ionic conductivity of 5.71 mS cm^(-1)coupled with an exceptional critical current density reaching 2.9 mA cm^(-2),indicating robust dendrite suppression capability.Notably,the P-doped into the LPSC electrolyte induces multifaceted interfacial enhancements:a composite interphase layer consisting of LiCl and Li_(3)OCl phases is spontaneously formed at the lithium/electrolyte interface.Physical field simulations demonstrate that the electrolyte exhibits excellent mechanical stability,effectively suppressing the penetration of lithium dendrites.Chemically,Density functional theory calculations reveal that the electrolyte possesses a high lowest unoccupied molecular orbital potential,demonstrating good compatibility with lithium metal.This multifaced mechanism synergistically inhibits dendritic lithium growth by simultaneously passivating reactive interfaces and homogenizing ion transport dynamics.The assembled ASSLBS enables stable cycling performance,delivering an initial discharge capacity of 146.7 mAh g^(-1)and a capacity retention of 80.0%after 1000 cycles at 0.5 C.This work establishes a straightforward and effective doping paradigm that simultaneously addresses ionic transport efficiency,air stability,and interfacial compatibility in sulfide-based electrolytes.The proposed strategy provides critical insights into the rational design of high-energy-density ASSLBs with superior cyclability.展开更多
Tumor metastasis is responsible for most mortality in cancer patients,and remains a challenge in clinical cancer treatment.Platelets can be recruited and activated by tumor cells,then adhere to circulating tumor cells...Tumor metastasis is responsible for most mortality in cancer patients,and remains a challenge in clinical cancer treatment.Platelets can be recruited and activated by tumor cells,then adhere to circulating tumor cells(CTCs)and assist tumor cells extravasate in distant organs.Therefore,nanoparticles specially hitchhiking on activated platelets are considered to have excellent targeting ability for primary tumor,CTCs and metastasis in distant organs.However,the activated tumor-homing platelets will release transforming growth factor-β(TGF-β),which promotes tumor metastasis and forms immunosuppressive microenvironment.Therefore,a multitalent strategy is needed to balance the accurate tumor tracking and alleviate the immunosuppressive signals.In this study,a fucoidan-functionalized micelle(FD/DOX)was constructed,which could efficiently adhere to activated platelets through P-selectin.Compared with the micelle without P-selectin targeting effect,FD/DOX had increased distribution in both tumor tissue and metastasis niche,and exhibited excellent anti-tumor and anti-metastasis efficacy on 4 T1 spontaneous metastasis model.In addition,due to the contribution of fucoidan,FD/DOXtreatment was confirmed to inhibit the expression of TGF-β,thereby stimulating anti-tumor immune response and reversing the immunosuppressive microenvironment.The fucoidan-functionalized activated platelets-hitchhiking micelle was promising for the metastatic cancer treatment.展开更多
Oxidative stress and inflammation are key drivers of osteoarthritis(OA)pathogenesis and disease progression.Herein we report the synthesis of poly(p-coumaric)nanoparticles(PCA NPs)from p-courmaic acid(p-CA),a naturall...Oxidative stress and inflammation are key drivers of osteoarthritis(OA)pathogenesis and disease progression.Herein we report the synthesis of poly(p-coumaric)nanoparticles(PCA NPs)from p-courmaic acid(p-CA),a naturally occurring phytophenolic acid,to be a multifunctional and drug-free therapeutic for temporomandibular joint osteoarthritis(TMJOA).Compared to hyaluronic acid(HA)that is clinically given as viscosupplementation,PCA NPs exhibited long-term efficacy,superior anti-oxidant and anti-inflammatory properties in alleviating TMJOA and repairing the TMJ cartilage and subchondral bone in a rat model of TMJOA.Notably,TMJ repair mediated by PCA NPs could be attributed to their anti-oxidant and anti-inflammatory properties in enhancing cell proliferation and matrix synthesis,while reducing inflammation,oxidative stress,matrix degradation,and chondrocyte ferroptosis.Overall,our study demonstrates a multifunctional nanoparticle,synthesized from natural p-coumaric acid,that is stable and possess potent antioxidant,anti-inflammatory properties and ferroptosis inhibition,beneficial for treatment of TMJOA.展开更多
Purpose:Different arch structures may cause different foot function injuries.In the past,the arch structure and flexibility of the foot were often defined by the height of the arch,and there was no three-dimensional(3...Purpose:Different arch structures may cause different foot function injuries.In the past,the arch structure and flexibility of the foot were often defined by the height of the arch,and there was no three-dimensional(3D)structure classification method.In order to form a more complete 3D description,we propose a new classification system of arch volume flexibility(AVF),and then use this new classification system to investigate the relationship between the AVF and arch index(AI),and the arch height flexibility(AHF)and AI,respectively.Methods:It is proposed to recruit 180 young male adults for the test.We obtained arch volume and AI through 3D scanning and obtained the navicular height through manual measurement.Based on these data,we calculated the AHF and the AVF.Using the quintile method,these arches are divided into very stiff,stiff,neutral,flexible,and very flexible.According to AI value,all arches were divided into cavus,rectus,and planus.The distribution of AVF was compared usingχ^(2)goodness of fit test.The spearman correlation test was used to compare the AHF and AVF.A p<0.05 indicates that the difference is statistically significant.Results:All participants'plantar data was obtained through 3D scanning,but only 159 of them were complete,so only 318 feet had valid data.The left AHF is(21.23±12.91)mm/kN,and the right AHF is(21.71±12.69)mm/kN.The AVF of the left foot arch is(207.35±118.28)mm^(3)/kg,while the right one is(203.00±117.92)mm^(3)/kg,and the total AVF of the arch was(205.17±117.94)mm^(3)/kg.There was no statistical difference in the AVF between the left and right feet for the same participant(n=159,p=0.654).In cavus,the percentage of arch with AVF is 21.4%(very stiff),21.4%(stiff),14.3%(neutral),7.1%(flexible),and 35.7%(very flexible).In rectus,the percentage of arch with AVF is 23.9%(very stiff),19.6%(stiff),14.7%(neutral),24.5%(flexible),and 17.2%(very flexible).In planus,the percentage of arch with AVF is 14.9%(very stiff),20.6%(stiff),27.0%(neutral),16.3%(flexible),and 21.3%(very flexible).Moreover,the correlation between AHF and AVF is not significant(p=0.060).Conclusion:In cavus,rectus,and planus,different AVF accounts different percentage,but the difference is not statistically significant.AVF is evenly distributed in the arches of the feet at different heights.We further found the relationship between AHF and AVF is not significant.As a 3D index,AVF may be able to describe the flexibility of the arch more comprehensively than AHF.展开更多
Chemotherapy agents have been widely used for cancer treatment,while the insolubility,instability and toxicity seriously restrict their efficacy.Thus,prodrug strategy was devised.Since some prodrugs are still with poo...Chemotherapy agents have been widely used for cancer treatment,while the insolubility,instability and toxicity seriously restrict their efficacy.Thus,prodrug strategy was devised.Since some prodrugs are still with poor solubility or stability,a synergy strategy is needed to enhance their efficacy.Gemcitabine(GEM)is a prescribed anticancer drug,however,the rapid clearance,growing resistance and serious side effects limit its clinical efficacy.Conjugating GEM with D-a-tocopherol succinate(TOS)is an effective solution,while the GEM-TOS(GT)is unstable in aqueous solution.D-a-Tocopherol polyethylene glycol succinate(TPGS)has been used to enhance the stability,but GT stabilized by TPGS(GTT)has limited effect on tumor metastases.Tumor metastases lead to high mortality in patients suffering from cancers.In order to further achieve antimetastatic effect,an amphiphilic polymer(LT)was synthesized by connecting low-molecular-weight heparin(LMWH)with TOS,and eventually obtained desired selfdelivery micellar NPs(GLT)by co-assembly GT with LT.The GLT not only possessed excellent stability,but also inhibited the metastases by acting on different phases of the metastatic cascade.The hydrophobic TOS inhibited the secretion of matrix metalloproteinase-9(MMP-9),the hydrophilic LMWH inhibited the interaction between tumor cells and platelets.As a result,GLT reduced tumor cells entering the blood and implanting at the distant organs,leading to a much more excellent inhibitory effect on the lung metastasis than GEM and GTT.展开更多
基金supported by the National Key Research and Development Program of China(2021YFB2500200)the National Natural Science Foundation of China(52177214)+1 种基金the Basic Science Research Fund in Xidian University(ZYTS24132)the Postdoctoral Science Research Program of Shaanxi(30102230001)。
文摘Chlorine-rich argyrodite electrolytes,despite their exceptional ionic conductivity,face critical challenges in industrial utilization of all-solid-state lithium batteries(ASSLBs)due to inherent air instability and unsatisfactory compatibility with lithium metal anodes.To solve this problem,this work doped the P unit in Li_(5.5)PS_(4.5)Cl_(1.5),yielding a modified electrolyte LPSC-5%Li_(3)PO_(4)with significantly enhanced chemical/electrochemical stability.The integration of P units within the bulk structure reinforces lattice stability through robust P-O bonding while inhibiting reactive sulfur species responsible for moisture-triggered H_(2)S generation,resulting in enhanced air/moisture stability.Moreover,the electrolyte demonstrates an ionic conductivity of 5.71 mS cm^(-1)coupled with an exceptional critical current density reaching 2.9 mA cm^(-2),indicating robust dendrite suppression capability.Notably,the P-doped into the LPSC electrolyte induces multifaceted interfacial enhancements:a composite interphase layer consisting of LiCl and Li_(3)OCl phases is spontaneously formed at the lithium/electrolyte interface.Physical field simulations demonstrate that the electrolyte exhibits excellent mechanical stability,effectively suppressing the penetration of lithium dendrites.Chemically,Density functional theory calculations reveal that the electrolyte possesses a high lowest unoccupied molecular orbital potential,demonstrating good compatibility with lithium metal.This multifaced mechanism synergistically inhibits dendritic lithium growth by simultaneously passivating reactive interfaces and homogenizing ion transport dynamics.The assembled ASSLBS enables stable cycling performance,delivering an initial discharge capacity of 146.7 mAh g^(-1)and a capacity retention of 80.0%after 1000 cycles at 0.5 C.This work establishes a straightforward and effective doping paradigm that simultaneously addresses ionic transport efficiency,air stability,and interfacial compatibility in sulfide-based electrolytes.The proposed strategy provides critical insights into the rational design of high-energy-density ASSLBs with superior cyclability.
基金supported by National Natural Science Foundation of China(81974499 and 81690261)Sichuan Science and Technology Program(2018RZ0136)。
文摘Tumor metastasis is responsible for most mortality in cancer patients,and remains a challenge in clinical cancer treatment.Platelets can be recruited and activated by tumor cells,then adhere to circulating tumor cells(CTCs)and assist tumor cells extravasate in distant organs.Therefore,nanoparticles specially hitchhiking on activated platelets are considered to have excellent targeting ability for primary tumor,CTCs and metastasis in distant organs.However,the activated tumor-homing platelets will release transforming growth factor-β(TGF-β),which promotes tumor metastasis and forms immunosuppressive microenvironment.Therefore,a multitalent strategy is needed to balance the accurate tumor tracking and alleviate the immunosuppressive signals.In this study,a fucoidan-functionalized micelle(FD/DOX)was constructed,which could efficiently adhere to activated platelets through P-selectin.Compared with the micelle without P-selectin targeting effect,FD/DOX had increased distribution in both tumor tissue and metastasis niche,and exhibited excellent anti-tumor and anti-metastasis efficacy on 4 T1 spontaneous metastasis model.In addition,due to the contribution of fucoidan,FD/DOXtreatment was confirmed to inhibit the expression of TGF-β,thereby stimulating anti-tumor immune response and reversing the immunosuppressive microenvironment.The fucoidan-functionalized activated platelets-hitchhiking micelle was promising for the metastatic cancer treatment.
基金supported by grants from the National Natural Science Foundation of China(Grant No.82170960 and No.52173150)the Science and Technology Program of Guangzhou,China(Grant No.202206080009)+1 种基金Guangzhou Science and Technology Program City-University Joint Funding Project(Grant No.2023A03J0001)China Postdoctoral Science Foundation(Grant No.2022M723670).
文摘Oxidative stress and inflammation are key drivers of osteoarthritis(OA)pathogenesis and disease progression.Herein we report the synthesis of poly(p-coumaric)nanoparticles(PCA NPs)from p-courmaic acid(p-CA),a naturally occurring phytophenolic acid,to be a multifunctional and drug-free therapeutic for temporomandibular joint osteoarthritis(TMJOA).Compared to hyaluronic acid(HA)that is clinically given as viscosupplementation,PCA NPs exhibited long-term efficacy,superior anti-oxidant and anti-inflammatory properties in alleviating TMJOA and repairing the TMJ cartilage and subchondral bone in a rat model of TMJOA.Notably,TMJ repair mediated by PCA NPs could be attributed to their anti-oxidant and anti-inflammatory properties in enhancing cell proliferation and matrix synthesis,while reducing inflammation,oxidative stress,matrix degradation,and chondrocyte ferroptosis.Overall,our study demonstrates a multifunctional nanoparticle,synthesized from natural p-coumaric acid,that is stable and possess potent antioxidant,anti-inflammatory properties and ferroptosis inhibition,beneficial for treatment of TMJOA.
基金This work was supported by the Research Mission of Military Training Injury Prevention and Control(21XLS06)the Key Talents Support Project of the Army Medical University(No.B-3261).
文摘Purpose:Different arch structures may cause different foot function injuries.In the past,the arch structure and flexibility of the foot were often defined by the height of the arch,and there was no three-dimensional(3D)structure classification method.In order to form a more complete 3D description,we propose a new classification system of arch volume flexibility(AVF),and then use this new classification system to investigate the relationship between the AVF and arch index(AI),and the arch height flexibility(AHF)and AI,respectively.Methods:It is proposed to recruit 180 young male adults for the test.We obtained arch volume and AI through 3D scanning and obtained the navicular height through manual measurement.Based on these data,we calculated the AHF and the AVF.Using the quintile method,these arches are divided into very stiff,stiff,neutral,flexible,and very flexible.According to AI value,all arches were divided into cavus,rectus,and planus.The distribution of AVF was compared usingχ^(2)goodness of fit test.The spearman correlation test was used to compare the AHF and AVF.A p<0.05 indicates that the difference is statistically significant.Results:All participants'plantar data was obtained through 3D scanning,but only 159 of them were complete,so only 318 feet had valid data.The left AHF is(21.23±12.91)mm/kN,and the right AHF is(21.71±12.69)mm/kN.The AVF of the left foot arch is(207.35±118.28)mm^(3)/kg,while the right one is(203.00±117.92)mm^(3)/kg,and the total AVF of the arch was(205.17±117.94)mm^(3)/kg.There was no statistical difference in the AVF between the left and right feet for the same participant(n=159,p=0.654).In cavus,the percentage of arch with AVF is 21.4%(very stiff),21.4%(stiff),14.3%(neutral),7.1%(flexible),and 35.7%(very flexible).In rectus,the percentage of arch with AVF is 23.9%(very stiff),19.6%(stiff),14.7%(neutral),24.5%(flexible),and 17.2%(very flexible).In planus,the percentage of arch with AVF is 14.9%(very stiff),20.6%(stiff),27.0%(neutral),16.3%(flexible),and 21.3%(very flexible).Moreover,the correlation between AHF and AVF is not significant(p=0.060).Conclusion:In cavus,rectus,and planus,different AVF accounts different percentage,but the difference is not statistically significant.AVF is evenly distributed in the arches of the feet at different heights.We further found the relationship between AHF and AVF is not significant.As a 3D index,AVF may be able to describe the flexibility of the arch more comprehensively than AHF.
基金supported by Major Projects of the National Natural Science Foundation of China(81690261)Sichuan Science and Technology Program(2018RZ0136,China)
文摘Chemotherapy agents have been widely used for cancer treatment,while the insolubility,instability and toxicity seriously restrict their efficacy.Thus,prodrug strategy was devised.Since some prodrugs are still with poor solubility or stability,a synergy strategy is needed to enhance their efficacy.Gemcitabine(GEM)is a prescribed anticancer drug,however,the rapid clearance,growing resistance and serious side effects limit its clinical efficacy.Conjugating GEM with D-a-tocopherol succinate(TOS)is an effective solution,while the GEM-TOS(GT)is unstable in aqueous solution.D-a-Tocopherol polyethylene glycol succinate(TPGS)has been used to enhance the stability,but GT stabilized by TPGS(GTT)has limited effect on tumor metastases.Tumor metastases lead to high mortality in patients suffering from cancers.In order to further achieve antimetastatic effect,an amphiphilic polymer(LT)was synthesized by connecting low-molecular-weight heparin(LMWH)with TOS,and eventually obtained desired selfdelivery micellar NPs(GLT)by co-assembly GT with LT.The GLT not only possessed excellent stability,but also inhibited the metastases by acting on different phases of the metastatic cascade.The hydrophobic TOS inhibited the secretion of matrix metalloproteinase-9(MMP-9),the hydrophilic LMWH inhibited the interaction between tumor cells and platelets.As a result,GLT reduced tumor cells entering the blood and implanting at the distant organs,leading to a much more excellent inhibitory effect on the lung metastasis than GEM and GTT.
