Activated G-protein-coupled receptor 39(GPR39)has been shown to attenuate inflammation by interacting with sirtuin 1(SIRT1)and peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α).However,whether GPR3...Activated G-protein-coupled receptor 39(GPR39)has been shown to attenuate inflammation by interacting with sirtuin 1(SIRT1)and peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α).However,whether GPR39 attenuates neuropathic pain remains unclear.In this study,we established a Sprague-Dawley rat model of spared nerve injury-induced neuropathic pain and found that GPR39 expression was significantly decreased in neurons and microglia in the spinal dorsal horn compared with sham-operated rats.Intrathecal injection of TC-G 1008,a specific agonist of GPR39,significantly alleviated mechanical allodynia in the rats with spared nerve injury,improved spinal cord mitochondrial biogenesis,and alleviated neuroinflammation.These changes were abolished by GPR39 small interfering RNA(siRNA),Ex-527(SIRT1 inhibitor),and PGC-1αsiRNA.Taken together,these findings show that GPR39 activation ameliorates mechanical allodynia by activating the SIRT1/PGC-1αpathway in rats with spared nerve injury.展开更多
Multiple drug resistance(MDR)is a tough problem in developing hepatocellular carcinoma(HCC)therapy.Here,we developed TPGS-coated cationic liposomes with Bcl-2 siRNA corona to load doxorubicin(Dox)i.e.,Bcl-2 siRNA/Dox-...Multiple drug resistance(MDR)is a tough problem in developing hepatocellular carcinoma(HCC)therapy.Here,we developed TPGS-coated cationic liposomes with Bcl-2 siRNA corona to load doxorubicin(Dox)i.e.,Bcl-2 siRNA/Dox-TPGS-LPs,to enhance anticancer effect of Dox in HCC-MDR.TPGS i.e.,d-α-tocopheryl polyethylene glycol 1000 succinate,inhibited Pglycoprotein(P-gp)efflux pump and Bcl-2 siRNA suppressed anti-apoptotic Bcl-2 protein.The Bcl-2 siRNA loaded in the liposomal corona was observed under transmission electron microscopy.The stability and hemolysis evaluation demonstrated Bcl-2 siRNA/Dox-TPGSLPs had good biocompatibility and siRNA-corona could protect the liposomal core to avoid the attachment of fetal bovine serum.In drug-resistant cells,TPGS effectively prolonged intracellular Dox retention time and siRNA-corona did improve the internalization of Dox from liposomes.In vitro and in vivo anticancer effect of this dual-functional nanostructure was examined in HCC-MDR Bel7402/5-FU tumor model.MTT assay confirmed the IC50 value of Dox was 20–50 fold higher in Bel7402/5-FU MDR cells than that in sensitive Bel7402 cells.Bcl-2 siRNA corona successfully entered the cytosol of Bel7402/5-FU MDR cells to downregulate Bcl-2 protein levels in vitro and in vivo.Bcl-2 siRNA/Dox-TPGS-LPs showed superior to TPGS-(or siRNA-)linked Dox liposomes in cell apoptosis and cytotoxicity assay in Bel7402/5-FU MDR cells,and 7-fold greater effect than free Dox in tumor growth inhibition of Bel7402/5-FU xenograft nude mice.In conclusion,TPGS-coated cationic liposomes with Bcl-2 siRNA corona had the capacity to inhibit MDR dual-pathways and subsequently improved the anti-tumor activity of the chemotherapeutic agent co-delivered to a level that cannot be achieved by inhibiting a MDR single way.展开更多
Objective: The purpose of this empirical study was to investigate the evaluation indexes of nursing research results and to provide references for the optimization of nursing research results and their clinical applic...Objective: The purpose of this empirical study was to investigate the evaluation indexes of nursing research results and to provide references for the optimization of nursing research results and their clinical applications.Methods: A total of 150 clinical nursing studies were randomly selected, the clinical applications of their results were investigated,and the results were evaluated using the evaluation indexes of nursing research achievements.Results: The results of 101 clinical nursing studies were promoted through their application, accounting for 82.79%, but they were mostly promoted and applied in small areas. When the evaluation indexes of nursing research results were used to evaluate the results, the scores for the applied results were higher than those of unapplied results, and the difference was statistically significant(P < 0.05). Considering the levels of the results, the scores of the results of studies at the national level were higher than those of studies at the municipal and hospital levels; the scores of the results of studies at the provincial level were higher than those at the hospital level; and the scores of the results of originally innovative studies were higher than those of partially innovative studies. The differences were statistically significant(P < 0.05). In terms of overall scores, the scores of the results at the provincial level were higher than those at the hospital level, and the difference was statistically significant(P < 0.05).Conclusions: The evaluation indexes of nursing research results in this study can scientifically and effectively evaluate the level,value, and effectiveness of the nursing research results and can promote the clinical application of the optimized results.展开更多
Combining adiabatic passage and Rydberg antiblockade, we propose a scheme to implement a two-qubit phase gate between two Rydberg atoms. Detuning parameters between frequencies of atomic transitions and those of the c...Combining adiabatic passage and Rydberg antiblockade, we propose a scheme to implement a two-qubit phase gate between two Rydberg atoms. Detuning parameters between frequencies of atomic transitions and those of the corresponding driving lasers are carefully chosen to offset the blockade effect of two Rydberg atoms, so that an effective Hamiltonian,representing a single-photon detuning L-type three-level system and concluding the quantum state of two Rydberg atoms excited simultaneously, is obtained. The adiabatic-passage technique, based on the effective Hamiltonian, is adopted to implement a two-atom phase gate by using two time-dependent Rabi frequencies. Numerical simulations indicate that a high-fidelity two-qubit p-phase gate is constructed and its operation time does not have to be controlled accurately. Besides,owing to the long coherence time of the Rydberg state, the phase gate is robust against atomic spontaneous emission.展开更多
Objective: The aims of this study were to understand the status quo of authors, collaborations between institutions, research hotspots,and research frontiers of fund-sponsored clinical nursing papers and to provide a ...Objective: The aims of this study were to understand the status quo of authors, collaborations between institutions, research hotspots,and research frontiers of fund-sponsored clinical nursing papers and to provide a reference for Chinese scholars to conduct clinical nursing studies in the future.Methods: The visualization software CiteSpace was used to analyze fund-sponsored clinical nursing papers published between 2012 and 2016 in 12 core journals of nursing.Results: In the clinical nursing field, there are many cooperative author groups; however, the collaborations between institutions are not close and exist mainly within the same province or city. High-frequency keywords have revealed the four clinical nursing research hotspots of population, diseases, nursing intervention, and others. Chinese medicine nursing, prevention, treatment and nursing, and new technology-aided nursing of ventilator-associated pneumonia are the study frontiers of clinical nursing.Conclusions: Clinical nursing studies are rich in content and cover a wide range of areas, and their hotspots and frontiers are closely related to the requirements of clinical nursing. Collaborations across regions, provinces, and cities are not adequate; there is an urgent need to strengthen the cross-regional exchanges and collaborations to promote the further development of clinical nursing.展开更多
Perfuorinated compounds(PFCs)are toxic and widely present in the environment,and therefore effective adsorbents are required to remove PFCs from environmental water.In the present study,a new type of fuorinated biomas...Perfuorinated compounds(PFCs)are toxic and widely present in the environment,and therefore effective adsorbents are required to remove PFCs from environmental water.In the present study,a new type of fuorinated biomass materials was synthesized via an ingenious fuorosilanization reaction.These adsorbents were applied for the adsorption of 13typical PFCs,including perfuorocarboxylic acids(PFCAs)and perfuorosulfonic acids(PFSAs).By comparing their adsorption performance,Fluorinated cedar slag(FCS)was discovered to have the best absorption efficiency and enabled highly efficient enrichment of PFCs.The adsorption recovery of FCS with the investigated PFCs is greater than 90%under the optimal adsorption condition.Ascribed to the high affinity of F-F sorbent-sorbate interaction,FCS had good adsorption capacities of PFCs from aqueous solution,with the maximum adsorption capacity of 15.80 mg/g for PFOS and 10.71 mg/g for PFOA,respectively.Moreover,the adsorption time could be achieved in a short time(8 min).Using the FCS absorbent,an innovative FCS-solid phase extraction assisted with high performance liquid chromatography-electrospray-tandem mass spectrometry(FCS-SPE-HPLC-ESI-MS/MS)method was first developed to sensitively detect PFCs in the environmental water samples.The intra-day and inter-day recovery rates of the 13 compounds ranged from 90.7%-104.3%,with the RSD of 2.1%-4.7%(intra-day)and 2.5%-8.5%(inter-day),respectively.This research demonstrates the potential of the newly fuoro-functionalized plant biomass to adsorb PFCs from environmental water,with the advantages of high adsorption efficiencies,high antiinterference,easy operation and low economic cost.展开更多
ZrO_(2)-7 wt% Y_(2)O_(3)(7YSZ)thermal barrier coatings(TBCs)with three different structures were prepared by atmospheric plasma spraying(APS),electron beam physical vapor deposition(EB-PVD)and plasma spray-physical va...ZrO_(2)-7 wt% Y_(2)O_(3)(7YSZ)thermal barrier coatings(TBCs)with three different structures were prepared by atmospheric plasma spraying(APS),electron beam physical vapor deposition(EB-PVD)and plasma spray-physical vapor deposition(PS-PVD).Al films were deposited onto the top 7YSZ TBCs by magnetron sputtering,and the Al-deposited 7YSZ TBCs were subjected to vacuum heat treatment.The effects of Al modification on the thermal insulation properties of 7YSZ TBCs were investigated.The results showed that Al modification could significantly improve the thermal insulation of 7YSZ TBCs at 1000℃.Moreover,the maximum improvement of thermal insulation for PS-PVD 7YSZ TBCs was approximately 100℃,but the improvement decreased with increasing temperature.This is mainly because with increasing temperature,the rate of radiation heat transfer increases,and the effects of convection heat transfer and thermal conductivity on thermal insulation are weakened.At the same temperature,Al modification of PS-PVD7YSZ TBCs provides better temperature insulation than those of APS 7YSZ TBCs and EB-PVD 7YSZ TBCs because of its wider and deeper inter-columnar gaps.When the temperature was 12000C,Al modification still caused a good insulation effect in PS-PVD 7YSZ TBCs;the improvement was approximately 50℃,but in APS and EB-PVD 7YSZ TBCs,the insulation effect disappeared.展开更多
The combinational chemo-immunotherapy as a novel treatment strategy has been widely studied and applied in clinic to enhance antitumor therapeutic efficacy and relieve side effects.RNA interference(RNAi)targeting PD-L...The combinational chemo-immunotherapy as a novel treatment strategy has been widely studied and applied in clinic to enhance antitumor therapeutic efficacy and relieve side effects.RNA interference(RNAi)targeting PD-L1 via inhibiting novo production of PD-L1 will overcome the innate and adaptive PD-L1 expression during chemotherapy,thus enable sustained and efficient immune checkpoint blockade(ICB)to active antitumor immune response.Herein,we designed a glutathione(GSH)-responsive camptothecin(CPT)prodrug-based hybrid micellar nanoparticles(siPD-L1@HM-CPT)to achieve synergistic antitumor chemoimmunotherapy by PD-L1 knockdown.siPD-L1@HM-CPT derived from the one-step loading PD-L1 siRNA(siPD-L1)into the CPT prodrug-based hybrid micelles(HM-CPT)which were co-assembled from biodegradable polyphosphoesters-based prodrug CPT-ss-PAEEP15 and stabilizer DSPE-PEG,showed high loading efficiency,GSH-responsive drug release,and excellent stability and biosafety.siPD-L1@HM-CPT achieved simultaneously the co-delivery of CPT and siPD-L1 in vitro and in vivo,high accumulation at the tumor sites,and rapid intracellular release to promote antitumor efficacy via sensitizing CPT chemotherapy,inducing strong immunogenic cell death(ICD)and sustained ICB to improve intratumoral CD8+T cells infiltration.In addition,the antitumor immunity response limited by the differentiated immunogenicity,intrinsic PD-L1 expression,and intracellular GSH level was facilitated by efficient ICD and ICB from silencing PD-L1 and synergistic CPT chemosensitization in our experimental B16-F10 and 4T1 tumor models.Our study might offer a perspective on designing novel co-delivery nanoparticles by convenient and controllable preparation for antitumor chemo-immunotherapy.展开更多
BACKGROUND Low-molecular-weight heparins(LMWH)are the most commonly used anticoagulants during pregnancy.It is considered to be the drug of choice due to its safety in not crossing placenta.Considering the beneficial ...BACKGROUND Low-molecular-weight heparins(LMWH)are the most commonly used anticoagulants during pregnancy.It is considered to be the drug of choice due to its safety in not crossing placenta.Considering the beneficial effect in the improvement of microcirculation,prophylactic application of LMWH in patients with preeclampsia became a trend.However,the bleeding risk related with LMWH in preeclampsia patients has seldomly been evaluated.This current study aimed to identify the potential risks regarding LMWH application in patients with preeclampsia.CASE SUMMARY Herein we present a case series of three pregnant women diagnosed with preeclampsia on LMWH therapy during pregnancy.All the cases experienced catastrophic hemorrhagic events.After reviewing the twenty-one meta-analyses,the bleeding risk related with LMWH seems ignorable.Only one study analyzed the bleeding risk of LMWH and found a significantly higher risk of developing PPH in women receiving LMWH.Other studies reported minor bleeding risks,none of these were serious enough to stop LMWH treatment.Possibilities of bleeding either from uterus or from intrabdominal organs in preeclampsia patients on LMWH therapy should not be ignored.Intensive management of blood pressure even after delivery and homeostasis suture in surgery are crucial.CONCLUSION Consideration should be given to the balance between benefits and risks of LMWH in patients with preeclampsia.展开更多
Fungal infections cause~1.5 million deaths each year worldwide,and the mortality rate of disseminated candidiasis currently exceeds that of breast cancer and malaria.The major reasons for the high mortality of candidi...Fungal infections cause~1.5 million deaths each year worldwide,and the mortality rate of disseminated candidiasis currently exceeds that of breast cancer and malaria.The major reasons for the high mortality of candidiasis are the limited number of antifungal drugs and the emergence of drug-resistant species.Therefore,a better understanding of antifungal host defense mechanisms is crucial for the development of effective preventive and therapeutic strategies.Here,we report that DOCK2(dedicator of cytokinesis 2)promotes indispensable antifungal innate immune signaling and proinflammatory gene expression in macrophages.DOCK2-deficient macrophages exhibit decreased RAC GTPase(Rac family small GTPase)activation and ROS(reactive oxygen species)production,which in turn attenuates the killing of intracellular fungi and the activation of downstream signaling pathways.Mechanistically,after fungal stimulation,activated SYK(spleen-associated tyrosine kinase)phosphorylates DOCK2 at tyrosine 985 and 1405,which promotes the recruitment and activation of RAC GTPases and then increases ROS production and downstream signaling activation.Importantly,nanoparticle-mediated delivery of in vitro transcribed(IVT)Rac1 mRNA promotes the activity of Rac1 and helps to eliminate fungal infection in vivo.Taken together,this study not only identifies a critical role of DOCK2 in antifungal immunity via regulation of RAC GTPase activity but also provides proof of concept for the treatment of invasive fungal infections by using IVT mRNA.展开更多
基金supported by the National Notural Science Foundation of China,Nos.82071556 and 82271291 (both to WM)
文摘Activated G-protein-coupled receptor 39(GPR39)has been shown to attenuate inflammation by interacting with sirtuin 1(SIRT1)and peroxisome proliferator-activated receptor-γcoactivator 1α(PGC-1α).However,whether GPR39 attenuates neuropathic pain remains unclear.In this study,we established a Sprague-Dawley rat model of spared nerve injury-induced neuropathic pain and found that GPR39 expression was significantly decreased in neurons and microglia in the spinal dorsal horn compared with sham-operated rats.Intrathecal injection of TC-G 1008,a specific agonist of GPR39,significantly alleviated mechanical allodynia in the rats with spared nerve injury,improved spinal cord mitochondrial biogenesis,and alleviated neuroinflammation.These changes were abolished by GPR39 small interfering RNA(siRNA),Ex-527(SIRT1 inhibitor),and PGC-1αsiRNA.Taken together,these findings show that GPR39 activation ameliorates mechanical allodynia by activating the SIRT1/PGC-1αpathway in rats with spared nerve injury.
基金financially supported by National Basic Research Program of China(973 Program,2015CB931802)Natural Science Foundation of China(31470968 and 81627901)。
文摘Multiple drug resistance(MDR)is a tough problem in developing hepatocellular carcinoma(HCC)therapy.Here,we developed TPGS-coated cationic liposomes with Bcl-2 siRNA corona to load doxorubicin(Dox)i.e.,Bcl-2 siRNA/Dox-TPGS-LPs,to enhance anticancer effect of Dox in HCC-MDR.TPGS i.e.,d-α-tocopheryl polyethylene glycol 1000 succinate,inhibited Pglycoprotein(P-gp)efflux pump and Bcl-2 siRNA suppressed anti-apoptotic Bcl-2 protein.The Bcl-2 siRNA loaded in the liposomal corona was observed under transmission electron microscopy.The stability and hemolysis evaluation demonstrated Bcl-2 siRNA/Dox-TPGSLPs had good biocompatibility and siRNA-corona could protect the liposomal core to avoid the attachment of fetal bovine serum.In drug-resistant cells,TPGS effectively prolonged intracellular Dox retention time and siRNA-corona did improve the internalization of Dox from liposomes.In vitro and in vivo anticancer effect of this dual-functional nanostructure was examined in HCC-MDR Bel7402/5-FU tumor model.MTT assay confirmed the IC50 value of Dox was 20–50 fold higher in Bel7402/5-FU MDR cells than that in sensitive Bel7402 cells.Bcl-2 siRNA corona successfully entered the cytosol of Bel7402/5-FU MDR cells to downregulate Bcl-2 protein levels in vitro and in vivo.Bcl-2 siRNA/Dox-TPGS-LPs showed superior to TPGS-(or siRNA-)linked Dox liposomes in cell apoptosis and cytotoxicity assay in Bel7402/5-FU MDR cells,and 7-fold greater effect than free Dox in tumor growth inhibition of Bel7402/5-FU xenograft nude mice.In conclusion,TPGS-coated cationic liposomes with Bcl-2 siRNA corona had the capacity to inhibit MDR dual-pathways and subsequently improved the anti-tumor activity of the chemotherapeutic agent co-delivered to a level that cannot be achieved by inhibiting a MDR single way.
基金supported by the Department of Health,Shanxi Province,China(no.201301008)
文摘Objective: The purpose of this empirical study was to investigate the evaluation indexes of nursing research results and to provide references for the optimization of nursing research results and their clinical applications.Methods: A total of 150 clinical nursing studies were randomly selected, the clinical applications of their results were investigated,and the results were evaluated using the evaluation indexes of nursing research achievements.Results: The results of 101 clinical nursing studies were promoted through their application, accounting for 82.79%, but they were mostly promoted and applied in small areas. When the evaluation indexes of nursing research results were used to evaluate the results, the scores for the applied results were higher than those of unapplied results, and the difference was statistically significant(P < 0.05). Considering the levels of the results, the scores of the results of studies at the national level were higher than those of studies at the municipal and hospital levels; the scores of the results of studies at the provincial level were higher than those at the hospital level; and the scores of the results of originally innovative studies were higher than those of partially innovative studies. The differences were statistically significant(P < 0.05). In terms of overall scores, the scores of the results at the provincial level were higher than those at the hospital level, and the difference was statistically significant(P < 0.05).Conclusions: The evaluation indexes of nursing research results in this study can scientifically and effectively evaluate the level,value, and effectiveness of the nursing research results and can promote the clinical application of the optimized results.
基金Project supported by the National Natural Science Foundation of China(Grant No.11464046)
文摘Combining adiabatic passage and Rydberg antiblockade, we propose a scheme to implement a two-qubit phase gate between two Rydberg atoms. Detuning parameters between frequencies of atomic transitions and those of the corresponding driving lasers are carefully chosen to offset the blockade effect of two Rydberg atoms, so that an effective Hamiltonian,representing a single-photon detuning L-type three-level system and concluding the quantum state of two Rydberg atoms excited simultaneously, is obtained. The adiabatic-passage technique, based on the effective Hamiltonian, is adopted to implement a two-atom phase gate by using two time-dependent Rabi frequencies. Numerical simulations indicate that a high-fidelity two-qubit p-phase gate is constructed and its operation time does not have to be controlled accurately. Besides,owing to the long coherence time of the Rydberg state, the phase gate is robust against atomic spontaneous emission.
基金supported by scientific research project of the Health Department of Shanxi Province(No.201301008)
文摘Objective: The aims of this study were to understand the status quo of authors, collaborations between institutions, research hotspots,and research frontiers of fund-sponsored clinical nursing papers and to provide a reference for Chinese scholars to conduct clinical nursing studies in the future.Methods: The visualization software CiteSpace was used to analyze fund-sponsored clinical nursing papers published between 2012 and 2016 in 12 core journals of nursing.Results: In the clinical nursing field, there are many cooperative author groups; however, the collaborations between institutions are not close and exist mainly within the same province or city. High-frequency keywords have revealed the four clinical nursing research hotspots of population, diseases, nursing intervention, and others. Chinese medicine nursing, prevention, treatment and nursing, and new technology-aided nursing of ventilator-associated pneumonia are the study frontiers of clinical nursing.Conclusions: Clinical nursing studies are rich in content and cover a wide range of areas, and their hotspots and frontiers are closely related to the requirements of clinical nursing. Collaborations across regions, provinces, and cities are not adequate; there is an urgent need to strengthen the cross-regional exchanges and collaborations to promote the further development of clinical nursing.
基金supported by the National Natural Science Foundation of China (No.22276221,and 21675176)the Fundamental Research Funds for the Central Universities,and South-Central Minzu University (No.CZP21002)。
文摘Perfuorinated compounds(PFCs)are toxic and widely present in the environment,and therefore effective adsorbents are required to remove PFCs from environmental water.In the present study,a new type of fuorinated biomass materials was synthesized via an ingenious fuorosilanization reaction.These adsorbents were applied for the adsorption of 13typical PFCs,including perfuorocarboxylic acids(PFCAs)and perfuorosulfonic acids(PFSAs).By comparing their adsorption performance,Fluorinated cedar slag(FCS)was discovered to have the best absorption efficiency and enabled highly efficient enrichment of PFCs.The adsorption recovery of FCS with the investigated PFCs is greater than 90%under the optimal adsorption condition.Ascribed to the high affinity of F-F sorbent-sorbate interaction,FCS had good adsorption capacities of PFCs from aqueous solution,with the maximum adsorption capacity of 15.80 mg/g for PFOS and 10.71 mg/g for PFOA,respectively.Moreover,the adsorption time could be achieved in a short time(8 min).Using the FCS absorbent,an innovative FCS-solid phase extraction assisted with high performance liquid chromatography-electrospray-tandem mass spectrometry(FCS-SPE-HPLC-ESI-MS/MS)method was first developed to sensitively detect PFCs in the environmental water samples.The intra-day and inter-day recovery rates of the 13 compounds ranged from 90.7%-104.3%,with the RSD of 2.1%-4.7%(intra-day)and 2.5%-8.5%(inter-day),respectively.This research demonstrates the potential of the newly fuoro-functionalized plant biomass to adsorb PFCs from environmental water,with the advantages of high adsorption efficiencies,high antiinterference,easy operation and low economic cost.
基金financially supported by the National Natural Science Foundation of China(Nos.51801034 and 52172067)Guangdong Province Outstanding Youth Foundation(No.2021B1515020038)+2 种基金Guangdong Special Support Program(No.2019BT02C629)Key R&D project in ShanXi Province(No.2019ZDLGY01-07)Guangdong Academy of Sciences Program(No.2020GDASYL-20200104030)。
文摘ZrO_(2)-7 wt% Y_(2)O_(3)(7YSZ)thermal barrier coatings(TBCs)with three different structures were prepared by atmospheric plasma spraying(APS),electron beam physical vapor deposition(EB-PVD)and plasma spray-physical vapor deposition(PS-PVD).Al films were deposited onto the top 7YSZ TBCs by magnetron sputtering,and the Al-deposited 7YSZ TBCs were subjected to vacuum heat treatment.The effects of Al modification on the thermal insulation properties of 7YSZ TBCs were investigated.The results showed that Al modification could significantly improve the thermal insulation of 7YSZ TBCs at 1000℃.Moreover,the maximum improvement of thermal insulation for PS-PVD 7YSZ TBCs was approximately 100℃,but the improvement decreased with increasing temperature.This is mainly because with increasing temperature,the rate of radiation heat transfer increases,and the effects of convection heat transfer and thermal conductivity on thermal insulation are weakened.At the same temperature,Al modification of PS-PVD7YSZ TBCs provides better temperature insulation than those of APS 7YSZ TBCs and EB-PVD 7YSZ TBCs because of its wider and deeper inter-columnar gaps.When the temperature was 12000C,Al modification still caused a good insulation effect in PS-PVD 7YSZ TBCs;the improvement was approximately 50℃,but in APS and EB-PVD 7YSZ TBCs,the insulation effect disappeared.
基金The authors acknowledge the support by the National Basic Research Program of China(Nos.2020YFA0710700 and 2018YFA0208900)the National Natural Science Foundation of China(No.31470968).
文摘The combinational chemo-immunotherapy as a novel treatment strategy has been widely studied and applied in clinic to enhance antitumor therapeutic efficacy and relieve side effects.RNA interference(RNAi)targeting PD-L1 via inhibiting novo production of PD-L1 will overcome the innate and adaptive PD-L1 expression during chemotherapy,thus enable sustained and efficient immune checkpoint blockade(ICB)to active antitumor immune response.Herein,we designed a glutathione(GSH)-responsive camptothecin(CPT)prodrug-based hybrid micellar nanoparticles(siPD-L1@HM-CPT)to achieve synergistic antitumor chemoimmunotherapy by PD-L1 knockdown.siPD-L1@HM-CPT derived from the one-step loading PD-L1 siRNA(siPD-L1)into the CPT prodrug-based hybrid micelles(HM-CPT)which were co-assembled from biodegradable polyphosphoesters-based prodrug CPT-ss-PAEEP15 and stabilizer DSPE-PEG,showed high loading efficiency,GSH-responsive drug release,and excellent stability and biosafety.siPD-L1@HM-CPT achieved simultaneously the co-delivery of CPT and siPD-L1 in vitro and in vivo,high accumulation at the tumor sites,and rapid intracellular release to promote antitumor efficacy via sensitizing CPT chemotherapy,inducing strong immunogenic cell death(ICD)and sustained ICB to improve intratumoral CD8+T cells infiltration.In addition,the antitumor immunity response limited by the differentiated immunogenicity,intrinsic PD-L1 expression,and intracellular GSH level was facilitated by efficient ICD and ICB from silencing PD-L1 and synergistic CPT chemosensitization in our experimental B16-F10 and 4T1 tumor models.Our study might offer a perspective on designing novel co-delivery nanoparticles by convenient and controllable preparation for antitumor chemo-immunotherapy.
基金Supported by National Natural Science Foundation of China,No.82301924.
文摘BACKGROUND Low-molecular-weight heparins(LMWH)are the most commonly used anticoagulants during pregnancy.It is considered to be the drug of choice due to its safety in not crossing placenta.Considering the beneficial effect in the improvement of microcirculation,prophylactic application of LMWH in patients with preeclampsia became a trend.However,the bleeding risk related with LMWH in preeclampsia patients has seldomly been evaluated.This current study aimed to identify the potential risks regarding LMWH application in patients with preeclampsia.CASE SUMMARY Herein we present a case series of three pregnant women diagnosed with preeclampsia on LMWH therapy during pregnancy.All the cases experienced catastrophic hemorrhagic events.After reviewing the twenty-one meta-analyses,the bleeding risk related with LMWH seems ignorable.Only one study analyzed the bleeding risk of LMWH and found a significantly higher risk of developing PPH in women receiving LMWH.Other studies reported minor bleeding risks,none of these were serious enough to stop LMWH treatment.Possibilities of bleeding either from uterus or from intrabdominal organs in preeclampsia patients on LMWH therapy should not be ignored.Intensive management of blood pressure even after delivery and homeostasis suture in surgery are crucial.CONCLUSION Consideration should be given to the balance between benefits and risks of LMWH in patients with preeclampsia.
基金supported by a grant from the National Key Research and Development Program of China (2020YFA0710700 to CHW)the National Natural Science Foundation of China (Grant No.82101859 to WWS)+4 种基金the Original Exploration Program of National Natural Science Foundation of China (82150102,to CHW)the Key Research and Development Program of Sichuan Province (22ZDYF3738,to CHW)the Fundamental Research Funds for the Central Universities,HUST (2021GCRC031 to CHW)the National Natural Science Foundation of China (31870165 to BZ)the Shenzhen Science and Technology Innovation Fund (JCYJ20210324115811032 to BZ).
文摘Fungal infections cause~1.5 million deaths each year worldwide,and the mortality rate of disseminated candidiasis currently exceeds that of breast cancer and malaria.The major reasons for the high mortality of candidiasis are the limited number of antifungal drugs and the emergence of drug-resistant species.Therefore,a better understanding of antifungal host defense mechanisms is crucial for the development of effective preventive and therapeutic strategies.Here,we report that DOCK2(dedicator of cytokinesis 2)promotes indispensable antifungal innate immune signaling and proinflammatory gene expression in macrophages.DOCK2-deficient macrophages exhibit decreased RAC GTPase(Rac family small GTPase)activation and ROS(reactive oxygen species)production,which in turn attenuates the killing of intracellular fungi and the activation of downstream signaling pathways.Mechanistically,after fungal stimulation,activated SYK(spleen-associated tyrosine kinase)phosphorylates DOCK2 at tyrosine 985 and 1405,which promotes the recruitment and activation of RAC GTPases and then increases ROS production and downstream signaling activation.Importantly,nanoparticle-mediated delivery of in vitro transcribed(IVT)Rac1 mRNA promotes the activity of Rac1 and helps to eliminate fungal infection in vivo.Taken together,this study not only identifies a critical role of DOCK2 in antifungal immunity via regulation of RAC GTPase activity but also provides proof of concept for the treatment of invasive fungal infections by using IVT mRNA.
