The key and bottleneck of research on the tip-jet rotor compound helicopter lies in the power system. Computational Fluid Dynamics (CFD) was used to numerically simulate the gas generator and rotor inner passage of th...The key and bottleneck of research on the tip-jet rotor compound helicopter lies in the power system. Computational Fluid Dynamics (CFD) was used to numerically simulate the gas generator and rotor inner passage of the tip-jet rotor composite power system, studying the effects of intake mode, inner cavity structure, propellant components, and injection amount on the characteristics of the composite power system. The results show that when a single high-temperature exhaust gas enters, the gas generator outlet fluid is uneven and asymmetric;when two-way high-temperature exhaust gas enters, the outlet temperature of the gas generator with a tilted inlet is more uniform than that with a vertical inlet;adding an inner cavity improves the temperature and velocity distribution of the gas generator's internal flow field;increasing the energy of the propellant is beneficial for improving the available moment.展开更多
The pear is an economic fruit that is widely planted around the world and is loved by people for its rich nutritional value. Autophagy is a self-protection mechanism in eukaryotes, and its occurrence often accompanied...The pear is an economic fruit that is widely planted around the world and is loved by people for its rich nutritional value. Autophagy is a self-protection mechanism in eukaryotes, and its occurrence often accompanied by the degradation of damaged substances in cells and the recycling of nutrients. Autophagy is one of the mechanisms through which plants respond to environmental stress and plays an important role in plant development and stress resistance. Functional studies of autophagy-related genes (ATGs) have been performed on a variety of plant species, but little information is available on the ATG family in pear (Pyrus bretschneideri Rehd). Therefore, we analyzed the evolutionary dynamics and performed a genome-wide characterization of the PbrATG gene family. A total of 28 PbrATG members were identified.Phylogenetic analysis showed that PbrATGs were more closely related to ATGs of European pear and apple. Evolutionary analysis revealed that whole-genome duplication (WGD) and dispersed duplication events were the main driving forces of PbrATG family expansion.Expression analysis of different pear tissues showed that all the genes were expressed in different pear tissues, and different PbrATGs are expressed at different times and in different locations. Moreover, all PbrATGs also responded to different abiotic stresses, especially salt and drought stress, which elicited the highest expression levels. Pear seedlings were subsequently infected with Botryosphaeria dothidea (B.dothidea). The results showed that different PbrATGs had different expression patterns at different infection stages. According to the gene expression data, PbrATG1a was selected as a key autophagy gene for further analysis. Silencing of PbrATG1a reduced the resistance of pear to B. dothidea, which resulted in increased lesions, reactive oxygen species (ROS) contents, antioxidant enzyme activity, and gene expression levels in the silenced pear seedlings after B. dothidea inoculation. In this study, a comprehensive bioinformatic analysis of ATGs was conducted, and the functions of PbrATGs in pear development and in response to stress were elucidated, which laid a foundation for further study of the molecular mechanism of autophagy and a new strategy for pear resistance breeding.展开更多
Increasing effective panicle number per plant(EPN)is one approach to increase yield potential in rice.However,molecular mechanisms underlying EPN remain unclear.In this study,we integrated mapbased cloning and genome-...Increasing effective panicle number per plant(EPN)is one approach to increase yield potential in rice.However,molecular mechanisms underlying EPN remain unclear.In this study,we integrated mapbased cloning and genome-wide association analysis to identify the EPN4 gene,which is allelic to NARROW LEAF1(NAL1).Overexpression lines containing the Teqing allele(TQ)of EPN4 had significantly increased EPN.NIL-EPN4^(TQ) in japonica(geng)cultivar Lemont(LT)exhibited significantly improved EPN but decreased grain number and flag leaf size relative to LT.Haplotype analysis indicated that accessions with EPN4-1 had medium EPN,medium grain number,and medium grain weight,but had the highest grain yield among seven haplotypes,indicating that EPN4-1 is an elite haplotype of EPN4 for positive coordination of the three components of grain yield.Furthermore,accessions carrying the combination of EPN4-1 and haplotype GNP1-6 of GNP1 for grain number per panicle showed higher grain yield than those with other allele combinations.Therefore,pyramiding of EPN4-1 and GNP1-6 could be a preferred approach to obtain high yield potential in breeding.展开更多
Millimeter-wave systems with high integration level have been rapidly developed to enable modern wireless communication,sensing,and imaging.The millimeter-wave power amplifier(PA)is one of the most challenging and cri...Millimeter-wave systems with high integration level have been rapidly developed to enable modern wireless communication,sensing,and imaging.The millimeter-wave power amplifier(PA)is one of the most challenging and critical components in a millimeter-wave transceiver,it is the last active stage in a transmitter amplifying spectrally efficient complex modulation signal for radiation with high output power.展开更多
With the changes in disease spectrum and the popularization of screening of low-dose spiral CT (CT) in the chest, more and more pulmonary nodules have been detected, most of which are bipulmonary multiple nodules. The...With the changes in disease spectrum and the popularization of screening of low-dose spiral CT (CT) in the chest, more and more pulmonary nodules have been detected, most of which are bipulmonary multiple nodules. The existence of multiple pulmonary nodules means that it may be a pathological state of benign and malignant co-existence. The origin and evolution of pulmonary nodules in different histopathological states have a great impact on the choice of treatment methods. In recent years, the rise of immunotherapy has brought a breakthrough in the treatment of refractory lung cancer. However, some patients are still ineffective in immunotherapy, which may be related to the immune microenvironment where nodules are proportioned in different components in different pathological states. This review article mainly predicts the development process of nodules by analyzing the origin of multiple pulmonary nodules and the immune microenvironment of nodules in different pathological conditions, so as to provide guidance for clinical treatment.展开更多
BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of complications.However,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy optio...BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of complications.However,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy options are still lacking.Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1(NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis,but its role in diseases including hepatic fibrosis remains undefined.Therefore,additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment.AIM To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1.METHODS Twenty-four male C57BL/6 mice were randomized and separated into three groups,comprising the normal,fibrosis,and calcitriol treatment groups,and liver fibrosis was modeled by carbon tetrachloride(CCl4).To evaluate the level of hepatic fibrosis in every group,serological and pathological examinations of the liver were conducted.TGF-β1 was administered to boost the in vitro cultivation of LX-2 cells.NS3TP1,α-smooth muscle actin(α-SMA),collagen I,and collagen Ⅲ in every group were examined using a Western blot and real-time quantitative polymerase chain reaction.The activity of the transforming growth factor beta 1(TGFβ1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected.The statistical analysis of the data was performed using the Student’s t test.RESULTS NS3TP1 promoted the activation,proliferation,and differentiation of hepatic stellate cells(HSCs)and enhanced hepatic fibrosis via the TGFβ1/Smad3 and NF-κB signaling pathways,as evidenced by the presence of α-SMA,collagen I,collagen Ⅲ,p-smad3,and p-p65 in LX-2 cells,which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference.The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression,as shown by the luciferase assay.NS3TP1 inhibited the apoptosis of HSCs.Moreover,both Smad3 and p65 could bind to NS3TP1,and p65 increased the promoter activity of NS3TP1,while NS3TP1 increased the promoter activity of TGFβ1 receptor I,as indicated by coimmunoprecipitation and luciferase assay results.Both in vivo and in vitro,treatment with calcitriol dramatically reduced the expression of NS3TP1.Calcitriol therapy-controlled HSCs activation,proliferation,and differentiation and substantially suppressed CCl4-induced hepatic fibrosis in mice.Furthermore,calcitriol modulated the activities of the above signaling pathways via downregulation of NS3TP1.CONCLUSION Our results suggest that calcitriol may be employed as an adjuvant therapy for hepatic fibrosis and that NS3TP1 is a unique,prospective therapeutic target in hepatic fibrosis.展开更多
AIM:To evaluate the potential of two trabecular meshwork(TM)-specific promoters,Chitinase 3-like 1(Ch3L1)and matrix gla protein(MGP),for improving specificity and safety in glaucoma gene therapy based on self-compleme...AIM:To evaluate the potential of two trabecular meshwork(TM)-specific promoters,Chitinase 3-like 1(Ch3L1)and matrix gla protein(MGP),for improving specificity and safety in glaucoma gene therapy based on self-complementary AAV2(scAAV2)vector technologies.METHODS:An scAAV2 vector with C3 transferase(C3)as the reporter gene(scAAV2-C3)was selected.The scAAV2-C3 vectors were driven by Ch3L1(scAAV2-Ch3L1-C3),MGP(scAAV2-MGP-C3),enhanced MGP(scAAV2-eMGP-C3)and cytomegalovirus(scAAV2-CMV-C3),respectively.The cultured primary human TM cells were treated with each vector at different multiplicities of infections.Changes in cell morphology were observed by phase contrast microscopy.Actin stress fibers and Rho GTPases/Rho-associated protein kinase pathway-related molecules were assessed by immunofluorescence staining,real-time quantitative polymerase chain reaction and Western blot.Each vector was injected intracamerally into the one eye of each rat at low and high doses respectively.In vivo green fluorescence was visualized by a Micron III Retinal Imaging Microscope.Intraocular pressure(IOP)was monitored using a rebound tonometer.Ocular responses were evaluated by slit-lamp microscopy.Ocular histopathology analysis was examined by hematoxylin and eosin staining.RESULTS:In TM cell culture studies,the vectormediated C3 expression induced morphologic changes,disruption of actin cytoskeleton and reduction of fibronectin expression in TM cells by inhibiting the Rho GTPases/Rhoassociated protein kinase signaling pathway.At the same dose,these changes were significant in TM cells treated with scAAV2-CMV-C3 or scAAV2-Ch3L1-C3,but not in cells treated with scAAV2-eMGP-C3 or scAAV2-MGP-C3.At lowinjected dose,the IOP was significantly decreased in the scAAV2-Ch3L1-C3-injected eyes but not in scAAV2-MGPC3-injected and scAAV2-eMGP-C3-injected eyes.At highinjected dose,significant IOP reduction was observed in the scAAV2-eMGP-C3-injected eyes but not in scAAV2-MGP-C3-injected eyes.Similar to scAAV2-CMV-C3,scAAV2-Ch3L1-C3 vector showed efficient transduction both in the TM and corneal endothelium.In anterior segment tissues of scAAV2-eMGP-C3-injected eyes,no obvious morphological changes were found except for the TM.Inflammation was absent.CONCLUSION:In scAAV2-transduced TM cells,the promoter-driven efficiency of Ch3L1 is close to that of cytomegalovirus,but obviously higher than that of MGP.In the anterior chamber of rat eye,the transgene expression pattern of scAAV2 vector is presumably affected by MGP promoter,but not by Ch3L1 promoter.These findings would provide a useful reference for improvement of specificity and safety in glaucoma gene therapy using scAAV2 vector.展开更多
Cavitation generation methods have been used in multifarious directions because of their diversity,and numerous studies and discussions have been conducted on cavitation generation methods.This study aims to explore t...Cavitation generation methods have been used in multifarious directions because of their diversity,and numerous studies and discussions have been conducted on cavitation generation methods.This study aims to explore the generating mechanism and evolution law of volume alternate cavitation(VAC).In the VAC,liquid water is placed in an airtight container with a variable volume.As the volume alternately changes,the liquid water inside the container continues to cavitate.Then,the mixture turbulence model and in-cylinder dynamic grid model are adopted to conduct computational fluid dynamics simulation of volume alternate cavitation.In the simulation,the cloud images at seven heights on the central axis are monitored,and the phenomenon and mechanism of height and eccentricity are analyzed in detail.By employing the cavitation flow visualization method,the generating mechanism and evolution law of cavitation are revealed.The synergistic effects of experiments and high-speed camera capturing confirm the correctness of the simulation results.In the experiment,the volume change stroke of the airtight container is set to 20 mm,the volume change frequency is 18 Hz,and the shooting frequency of the high-speed camera is set to 10000 FPS.The experimental results indicate that the position of the cavitation phenomenon has a reasonable law during the whole evolution cycle of the cavitation cloud.Also,the volume alternation cycle corresponds to the generation,development,and collapse stages of cavitation bubbles.展开更多
Drug-loaded microspheres are significant for the development of modern pharmaceutical products. It is well known that the taken of aspirin for long-term increases the risk of serious gastrointestinal complications, th...Drug-loaded microspheres are significant for the development of modern pharmaceutical products. It is well known that the taken of aspirin for long-term increases the risk of serious gastrointestinal complications, therefore a controllable delivery of aspirin is of importance to lighten those side effects. In this work, poly(lactic acid)(PLA) was chosen as the carrier to prepare PLA-aspirin microspheres by using the traditional and the improved solvent evaporation methods. It was found that no matter which experimental condition was, the encapsulation efficiency of aspirin was higher by using the improved method than that of the traditional method. Specifically, when the concentration of polyvinyl alcohol = 1%(mass),the polymer concentration = 1:20, the oil/water rate = 1:2.5, PLA-aspirin microspheres were obtained via the improved method with a high yield of 82.83%(mass) and an encapsulation efficiency of 44.09%. PLAaspirin microspheres were then prepared continuously using the improved method, which further enhanced the encapsulation efficiency to 54.56%. Approximate 85% aspirin released from microspheres within 7 days. Obvious degradation which was represented by reduction on hardness was observed by soaking microspheres in PBS for 60 days. This work is of interest because it provides a continuous route to prepare PLA-aspirin microspheres continuously with a high drug encapsulation efficiency.展开更多
Metal-air batteries face a great challenge in developing efficient and durable low-cost oxygen reduction reaction(ORR)electrocatalysts.Single-atom iron catalysts embedded into nitrogen doped carbon(Fe-N-C)have emerged...Metal-air batteries face a great challenge in developing efficient and durable low-cost oxygen reduction reaction(ORR)electrocatalysts.Single-atom iron catalysts embedded into nitrogen doped carbon(Fe-N-C)have emerged as attractive materials for potential replacement of Pt in ORR,but their catalytic performance was limited by the symmetrical electronic structure distribution around the single-atom Fe site.Here,we report our findings in significantly enhancing the ORR performance of Fe-N-C by moderate Fe_(2)O_(3) integration via the strong electronic interaction.Remarkably,the optimized catalyst(M-Fe_(2)O_(3)/Fe_(SA)@NC)exhibits excellent activity,durability and good tolerance to methanol,outperforming the benchmark Pt/C catalyst.When M-Fe_(2)O_(3)/Fe_(SA)@NC catalyst was used in a practical zinc-air battery assembly,peak power density of 155 mW cm^(-2)and specific capacity of 762 mA h g_(Zn)^(-1)were achieved and the battery assembly has shown superior cycling stability over a period of 200 h.More importantly,theoretical studies suggest that the introduction of Fe_(2)O_(3) can evoke the crystal field alteration and electron redistribution on single Fe atoms,which can break the symmetric charge distribution of Fe-N_(4) and thereby optimize the corresponding adsorption energy of intermediates to promote the O_(2)reduction.This study provides a new pathway to promote the catalytic performance of single-atom catalysts.展开更多
Background:Hippocampal damage caused by status epilepticus(SE)can bring about cognitive decline and emotional disorders,which are common clinical comorbidities in patients with epilepsy.It is therefore imperative to d...Background:Hippocampal damage caused by status epilepticus(SE)can bring about cognitive decline and emotional disorders,which are common clinical comorbidities in patients with epilepsy.It is therefore imperative to develop a novel therapeutic strat-egy for protecting hippocampal damage after SE.Mitochondrial dysfunction is one of contributing factors in epilepsy.Given the therapeutic benefits of mitochondrial replenishment by exogenous mitochondria,we hypothesized that transplantation of mitochondria would be capable of ameliorating hippocampal damage following SE.Methods:Pilocarpine was used to induced SE in mice.SE-generated cognitive de-cline and emotional disorders were determined using novel object recognition,the tail suspension test,and the open field test.SE-induced hippocampal pathology was assessed by quantifying loss of neurons and activation of microglia and astrocytes.The metabolites underlying mitochondrial transplantation were determined using metabonomics.Results:The results showed that peripheral administration of isolated mitochon-dria could improve cognitive deficits and depressive and anxiety-like behaviors.Exogenous mitochondria blunted the production of reactive oxygen species,pro-liferation of microglia and astrocytes,and loss of neurons in the hippocampus.The metabonomic profiles showed that mitochondrial transplantation altered multiple metabolic pathways such as sphingolipid signaling pathway and carbon metabolism.Among potential affected metabolites,mitochondrial transplantation decreased levels of sphingolipid(d18:1/18:0)and methylmalonic acid,and elevated levels of D-fructose-1,6-bisphosphate.Conclusion:To the best of our knowledge,these findings provide the first direct ex-perimental evidence that artificial mitochondrial transplantation is capable of amelio-rating hippocampal damage following SE.These new findings support mitochondrial transplantation as a promising therapeutic strategy for epilepsy-associated psychiat-ric and cognitive disorders.展开更多
The increasing demands for electronic devices to achieve high miniaturization,functional integration,and wide bandwidth will exacerbate the heat generation and electromagnetic interference,which hinders the further de...The increasing demands for electronic devices to achieve high miniaturization,functional integration,and wide bandwidth will exacerbate the heat generation and electromagnetic interference,which hinders the further development of electronic devices.Therefore,both the issues of microwave absorption and heat dissipation of materials need to be addressed simultaneously.Herein,a multifunctional composite material is proposed by periodic arrangement of copper pillars in a matrix,based on the wave-absorbing material.As a result,the equivalent thermal conductivity of the composite structure is nearly 35 times higher than the wave-absorbing matrix,with the area filling proportion of the thermal conductivity material being 3.14%.Meanwhile,the reflectivity of the composite structure merely changes from-15.05 d B to-13.70 d B.It is proved that the designed composite structure possesses both high thermal conduction and strong microwave absorption.The measured results accord well with the simulation results,which demonstrates that the thermal conductivity of the composite structure can reach more than 10 W·m^(-1)·K^(-1)without significant deterioration of the absorption performance.展开更多
文摘The key and bottleneck of research on the tip-jet rotor compound helicopter lies in the power system. Computational Fluid Dynamics (CFD) was used to numerically simulate the gas generator and rotor inner passage of the tip-jet rotor composite power system, studying the effects of intake mode, inner cavity structure, propellant components, and injection amount on the characteristics of the composite power system. The results show that when a single high-temperature exhaust gas enters, the gas generator outlet fluid is uneven and asymmetric;when two-way high-temperature exhaust gas enters, the outlet temperature of the gas generator with a tilted inlet is more uniform than that with a vertical inlet;adding an inner cavity improves the temperature and velocity distribution of the gas generator's internal flow field;increasing the energy of the propellant is beneficial for improving the available moment.
基金supported by the National Natural Science Foundation of China (Grant No.31901989)Natural Science Foundation of Jiangsu Province (Grant No.BK20190534)+1 种基金China Postdoctoral Science Foundation (Grant No.2021T140332)Postgraduate Research&Practice Innovation Program of Jiangsu Province (Grant No.KYCX20_0584)。
文摘The pear is an economic fruit that is widely planted around the world and is loved by people for its rich nutritional value. Autophagy is a self-protection mechanism in eukaryotes, and its occurrence often accompanied by the degradation of damaged substances in cells and the recycling of nutrients. Autophagy is one of the mechanisms through which plants respond to environmental stress and plays an important role in plant development and stress resistance. Functional studies of autophagy-related genes (ATGs) have been performed on a variety of plant species, but little information is available on the ATG family in pear (Pyrus bretschneideri Rehd). Therefore, we analyzed the evolutionary dynamics and performed a genome-wide characterization of the PbrATG gene family. A total of 28 PbrATG members were identified.Phylogenetic analysis showed that PbrATGs were more closely related to ATGs of European pear and apple. Evolutionary analysis revealed that whole-genome duplication (WGD) and dispersed duplication events were the main driving forces of PbrATG family expansion.Expression analysis of different pear tissues showed that all the genes were expressed in different pear tissues, and different PbrATGs are expressed at different times and in different locations. Moreover, all PbrATGs also responded to different abiotic stresses, especially salt and drought stress, which elicited the highest expression levels. Pear seedlings were subsequently infected with Botryosphaeria dothidea (B.dothidea). The results showed that different PbrATGs had different expression patterns at different infection stages. According to the gene expression data, PbrATG1a was selected as a key autophagy gene for further analysis. Silencing of PbrATG1a reduced the resistance of pear to B. dothidea, which resulted in increased lesions, reactive oxygen species (ROS) contents, antioxidant enzyme activity, and gene expression levels in the silenced pear seedlings after B. dothidea inoculation. In this study, a comprehensive bioinformatic analysis of ATGs was conducted, and the functions of PbrATGs in pear development and in response to stress were elucidated, which laid a foundation for further study of the molecular mechanism of autophagy and a new strategy for pear resistance breeding.
基金This work was funded by the National Key Research and Development Program of China(2023YFF1000404)the Shenzhen Basic Research and Development Key Program of China(JCYJ20200109150713553)Hainan Key Research and Development in Modern Agriculture of China(ZDYF2021Y128).
文摘Increasing effective panicle number per plant(EPN)is one approach to increase yield potential in rice.However,molecular mechanisms underlying EPN remain unclear.In this study,we integrated mapbased cloning and genome-wide association analysis to identify the EPN4 gene,which is allelic to NARROW LEAF1(NAL1).Overexpression lines containing the Teqing allele(TQ)of EPN4 had significantly increased EPN.NIL-EPN4^(TQ) in japonica(geng)cultivar Lemont(LT)exhibited significantly improved EPN but decreased grain number and flag leaf size relative to LT.Haplotype analysis indicated that accessions with EPN4-1 had medium EPN,medium grain number,and medium grain weight,but had the highest grain yield among seven haplotypes,indicating that EPN4-1 is an elite haplotype of EPN4 for positive coordination of the three components of grain yield.Furthermore,accessions carrying the combination of EPN4-1 and haplotype GNP1-6 of GNP1 for grain number per panicle showed higher grain yield than those with other allele combinations.Therefore,pyramiding of EPN4-1 and GNP1-6 could be a preferred approach to obtain high yield potential in breeding.
文摘Millimeter-wave systems with high integration level have been rapidly developed to enable modern wireless communication,sensing,and imaging.The millimeter-wave power amplifier(PA)is one of the most challenging and critical components in a millimeter-wave transceiver,it is the last active stage in a transmitter amplifying spectrally efficient complex modulation signal for radiation with high output power.
文摘With the changes in disease spectrum and the popularization of screening of low-dose spiral CT (CT) in the chest, more and more pulmonary nodules have been detected, most of which are bipulmonary multiple nodules. The existence of multiple pulmonary nodules means that it may be a pathological state of benign and malignant co-existence. The origin and evolution of pulmonary nodules in different histopathological states have a great impact on the choice of treatment methods. In recent years, the rise of immunotherapy has brought a breakthrough in the treatment of refractory lung cancer. However, some patients are still ineffective in immunotherapy, which may be related to the immune microenvironment where nodules are proportioned in different components in different pathological states. This review article mainly predicts the development process of nodules by analyzing the origin of multiple pulmonary nodules and the immune microenvironment of nodules in different pathological conditions, so as to provide guidance for clinical treatment.
基金supported by the National Natural Science Foundation of China(No.51674021)the Major Science and Technology Innovation Project of Shandong Province,China(No.2019JZZY010358)。
基金the National Key Research and Development Program of China,No.2017YFC0908104National Science and Technology Projects,No.2017ZX10203201,No.2017ZX10201201,and No.2017ZX10202202.
文摘BACKGROUND Hepatic fibrosis is a serious condition,and the development of hepatic fibrosis can lead to a series of complications.However,the pathogenesis of hepatic fibrosis remains unclear,and effective therapy options are still lacking.Our group identified hepatitis C virus nonstructural protein 3-transactivated protein 1(NS3TP1) by suppressive subtractive hybridization and bioinformatics analysis,but its role in diseases including hepatic fibrosis remains undefined.Therefore,additional studies on the function of NS3TP1 in hepatic fibrosis are urgently needed to provide new targets for treatment.AIM To elucidate the mechanism of NS3TP1 in hepatic fibrosis and the regulatory effects of calcitriol on NS3TP1.METHODS Twenty-four male C57BL/6 mice were randomized and separated into three groups,comprising the normal,fibrosis,and calcitriol treatment groups,and liver fibrosis was modeled by carbon tetrachloride(CCl4).To evaluate the level of hepatic fibrosis in every group,serological and pathological examinations of the liver were conducted.TGF-β1 was administered to boost the in vitro cultivation of LX-2 cells.NS3TP1,α-smooth muscle actin(α-SMA),collagen I,and collagen Ⅲ in every group were examined using a Western blot and real-time quantitative polymerase chain reaction.The activity of the transforming growth factor beta 1(TGFβ1)/Smad3 and NF-κB signaling pathways in each group of cells transfected with pcDNA-NS3TP1 or siRNA-NS3TP1 was detected.The statistical analysis of the data was performed using the Student’s t test.RESULTS NS3TP1 promoted the activation,proliferation,and differentiation of hepatic stellate cells(HSCs)and enhanced hepatic fibrosis via the TGFβ1/Smad3 and NF-κB signaling pathways,as evidenced by the presence of α-SMA,collagen I,collagen Ⅲ,p-smad3,and p-p65 in LX-2 cells,which were upregulated after NS3TP1 overexpression and downregulated after NS3TP1 interference.The proliferation of HSCs was lowered after NS3TP1 interference and elevated after NS3TP1 overexpression,as shown by the luciferase assay.NS3TP1 inhibited the apoptosis of HSCs.Moreover,both Smad3 and p65 could bind to NS3TP1,and p65 increased the promoter activity of NS3TP1,while NS3TP1 increased the promoter activity of TGFβ1 receptor I,as indicated by coimmunoprecipitation and luciferase assay results.Both in vivo and in vitro,treatment with calcitriol dramatically reduced the expression of NS3TP1.Calcitriol therapy-controlled HSCs activation,proliferation,and differentiation and substantially suppressed CCl4-induced hepatic fibrosis in mice.Furthermore,calcitriol modulated the activities of the above signaling pathways via downregulation of NS3TP1.CONCLUSION Our results suggest that calcitriol may be employed as an adjuvant therapy for hepatic fibrosis and that NS3TP1 is a unique,prospective therapeutic target in hepatic fibrosis.
基金Supported by the National Natural Science Foundation of China(No.81900829,No.82070963)the Xiamen Medical and Health Guiding Project Fund Project(No.3502Z20214ZD1214)+1 种基金the Guangdong Basic and Applied Basic Research Foundation(No.2019A1515011234)the Science and Technology Innovation Committee of Shenzhen(No.JCYJ20210324125614039)。
文摘AIM:To evaluate the potential of two trabecular meshwork(TM)-specific promoters,Chitinase 3-like 1(Ch3L1)and matrix gla protein(MGP),for improving specificity and safety in glaucoma gene therapy based on self-complementary AAV2(scAAV2)vector technologies.METHODS:An scAAV2 vector with C3 transferase(C3)as the reporter gene(scAAV2-C3)was selected.The scAAV2-C3 vectors were driven by Ch3L1(scAAV2-Ch3L1-C3),MGP(scAAV2-MGP-C3),enhanced MGP(scAAV2-eMGP-C3)and cytomegalovirus(scAAV2-CMV-C3),respectively.The cultured primary human TM cells were treated with each vector at different multiplicities of infections.Changes in cell morphology were observed by phase contrast microscopy.Actin stress fibers and Rho GTPases/Rho-associated protein kinase pathway-related molecules were assessed by immunofluorescence staining,real-time quantitative polymerase chain reaction and Western blot.Each vector was injected intracamerally into the one eye of each rat at low and high doses respectively.In vivo green fluorescence was visualized by a Micron III Retinal Imaging Microscope.Intraocular pressure(IOP)was monitored using a rebound tonometer.Ocular responses were evaluated by slit-lamp microscopy.Ocular histopathology analysis was examined by hematoxylin and eosin staining.RESULTS:In TM cell culture studies,the vectormediated C3 expression induced morphologic changes,disruption of actin cytoskeleton and reduction of fibronectin expression in TM cells by inhibiting the Rho GTPases/Rhoassociated protein kinase signaling pathway.At the same dose,these changes were significant in TM cells treated with scAAV2-CMV-C3 or scAAV2-Ch3L1-C3,but not in cells treated with scAAV2-eMGP-C3 or scAAV2-MGP-C3.At lowinjected dose,the IOP was significantly decreased in the scAAV2-Ch3L1-C3-injected eyes but not in scAAV2-MGPC3-injected and scAAV2-eMGP-C3-injected eyes.At highinjected dose,significant IOP reduction was observed in the scAAV2-eMGP-C3-injected eyes but not in scAAV2-MGP-C3-injected eyes.Similar to scAAV2-CMV-C3,scAAV2-Ch3L1-C3 vector showed efficient transduction both in the TM and corneal endothelium.In anterior segment tissues of scAAV2-eMGP-C3-injected eyes,no obvious morphological changes were found except for the TM.Inflammation was absent.CONCLUSION:In scAAV2-transduced TM cells,the promoter-driven efficiency of Ch3L1 is close to that of cytomegalovirus,but obviously higher than that of MGP.In the anterior chamber of rat eye,the transgene expression pattern of scAAV2 vector is presumably affected by MGP promoter,but not by Ch3L1 promoter.These findings would provide a useful reference for improvement of specificity and safety in glaucoma gene therapy using scAAV2 vector.
基金Supported by National Nature Science Foundation of China(Grant No.51575245)Jiangsu Provincial Key research and development program(Grant No.BE2015134)Zhenjiang Municipal Key Research and Development Project(Grant No.KZ2020001).
文摘Cavitation generation methods have been used in multifarious directions because of their diversity,and numerous studies and discussions have been conducted on cavitation generation methods.This study aims to explore the generating mechanism and evolution law of volume alternate cavitation(VAC).In the VAC,liquid water is placed in an airtight container with a variable volume.As the volume alternately changes,the liquid water inside the container continues to cavitate.Then,the mixture turbulence model and in-cylinder dynamic grid model are adopted to conduct computational fluid dynamics simulation of volume alternate cavitation.In the simulation,the cloud images at seven heights on the central axis are monitored,and the phenomenon and mechanism of height and eccentricity are analyzed in detail.By employing the cavitation flow visualization method,the generating mechanism and evolution law of cavitation are revealed.The synergistic effects of experiments and high-speed camera capturing confirm the correctness of the simulation results.In the experiment,the volume change stroke of the airtight container is set to 20 mm,the volume change frequency is 18 Hz,and the shooting frequency of the high-speed camera is set to 10000 FPS.The experimental results indicate that the position of the cavitation phenomenon has a reasonable law during the whole evolution cycle of the cavitation cloud.Also,the volume alternation cycle corresponds to the generation,development,and collapse stages of cavitation bubbles.
基金financially supported by National Natural Science Foundation of China (22068018)Yunnan Ten Thousand Talents Plan Young & Elite Talents Project。
文摘Drug-loaded microspheres are significant for the development of modern pharmaceutical products. It is well known that the taken of aspirin for long-term increases the risk of serious gastrointestinal complications, therefore a controllable delivery of aspirin is of importance to lighten those side effects. In this work, poly(lactic acid)(PLA) was chosen as the carrier to prepare PLA-aspirin microspheres by using the traditional and the improved solvent evaporation methods. It was found that no matter which experimental condition was, the encapsulation efficiency of aspirin was higher by using the improved method than that of the traditional method. Specifically, when the concentration of polyvinyl alcohol = 1%(mass),the polymer concentration = 1:20, the oil/water rate = 1:2.5, PLA-aspirin microspheres were obtained via the improved method with a high yield of 82.83%(mass) and an encapsulation efficiency of 44.09%. PLAaspirin microspheres were then prepared continuously using the improved method, which further enhanced the encapsulation efficiency to 54.56%. Approximate 85% aspirin released from microspheres within 7 days. Obvious degradation which was represented by reduction on hardness was observed by soaking microspheres in PBS for 60 days. This work is of interest because it provides a continuous route to prepare PLA-aspirin microspheres continuously with a high drug encapsulation efficiency.
基金supported by the Australian Research Council Australian Laureate Fellowship(No.FL200100049)the support of Natural Science Foundation for Young Scholars of Jiangsu Province(No.BK20220879)+1 种基金National Natural Science Foundation for Young Scholars of China(No.22209072)Monash University for a PhD scholarship as part of the university support for establishment of the ARC Research Hub for Energy-efficient Separation(H170100009)。
文摘Metal-air batteries face a great challenge in developing efficient and durable low-cost oxygen reduction reaction(ORR)electrocatalysts.Single-atom iron catalysts embedded into nitrogen doped carbon(Fe-N-C)have emerged as attractive materials for potential replacement of Pt in ORR,but their catalytic performance was limited by the symmetrical electronic structure distribution around the single-atom Fe site.Here,we report our findings in significantly enhancing the ORR performance of Fe-N-C by moderate Fe_(2)O_(3) integration via the strong electronic interaction.Remarkably,the optimized catalyst(M-Fe_(2)O_(3)/Fe_(SA)@NC)exhibits excellent activity,durability and good tolerance to methanol,outperforming the benchmark Pt/C catalyst.When M-Fe_(2)O_(3)/Fe_(SA)@NC catalyst was used in a practical zinc-air battery assembly,peak power density of 155 mW cm^(-2)and specific capacity of 762 mA h g_(Zn)^(-1)were achieved and the battery assembly has shown superior cycling stability over a period of 200 h.More importantly,theoretical studies suggest that the introduction of Fe_(2)O_(3) can evoke the crystal field alteration and electron redistribution on single Fe atoms,which can break the symmetric charge distribution of Fe-N_(4) and thereby optimize the corresponding adsorption energy of intermediates to promote the O_(2)reduction.This study provides a new pathway to promote the catalytic performance of single-atom catalysts.
基金the National Natural Science Foundation of China(Grant No.82173803,81872847).
文摘Background:Hippocampal damage caused by status epilepticus(SE)can bring about cognitive decline and emotional disorders,which are common clinical comorbidities in patients with epilepsy.It is therefore imperative to develop a novel therapeutic strat-egy for protecting hippocampal damage after SE.Mitochondrial dysfunction is one of contributing factors in epilepsy.Given the therapeutic benefits of mitochondrial replenishment by exogenous mitochondria,we hypothesized that transplantation of mitochondria would be capable of ameliorating hippocampal damage following SE.Methods:Pilocarpine was used to induced SE in mice.SE-generated cognitive de-cline and emotional disorders were determined using novel object recognition,the tail suspension test,and the open field test.SE-induced hippocampal pathology was assessed by quantifying loss of neurons and activation of microglia and astrocytes.The metabolites underlying mitochondrial transplantation were determined using metabonomics.Results:The results showed that peripheral administration of isolated mitochon-dria could improve cognitive deficits and depressive and anxiety-like behaviors.Exogenous mitochondria blunted the production of reactive oxygen species,pro-liferation of microglia and astrocytes,and loss of neurons in the hippocampus.The metabonomic profiles showed that mitochondrial transplantation altered multiple metabolic pathways such as sphingolipid signaling pathway and carbon metabolism.Among potential affected metabolites,mitochondrial transplantation decreased levels of sphingolipid(d18:1/18:0)and methylmalonic acid,and elevated levels of D-fructose-1,6-bisphosphate.Conclusion:To the best of our knowledge,these findings provide the first direct ex-perimental evidence that artificial mitochondrial transplantation is capable of amelio-rating hippocampal damage following SE.These new findings support mitochondrial transplantation as a promising therapeutic strategy for epilepsy-associated psychiat-ric and cognitive disorders.
文摘The increasing demands for electronic devices to achieve high miniaturization,functional integration,and wide bandwidth will exacerbate the heat generation and electromagnetic interference,which hinders the further development of electronic devices.Therefore,both the issues of microwave absorption and heat dissipation of materials need to be addressed simultaneously.Herein,a multifunctional composite material is proposed by periodic arrangement of copper pillars in a matrix,based on the wave-absorbing material.As a result,the equivalent thermal conductivity of the composite structure is nearly 35 times higher than the wave-absorbing matrix,with the area filling proportion of the thermal conductivity material being 3.14%.Meanwhile,the reflectivity of the composite structure merely changes from-15.05 d B to-13.70 d B.It is proved that the designed composite structure possesses both high thermal conduction and strong microwave absorption.The measured results accord well with the simulation results,which demonstrates that the thermal conductivity of the composite structure can reach more than 10 W·m^(-1)·K^(-1)without significant deterioration of the absorption performance.
