Agrobacterium-mediated plant transformation is widely used in plant genetic engineering.However,its efficiency is limited by plant immunity against Agrobacterium.Chili pepper(Capsicum annuum L.)is an important vegetab...Agrobacterium-mediated plant transformation is widely used in plant genetic engineering.However,its efficiency is limited by plant immunity against Agrobacterium.Chili pepper(Capsicum annuum L.)is an important vegetable that is recalcitrant to Agrobacterium-mediated transformation.In this work,Agrobacterium was found to induce a strong immune response in pepper,which might be the reason for T-DNA being difficult to express in pepper.An Agrobacterium mutant screen was conducted and a point mutation in the hisI gene was identified due to a weak immune response and enhanced transient expression mediated by this Agrobacterium mutant in pepper leaves.Further genetic analysis revealed that histidine biosynthesis deficiency caused by mutations in many genes of this pathway led to reduced pepper cell death,presumably due to reduced bacterial growth.However,mutation analysis of threonine and tryptophan biosynthesis genes showed that the biosynthesis of different amino acids may play different roles in Agrobacterium growth and stimulating the pepper immune response.The possible application of Agrobacterium amino acid biosynthesis mutations in plant biology was discussed.展开更多
For a single machine infinite power system with thyristor controlled series compensation(TCSC) device, which is affected by system model uncertainties, nonlinear time-delays and external unknown disturbances, we prese...For a single machine infinite power system with thyristor controlled series compensation(TCSC) device, which is affected by system model uncertainties, nonlinear time-delays and external unknown disturbances, we present a robust adaptive backstepping control scheme based on the radial basis function neural network(RBFNN). The RBFNN is introduced to approximate the complex nonlinear function involving uncertainties and external unknown disturbances, and meanwhile a new robust term is constructed to further estimate the system residual error,which removes the requirement of knowing the upper bound of the disturbances and uncertainty terms. The stability analysis of the power system is presented based on the Lyapunov function,which can guarantee the uniform ultimate boundedness(UUB) of all parameters and states of the whole closed-loop system. A comparison is made between the RBFNN-based robust adaptive control and the general backstepping control in the simulation part to verify the effectiveness of the proposed control scheme.展开更多
Objective The objective of this study was to identify new carcinogenetic hub genes and develop the integration of differentially expressed genes to predict the prognosis of lung cancer.Methods GSE139032 microarray dat...Objective The objective of this study was to identify new carcinogenetic hub genes and develop the integration of differentially expressed genes to predict the prognosis of lung cancer.Methods GSE139032 microarray data packages were downloaded from the Gene Expression Omnibus for planning,testing,and review of data.We identified KRT6C,LAMC2,LAMB3,KRT6A,and MYEOV from a key module for validation.Results We found that the five genes were related to a poor prognosis,and the expression levels of these genes were associated with tumor stage.Furthermore,Kaplan-Meier plotter showed that the five hub genes had better prognostic values.The mean levels of methylation in lung adenocarcinoma(LUAD)were significantly lower than those in healthy lung tissues for the hub genes.However,gene set enrichment analysis(GSEA)for single hub genes showed that all of them were immune-related.Conclusion Our findings demonstrated that KRT6C,LAMC2,LAMB3,KRT6A,and MYEOV are all candidate diagnostic and prognostic biomarkers for LUAD.They may have clinical implications in LUAD patients not only for the improvement of risk stratification but also for therapeutic decisions and prognosis prediction.展开更多
Objective Neurotrophin 3(NTF3)is involved in numerous biological processes;however,its role in hepatocellular carcinoma(HCC)is not well studied.This study investigated NTF3 function in HCC progression and revealed its...Objective Neurotrophin 3(NTF3)is involved in numerous biological processes;however,its role in hepatocellular carcinoma(HCC)is not well studied.This study investigated NTF3 function in HCC progression and revealed its underlying molecular mechanisms.Methods The prognostic relevance of NTF3 was determined through a bioinformatical analysis of publicly available TCGA data.Immunohistochemistry of HCC biopsies was performed to explore the expression of NTF3.Cell growth and proliferation were analyzed using a Cell Counting Kit-8(CCK-8)assay.Cell invasion and migration were analyzed using Boyden Transwell and wound healing assays.Protein expression and mRNA levels were evaluated through immunoblotting and quantitative polymerase chain reaction(qPCR).Cell apoptosis was evaluated with flow cytometry.Results NTF3 expression was significantly lower in HCC tissues than in adjacent non-tumor tissues.Low NTF3 expression was significantly associated with decreased patient survival and specific clinicopathological features.NTF3 overexpression reduced the proliferation,migration,and invasion abilities of HCC cell lines.Conclusion Decreased expression of NTF3 is associated with poor prognosis in HCC patients,likely due to its action in promoting HCC cell proliferation,migration,and invasion.Our findings provide a novel understanding into the pathogenesis of HCC and the role of NTF3 in tumor progression,suggesting that targeting NTF3 has potential therapeutic and diagnostic value for HCC.展开更多
Anaerobic digestion is one of the effective ways to dispose of antibiotic pharmaceutical waste. However,the inhibition of antibiotics on anaerobic fermentation microorganisms seriously hinders the normal physiological...Anaerobic digestion is one of the effective ways to dispose of antibiotic pharmaceutical waste. However,the inhibition of antibiotics on anaerobic fermentation microorganisms seriously hinders the normal physiological activities of anaerobic microorganisms and then affects the efficiency of anaerobic digestion. In order to solve this problem,related scholars have done a lot of research. It has been found that pretreatment of anaerobic microorganisms and antibiotic pharmaceutical waste can significantly improve the efficiency of anaerobic digestion. In this paper,the current feasible pretreatment methods were summarized,and the application of different pretreatment methods was analyzed to provide reference for improving pretreatment methods and improving anaerobic biological treatment ability of antibiotic waste.展开更多
Medical images are important for medical research and clinical diagnosis.The research of medical images includes image acquisition,processing,analysis and other related research fields.Crowdsourcing is attracting grow...Medical images are important for medical research and clinical diagnosis.The research of medical images includes image acquisition,processing,analysis and other related research fields.Crowdsourcing is attracting growing interests in recent years as an effective tool.It can harness human intelligence to solve problems that computers cannot perform well,such as sentiment analysis and image recognition.Crowdsourcing can achieve higher accuracies in medical image classification,but it cannot be widely used for its low efficiency and the monetary cost.We adopt a hybrid approach which combines computer’s algorithm and crowdsourcing system for image classification.Medical image classification algorithms have a high error rate near the threshold.And it is not significant by improving these classification algorithms to achieve a higher accuracy.To address the problem,we propose a hybrid framework,which can achieve a higher accuracy significantly than only use classification algorithms.At the same time,it only processes the images that classification algorithms perform not well,so it has a lower monetary cost.In the framework,we device an effective algorithm to generate a range-threshold that assign images to crowdsourcing or classification algorithm.Experimental results show that our method can improve the accuracy of medical images classification and reduce the crowdsourcing monetary cost.展开更多
This study is carried out to promote the precise supervision of dangerous goods transportation training,improve the efficiency of civil aviation supervision and further ensure the safety of air transportation.First,fr...This study is carried out to promote the precise supervision of dangerous goods transportation training,improve the efficiency of civil aviation supervision and further ensure the safety of air transportation.First,from the perspective of behaviour interaction and interest demands,evolutionary game theory is used to construct a tripartite evolutionary game model of dangerous goods transportation training institutions,the Civil Aviation Administration of China(CAAC)and the public.Then,the evolutionary game equilibrium of the system is further analysed under the joint action of the three parties.Finally,the influences of important parameters of the model on the behavioural strategy selection of the three parties are investigated via MATLAB numerical simulation.The conclusions reveal that the system has three evolutionarily stable strategies under different parameters,namely(non-compliant training,supervision,non-participation in supervision),(non-compliant training,supervision,participation in supervision)and(compliant training,supervision,non-participation in supervision).Moreover,the CAAC supervision cost,the fine amount,the supervision cost of public participation,the supervision success rate and the reporting reward amount are the main parameters that affect the behavioural strategy selection of the tripartite game players.The conclusions and suggestions of this study provide a decision-making basis and guidance for the supervision and management of civil aviation dangerous goods transportation training.展开更多
To the Editor:Male breast cancer is relatively rare,accounting for just 1%of all breast cancer cases.[1]The management strategies for male breast cancer are mainly based on a limited number of retrospective studies an...To the Editor:Male breast cancer is relatively rare,accounting for just 1%of all breast cancer cases.[1]The management strategies for male breast cancer are mainly based on a limited number of retrospective studies and speculation based on female breast cancer.This study presents a comprehensive account of a decade-long observation of male metastatic breast cancer(mMBC)in our institution.The Affiliated Cancer Hospital of Zhengzhou University database had records of 2853 advanced breast cancer cases that were treated from January 1,2010 to December 31,2019.Out of the total number,18 cases were identified as mMBC.The analysis encompassed data about the treatment administered,the treatment’s effectiveness,and the patient’s survival outcomes.The present investigation entails a retrospective examination of our institution’s 10-year experience with patients diagnosed with mMBC and a comprehensive evaluation of relevant literature.展开更多
Hypertension is the leading risk factor for death and disability, and hypertensive patients always need long-term oral antihypertensive drugs. Some bioactive peptides that extracted from animals or plants have shown e...Hypertension is the leading risk factor for death and disability, and hypertensive patients always need long-term oral antihypertensive drugs. Some bioactive peptides that extracted from animals or plants have shown excellent advantages on antihypertension. However, the oral delivery of these peptides is always failure on account of instability and poor absorption in the gastrointestinal tract. Herein, we developed a core-shell lipid-polymeric nanoparticle for oral delivery of a highly efficient antihypertensive peptide KY5(KY5-CSs). KY5-CSs had a particle size of 216.7 ± 2.5 nm, with a narrow PDI of 0.07 ± 0.01.The zeta potential was-4.1 ± 0.1 m V. It exhibited good stability in 4 ℃ and possessed a controlled release behavior in gastrointestinal tract. The cellular uptake study proved that the lipid shell imparted unique capability of permeation across the mucus layer and internalization by Caco-2/HT-29 cells. In addition, KY5-CSs enhanced in situ intestinal absorption in SD rats. The pharmacokinetic studies and antihypertensive efficacy showed a superior oral absorption and antihypertensive effect of KY5-CSs than KY5-NPs. In conclusion, the core-shell lipid-polymeric nanoparticles will provide attractive potential for oral delivery of antihypertensive peptides.展开更多
Recent evidence indicates that artesunate has immunomodulatory properties that might be useful for treating autoimmune disease.In this study,we conducted a pilot study and explored the effect and mechanism of artesuna...Recent evidence indicates that artesunate has immunomodulatory properties that might be useful for treating autoimmune disease.In this study,we conducted a pilot study and explored the effect and mechanism of artesunate on the treatment of systemic lupus erythematosus using an MRL/lpr murine model.MRL/lpr mice were divided into control,cyclophosphamide(CTX)and artesunate treatment groups.Blood was collected to measure serum levels of creatinine,antinuclear antibody(ANA)and anti-double-stranded DNA(anti-dsDNA)antibody.Twenty-four-hour urine was collected to measure levels of proteinuria.The concentration of monocyte chemotactic protein-1(MCP-1)in serum and urine was measured.The expression of MCP-1 in kidney was detected by Western blot and immunohistochemistry assay,respectively.The expression of B cell activating factor(BAFF)in spleen was determined by real time-PCR and immunoblotting.We found that artesunate significantly increased the survival rate,body weight and blood leukocyte counts,and reduced the serum levels of ANA and anti-dsDNA antibody titer,24 h urinary protein,and serum creatinine.Our results indicated that artesunate could decrease MCP-1,major pro-inflammation cytokine,in serum,urine and kidney.We also found that the level of BAFF,the major B cell activation factor,was decreased in artesunate treated MRL/lpr mice.Its efficacy was comparable with that of CTX in this study.Taken together,we have demonstrated that artesunate can inhibit the progression of disease and reverse the pathologic lesion of lupus nephritis.展开更多
The rigidity of nanoparticles was newly reported to influence their oral delivery.Semi-elastic nanoparticles can enhance the penetration in mucus and uptake by epithelial cells.However,it is still challenging and uncl...The rigidity of nanoparticles was newly reported to influence their oral delivery.Semi-elastic nanoparticles can enhance the penetration in mucus and uptake by epithelial cells.However,it is still challenging and unclear that the semi-elastic core-shell nanoparticles can enhance the oral bioavailability of peptide drugs.This study was for the first time to validate the semi-elastic coreshell poly(lactic-co-glycolic acid)(PLGA)-lipid nanoparticles(LNPs)as the carrier of the oral peptide drug.The antihypertensive peptide Val-Leu-Pro-Val-Pro(VP5)loaded LNPs(VP5-LNPs)were prepared by a modified thin-film ultrasonic dispersion method.Uptake experiment was performed in Caco-2 and HT-29 cells and monito red by high content screening(HCS)and flow cyto metric(FCM).Pharmacokinetics of VP5-LNPs was carried out in Sprague-Dawley(SD)rats and analyzed by DAS 2.0.The optimal VP5-LNPs had an average particle size of 247.3±3.8 nm,zeta potential of-6.57±0.45 mV and excellent entrapment efficiency(EE)of 89.88%±1.23%.Transmission electron microscope(TEM)and Differential scanning calorimeter(DSC)further confirmed the core-shell structure.VP5-LNPs could increase the cellular uptake in vitro and have a 2.55-fold increase in AUC0-72 h,indicating a great promotion of the o ral bioavailability.The semi-elastic LNPs remarkably improved the oral availability of peptide and could be a promising oral peptide delivery system for peptide drugs in the future.展开更多
Background::Re-biopsy of metastasis in advanced breast cancer(ABC)has become an international convention to assist the diagnosis and evaluation of tumor heterogeneity.This study aimed to detect diagnostic diversity an...Background::Re-biopsy of metastasis in advanced breast cancer(ABC)has become an international convention to assist the diagnosis and evaluation of tumor heterogeneity.This study aimed to detect diagnostic diversity and inconsistencies among estrogen receptor(ER),progesterone receptor(PR),and human epidermal growth factor receptor 2(HER2)expression levels between primary and metastatic lesions.Methods::We conducted a retrospective analysis of 1670 cases of ABC patients who had undergone at least one lesion re-biopsy from January 2010 to December 2018.The pathological diagnosis of biopsies,distribution of biopsy sites,and severe puncture complications at each site were collected.In addition,the inconsistency rates and related factors of ER,PR,and HER2 expression between primary and metastatic lesions were analyzed fully considering patients’demographic profiles and disease characteristics.Results::In total,1670 cases of breast cancer(BC)patients diagnosed by pathology underwent one to four biopsies of recurrences or metastases in different sites or at different stages during the rescue treatment,producing 2019 histopathological specimens which were analyzed in the study.Pathological diagnosis showed that eight patients had benign pathological diagnoses,11 patients had second primary malignant tumors but without recurrences of breast cancer,and 17 patients had pathologically confirmed breast cancer recurrences combined with second primary cancer.In 1173 patients who presented ER,PR,and HER2 expressions in primary and metastatic lesions,the inconsistency rates of ER,PR,and HER2 were 17.5%(205/1173),31.3%(367/1173),and 13.9%(163/1173),respectively.The multivariate analysis showed that the age at the onset of breast cancer or adjuvant endocrine therapy was an independent factor affecting changes in PR expression level.Except one liver puncture with local hemorrhage and two lung punctures with hemopneumothorax,no other severe puncture complications occurred in 1950 non-surgical rebiopsies.Conclusions::The pathological diagnosis of metastasis re-biopsy of ABC was diverse,and the ER,PR,and HER2 expression levels were inconsistent between primary and metastatic lesions.Therefore,more attention should be paid to perform biopsies of relapsed and metastatic breast cancers routinely in clinical practice.展开更多
基金supported by the National Key Research and Development Program of China(Grant No.2018YFD1000800)National Natural Science Foundation of China(Grant No.32172600)。
文摘Agrobacterium-mediated plant transformation is widely used in plant genetic engineering.However,its efficiency is limited by plant immunity against Agrobacterium.Chili pepper(Capsicum annuum L.)is an important vegetable that is recalcitrant to Agrobacterium-mediated transformation.In this work,Agrobacterium was found to induce a strong immune response in pepper,which might be the reason for T-DNA being difficult to express in pepper.An Agrobacterium mutant screen was conducted and a point mutation in the hisI gene was identified due to a weak immune response and enhanced transient expression mediated by this Agrobacterium mutant in pepper leaves.Further genetic analysis revealed that histidine biosynthesis deficiency caused by mutations in many genes of this pathway led to reduced pepper cell death,presumably due to reduced bacterial growth.However,mutation analysis of threonine and tryptophan biosynthesis genes showed that the biosynthesis of different amino acids may play different roles in Agrobacterium growth and stimulating the pepper immune response.The possible application of Agrobacterium amino acid biosynthesis mutations in plant biology was discussed.
基金supported in part by the National Natural Science Foundation of China(61433004,61703289)
文摘For a single machine infinite power system with thyristor controlled series compensation(TCSC) device, which is affected by system model uncertainties, nonlinear time-delays and external unknown disturbances, we present a robust adaptive backstepping control scheme based on the radial basis function neural network(RBFNN). The RBFNN is introduced to approximate the complex nonlinear function involving uncertainties and external unknown disturbances, and meanwhile a new robust term is constructed to further estimate the system residual error,which removes the requirement of knowing the upper bound of the disturbances and uncertainty terms. The stability analysis of the power system is presented based on the Lyapunov function,which can guarantee the uniform ultimate boundedness(UUB) of all parameters and states of the whole closed-loop system. A comparison is made between the RBFNN-based robust adaptive control and the general backstepping control in the simulation part to verify the effectiveness of the proposed control scheme.
基金Supported by a grant from the Chinese Society of Clinical Oncology(No.Y-HR2018-293 and Y-HR2018-294).
文摘Objective The objective of this study was to identify new carcinogenetic hub genes and develop the integration of differentially expressed genes to predict the prognosis of lung cancer.Methods GSE139032 microarray data packages were downloaded from the Gene Expression Omnibus for planning,testing,and review of data.We identified KRT6C,LAMC2,LAMB3,KRT6A,and MYEOV from a key module for validation.Results We found that the five genes were related to a poor prognosis,and the expression levels of these genes were associated with tumor stage.Furthermore,Kaplan-Meier plotter showed that the five hub genes had better prognostic values.The mean levels of methylation in lung adenocarcinoma(LUAD)were significantly lower than those in healthy lung tissues for the hub genes.However,gene set enrichment analysis(GSEA)for single hub genes showed that all of them were immune-related.Conclusion Our findings demonstrated that KRT6C,LAMC2,LAMB3,KRT6A,and MYEOV are all candidate diagnostic and prognostic biomarkers for LUAD.They may have clinical implications in LUAD patients not only for the improvement of risk stratification but also for therapeutic decisions and prognosis prediction.
基金Supported by grants from the National Natural Science Foundation of China(No.ZR2015HM025)Technology Development Program of Shandong Province,China(No.2011YD18003)CSCO-Hengrui Cancer Research Fund(No.Y-HR2018-293 and Y-HR2018-294).
文摘Objective Neurotrophin 3(NTF3)is involved in numerous biological processes;however,its role in hepatocellular carcinoma(HCC)is not well studied.This study investigated NTF3 function in HCC progression and revealed its underlying molecular mechanisms.Methods The prognostic relevance of NTF3 was determined through a bioinformatical analysis of publicly available TCGA data.Immunohistochemistry of HCC biopsies was performed to explore the expression of NTF3.Cell growth and proliferation were analyzed using a Cell Counting Kit-8(CCK-8)assay.Cell invasion and migration were analyzed using Boyden Transwell and wound healing assays.Protein expression and mRNA levels were evaluated through immunoblotting and quantitative polymerase chain reaction(qPCR).Cell apoptosis was evaluated with flow cytometry.Results NTF3 expression was significantly lower in HCC tissues than in adjacent non-tumor tissues.Low NTF3 expression was significantly associated with decreased patient survival and specific clinicopathological features.NTF3 overexpression reduced the proliferation,migration,and invasion abilities of HCC cell lines.Conclusion Decreased expression of NTF3 is associated with poor prognosis in HCC patients,likely due to its action in promoting HCC cell proliferation,migration,and invasion.Our findings provide a novel understanding into the pathogenesis of HCC and the role of NTF3 in tumor progression,suggesting that targeting NTF3 has potential therapeutic and diagnostic value for HCC.
基金Supported by 2017 Innovation Project of Jilin Academy of Agricultural Sciences(c72083203)
文摘Anaerobic digestion is one of the effective ways to dispose of antibiotic pharmaceutical waste. However,the inhibition of antibiotics on anaerobic fermentation microorganisms seriously hinders the normal physiological activities of anaerobic microorganisms and then affects the efficiency of anaerobic digestion. In order to solve this problem,related scholars have done a lot of research. It has been found that pretreatment of anaerobic microorganisms and antibiotic pharmaceutical waste can significantly improve the efficiency of anaerobic digestion. In this paper,the current feasible pretreatment methods were summarized,and the application of different pretreatment methods was analyzed to provide reference for improving pretreatment methods and improving anaerobic biological treatment ability of antibiotic waste.
文摘Medical images are important for medical research and clinical diagnosis.The research of medical images includes image acquisition,processing,analysis and other related research fields.Crowdsourcing is attracting growing interests in recent years as an effective tool.It can harness human intelligence to solve problems that computers cannot perform well,such as sentiment analysis and image recognition.Crowdsourcing can achieve higher accuracies in medical image classification,but it cannot be widely used for its low efficiency and the monetary cost.We adopt a hybrid approach which combines computer’s algorithm and crowdsourcing system for image classification.Medical image classification algorithms have a high error rate near the threshold.And it is not significant by improving these classification algorithms to achieve a higher accuracy.To address the problem,we propose a hybrid framework,which can achieve a higher accuracy significantly than only use classification algorithms.At the same time,it only processes the images that classification algorithms perform not well,so it has a lower monetary cost.In the framework,we device an effective algorithm to generate a range-threshold that assign images to crowdsourcing or classification algorithm.Experimental results show that our method can improve the accuracy of medical images classification and reduce the crowdsourcing monetary cost.
基金This study was supported by the Central University Basic Scientific Research Fund Program of Civil Aviation University of China(Grant No.3122022037).
文摘This study is carried out to promote the precise supervision of dangerous goods transportation training,improve the efficiency of civil aviation supervision and further ensure the safety of air transportation.First,from the perspective of behaviour interaction and interest demands,evolutionary game theory is used to construct a tripartite evolutionary game model of dangerous goods transportation training institutions,the Civil Aviation Administration of China(CAAC)and the public.Then,the evolutionary game equilibrium of the system is further analysed under the joint action of the three parties.Finally,the influences of important parameters of the model on the behavioural strategy selection of the three parties are investigated via MATLAB numerical simulation.The conclusions reveal that the system has three evolutionarily stable strategies under different parameters,namely(non-compliant training,supervision,non-participation in supervision),(non-compliant training,supervision,participation in supervision)and(compliant training,supervision,non-participation in supervision).Moreover,the CAAC supervision cost,the fine amount,the supervision cost of public participation,the supervision success rate and the reporting reward amount are the main parameters that affect the behavioural strategy selection of the tripartite game players.The conclusions and suggestions of this study provide a decision-making basis and guidance for the supervision and management of civil aviation dangerous goods transportation training.
文摘To the Editor:Male breast cancer is relatively rare,accounting for just 1%of all breast cancer cases.[1]The management strategies for male breast cancer are mainly based on a limited number of retrospective studies and speculation based on female breast cancer.This study presents a comprehensive account of a decade-long observation of male metastatic breast cancer(mMBC)in our institution.The Affiliated Cancer Hospital of Zhengzhou University database had records of 2853 advanced breast cancer cases that were treated from January 1,2010 to December 31,2019.Out of the total number,18 cases were identified as mMBC.The analysis encompassed data about the treatment administered,the treatment’s effectiveness,and the patient’s survival outcomes.The present investigation entails a retrospective examination of our institution’s 10-year experience with patients diagnosed with mMBC and a comprehensive evaluation of relevant literature.
基金supported by the Youth Fund of National Natural Science Foundation of China (No. 82104081)the Science and Technology Project of Shenzhen (No. JCYJ20170413155047512)+2 种基金the 1.3.5 project for disciplines of excellence,West China Hospital,Sichuan University (No. ZYGD18020/ZYJC18006)the Sichuan Province Science and Technology Support Program (No. 2020JDRC0052)the Science and Technology Project of Xinjiang Production and Construction Corps (No. 2022AB020)。
文摘Hypertension is the leading risk factor for death and disability, and hypertensive patients always need long-term oral antihypertensive drugs. Some bioactive peptides that extracted from animals or plants have shown excellent advantages on antihypertension. However, the oral delivery of these peptides is always failure on account of instability and poor absorption in the gastrointestinal tract. Herein, we developed a core-shell lipid-polymeric nanoparticle for oral delivery of a highly efficient antihypertensive peptide KY5(KY5-CSs). KY5-CSs had a particle size of 216.7 ± 2.5 nm, with a narrow PDI of 0.07 ± 0.01.The zeta potential was-4.1 ± 0.1 m V. It exhibited good stability in 4 ℃ and possessed a controlled release behavior in gastrointestinal tract. The cellular uptake study proved that the lipid shell imparted unique capability of permeation across the mucus layer and internalization by Caco-2/HT-29 cells. In addition, KY5-CSs enhanced in situ intestinal absorption in SD rats. The pharmacokinetic studies and antihypertensive efficacy showed a superior oral absorption and antihypertensive effect of KY5-CSs than KY5-NPs. In conclusion, the core-shell lipid-polymeric nanoparticles will provide attractive potential for oral delivery of antihypertensive peptides.
基金The study was supported by grants from Chinese National Natural Science Foundation(No.30972736)Chinese National 115 Supporting Program(2008BAI59B02)+2 种基金Jiangsu Province 135 Talent Foundation(RC2007002)Jiangsu Province Natural Science Foundation(No.09KJB320010)The Six Projects Sponsoring Talent Summits of Jiangsu Province.
文摘Recent evidence indicates that artesunate has immunomodulatory properties that might be useful for treating autoimmune disease.In this study,we conducted a pilot study and explored the effect and mechanism of artesunate on the treatment of systemic lupus erythematosus using an MRL/lpr murine model.MRL/lpr mice were divided into control,cyclophosphamide(CTX)and artesunate treatment groups.Blood was collected to measure serum levels of creatinine,antinuclear antibody(ANA)and anti-double-stranded DNA(anti-dsDNA)antibody.Twenty-four-hour urine was collected to measure levels of proteinuria.The concentration of monocyte chemotactic protein-1(MCP-1)in serum and urine was measured.The expression of MCP-1 in kidney was detected by Western blot and immunohistochemistry assay,respectively.The expression of B cell activating factor(BAFF)in spleen was determined by real time-PCR and immunoblotting.We found that artesunate significantly increased the survival rate,body weight and blood leukocyte counts,and reduced the serum levels of ANA and anti-dsDNA antibody titer,24 h urinary protein,and serum creatinine.Our results indicated that artesunate could decrease MCP-1,major pro-inflammation cytokine,in serum,urine and kidney.We also found that the level of BAFF,the major B cell activation factor,was decreased in artesunate treated MRL/lpr mice.Its efficacy was comparable with that of CTX in this study.Taken together,we have demonstrated that artesunate can inhibit the progression of disease and reverse the pathologic lesion of lupus nephritis.
基金financially supported by the Science and Technology Project of Shenzhen(No.JCYJ20170413155047512)Scientific Research Foundation of the Science and Technology Department of Sichuan Province,China(No.2018JY0143)。
文摘The rigidity of nanoparticles was newly reported to influence their oral delivery.Semi-elastic nanoparticles can enhance the penetration in mucus and uptake by epithelial cells.However,it is still challenging and unclear that the semi-elastic core-shell nanoparticles can enhance the oral bioavailability of peptide drugs.This study was for the first time to validate the semi-elastic coreshell poly(lactic-co-glycolic acid)(PLGA)-lipid nanoparticles(LNPs)as the carrier of the oral peptide drug.The antihypertensive peptide Val-Leu-Pro-Val-Pro(VP5)loaded LNPs(VP5-LNPs)were prepared by a modified thin-film ultrasonic dispersion method.Uptake experiment was performed in Caco-2 and HT-29 cells and monito red by high content screening(HCS)and flow cyto metric(FCM).Pharmacokinetics of VP5-LNPs was carried out in Sprague-Dawley(SD)rats and analyzed by DAS 2.0.The optimal VP5-LNPs had an average particle size of 247.3±3.8 nm,zeta potential of-6.57±0.45 mV and excellent entrapment efficiency(EE)of 89.88%±1.23%.Transmission electron microscope(TEM)and Differential scanning calorimeter(DSC)further confirmed the core-shell structure.VP5-LNPs could increase the cellular uptake in vitro and have a 2.55-fold increase in AUC0-72 h,indicating a great promotion of the o ral bioavailability.The semi-elastic LNPs remarkably improved the oral availability of peptide and could be a promising oral peptide delivery system for peptide drugs in the future.
文摘Background::Re-biopsy of metastasis in advanced breast cancer(ABC)has become an international convention to assist the diagnosis and evaluation of tumor heterogeneity.This study aimed to detect diagnostic diversity and inconsistencies among estrogen receptor(ER),progesterone receptor(PR),and human epidermal growth factor receptor 2(HER2)expression levels between primary and metastatic lesions.Methods::We conducted a retrospective analysis of 1670 cases of ABC patients who had undergone at least one lesion re-biopsy from January 2010 to December 2018.The pathological diagnosis of biopsies,distribution of biopsy sites,and severe puncture complications at each site were collected.In addition,the inconsistency rates and related factors of ER,PR,and HER2 expression between primary and metastatic lesions were analyzed fully considering patients’demographic profiles and disease characteristics.Results::In total,1670 cases of breast cancer(BC)patients diagnosed by pathology underwent one to four biopsies of recurrences or metastases in different sites or at different stages during the rescue treatment,producing 2019 histopathological specimens which were analyzed in the study.Pathological diagnosis showed that eight patients had benign pathological diagnoses,11 patients had second primary malignant tumors but without recurrences of breast cancer,and 17 patients had pathologically confirmed breast cancer recurrences combined with second primary cancer.In 1173 patients who presented ER,PR,and HER2 expressions in primary and metastatic lesions,the inconsistency rates of ER,PR,and HER2 were 17.5%(205/1173),31.3%(367/1173),and 13.9%(163/1173),respectively.The multivariate analysis showed that the age at the onset of breast cancer or adjuvant endocrine therapy was an independent factor affecting changes in PR expression level.Except one liver puncture with local hemorrhage and two lung punctures with hemopneumothorax,no other severe puncture complications occurred in 1950 non-surgical rebiopsies.Conclusions::The pathological diagnosis of metastasis re-biopsy of ABC was diverse,and the ER,PR,and HER2 expression levels were inconsistent between primary and metastatic lesions.Therefore,more attention should be paid to perform biopsies of relapsed and metastatic breast cancers routinely in clinical practice.