Introduction:With the incidence of chronic kidney disease(CKD)increasing year by year,it is particularly important to intervene in the early stage of CKD(stages 1–3).Unfortunately,the effective drug treatment methods...Introduction:With the incidence of chronic kidney disease(CKD)increasing year by year,it is particularly important to intervene in the early stage of CKD(stages 1–3).Unfortunately,the effective drug treatment methods for CKD(stages 1–3)are lacking.Guben Tongluo Formula(GTF)is the experience formula of Professor Liqun He,a famous traditional Chinese medicine(TCM)doctor in Shanghai.Our previous studies demonstrated that GTF might effectively alleviate CKD via multi-mechanisms.As the first angiotensin-2 receptor antagonist for treating hypertension,losartan potassium(LP)could effectively reduce blood pressure,decrease cardiovascular risk,and delay the occurrence of end-stage renal disease.Thus,we design this clinical protocol of GTF combining LP to observe the efficacy and safety of GTF and try to provide a novel drug treatment method for treating CKD(stages 1–3)patients.Methods and analysis:This is a multicenter randomized controlled clinical trial.160 participants will be enrolled in this trial and divided into LP group,GTF group,LP+GTF group,and placebo group randomly assigning 1:1:1:1 principle.LP group will receive general treatments combining LP,GTF group will receive general treatments combining GTF,and the GTF+LP group will receive general treatments combining GTF and LP.Placebo group will receive general treatments combining placebo treatment.The primary evaluation index will be the change of serum creatinine after treatment.Secondary evaluation indexes include changes in blood urea nitrogen,serum uric acid,estimated glomerular filtration rate,etc.;immune indicators and renal fibrosis indicators,as well as TCM symptoms.Besides,vital sign indicators and adverse events will be closely observed.Ethics and dissemination:The protocol has been approved by the Ethics Committee of Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine(reference number:2024-7th-HIRB-094)and other ethics committees at each center.With the implementation of this clinical trial,it would offer a TCM formula for the treatment of CKD(stages 1–3)and clarify the underlying mechanism of GTF for alleviating CKD.Trial registration:This trial is registered with ChiCTR2400090125 and registered on September 24,2024.展开更多
Bacterial pneumonia is one of the most common infectious diseases,a great threat to the health of children and the elderly.In the clinic,due to the extensive use of antibiotics,multi-drug-resistant bacteria have incre...Bacterial pneumonia is one of the most common infectious diseases,a great threat to the health of children and the elderly.In the clinic,due to the extensive use of antibiotics,multi-drug-resistant bacteria have increased in large numbers,seriously affects the treatment of patients with bacterial pneumonia.With the development of nanomedicine,it shows great potential in the treatment of bacterial pneumonia.In this review,it initially comprehensively describes the pathological process of bacterial pneumonia and the current status of its clinical treatment.Then it summarizes the strategies of nanomedicine for the treatment of bacterial pneumonia,including inorganic nanomaterials,polymer nanoparticles,natural source nanomaterials and artificial antimicrobial peptides,with a focus on novel nanomaterials for the treatment of bacterial pneumonia(biomimetic nanomaterials,nanovaccines and genetically engineered nanomaterials).Finally,the prospect of nanomedicine for bacterial pneumonia therapy is discussed in the hope of providing new ideas for the clinical treatment of bacterial pneumonia.展开更多
Background:The main cause of restenosis after percutaneous transluminal angioplasty(PTA)is the excessive proliferation and migration of vascular smooth muscle cells(VSMCs).Lin28a has been reported to play critical reg...Background:The main cause of restenosis after percutaneous transluminal angioplasty(PTA)is the excessive proliferation and migration of vascular smooth muscle cells(VSMCs).Lin28a has been reported to play critical regulatory roles in this process.However,whether CCAAT/enhancer-binding proteinsβ(C/EBPβ)binds to the Lin28a promoter and drives the progression of restenosis has not been clarified.Therefore,in the present study,we aim to clarify the role of C/EBPβ-Lin28a axis in restenosis.Methods:Restenosis and atherosclerosis rat models of type 2 diabetes(n=20,for each group)were established by subjecting to PTA.Subsequently,the difference in DNA methylation status and expression of C/EBPβbetween the two groups were assessed.EdU,Transwell,and rescue assays were performed to assess the effect of C/EBPβon the proliferation and migration of VSMCs.DNA methylation status was further assessed using Methyltarget sequencing.The interaction between Lin28a and ten-eleven translocation 1(TET1)was analysed using co-immunoprecipitation(Co-IP)assay.Student’s t-test and one-way analysis of variance were used for statistical analysis.Results:C/EBPβexpression was upregulated and accompanied by hypomethylation of its promoter in restenosis when compared with atherosclerosis.In vitro C/EBPβoverexpression facilitated the proliferation and migration of VSMCs and was associated with increased Lin28a expression.Conversely,C/EBPβknockdown resulted in the opposite effects.Chromatin immunoprecipitation assays further demonstrated that C/EBPβcould directly bind to Lin28a promoter.Increased C/EBPβexpression and enhanced proliferation and migration of VSMCs were observed after decitabine treatment.Further,mechanical stretch promoted C/EBPβand Lin28a expression accompanied by C/EBPβhypomethylation.Additionally,Lin28a overexpression reduced C/EBPβmethylation via recruiting TET1 and enhanced C/EBPβ-mediated proliferation and migration of VSMCs.The opposite was noted in Lin28a knockdown cells.Conclusion:Our findings suggest that the C/EBPβ-Lin28a axis is a driver of restenosis progression,and presents a promising therapeutic target for restenosis.展开更多
Objective To investigate the association between total homocysteine(tHcy)level in plasma and methylenetetrahydrofblate reductase(MTHFR)C677T and A1298C genetic polymorphisms in a Chinese Han nationality population wit...Objective To investigate the association between total homocysteine(tHcy)level in plasma and methylenetetrahydrofblate reductase(MTHFR)C677T and A1298C genetic polymorphisms in a Chinese Han nationality population with type 2 diabetes mellitus(T2DM)accompanied by dyslipidemia.Methods This case-control study enrolled T2DM patients with dyslipidemia and without dyslipidemia respectively.Sanger dideoxy-mediated chain-termination method was used to detect the gene polymorphisms of MTHFR C677T and A1298C.Plasma tHcy and lipid levels were measured as well.The genotype frequency and allele frequency between the dyslipidemia and non-dyslipidemia groups were compared by using Chi-square test.Plasma tHcy level ofT2DM patients who carried the different genotypes was compared by Student's t test.Results Finally,82 T2DM patients with dyslipidemia and 94 ones without dyslipidemia were included in this study.There was a significant correlation between tHcy level and MTHFR C677T gene polymorphism inT2DM patients(t=2.27,P=0.02).Moreover,the plasma tHcy level in the dyslipidemia patients who carried MTHFR 677TT genotype was significantly higher than that in those with CT+CC genotype(13.62+6.97 vs.10.95+3.62pmol/L,t=2.2O,P=0.03);while for patients without dyslipidemia,comparison of the tHcy level between those who carried the above two alleles showed no significantly difference(13.34±6.03 vs.12.04±5.09μmol/L,t=1.08,P=0.29).Conclusion MTHFR 677TT genotype might associate with higher tHcy level in T2DM patients with dyslipidemia.展开更多
Multilayer network is a frontier direction of network science research. In this paper, the cluster ring network is extended to a two-layer network model, and the inner structures of the cluster blocks are random, smal...Multilayer network is a frontier direction of network science research. In this paper, the cluster ring network is extended to a two-layer network model, and the inner structures of the cluster blocks are random, small world or scale-free. We study the influence of network scale, the interlayer linking weight and interlayer linking fraction on synchronizability. It is found that the synchronizability of the two-layer cluster ring network decreases with the increase of network size. There is an optimum value of the interlayer linking weight in the two-layer cluster ring network, which makes the synchronizability of the network reach the optimum. When the interlayer linking weight and the interlayer linking fraction are very small, the change of them will affect the synchronizability.展开更多
Melt processing is a promising process to fabricate Mg-CNTs(carbon nanotubes)composites with high performance and large dimensions.In this work,the liquidmixing technique and ball-milling processes as well as the stir...Melt processing is a promising process to fabricate Mg-CNTs(carbon nanotubes)composites with high performance and large dimensions.In this work,the liquidmixing technique and ball-milling processes as well as the stirring casting method were used to prepare ZM1-1.0 CNTs-L and ZM1-1.0 CNTs-B composites,respectively.The composites were studied using optical microscopy(OM),Raman spectroscopy,scanning electron microscope(SEM),transmission electron microscope(TEM)and room-temperature tensile test.The results show that the yield strength(YS),ultimate tensile strength(UTS),elongation and microhardness values of the ZM1-1.OCNTs-L composite are improved by 37.3%,29.6%,37.0%and33.3%,respectively,compared with those of ZM1 alloy.The uniform dispersion of CNTs as well as the strong interfacial bonds with the Mg matrix is the main reason for the significant improvement in mechanical properties of the as-cast composite.Liquid mixing combined with the stirring casting method is favorable to fabricate Mg-CNTs composite with high mechanical properties.展开更多
With the rapid development of big data, the scale of realistic networks is increasing continually. In order to reduce the network scale, some coarse-graining methods are proposed to transform large-scale networks into...With the rapid development of big data, the scale of realistic networks is increasing continually. In order to reduce the network scale, some coarse-graining methods are proposed to transform large-scale networks into mesoscale networks. In this paper, a new coarse-graining method based on hierarchical clustering (HCCG) on complex networks is proposed. The network nodes are grouped by using the hierarchical clustering method, then updating the weights of edges between clusters extract the coarse-grained networks. A large number of simulation experiments on several typical complex networks show that the HCCG method can effectively reduce the network scale, meanwhile maintaining the synchronizability of the original network well. Furthermore, this method is more suitable for these networks with obvious clustering structure, and we can choose freely the size of the coarse-grained networks in the proposed method.展开更多
Ovulatory dysfunction(OD)is one of the main causes of infertility in women of childbearing age,which not only affects their reproductive ability,but also physical and mental health.Traditional treatment strategies hav...Ovulatory dysfunction(OD)is one of the main causes of infertility in women of childbearing age,which not only affects their reproductive ability,but also physical and mental health.Traditional treatment strategies have limited efficacies,and the emergence of biomedicines provides a promising alternative solution via the strategies of combining engineered design with modern advanced technology.This review explores the pathophysiological characteristics and related induction mechanisms of OD,and evaluates the current cutting-edge advances in its treatments.It emphasizes the potentials of biomedicines strategies such as hydrogels,nanoparticles and extracellular vesicles in improving therapeutic precision and efficacy.By mimicking natural physiological processes,and achieving controlled drug release,these advanced drug carriers are expected to address the challenges in ovarian microenvironment reprogramming,tissue repair,and metabolic and immune regulation.Despite the promising progress,there are still challenges in terms of biomedical complexity,differences between animal models and human physiology,and the demand for intelligent drug carriers in the therapy of OD.Future researches are mainly dedicated to developing precise personalized biomedicines in OD therapy through interdisciplinary collaboration,promoting the development of reproductive regenerative medicine.展开更多
Background:Excessive proliferation and migration of vascular smooth muscle cells(VSMCs)are the main causes of restenosis(RS)in diabetic lower extremity arterial disease(LEAD).However,the relevant pathogenic mechanisms...Background:Excessive proliferation and migration of vascular smooth muscle cells(VSMCs)are the main causes of restenosis(RS)in diabetic lower extremity arterial disease(LEAD).However,the relevant pathogenic mechanisms are poorly understood.Methods:In this study,we introduced a“two-step injury protocol”rat RS model,which started with the induction of atherosclerosis(AS)and was followed by percutaneous transluminal angioplasty(PTA).Hematoxylin-eosin(HE)staining and immunohistochemistry staining were used to verify the form of RS.Two-step transfection was performed,with the first transfection of Lin28a followed by a second transfection of let-7c and let-7g,to explore the possible mechanism by which Lin28a exerted effects.5-ethynyl-2΄-deoxyuridine(EdU)and Transwell assay were performed to evaluate the ability of proliferation and migration of VSMCs.Western blotting and quantitative real-time polymerase chain reaction(qRT-PCR)were performed to detect the expression of Lin28a protein and let-7 family members.Results:Using a combination of in vitro and in vivo experiments,we discovered that let-7c,let-7g,and microRNA98(miR98)were downstream targets of Lin28a.More importantly,decreased expression of let-7c/let-7g increased Lin28a,leading to further inhibition of let-7c/let-7g.We also found an increased level of let-7d in the RS pathological condition,suggesting that it may function as a protective regulator of the Lin28a/let-7 loop by inhibiting the proliferation and migration of VSMCs.Conclusion:These findings indicated the presence of a double-negative feedback loop consisting of Lin28a and let-7c/let-7g,which may be responsible for the vicious behavior of VSMCs in RS.展开更多
The aim of this study is to appraise the potential of calcium sulfoaluminate(CSA)cement-based grouts in simulated permafrost environments.The hydration and performance of CSA cement-based grouts cured in cold environm...The aim of this study is to appraise the potential of calcium sulfoaluminate(CSA)cement-based grouts in simulated permafrost environments.The hydration and performance of CSA cement-based grouts cured in cold environments(10,0,and−10℃)are investigated using a combination of tests,including temperature recording,X-ray diffraction(XRD)tests,thermogravimetric analysis(TGA),and unconfined compressive strength(UCS)tests.The recorded temperature shows a rapid increase in temperature at the early stage in all the samples.Meanwhile,results of the TGA and XRD tests show the generation of a significant quantity of hydration products,which indicates the rapid hydration of CSA cement-based grouts at the early stage at low temperatures.Consequently,the CSA cement-based grouts exhibit remarkably high early strength.The UCS values of the samples cured for 2 h at−10,0,and 10℃ are 6.5,12.0,and 12.3 MPa,respectively.The UCS of the grouts cured at−10,0,and 10℃ increases continuously with age and ultimately reached 14.9,19.0,and 30.6 MPa at 28 d,respectively.The findings show that the strength of grouts fabricated using CSA cement can develop rapidly in cold environments,thus rendering them promising for permafrost applications.展开更多
基金supported by grants from Pudong New Area Traditional Chinese Medicine Brand Multiplication Plan-Chronic Nephropathy(PDZY-2021-0302)Construction of He Liqun’s famous TCM studio(PDZY-2022-0703)+2 种基金Clinical Observation on the Efficacy of Guben Tongluo Formula in Treating Chronic Kidney Disease Phase 1-3(PW2022D-12)Pilot Project of Inheritance,Innovation and Development of Traditional Chinese Medicine in Pudong New Area(YC-2023-0602)Pudong New Area’s Peak and Plateau Discipline Development in Clinical Medicine for Novel and Special Diseases(2025-PWXZ-15).
文摘Introduction:With the incidence of chronic kidney disease(CKD)increasing year by year,it is particularly important to intervene in the early stage of CKD(stages 1–3).Unfortunately,the effective drug treatment methods for CKD(stages 1–3)are lacking.Guben Tongluo Formula(GTF)is the experience formula of Professor Liqun He,a famous traditional Chinese medicine(TCM)doctor in Shanghai.Our previous studies demonstrated that GTF might effectively alleviate CKD via multi-mechanisms.As the first angiotensin-2 receptor antagonist for treating hypertension,losartan potassium(LP)could effectively reduce blood pressure,decrease cardiovascular risk,and delay the occurrence of end-stage renal disease.Thus,we design this clinical protocol of GTF combining LP to observe the efficacy and safety of GTF and try to provide a novel drug treatment method for treating CKD(stages 1–3)patients.Methods and analysis:This is a multicenter randomized controlled clinical trial.160 participants will be enrolled in this trial and divided into LP group,GTF group,LP+GTF group,and placebo group randomly assigning 1:1:1:1 principle.LP group will receive general treatments combining LP,GTF group will receive general treatments combining GTF,and the GTF+LP group will receive general treatments combining GTF and LP.Placebo group will receive general treatments combining placebo treatment.The primary evaluation index will be the change of serum creatinine after treatment.Secondary evaluation indexes include changes in blood urea nitrogen,serum uric acid,estimated glomerular filtration rate,etc.;immune indicators and renal fibrosis indicators,as well as TCM symptoms.Besides,vital sign indicators and adverse events will be closely observed.Ethics and dissemination:The protocol has been approved by the Ethics Committee of Seventh People’s Hospital of Shanghai University of Traditional Chinese Medicine(reference number:2024-7th-HIRB-094)and other ethics committees at each center.With the implementation of this clinical trial,it would offer a TCM formula for the treatment of CKD(stages 1–3)and clarify the underlying mechanism of GTF for alleviating CKD.Trial registration:This trial is registered with ChiCTR2400090125 and registered on September 24,2024.
基金supported by the Joint Project on Regional High-Incidence Diseases Research of Guangxi Natural Science Foundation(Nos.2023GXNSFDA026023 and 2024GXNSFAA010089)the Key Research&Development Program of Guangxi(No.Gui Ke AB22080088)+2 种基金the National Natural Science Foundation of China(No.82360372)the First-class Discipline Innovation-driven Talent Program of Guangxi Medical Universitythe Major Talent Project of Guangxi Autonomous Region。
文摘Bacterial pneumonia is one of the most common infectious diseases,a great threat to the health of children and the elderly.In the clinic,due to the extensive use of antibiotics,multi-drug-resistant bacteria have increased in large numbers,seriously affects the treatment of patients with bacterial pneumonia.With the development of nanomedicine,it shows great potential in the treatment of bacterial pneumonia.In this review,it initially comprehensively describes the pathological process of bacterial pneumonia and the current status of its clinical treatment.Then it summarizes the strategies of nanomedicine for the treatment of bacterial pneumonia,including inorganic nanomaterials,polymer nanoparticles,natural source nanomaterials and artificial antimicrobial peptides,with a focus on novel nanomaterials for the treatment of bacterial pneumonia(biomimetic nanomaterials,nanovaccines and genetically engineered nanomaterials).Finally,the prospect of nanomedicine for bacterial pneumonia therapy is discussed in the hope of providing new ideas for the clinical treatment of bacterial pneumonia.
文摘Background:The main cause of restenosis after percutaneous transluminal angioplasty(PTA)is the excessive proliferation and migration of vascular smooth muscle cells(VSMCs).Lin28a has been reported to play critical regulatory roles in this process.However,whether CCAAT/enhancer-binding proteinsβ(C/EBPβ)binds to the Lin28a promoter and drives the progression of restenosis has not been clarified.Therefore,in the present study,we aim to clarify the role of C/EBPβ-Lin28a axis in restenosis.Methods:Restenosis and atherosclerosis rat models of type 2 diabetes(n=20,for each group)were established by subjecting to PTA.Subsequently,the difference in DNA methylation status and expression of C/EBPβbetween the two groups were assessed.EdU,Transwell,and rescue assays were performed to assess the effect of C/EBPβon the proliferation and migration of VSMCs.DNA methylation status was further assessed using Methyltarget sequencing.The interaction between Lin28a and ten-eleven translocation 1(TET1)was analysed using co-immunoprecipitation(Co-IP)assay.Student’s t-test and one-way analysis of variance were used for statistical analysis.Results:C/EBPβexpression was upregulated and accompanied by hypomethylation of its promoter in restenosis when compared with atherosclerosis.In vitro C/EBPβoverexpression facilitated the proliferation and migration of VSMCs and was associated with increased Lin28a expression.Conversely,C/EBPβknockdown resulted in the opposite effects.Chromatin immunoprecipitation assays further demonstrated that C/EBPβcould directly bind to Lin28a promoter.Increased C/EBPβexpression and enhanced proliferation and migration of VSMCs were observed after decitabine treatment.Further,mechanical stretch promoted C/EBPβand Lin28a expression accompanied by C/EBPβhypomethylation.Additionally,Lin28a overexpression reduced C/EBPβmethylation via recruiting TET1 and enhanced C/EBPβ-mediated proliferation and migration of VSMCs.The opposite was noted in Lin28a knockdown cells.Conclusion:Our findings suggest that the C/EBPβ-Lin28a axis is a driver of restenosis progression,and presents a promising therapeutic target for restenosis.
基金the National Key Development Plan for Precision Medicine Research(2017YFC0910004)Jinan Science Project(201602171),and Jinan Science and Technology Plan Project(201503009).
文摘Objective To investigate the association between total homocysteine(tHcy)level in plasma and methylenetetrahydrofblate reductase(MTHFR)C677T and A1298C genetic polymorphisms in a Chinese Han nationality population with type 2 diabetes mellitus(T2DM)accompanied by dyslipidemia.Methods This case-control study enrolled T2DM patients with dyslipidemia and without dyslipidemia respectively.Sanger dideoxy-mediated chain-termination method was used to detect the gene polymorphisms of MTHFR C677T and A1298C.Plasma tHcy and lipid levels were measured as well.The genotype frequency and allele frequency between the dyslipidemia and non-dyslipidemia groups were compared by using Chi-square test.Plasma tHcy level ofT2DM patients who carried the different genotypes was compared by Student's t test.Results Finally,82 T2DM patients with dyslipidemia and 94 ones without dyslipidemia were included in this study.There was a significant correlation between tHcy level and MTHFR C677T gene polymorphism inT2DM patients(t=2.27,P=0.02).Moreover,the plasma tHcy level in the dyslipidemia patients who carried MTHFR 677TT genotype was significantly higher than that in those with CT+CC genotype(13.62+6.97 vs.10.95+3.62pmol/L,t=2.2O,P=0.03);while for patients without dyslipidemia,comparison of the tHcy level between those who carried the above two alleles showed no significantly difference(13.34±6.03 vs.12.04±5.09μmol/L,t=1.08,P=0.29).Conclusion MTHFR 677TT genotype might associate with higher tHcy level in T2DM patients with dyslipidemia.
文摘Multilayer network is a frontier direction of network science research. In this paper, the cluster ring network is extended to a two-layer network model, and the inner structures of the cluster blocks are random, small world or scale-free. We study the influence of network scale, the interlayer linking weight and interlayer linking fraction on synchronizability. It is found that the synchronizability of the two-layer cluster ring network decreases with the increase of network size. There is an optimum value of the interlayer linking weight in the two-layer cluster ring network, which makes the synchronizability of the network reach the optimum. When the interlayer linking weight and the interlayer linking fraction are very small, the change of them will affect the synchronizability.
基金financially supported by the National Natural Science Foundation of China(No.51761037)the Scientific Research Foundation of the Education Department of Jiangxi Province(No.GJJ170897)。
文摘Melt processing is a promising process to fabricate Mg-CNTs(carbon nanotubes)composites with high performance and large dimensions.In this work,the liquidmixing technique and ball-milling processes as well as the stirring casting method were used to prepare ZM1-1.0 CNTs-L and ZM1-1.0 CNTs-B composites,respectively.The composites were studied using optical microscopy(OM),Raman spectroscopy,scanning electron microscope(SEM),transmission electron microscope(TEM)and room-temperature tensile test.The results show that the yield strength(YS),ultimate tensile strength(UTS),elongation and microhardness values of the ZM1-1.OCNTs-L composite are improved by 37.3%,29.6%,37.0%and33.3%,respectively,compared with those of ZM1 alloy.The uniform dispersion of CNTs as well as the strong interfacial bonds with the Mg matrix is the main reason for the significant improvement in mechanical properties of the as-cast composite.Liquid mixing combined with the stirring casting method is favorable to fabricate Mg-CNTs composite with high mechanical properties.
文摘With the rapid development of big data, the scale of realistic networks is increasing continually. In order to reduce the network scale, some coarse-graining methods are proposed to transform large-scale networks into mesoscale networks. In this paper, a new coarse-graining method based on hierarchical clustering (HCCG) on complex networks is proposed. The network nodes are grouped by using the hierarchical clustering method, then updating the weights of edges between clusters extract the coarse-grained networks. A large number of simulation experiments on several typical complex networks show that the HCCG method can effectively reduce the network scale, meanwhile maintaining the synchronizability of the original network well. Furthermore, this method is more suitable for these networks with obvious clustering structure, and we can choose freely the size of the coarse-grained networks in the proposed method.
基金supported by the Joint Project on Regional High-Incidence Diseases Research of Guangxi Natural Science Foundation(Grant Nos.2025GXNSFDA069002,China and 2024GXNSFAA010089,China)the Guangxi Key Research and Development Program(Grant No.Guike AB22080045,China)the Major Talent Project of Guangxi Autonomous Region.
文摘Ovulatory dysfunction(OD)is one of the main causes of infertility in women of childbearing age,which not only affects their reproductive ability,but also physical and mental health.Traditional treatment strategies have limited efficacies,and the emergence of biomedicines provides a promising alternative solution via the strategies of combining engineered design with modern advanced technology.This review explores the pathophysiological characteristics and related induction mechanisms of OD,and evaluates the current cutting-edge advances in its treatments.It emphasizes the potentials of biomedicines strategies such as hydrogels,nanoparticles and extracellular vesicles in improving therapeutic precision and efficacy.By mimicking natural physiological processes,and achieving controlled drug release,these advanced drug carriers are expected to address the challenges in ovarian microenvironment reprogramming,tissue repair,and metabolic and immune regulation.Despite the promising progress,there are still challenges in terms of biomedical complexity,differences between animal models and human physiology,and the demand for intelligent drug carriers in the therapy of OD.Future researches are mainly dedicated to developing precise personalized biomedicines in OD therapy through interdisciplinary collaboration,promoting the development of reproductive regenerative medicine.
基金supported by the National Natural Science Foundation of China Grants(Nos.82100891,81670757,82270888,82170824,81770822,81800732,and 81900685)Natural Science Foundation of Shandong Province(No.ZR2017LH025)+1 种基金Shandong Provincial Medicine and Health Science and Technology Development Program(No.2017WS461)China Postdoctoral Science Foundation(No.2021M691957).
文摘Background:Excessive proliferation and migration of vascular smooth muscle cells(VSMCs)are the main causes of restenosis(RS)in diabetic lower extremity arterial disease(LEAD).However,the relevant pathogenic mechanisms are poorly understood.Methods:In this study,we introduced a“two-step injury protocol”rat RS model,which started with the induction of atherosclerosis(AS)and was followed by percutaneous transluminal angioplasty(PTA).Hematoxylin-eosin(HE)staining and immunohistochemistry staining were used to verify the form of RS.Two-step transfection was performed,with the first transfection of Lin28a followed by a second transfection of let-7c and let-7g,to explore the possible mechanism by which Lin28a exerted effects.5-ethynyl-2΄-deoxyuridine(EdU)and Transwell assay were performed to evaluate the ability of proliferation and migration of VSMCs.Western blotting and quantitative real-time polymerase chain reaction(qRT-PCR)were performed to detect the expression of Lin28a protein and let-7 family members.Results:Using a combination of in vitro and in vivo experiments,we discovered that let-7c,let-7g,and microRNA98(miR98)were downstream targets of Lin28a.More importantly,decreased expression of let-7c/let-7g increased Lin28a,leading to further inhibition of let-7c/let-7g.We also found an increased level of let-7d in the RS pathological condition,suggesting that it may function as a protective regulator of the Lin28a/let-7 loop by inhibiting the proliferation and migration of VSMCs.Conclusion:These findings indicated the presence of a double-negative feedback loop consisting of Lin28a and let-7c/let-7g,which may be responsible for the vicious behavior of VSMCs in RS.
基金This study was supported by a research project(RES0049413)at the University of Alberta.The first author is grateful for the scholarship provided by the China Scholarship Council。
文摘The aim of this study is to appraise the potential of calcium sulfoaluminate(CSA)cement-based grouts in simulated permafrost environments.The hydration and performance of CSA cement-based grouts cured in cold environments(10,0,and−10℃)are investigated using a combination of tests,including temperature recording,X-ray diffraction(XRD)tests,thermogravimetric analysis(TGA),and unconfined compressive strength(UCS)tests.The recorded temperature shows a rapid increase in temperature at the early stage in all the samples.Meanwhile,results of the TGA and XRD tests show the generation of a significant quantity of hydration products,which indicates the rapid hydration of CSA cement-based grouts at the early stage at low temperatures.Consequently,the CSA cement-based grouts exhibit remarkably high early strength.The UCS values of the samples cured for 2 h at−10,0,and 10℃ are 6.5,12.0,and 12.3 MPa,respectively.The UCS of the grouts cured at−10,0,and 10℃ increases continuously with age and ultimately reached 14.9,19.0,and 30.6 MPa at 28 d,respectively.The findings show that the strength of grouts fabricated using CSA cement can develop rapidly in cold environments,thus rendering them promising for permafrost applications.
