Judiciously engineering the electrocatalysts is attractive and challenging to exploit materials with high electrocatalytic performance for hydrogen evolution reaction.Herein,we successfully perform the interface engin...Judiciously engineering the electrocatalysts is attractive and challenging to exploit materials with high electrocatalytic performance for hydrogen evolution reaction.Herein,we successfully perform the interface engineering by alternately depositing Co±P and Ni±Fe±P films on nickel foam,via facile electroless plating and de-alloying process.This work shows that there is a significant effect of de-alloying process on alloy growth.The electronic structure of layered alloys is improved by interface engineering.The multilayer strategy significantly promotes the charge transfer.Importantly,the Co±P/Ni±Fe±P/NF electrode fabricated by interface engineering exhibits excellent electrocatalytic hydrogen evolution activity with an overpotential of 43.4 mV at 10 mA cm^(-2)and long-term durability for 72 h in alkaline medium(1 mol L^(-1)KOH).The innovative strategy of this work may aid further development of commercial electrocatalysts.展开更多
Objective Diabetic patients pose a greater challenge in managing chronic wound healing,leading to a higher amputation risk compared to non-diabetic patients.Due to their paracrine function by secreting various cytokin...Objective Diabetic patients pose a greater challenge in managing chronic wound healing,leading to a higher amputation risk compared to non-diabetic patients.Due to their paracrine function by secreting various cytokines and angiogenic factors,mesenchymal stem cells(MSCs)have been acknowledged to be a potential agent in modulating wound healing process.However,post-transplanted MSCs are vulnerable to death,indicating poor survival and migration ability in the wound site of the host,especially under hyperglycemia.As hyperglycemia induces reactive oxygen species(ROS)generation and cellular apoptosis,improvement of MSCs survival and migration potentials under hyperglycemia could contribute to a more efficient MSCs-based wound healing therapy.Salidroside(Sa),a small-molecule drug derived from Rhodiola plant,has been proved to enhance the paracrine function of skeletal muscle cells,as well as their migration even under hypoxichyperglycemia.Herein,we investigated whether Sa could improve the survival and migration potentials of MSCs,subsequently enhance the wound healing process under hyperglycemia.Methods MSCs were cultured under three conditions:low glucose,high glucose,and high glucose+Sa.qPCR analysis and western blotting were done to examine the mRNA and protein expression level of several factors which are important in upregulating the wound healing process.MTT colorimetric assay,intracellular ROS detection,and flow cytometry assay were employed to examine the effect of Sa in MSCs survival.Transwell chamber assay,scratch assay,and phalloidin staining were done to elucidate the role of Sa in regulating MSCs migration potential.For in vivo experiment,diabetic wound healing mice model was generated to elucidate the effect of Sa-pretreated MSCs transplantation in wound closure rate,as well as re-epithelization status,observed with hematoxylin and eosin staining.The diabetic wound healing mice model were divided into three groups:1)mice injected with PBS,2)mice transplanted with PBS-pretreated MSCs,and 3)mice transplanted with Sa-pretreated MSCs.Results(1)Hyperglycemic condition induced the generation of ROS and suppressed total cell number of MSCs,while Sa treatment into MSCs restored these hyperglycemia-induced alterations.In line with this,total apoptotic cells were also suppressed by treating MSCs with Sa.The expression level of cell survival factor,heme-oxygenase 1(HO-1),was enhanced in Sa-pretreated MSCs.Further treatment of HO-1 inhibitor into Sa-pretreated MSCs nullified the ROS level and total apoptotic cells,indica-ting the importance of HO-1 in mediating the Sa-induced survival of MSCs under hyperglycemia.(2)Transwell chamber and scratch assay results showed that Sa-pretreated MSCs have a higher migration potential under hyperglycemia,supported by higher F-actin polymerization fractal dimension.Fibroblast growth factor 2(FGF2)and hepatocyte growth factor(HGF)expression level,which are essential factors for cell migration,were also improved in Sa-pretreated MSCs under hyperglycemia.(3)In diabetic wound healing mice model,transplantation of Sa-pretreated MSCs resulted in significantly improved wound closure rate and re-epithelization.The protein levels of HO-1,FGF2,and HGF were also enhanced in the tissues obtained from the wound site of diabetic wound healing mice model which were transplanted with Sa-pretreated MSCs.Conclusions Salidroside pretreatment on MSCs could improve their survival and migration potentials,subsequently promoting wound healing process under hyperglycemia.This prospective MSC-based therapy could serve as a novel strategy to improve diabetic wound healing.展开更多
Objective Mitral valve(MV)plays an importance role in regulating blood flow from left atrium to left ventricle and preventing backflow to left atrium.Mitral Valve consist of four important parts;anterior leaflet,poste...Objective Mitral valve(MV)plays an importance role in regulating blood flow from left atrium to left ventricle and preventing backflow to left atrium.Mitral Valve consist of four important parts;anterior leaflet,posterior leaflet,chordae tendineae,and papillary muscles,which all work in harmony.The material properties alteration on the leaflet causes MV malfunction,and leading to valve diseases such as regurgitation and stenosis.The alteration may be caused by several factors such as calcification,genetic disorders,and infection,which usually have an influence to the mechanical properties,and thus affecting the mechanical behavior of MV.In consequence,some of the patients need MV replacement or repair to restore the normal function of MV.The important point for succeeding such a medical treatment depends on the technique,design,and material used in the treatment shall help rebuild the normal mechanical environment and behavior of MV.Therefore,the mechanical and materials characteristics of MV become a magnetism to explore.In this study,we present an integrated experimental and mathematical constitutive study base in collagen distribution aiming at the mechanical property differences in various region on MV.Methods and materials Both the size and composition of porcine valves are similar to human’s,so the porcine heart valve is often being used in experimental research.Mitral valve was isolated from fresh eight porcine hearts(250-500 gr),and perfused in PBS solution to maintain moist.Anterior and posterior leaflets were separated and dissected into 4 part(two 8~*8 mm rough zone and two clear zone samples)and 2 part(8~*8 mm belly and edge of the clear zone)respectively.Tracking markers(glass bean)were stickled on specimen with superglue(cyanoacrylate adhesive).Then,the specimen was mounted onto biaxial tester machine(CeIIScale,Biotester),and the tests are run by force control.During mechanical test,the specimen is immersed into PBS solution in physiological temperature(37℃).Every test procedure contains 8 preconditioning cycles and 8 loading cycles.The mechanical behavior was determined from the relationship between first Piola-Kirchoff stress and stretch.Constitutive model was reconstructed and material parameters were fitted from biaxial tensile result.Histological analyses were performed in the specimen before and after test.First,a piece of the specimen was cut and immersed in fixation solution(4%paraformaldehyde),then it was dehydrated in graded alcohol solution,and next embedding in paraffin wax block.Paraffin block was then cut and stained with VVG and Picro-sirius red.The collagen fibril orientation was observed from those histological results.Results The experimental results of the clear zone of MV’s first Piola-Kirchhoff stress and stretch curve are similar to those of the recent study from others,while result of the rough zone shows a different trend.This can be explained by differences in collagen distribution between clear zone and rough zone of MV.Our result thus allows for a refinement of computational models for more accurately predicting MV condition,where tissue heterogeneity plays an important role in the MV function.展开更多
Devices for the rotational culture of cells and the study of biological reactions have been widely applied in tissue engineering.However,there are few reports exploring the effects of rotational culture on cell morpho...Devices for the rotational culture of cells and the study of biological reactions have been widely applied in tissue engineering.However,there are few reports exploring the effects of rotational culture on cell morphology,nitric oxide(NO)production,and cell cycle of the endothelial cells from human umbili-cal vein on the stent surface.This study focuses on these parameters after the cells are seeded on the stents.Results showed that covering of stents by endothelial cells was improved by rotational culture.NO produc-tion decreased within 24 h in both rotational and static culture groups.In addition,rotational culture signifi-cantly increased NO production by 37.9%at 36 h and 28.9%at 48 h compared with static culture.Flow cytometry showed that the cell cycle was not obviously influenced by rotational culture.Results indicate that rotational culture may be helpful for preparation of cell-seeded vascular grafts and intravascular stents,which are expected to be the most frequently implanted materials in the future.展开更多
Objectives:To examine the 16-year developmental history,research hotspots,and emerging trends of zinc-based biodegradable metallic materials from the perspective of structural and temporal dynamics.Methods:The literat...Objectives:To examine the 16-year developmental history,research hotspots,and emerging trends of zinc-based biodegradable metallic materials from the perspective of structural and temporal dynamics.Methods:The literature on zinc-based biodegradable metallic materials in WoSCC was searched.Historical characteristics,the evolution of active topics and development trends in the field of zinc-based biodegradable metallic materials were analyzed using the bibliometric tools CiteSpace and HistCite.Results:Over the past 16 years,the field of zinc-based biodegradable metal materials has remained in a hotspot stage,with extensive scientific collaboration.In addition,there are 45 subject categories and 51 keywords in different research periods,and 80 papers experience citation bursts.Keyword clustering anchored 3 emerging research subfields,namely,#1 plastic deformation#4 additive manufacturing#5 surface modification.The keyword alluvial map shows that the longest-lasting research concepts in the field are mechanical property,microstructure,corrosion behavior,etc.,and emerging keywords are additive manufacturing,surface modification,dynamic recrystallization,etc.The most recent research on reference clustering has six subfields.Namely,#0 microstructure,#2 sem,#3 additive manufacturing,#4 laser powder bed fusion,#5 implant,and#7 Zn-1Mg.Conclusion:The results of the bibliometric study provide the current status and trends of research on zinc-based biodegradable metallic materials,which can help researchers identify hot spots and explore new research directions in the field.展开更多
Demand for biliary stents has expanded with the increasing incidence of biliary disease.The implantation of plastic or self-expandable metal stents can be an effective treatment for biliary strictures.However,these st...Demand for biliary stents has expanded with the increasing incidence of biliary disease.The implantation of plastic or self-expandable metal stents can be an effective treatment for biliary strictures.However,these stents are nondegradable and prone to restenosis.Surgical removal or replacement of the nondegradable stents is necessary in cases of disease resolution or restenosis.To overcome these shortcomings,improvements were made to the materials and surfaces used for the stents.First,this paper reviews the advantages and limitations of nondegradable stents.Second,emphasis is placed on biodegradable polymer and biodegradable metal stents,along with functional coatings.This also encompasses tissue engineering&3D-printed stents were highlighted.Finally,the future perspectives of biliary stents,including pro-epithelialization coatings,multifunctional coated stents,biodegradable shape memory stents,and 4D bioprinting,were discussed.展开更多
Atherosclerotic cardiovascular disease and its complications are a high-incidence disease worldwide.Numerous studies have shown that blood flow shear has a huge impact on the function of vascular endothelial cells,and...Atherosclerotic cardiovascular disease and its complications are a high-incidence disease worldwide.Numerous studies have shown that blood flow shear has a huge impact on the function of vascular endothelial cells,and it plays an important role in gene regulation of pro-inflammatory,pro-thrombotic,pro-oxidative stress,and cell permeability.Many impor-tant endothelial cell mechanosensitive genes have been discovered,including KLK10,CCN gene family,NRP2,YAP,TAZ,HIF-1α,NF-kB,FOS,JUN,TFEB,KLF2/KLF4,NRF2,and ID1.Some of them have been intensively studied,whereas the relevant regulatory mechanism of other genes remains unclear.Focusing on these mechanosensitive genes will provide new strategies for therapeutic intervention in atherosclerotic vascular disease.Thus,this article reviews the mechanosensitive genes affecting vascular endothelial cells,including classical pathways and some newly screened genes,and summarizes the latest research progress on their roles in the pathogenesis of atherosclerosis to reveal effective therapeutic targets of drugs and provide new insights foranti-atherosclerosis.展开更多
The clearance of apoptotic cell debris,containing professional phagocytosis and non-professional phagocytosis,is essential for maintaining the homeostasis of healthy tissues.Here,we discovered that endothelial cells c...The clearance of apoptotic cell debris,containing professional phagocytosis and non-professional phagocytosis,is essential for maintaining the homeostasis of healthy tissues.Here,we discovered that endothelial cells could engulf apoptotic cell debris in atherosclerotic plaque.Single-cell RNA sequencing(RNA-seq)has revealed a unique endothelial cell subpopulation in atherosclerosis,which was strongly associated with vascular injury-related pathways.Moreover,integrated analysis of three vascular injury-related RNA-seq datasets showed that the expression of scavenger receptor class B type 1(SR-B1)was up-regulated and specifically enriched in the phagocytosis pathway under vascular injury circumstances.Single-cell RNA-seq and bulk RNA-seq indicate that SR-B1 was highly expressed in a unique endothelial cell subpopulation of mouse aorta and strongly associated with the reorganization of cellular adherent junctions and cytoskeleton which were necessary for phagocytosis.Furthermore,SR-B1 was strongly required for endothelial cells to engulf apoptotic cell debris in atherosclerotic plaque of both mouse and human aorta.Overall,this study demonstrated that apoptotic cell debris could be engulfed by endothelial cells through SR-B1 and associated with the reorganization of cellular adherent junctions and cytoskeleton.展开更多
CovID-19,also known as coronavirus disease 2019,is a novel coronavirus disease with high infectivity,strong heterogeneity,and long incubation period(generally 3-14 days).Its main symptoms and signs include fever,dry c...CovID-19,also known as coronavirus disease 2019,is a novel coronavirus disease with high infectivity,strong heterogeneity,and long incubation period(generally 3-14 days).Its main symptoms and signs include fever,dry cough,nasal congestion,fatigue,disorientation,lymphopenia,and dyspnea.The short-term and long-term impacts of covID-19 on human health,particularly its effects on human reproduction and offspring development,continue to receive significant concerns,as they may lead to potential sequelae for several decades or even centuries.展开更多
Tumor cells progressively remodel cytoskeletal structures and reduce cellular stiffness during tumor progression,implicating the correlation between cell mechanics and malignancy.However,the roles of tumor cell cytosk...Tumor cells progressively remodel cytoskeletal structures and reduce cellular stiffness during tumor progression,implicating the correlation between cell mechanics and malignancy.However,the roles of tumor cell cytoskeleton and the mechanics in tumor progression remain incompletely understood.We report that softening/stiffening tumor cells by targeting actomyosin promotes/suppresses self-renewal in vitro and tumorigenic potential in vivo.Weakening/strengthening actin cytoskeleton impairs/reinforces the interaction between adenomatous polyposis coli(APC)andβ-catenin,which facilitatesβ-catenin nuclear/cytoplasmic localization.Nuclearβ-catenin binds to the promoter of Oct4,which enhances its transcription that is crucial in sustaining self-renewal and malignancy.These results demonstrate that the mechanics of tumor cells dictate self-renewal through cytoskeleton-APC-Wnt/β-catenin-Oct4 signaling,which are correlated with tumor differentiation and patient survival.This study unveils an uncovered regulatory role of cell mechanics in self-renewal and malignancy,and identifies tumor cell mechanics as a hallmark not only for cancer diagnosis but also for mechanotargeting.展开更多
Although neuroelectrochemical sensing technology offers unique benefits for neuroscience research,its application is limited by substantial interference in complex brain environments while ensuring biosafety requireme...Although neuroelectrochemical sensing technology offers unique benefits for neuroscience research,its application is limited by substantial interference in complex brain environments while ensuring biosafety requirements.In this study,we introduced poly(3-hexylthiophene)(P3HT)and nitrogen-doped multiwalled carbon nanotubes(N-MWCNTs)to construct a composite membrane-modified carbon fiber microelectrode(CFME/P3HT-N-MWCNTs)for ascorbic acid(AA)detection.The microelectrode presented good linearity,selectivity,stability,antifouling,and biocompatibility and exhibited great performance for application in neuroelectrochemical sensing.Subsequently,we applied CFME/P3HT-N-MWCNTs to monitor AA release from in vitro nerve cells,ex vivo brain slices,and in vivo living rat brains and determined that glutamate can induce cell edema and AA release.We also found that glutamate activated the N-methyl-d-aspartic acid receptor,which enhanced Na^(+) and Cl^(−) inflow to induce osmotic stress,resulting in cytotoxic edema and ultimately AA release.This study is the first to observe the process of glutamate-induced brain cytotoxic edema with AA release and to reveal the mechanism.Our work can benefit the application of P3HT in in vivo implant microelectrode construction to monitor neurochemicals,understand the molecular basis of nervous system diseases,and discover certain biomarkers of brain diseases.展开更多
In recent years,cardiovascular health problems are becoming more and more serious.At the same time,mechanical stimulation closely relates to cardiovascular health.In this context,Piezo1,which is very sensitive to mech...In recent years,cardiovascular health problems are becoming more and more serious.At the same time,mechanical stimulation closely relates to cardiovascular health.In this context,Piezo1,which is very sensitive to mechanical stimulation,has attracted our attention.Here,we review the critical significance of Piezo1 in mechanical stimulation of endothelial cells,NO production,lipid metabolism,DNA damage protection,the development of new blood vessels and maturation,narrowing of blood vessels,blood pressure regulation,vascular permeability,insulin sensitivity,and maintenance of red blood cell function.Besides,Piezo1 may participate in the occurrence and development of atherosclerosis,diabetes,hypertension,and other cardiovascular diseases.It is worth noting that Piezo1 has dual effects on maintaining cardiovascular health.On the one hand,the function of Piezo1 is necessary to maintain cardiovascular health;on the other hand,under some extreme mechanical stimulation,the overexpression of Piezo1 may bring adverse factors such as inflammation.Therefore,this review discusses the Janus-faced role of Piezo1 in maintaining cardiovascular health and puts forward new ideas to provide references for gene therapy or nanoagents targeting Piezo1.展开更多
Purpose:This review aims to explore the history,research hotspots,and emerging trends of drug-eluting stents(DES)in the last two decades from the perspective of structural and temporal dynamics.Methods:Publications on...Purpose:This review aims to explore the history,research hotspots,and emerging trends of drug-eluting stents(DES)in the last two decades from the perspective of structural and temporal dynamics.Methods:Publications on DES were retrieved from WoSCC.The bibliometric tools including CiteSpace and HistCite were used to identify the historical features,the evolution of active topics,and emerging trends on the DES field.Results:In the last 20 years,the field of DES is still in the hot phase and there is a wide range of extensive scientific collaborations.In addition,active topics emerge in different periods,as evidenced by a total of 41 disciplines,511 keywords,and 1377 papers with citation bursts.Keyword clustering anchored five emerging research subfields,namely#0 dual antiplatelet therapy,#3 drug-coated balloon,#4 bifurcation,5#rotational atherectomy,and 6#quantitative flow ratio.The keyword alluvial map shows that the most persistent research concepts in this field are thrombosis,restenosis,etc.,and the emerging keywords are paclitaxel eluting balloon,coated balloon,drug-eluting balloon,etc.There are 7 recent research subfields anchored by reference clustering,namely#2 dual antiplatelet therapy,#4 drug-coated balloon,#5 peripheral artery disease,#8 fractional flow reserve,#10 bioresorbable vascular scaffold,#13 intravascular ultrasound,#14 biodegradable polymer.Conclusion:The findings based on the bibliometric studies provide the current status and trends in DES research and may help researchers to identify hot topics and explore new research directions in this field.展开更多
Atherosclerosis is a chronic inflammatory disease, occurring preferentially in bifurcation, branching, and bending of blood vessels exposed to disturbed flow. Disturbed flow in atheroprone areas activates elevated pro...Atherosclerosis is a chronic inflammatory disease, occurring preferentially in bifurcation, branching, and bending of blood vessels exposed to disturbed flow. Disturbed flow in atheroprone areas activates elevated proteases, degrading elastin lamellae and collagenous matrix, resulting in endothelial dysfunction and vascular remodeling. As a mediator for extracellular matrix protein degradation, cathepsin K (CTSK) was directly regulated by hemodynamics and contributed to atherosclerosis. The mechanism of CTSK responding to disturbed flow and contributing to disturbed flow-induced atherosclerosis is unclear. In this study, the partial carotid ligation model of mice and in vitro disturbed shear stress model were constructed to explore the contribution and potential mechanism of CTSK in atherosclerosis. Our results indicated that CTSK elevated in the disturbed flow area in vivo and in vitro along with endothelial inflammation and atherogenesis. Additionally, the expression of integrin αvβ3 was upregulated in these atheroprone areas. We found that inhibition of the integrin αvβ3-cytoskeleton pathway could significantly block the activation of NF-κB and the expression of CTSK. Collectively, our findings unraveled that disturbed flow induces increased CTSK expression, and contributes to endothelial inflammation and vascular remodeling, leading to atherogenesis eventually. This study is helpful to provide new enlightenment for the therapy of atherosclerosis.展开更多
Multiple signal strategies remarkably improve the accuracy and efficiency of electrochemiluminescence(ECL)immunoassays,but the lack of potential-resolved luminophore pairs and chemical cross talk hinders their develop...Multiple signal strategies remarkably improve the accuracy and efficiency of electrochemiluminescence(ECL)immunoassays,but the lack of potential-resolved luminophore pairs and chemical cross talk hinders their development.In this study,we synthesized a series of gold nanoparticles(AuNPs)/reduced graphene oxide(Au/rGO)composites as adjustable oxygen reduction reaction and oxygen evolution reaction catalysts to promote and modulate tris(2,2′-bipyridine)ruthenium(II)(Ru(bpy)_(3)^(2+))’s multisignal luminescence.With the increase in the diameter of AuNPs(3 to 30 nm),their ability to promote Ru(bpy)_(3)^(2+)’s anodic ECL was first impaired and then strengthened,and cathodic ECL was first enhanced and then weakened.Au/rGOs with medium-small and medium-large AuNP diameters remarkably increased Ru(bpy)_(3)^(2+)’s cathodic and anodic luminescence,respectively.Notably,the stimulation effects of Au/rGOs were superior to those of most existing Ru(bpy)_(3)^(2+)co-reactants.Moreover,we proposed a novel ratiometric immunosensor construction strategy using Ru(bpy)_(3)^(2+)’s luminescence promoter rather than luminophores as tags of antibodies to achieve signal resolution.This method avoids signal cross talk between luminophores and their respective co-reactants,which achieved a good linear range of 10−7 to 10−1 ng/ml and a limit of detection of 0.33 fg/ml for detecting carcinoembryonic antigen.This study addresses the previous scarcity of the macromolecular co-reactants of Ru(bpy)_(3)^(2+),broadening its application in biomaterial detection.Furthermore,the systematic clarification of the detailed mechanisms for converting the potential-resolved luminescence of Ru(bpy)_(3)^(2+)could facilitate an in-depth understanding of the ECL process and should inspire new designs of Ru(bpy)_(3)^(2+)luminescence enhancers or applications of Au/rGOs to other luminophores.This work removes some impediments to the development of multisignal ECL biodetection systems and provides vitality into their widespread applications.展开更多
The goal of this paper is to explore a method for virus inactivation based on ultrasonic treatment,and on this basis,to explore the synergistic effect of methylene blue as a sonosensitizer in virus inactivation.The ti...The goal of this paper is to explore a method for virus inactivation based on ultrasonic treatment,and on this basis,to explore the synergistic effect of methylene blue as a sonosensitizer in virus inactivation.The titer of human parainfluenza virus type 3(HPIV3),Autographacaliforinica nuclear polyhedrosis virus carried a green fluorescent reporter gene(AcNPV-GFP)and Enterovirus group D 68(EV-D68)were determined by plaque assays or TCID50 methods after treatment by MB combined with illumination(MB photochemical,MBP)or ultrasonic excitation.Different ultrasonic power and time,MB concentration gradient were set to determine the best antiviral combination.For the enveloped virus HPIV3 and AcNPV-GFP,pure ultrasonic or MBP treatment could reduce viral titer more than 104,and ultrasonic combined with MB could completely inactivate HPIV3 and AcNPV-GFP in 5min while traditional MBP methods could only reduce viral titer about 10X.For the nonenveloped virus EV-D68,pure ultrasonic or MBP treatment only reduced the viral titer about 102,but ultrasonic combined with MB treatment could reduce the viral titer about 103 in 5min and completely inactive EV-D68 in 10min(reduced 105).Compared with MBP method and pure ultrasonic inactivation,ultrasonic combined with MB has better inactivation effect on either enveloped or non-enveloped viruses,and the appropriate combination of parameters is expected to be a new blood transfusion transmitted virus inactivation method.展开更多
Atherosclerosis is a chronic progressive disease and one of the major causes of cardio-cerebral vascular diseases.Accumulating evidence indicates that endothelial dysfunc-tion is the initiating step in atherosclerosis...Atherosclerosis is a chronic progressive disease and one of the major causes of cardio-cerebral vascular diseases.Accumulating evidence indicates that endothelial dysfunc-tion is the initiating step in atherosclerosis.The pattern of local blood flow becomes disturbed(low and oscillatory shear stress[OSS])in the curved or branched segments of the arterial tree,causing endothelial cells(ECs)to exhibit athero-susceptible phenotypes,such as hyperproliferation and inflammation.展开更多
Genetic compensation is a remarkable biological concept to explain the genetic robustness in an organism to maintain its fitness and viability if there is a disruption occurred in the genetic variation by mutation.How...Genetic compensation is a remarkable biological concept to explain the genetic robustness in an organism to maintain its fitness and viability if there is a disruption occurred in the genetic variation by mutation.However,the underlying mechanism in genetic compensation remain unsolvable.The initial concept of genetic compensation has been studied in model organisms when there was a discrepancy between knockout-mediated and knockdown-mediated phenotypes.In the zebrafish model,several studies have reported that zebrafish mutants did not exhibit severe phenotype as shown in zebrafish morphants for the same genes.This phenomenon in zebrafish mutants but not morphants is due to the response of genetic compensation.In 2019,two amazing works partially uncovered genetic compensation could be triggered by the upregulation of compensating genes through regulating NMD and/or PTC-bearing mRNA in collaboration with epigenetic machinery in mutant zebrafish.In this review,we would like to update the recent advances and future perspectives of genetic compensation studies,which including the hypothesis of time-dependent involvement and addressing the discrepancy between knockout-mediated and knockdown-mediated to study gene function in the zebrafish model.At last,the study of genetic compensation could be a potential therapeutic strategy to treat human genetic disorder related diseases.展开更多
The most common socioeconomic healthcare issues in clinical are burns,surgical incisions and other skin injuries.Skin lesion healing can be achieved with nanomedicines and other drug application techniques.This study ...The most common socioeconomic healthcare issues in clinical are burns,surgical incisions and other skin injuries.Skin lesion healing can be achieved with nanomedicines and other drug application techniques.This study developed a nano-spray based on cross-linked amorphous calcium peroxide(CaO_(2))nanoparticles of polyacrylic acid(PAA)for treating skin wounds(PAA-CaO_(2)nanoparticles).CaO_(2)serves as a‘drug’precursor,steadily and continuously releasing calcium ions(Ca^(2+))and hydrogen peroxide(H_(2)O_(2))under mildly acidic conditions,while PAA-CaO_(2)nanoparticles exhibited good spray behavior in aqueous form.Tests demonstrated that PAA-CaO_(2)nanoparticles exhibited low cytotoxicity and allowed L929 cells proliferation and migration in vitro.The effectiveness of PAA-CaO_(2)nanoparticles in promoting wound healing and inhibiting bacterial growth in vivo was assessed in SD rats using full-thickness skin defect and Staphylococcus aureus(S.aureus)-infected wound models based thereon.The results revealed that PAA-CaO_(2)nanoparticles demonstrated significant advantages in both aspects.Notably,the infected rats’skin defects healed in 12 days.The benefits are linked to the functional role of Ca^(2+)coalesces with H_(2)O_(2)as known antibacterial and healing-promoted agents.Therefore,we developed nanoscale PAA-CaO_(2)sprays to prevent bacterial development and heal skin lesions.展开更多
Nanoparticles(NPs)hold tremendous targeting potential in cardiovascular disease and regenerative medicine,and exciting clinical applications are coming into light.Vascular endothelial cells(ECs)exposure to different m...Nanoparticles(NPs)hold tremendous targeting potential in cardiovascular disease and regenerative medicine,and exciting clinical applications are coming into light.Vascular endothelial cells(ECs)exposure to different magnitudes and patterns of shear stress(SS)generated by blood flow could engulf NPs in the blood.However,an unclear understanding of the role of SS on NP uptake is hindering the progress in improving the targeting of NP therapies.Here,the temporal and spatial distribution of SS in vascular ECs and the effect of different SS on NP uptake in ECs are highlighted.The mechanism of SS affecting NP uptake through regulating the cellular ROS level,endothelial glycocalyx and membrane fluidity is summarized,and the molecules containing clathrin and caveolin in the engulfment process are elucidated.SS targeting NPs are expected to overcome the current bottlenecks and change the field of targeting nanomedicine.This assessment on how SS affects the cell uptake of NPs and the marginalization of NPs in blood vessels could guide future research in cell biology and vascular targeting drugs.展开更多
基金financially supported by the Taishan scholar foundation of Shandong(ts201712046)the National Natural Science Foundation of China(Grant No.51672145)
文摘Judiciously engineering the electrocatalysts is attractive and challenging to exploit materials with high electrocatalytic performance for hydrogen evolution reaction.Herein,we successfully perform the interface engineering by alternately depositing Co±P and Ni±Fe±P films on nickel foam,via facile electroless plating and de-alloying process.This work shows that there is a significant effect of de-alloying process on alloy growth.The electronic structure of layered alloys is improved by interface engineering.The multilayer strategy significantly promotes the charge transfer.Importantly,the Co±P/Ni±Fe±P/NF electrode fabricated by interface engineering exhibits excellent electrocatalytic hydrogen evolution activity with an overpotential of 43.4 mV at 10 mA cm^(-2)and long-term durability for 72 h in alkaline medium(1 mol L^(-1)KOH).The innovative strategy of this work may aid further development of commercial electrocatalysts.
基金Supported by grants from the National Natural Science Foundation of China ( 81372202,81872273, 31871367)
文摘Objective Diabetic patients pose a greater challenge in managing chronic wound healing,leading to a higher amputation risk compared to non-diabetic patients.Due to their paracrine function by secreting various cytokines and angiogenic factors,mesenchymal stem cells(MSCs)have been acknowledged to be a potential agent in modulating wound healing process.However,post-transplanted MSCs are vulnerable to death,indicating poor survival and migration ability in the wound site of the host,especially under hyperglycemia.As hyperglycemia induces reactive oxygen species(ROS)generation and cellular apoptosis,improvement of MSCs survival and migration potentials under hyperglycemia could contribute to a more efficient MSCs-based wound healing therapy.Salidroside(Sa),a small-molecule drug derived from Rhodiola plant,has been proved to enhance the paracrine function of skeletal muscle cells,as well as their migration even under hypoxichyperglycemia.Herein,we investigated whether Sa could improve the survival and migration potentials of MSCs,subsequently enhance the wound healing process under hyperglycemia.Methods MSCs were cultured under three conditions:low glucose,high glucose,and high glucose+Sa.qPCR analysis and western blotting were done to examine the mRNA and protein expression level of several factors which are important in upregulating the wound healing process.MTT colorimetric assay,intracellular ROS detection,and flow cytometry assay were employed to examine the effect of Sa in MSCs survival.Transwell chamber assay,scratch assay,and phalloidin staining were done to elucidate the role of Sa in regulating MSCs migration potential.For in vivo experiment,diabetic wound healing mice model was generated to elucidate the effect of Sa-pretreated MSCs transplantation in wound closure rate,as well as re-epithelization status,observed with hematoxylin and eosin staining.The diabetic wound healing mice model were divided into three groups:1)mice injected with PBS,2)mice transplanted with PBS-pretreated MSCs,and 3)mice transplanted with Sa-pretreated MSCs.Results(1)Hyperglycemic condition induced the generation of ROS and suppressed total cell number of MSCs,while Sa treatment into MSCs restored these hyperglycemia-induced alterations.In line with this,total apoptotic cells were also suppressed by treating MSCs with Sa.The expression level of cell survival factor,heme-oxygenase 1(HO-1),was enhanced in Sa-pretreated MSCs.Further treatment of HO-1 inhibitor into Sa-pretreated MSCs nullified the ROS level and total apoptotic cells,indica-ting the importance of HO-1 in mediating the Sa-induced survival of MSCs under hyperglycemia.(2)Transwell chamber and scratch assay results showed that Sa-pretreated MSCs have a higher migration potential under hyperglycemia,supported by higher F-actin polymerization fractal dimension.Fibroblast growth factor 2(FGF2)and hepatocyte growth factor(HGF)expression level,which are essential factors for cell migration,were also improved in Sa-pretreated MSCs under hyperglycemia.(3)In diabetic wound healing mice model,transplantation of Sa-pretreated MSCs resulted in significantly improved wound closure rate and re-epithelization.The protein levels of HO-1,FGF2,and HGF were also enhanced in the tissues obtained from the wound site of diabetic wound healing mice model which were transplanted with Sa-pretreated MSCs.Conclusions Salidroside pretreatment on MSCs could improve their survival and migration potentials,subsequently promoting wound healing process under hyperglycemia.This prospective MSC-based therapy could serve as a novel strategy to improve diabetic wound healing.
基金funded by National Nature Foundation of China ( 11532004,1140204,11832008)
文摘Objective Mitral valve(MV)plays an importance role in regulating blood flow from left atrium to left ventricle and preventing backflow to left atrium.Mitral Valve consist of four important parts;anterior leaflet,posterior leaflet,chordae tendineae,and papillary muscles,which all work in harmony.The material properties alteration on the leaflet causes MV malfunction,and leading to valve diseases such as regurgitation and stenosis.The alteration may be caused by several factors such as calcification,genetic disorders,and infection,which usually have an influence to the mechanical properties,and thus affecting the mechanical behavior of MV.In consequence,some of the patients need MV replacement or repair to restore the normal function of MV.The important point for succeeding such a medical treatment depends on the technique,design,and material used in the treatment shall help rebuild the normal mechanical environment and behavior of MV.Therefore,the mechanical and materials characteristics of MV become a magnetism to explore.In this study,we present an integrated experimental and mathematical constitutive study base in collagen distribution aiming at the mechanical property differences in various region on MV.Methods and materials Both the size and composition of porcine valves are similar to human’s,so the porcine heart valve is often being used in experimental research.Mitral valve was isolated from fresh eight porcine hearts(250-500 gr),and perfused in PBS solution to maintain moist.Anterior and posterior leaflets were separated and dissected into 4 part(two 8~*8 mm rough zone and two clear zone samples)and 2 part(8~*8 mm belly and edge of the clear zone)respectively.Tracking markers(glass bean)were stickled on specimen with superglue(cyanoacrylate adhesive).Then,the specimen was mounted onto biaxial tester machine(CeIIScale,Biotester),and the tests are run by force control.During mechanical test,the specimen is immersed into PBS solution in physiological temperature(37℃).Every test procedure contains 8 preconditioning cycles and 8 loading cycles.The mechanical behavior was determined from the relationship between first Piola-Kirchoff stress and stretch.Constitutive model was reconstructed and material parameters were fitted from biaxial tensile result.Histological analyses were performed in the specimen before and after test.First,a piece of the specimen was cut and immersed in fixation solution(4%paraformaldehyde),then it was dehydrated in graded alcohol solution,and next embedding in paraffin wax block.Paraffin block was then cut and stained with VVG and Picro-sirius red.The collagen fibril orientation was observed from those histological results.Results The experimental results of the clear zone of MV’s first Piola-Kirchhoff stress and stretch curve are similar to those of the recent study from others,while result of the rough zone shows a different trend.This can be explained by differences in collagen distribution between clear zone and rough zone of MV.Our result thus allows for a refinement of computational models for more accurately predicting MV condition,where tissue heterogeneity plays an important role in the MV function.
基金grants from the NSFC of China(No.30970721)the National Key Tech-nology R&D Program of China(2012BAI18B02)+1 种基金the Fundamental Research Funds for the Central Universities(No.CDJZR10230009)as well as the Public Experiment Center of State Bioindustrial Base(Chongqing),China.Thanks to Mr.Yi Cao and Dr.Li Xiao for their technical assistance in this experiment.
文摘Devices for the rotational culture of cells and the study of biological reactions have been widely applied in tissue engineering.However,there are few reports exploring the effects of rotational culture on cell morphology,nitric oxide(NO)production,and cell cycle of the endothelial cells from human umbili-cal vein on the stent surface.This study focuses on these parameters after the cells are seeded on the stents.Results showed that covering of stents by endothelial cells was improved by rotational culture.NO produc-tion decreased within 24 h in both rotational and static culture groups.In addition,rotational culture signifi-cantly increased NO production by 37.9%at 36 h and 28.9%at 48 h compared with static culture.Flow cytometry showed that the cell cycle was not obviously influenced by rotational culture.Results indicate that rotational culture may be helpful for preparation of cell-seeded vascular grafts and intravascular stents,which are expected to be the most frequently implanted materials in the future.
基金supported by grants from the National Natural Science Foundation of China(12032007,31971242,82270535)the Science and Technology Innovation Project of JinFeng Laboratory,Chongqing,China(jfkyjf202203001)。
文摘Objectives:To examine the 16-year developmental history,research hotspots,and emerging trends of zinc-based biodegradable metallic materials from the perspective of structural and temporal dynamics.Methods:The literature on zinc-based biodegradable metallic materials in WoSCC was searched.Historical characteristics,the evolution of active topics and development trends in the field of zinc-based biodegradable metallic materials were analyzed using the bibliometric tools CiteSpace and HistCite.Results:Over the past 16 years,the field of zinc-based biodegradable metal materials has remained in a hotspot stage,with extensive scientific collaboration.In addition,there are 45 subject categories and 51 keywords in different research periods,and 80 papers experience citation bursts.Keyword clustering anchored 3 emerging research subfields,namely,#1 plastic deformation#4 additive manufacturing#5 surface modification.The keyword alluvial map shows that the longest-lasting research concepts in the field are mechanical property,microstructure,corrosion behavior,etc.,and emerging keywords are additive manufacturing,surface modification,dynamic recrystallization,etc.The most recent research on reference clustering has six subfields.Namely,#0 microstructure,#2 sem,#3 additive manufacturing,#4 laser powder bed fusion,#5 implant,and#7 Zn-1Mg.Conclusion:The results of the bibliometric study provide the current status and trends of research on zinc-based biodegradable metallic materials,which can help researchers identify hot spots and explore new research directions in the field.
基金supported by grants from the Fundamental Research Funds for the Central Universities(No.2024CDJCGJ-016)National Natural Science Foundation of China(No.82270535)+1 种基金the Science and Technology Innovation Project of Jinfeng Laboratory,Chongqing,China(jfkyjf202203001)China Postdoctoral Science Foundation(2023MD734198).
文摘Demand for biliary stents has expanded with the increasing incidence of biliary disease.The implantation of plastic or self-expandable metal stents can be an effective treatment for biliary strictures.However,these stents are nondegradable and prone to restenosis.Surgical removal or replacement of the nondegradable stents is necessary in cases of disease resolution or restenosis.To overcome these shortcomings,improvements were made to the materials and surfaces used for the stents.First,this paper reviews the advantages and limitations of nondegradable stents.Second,emphasis is placed on biodegradable polymer and biodegradable metal stents,along with functional coatings.This also encompasses tissue engineering&3D-printed stents were highlighted.Finally,the future perspectives of biliary stents,including pro-epithelialization coatings,multifunctional coated stents,biodegradable shape memory stents,and 4D bioprinting,were discussed.
基金supported in part by the National Natural Science Foundation of China(No.31971242,12032007)the Chongqing Science and Technology Bureau(China)(No.cstc2021jsyj-yzysbA0057)the Joint Medical Research Project of Chongqing Science and Technology Bureau and Chongqing Health Commission(China)(No.2018ZDXM032).
文摘Atherosclerotic cardiovascular disease and its complications are a high-incidence disease worldwide.Numerous studies have shown that blood flow shear has a huge impact on the function of vascular endothelial cells,and it plays an important role in gene regulation of pro-inflammatory,pro-thrombotic,pro-oxidative stress,and cell permeability.Many impor-tant endothelial cell mechanosensitive genes have been discovered,including KLK10,CCN gene family,NRP2,YAP,TAZ,HIF-1α,NF-kB,FOS,JUN,TFEB,KLF2/KLF4,NRF2,and ID1.Some of them have been intensively studied,whereas the relevant regulatory mechanism of other genes remains unclear.Focusing on these mechanosensitive genes will provide new strategies for therapeutic intervention in atherosclerotic vascular disease.Thus,this article reviews the mechanosensitive genes affecting vascular endothelial cells,including classical pathways and some newly screened genes,and summarizes the latest research progress on their roles in the pathogenesis of atherosclerosis to reveal effective therapeutic targets of drugs and provide new insights foranti-atherosclerosis.
基金the National Natural Science Foundation of China(No.12032007,31971242 to G.Wang)the Science and Technology Innovation Project of Jinfeng Laboratory,Chongqing,China(No.jfkyjf202203001 to G.Wang).
文摘The clearance of apoptotic cell debris,containing professional phagocytosis and non-professional phagocytosis,is essential for maintaining the homeostasis of healthy tissues.Here,we discovered that endothelial cells could engulf apoptotic cell debris in atherosclerotic plaque.Single-cell RNA sequencing(RNA-seq)has revealed a unique endothelial cell subpopulation in atherosclerosis,which was strongly associated with vascular injury-related pathways.Moreover,integrated analysis of three vascular injury-related RNA-seq datasets showed that the expression of scavenger receptor class B type 1(SR-B1)was up-regulated and specifically enriched in the phagocytosis pathway under vascular injury circumstances.Single-cell RNA-seq and bulk RNA-seq indicate that SR-B1 was highly expressed in a unique endothelial cell subpopulation of mouse aorta and strongly associated with the reorganization of cellular adherent junctions and cytoskeleton which were necessary for phagocytosis.Furthermore,SR-B1 was strongly required for endothelial cells to engulf apoptotic cell debris in atherosclerotic plaque of both mouse and human aorta.Overall,this study demonstrated that apoptotic cell debris could be engulfed by endothelial cells through SR-B1 and associated with the reorganization of cellular adherent junctions and cytoskeleton.
基金supported by the Novel Coronavirus Infection and Prevention Emergency Scientific Research Special Project of Chongqing Municipal Education Commission,China(No.KYYJ202001)G.X.Wang,and the State Key Project Specialized for Infectious Diseases(China)(No.2017ZX10201201-001-005)to Y.M.Wang.
文摘CovID-19,also known as coronavirus disease 2019,is a novel coronavirus disease with high infectivity,strong heterogeneity,and long incubation period(generally 3-14 days).Its main symptoms and signs include fever,dry cough,nasal congestion,fatigue,disorientation,lymphopenia,and dyspnea.The short-term and long-term impacts of covID-19 on human health,particularly its effects on human reproduction and offspring development,continue to receive significant concerns,as they may lead to potential sequelae for several decades or even centuries.
基金support from the National Natural Science Foundation of China(project no.11972316)Shenzhen Science and Technology Innovation Commission(project nos.JCYJ20200109142001798,SGDX2020110309520303,and JCYJ20220531091002006)+3 种基金General Research Fund of Hong Kong Research Grant Council(PolyU 15214320)Health and Medical Research Fund(HMRF18191421)the Research Institute for Smart Ageing in Hong Kong Polytechnic University(1-CD75)Hong Kong Polytechnic University(1-ZE2M,1-ZVY1).
文摘Tumor cells progressively remodel cytoskeletal structures and reduce cellular stiffness during tumor progression,implicating the correlation between cell mechanics and malignancy.However,the roles of tumor cell cytoskeleton and the mechanics in tumor progression remain incompletely understood.We report that softening/stiffening tumor cells by targeting actomyosin promotes/suppresses self-renewal in vitro and tumorigenic potential in vivo.Weakening/strengthening actin cytoskeleton impairs/reinforces the interaction between adenomatous polyposis coli(APC)andβ-catenin,which facilitatesβ-catenin nuclear/cytoplasmic localization.Nuclearβ-catenin binds to the promoter of Oct4,which enhances its transcription that is crucial in sustaining self-renewal and malignancy.These results demonstrate that the mechanics of tumor cells dictate self-renewal through cytoskeleton-APC-Wnt/β-catenin-Oct4 signaling,which are correlated with tumor differentiation and patient survival.This study unveils an uncovered regulatory role of cell mechanics in self-renewal and malignancy,and identifies tumor cell mechanics as a hallmark not only for cancer diagnosis but also for mechanotargeting.
基金the Natural Science Foundation of Chongqing(cstc2020jcyj-msxmX0330)the JinFeng Laboratory Foundation,Chongqing,China(jfkyjf202203001)+3 种基金the Project of Tutorial System of Medical Undergraduate in Lab Teaching and Management Center in Chongqing Medical University(LTMCMTS202109 and LTMCMTS202106)the Project of Scientific Research and Innovative Experiment for College Student in Chongqing Medical University(SRIEP202011,SRIEP202047,and SPIEP202167)the National Project of University Students Innovation and Entrepreneurship Training Program(S202010631016)Chongqing Municipal Education Commission Foundation(CYS22333).
文摘Although neuroelectrochemical sensing technology offers unique benefits for neuroscience research,its application is limited by substantial interference in complex brain environments while ensuring biosafety requirements.In this study,we introduced poly(3-hexylthiophene)(P3HT)and nitrogen-doped multiwalled carbon nanotubes(N-MWCNTs)to construct a composite membrane-modified carbon fiber microelectrode(CFME/P3HT-N-MWCNTs)for ascorbic acid(AA)detection.The microelectrode presented good linearity,selectivity,stability,antifouling,and biocompatibility and exhibited great performance for application in neuroelectrochemical sensing.Subsequently,we applied CFME/P3HT-N-MWCNTs to monitor AA release from in vitro nerve cells,ex vivo brain slices,and in vivo living rat brains and determined that glutamate can induce cell edema and AA release.We also found that glutamate activated the N-methyl-d-aspartic acid receptor,which enhanced Na^(+) and Cl^(−) inflow to induce osmotic stress,resulting in cytotoxic edema and ultimately AA release.This study is the first to observe the process of glutamate-induced brain cytotoxic edema with AA release and to reveal the mechanism.Our work can benefit the application of P3HT in in vivo implant microelectrode construction to monitor neurochemicals,understand the molecular basis of nervous system diseases,and discover certain biomarkers of brain diseases.
基金supported by National Natural Science Foundation of China(No.31971242,and 12032007)the Natural Science Foundation of Chongqing(No.cstc2019jcyjmsxmX0307,cstc2019jcyj-19zdxmx0009,and cstc2019jcyjzdxmX0028).
文摘In recent years,cardiovascular health problems are becoming more and more serious.At the same time,mechanical stimulation closely relates to cardiovascular health.In this context,Piezo1,which is very sensitive to mechanical stimulation,has attracted our attention.Here,we review the critical significance of Piezo1 in mechanical stimulation of endothelial cells,NO production,lipid metabolism,DNA damage protection,the development of new blood vessels and maturation,narrowing of blood vessels,blood pressure regulation,vascular permeability,insulin sensitivity,and maintenance of red blood cell function.Besides,Piezo1 may participate in the occurrence and development of atherosclerosis,diabetes,hypertension,and other cardiovascular diseases.It is worth noting that Piezo1 has dual effects on maintaining cardiovascular health.On the one hand,the function of Piezo1 is necessary to maintain cardiovascular health;on the other hand,under some extreme mechanical stimulation,the overexpression of Piezo1 may bring adverse factors such as inflammation.Therefore,this review discusses the Janus-faced role of Piezo1 in maintaining cardiovascular health and puts forward new ideas to provide references for gene therapy or nanoagents targeting Piezo1.
基金This work was supported in part by grants from the National Natural Science Foundation of China(12032007,31971242)Chongqing Research Program of Basic research and Frontier Technology(cstc2019jcyj-zdxmX0028)+1 种基金JinFeng Laboratory Foundation,Chongqing,China(jfkyjf202203001)Shanghai Clinical Research Center for Interventional Medicine(19MC1910300).
文摘Purpose:This review aims to explore the history,research hotspots,and emerging trends of drug-eluting stents(DES)in the last two decades from the perspective of structural and temporal dynamics.Methods:Publications on DES were retrieved from WoSCC.The bibliometric tools including CiteSpace and HistCite were used to identify the historical features,the evolution of active topics,and emerging trends on the DES field.Results:In the last 20 years,the field of DES is still in the hot phase and there is a wide range of extensive scientific collaborations.In addition,active topics emerge in different periods,as evidenced by a total of 41 disciplines,511 keywords,and 1377 papers with citation bursts.Keyword clustering anchored five emerging research subfields,namely#0 dual antiplatelet therapy,#3 drug-coated balloon,#4 bifurcation,5#rotational atherectomy,and 6#quantitative flow ratio.The keyword alluvial map shows that the most persistent research concepts in this field are thrombosis,restenosis,etc.,and the emerging keywords are paclitaxel eluting balloon,coated balloon,drug-eluting balloon,etc.There are 7 recent research subfields anchored by reference clustering,namely#2 dual antiplatelet therapy,#4 drug-coated balloon,#5 peripheral artery disease,#8 fractional flow reserve,#10 bioresorbable vascular scaffold,#13 intravascular ultrasound,#14 biodegradable polymer.Conclusion:The findings based on the bibliometric studies provide the current status and trends in DES research and may help researchers to identify hot topics and explore new research directions in this field.
基金supported by The National Natural Science Foundation of China(No.11932014,32071312,31870939,31971239 and 12032007).
文摘Atherosclerosis is a chronic inflammatory disease, occurring preferentially in bifurcation, branching, and bending of blood vessels exposed to disturbed flow. Disturbed flow in atheroprone areas activates elevated proteases, degrading elastin lamellae and collagenous matrix, resulting in endothelial dysfunction and vascular remodeling. As a mediator for extracellular matrix protein degradation, cathepsin K (CTSK) was directly regulated by hemodynamics and contributed to atherosclerosis. The mechanism of CTSK responding to disturbed flow and contributing to disturbed flow-induced atherosclerosis is unclear. In this study, the partial carotid ligation model of mice and in vitro disturbed shear stress model were constructed to explore the contribution and potential mechanism of CTSK in atherosclerosis. Our results indicated that CTSK elevated in the disturbed flow area in vivo and in vitro along with endothelial inflammation and atherogenesis. Additionally, the expression of integrin αvβ3 was upregulated in these atheroprone areas. We found that inhibition of the integrin αvβ3-cytoskeleton pathway could significantly block the activation of NF-κB and the expression of CTSK. Collectively, our findings unraveled that disturbed flow induces increased CTSK expression, and contributes to endothelial inflammation and vascular remodeling, leading to atherogenesis eventually. This study is helpful to provide new enlightenment for the therapy of atherosclerosis.
基金This work was supported by grants from the Natural Science Foundation of Chongqing(cstc2020jcyj-msxmX0330,cstc2021jsyj-yzysbA0057,and cstc2019jcyj-zdxmX0028)the National Natural Science Foundation of China(31971242 and 12032007)+4 种基金the Project of Tutorial System of Medical Undergraduate in Lab Teaching&Management Center in Chongqing Medical University(LTMCMTS202005 and LTMCMTS202110)the JinFeng Laboratory Foundation of Chongqing(jfkyjf202203001)the Scientific and Technological Research Program of Chongqing Municipal Education Commission(KJQN202200426)the Scientific Research,the CQMU Program for Youth Innovation in Future Medicine(W0015)the Innovation Experimental Project of Chongqing Medical University(SRIEP202105).
文摘Multiple signal strategies remarkably improve the accuracy and efficiency of electrochemiluminescence(ECL)immunoassays,but the lack of potential-resolved luminophore pairs and chemical cross talk hinders their development.In this study,we synthesized a series of gold nanoparticles(AuNPs)/reduced graphene oxide(Au/rGO)composites as adjustable oxygen reduction reaction and oxygen evolution reaction catalysts to promote and modulate tris(2,2′-bipyridine)ruthenium(II)(Ru(bpy)_(3)^(2+))’s multisignal luminescence.With the increase in the diameter of AuNPs(3 to 30 nm),their ability to promote Ru(bpy)_(3)^(2+)’s anodic ECL was first impaired and then strengthened,and cathodic ECL was first enhanced and then weakened.Au/rGOs with medium-small and medium-large AuNP diameters remarkably increased Ru(bpy)_(3)^(2+)’s cathodic and anodic luminescence,respectively.Notably,the stimulation effects of Au/rGOs were superior to those of most existing Ru(bpy)_(3)^(2+)co-reactants.Moreover,we proposed a novel ratiometric immunosensor construction strategy using Ru(bpy)_(3)^(2+)’s luminescence promoter rather than luminophores as tags of antibodies to achieve signal resolution.This method avoids signal cross talk between luminophores and their respective co-reactants,which achieved a good linear range of 10−7 to 10−1 ng/ml and a limit of detection of 0.33 fg/ml for detecting carcinoembryonic antigen.This study addresses the previous scarcity of the macromolecular co-reactants of Ru(bpy)_(3)^(2+),broadening its application in biomaterial detection.Furthermore,the systematic clarification of the detailed mechanisms for converting the potential-resolved luminescence of Ru(bpy)_(3)^(2+)could facilitate an in-depth understanding of the ECL process and should inspire new designs of Ru(bpy)_(3)^(2+)luminescence enhancers or applications of Au/rGOs to other luminophores.This work removes some impediments to the development of multisignal ECL biodetection systems and provides vitality into their widespread applications.
基金supported by grants from Joint Medical Research Project of Chongqing Science and Technology Bureau and Health Commission(2019MSXM048)Scientific Research Special Project of Chongqing Municipal Education Commission,China(KYYJ202001).
文摘The goal of this paper is to explore a method for virus inactivation based on ultrasonic treatment,and on this basis,to explore the synergistic effect of methylene blue as a sonosensitizer in virus inactivation.The titer of human parainfluenza virus type 3(HPIV3),Autographacaliforinica nuclear polyhedrosis virus carried a green fluorescent reporter gene(AcNPV-GFP)and Enterovirus group D 68(EV-D68)were determined by plaque assays or TCID50 methods after treatment by MB combined with illumination(MB photochemical,MBP)or ultrasonic excitation.Different ultrasonic power and time,MB concentration gradient were set to determine the best antiviral combination.For the enveloped virus HPIV3 and AcNPV-GFP,pure ultrasonic or MBP treatment could reduce viral titer more than 104,and ultrasonic combined with MB could completely inactivate HPIV3 and AcNPV-GFP in 5min while traditional MBP methods could only reduce viral titer about 10X.For the nonenveloped virus EV-D68,pure ultrasonic or MBP treatment only reduced the viral titer about 102,but ultrasonic combined with MB treatment could reduce the viral titer about 103 in 5min and completely inactive EV-D68 in 10min(reduced 105).Compared with MBP method and pure ultrasonic inactivation,ultrasonic combined with MB has better inactivation effect on either enveloped or non-enveloped viruses,and the appropriate combination of parameters is expected to be a new blood transfusion transmitted virus inactivation method.
基金supported by the Natural Science Foundation of China(No.31971242,12032007)Chongqing Science and Technology Bureau(China)(No.cstc2019jcyj-zdxmX0028,cstc2020jscx-msxmX0132)+1 种基金Chongqing Postdoctoral Science Foundation(China)(No.cstc2021jcyj-bsh0208,cstc2021jcyj-bshX0181)Fundamental Research Funds for Central Universities(China)(No.2021CDJCGJ007).
文摘Atherosclerosis is a chronic progressive disease and one of the major causes of cardio-cerebral vascular diseases.Accumulating evidence indicates that endothelial dysfunc-tion is the initiating step in atherosclerosis.The pattern of local blood flow becomes disturbed(low and oscillatory shear stress[OSS])in the curved or branched segments of the arterial tree,causing endothelial cells(ECs)to exhibit athero-susceptible phenotypes,such as hyperproliferation and inflammation.
基金supported by the National Natural Science Foundation of China(No.31971242,12032007,and 31771599)Key grants from Chongqing Science and Technology Bureau,China(No.cstc2019jcyj-zdxmX0028)+1 种基金the State Key Project Specialized for Infectious Diseases,China(No.2017ZX10201201-001-005,and 2017ZX10201201-002-005)as well as Visiting Scholar Foundation of Key Laboratory of Biorheological Science and Technology(Chongqing University),Ministry of Education,China(No.CQKLBST-2020-007).
文摘Genetic compensation is a remarkable biological concept to explain the genetic robustness in an organism to maintain its fitness and viability if there is a disruption occurred in the genetic variation by mutation.However,the underlying mechanism in genetic compensation remain unsolvable.The initial concept of genetic compensation has been studied in model organisms when there was a discrepancy between knockout-mediated and knockdown-mediated phenotypes.In the zebrafish model,several studies have reported that zebrafish mutants did not exhibit severe phenotype as shown in zebrafish morphants for the same genes.This phenomenon in zebrafish mutants but not morphants is due to the response of genetic compensation.In 2019,two amazing works partially uncovered genetic compensation could be triggered by the upregulation of compensating genes through regulating NMD and/or PTC-bearing mRNA in collaboration with epigenetic machinery in mutant zebrafish.In this review,we would like to update the recent advances and future perspectives of genetic compensation studies,which including the hypothesis of time-dependent involvement and addressing the discrepancy between knockout-mediated and knockdown-mediated to study gene function in the zebrafish model.At last,the study of genetic compensation could be a potential therapeutic strategy to treat human genetic disorder related diseases.
基金supported by grants from the Natural Science Foundation of Chongqing(cstc2020jcyj-msxmX0330,cstc2021jsyjyzysbA0057)the National Natural Science Foundation of China(31971242,12032007)+1 种基金the Science and Technology Innovation Project of Jinfeng Laboratory,Chongqing,China(jfkyjf202203001)the Project of Tutorial System of Medical Undergraduate in Lab Teaching&Management Center in Chongqing Medical University(LTMCMTS202107).
文摘The most common socioeconomic healthcare issues in clinical are burns,surgical incisions and other skin injuries.Skin lesion healing can be achieved with nanomedicines and other drug application techniques.This study developed a nano-spray based on cross-linked amorphous calcium peroxide(CaO_(2))nanoparticles of polyacrylic acid(PAA)for treating skin wounds(PAA-CaO_(2)nanoparticles).CaO_(2)serves as a‘drug’precursor,steadily and continuously releasing calcium ions(Ca^(2+))and hydrogen peroxide(H_(2)O_(2))under mildly acidic conditions,while PAA-CaO_(2)nanoparticles exhibited good spray behavior in aqueous form.Tests demonstrated that PAA-CaO_(2)nanoparticles exhibited low cytotoxicity and allowed L929 cells proliferation and migration in vitro.The effectiveness of PAA-CaO_(2)nanoparticles in promoting wound healing and inhibiting bacterial growth in vivo was assessed in SD rats using full-thickness skin defect and Staphylococcus aureus(S.aureus)-infected wound models based thereon.The results revealed that PAA-CaO_(2)nanoparticles demonstrated significant advantages in both aspects.Notably,the infected rats’skin defects healed in 12 days.The benefits are linked to the functional role of Ca^(2+)coalesces with H_(2)O_(2)as known antibacterial and healing-promoted agents.Therefore,we developed nanoscale PAA-CaO_(2)sprays to prevent bacterial development and heal skin lesions.
基金supported by the National Natural Science Foundation of China(12032007,31971242)to G.W.the Chongqing Science and Technology Bureau(cstc2019jcyj-zdxmX0028)to G.W.JinFeng Laboratory,Chongqing,China(jfkyjf202203001)to G.W.
文摘Nanoparticles(NPs)hold tremendous targeting potential in cardiovascular disease and regenerative medicine,and exciting clinical applications are coming into light.Vascular endothelial cells(ECs)exposure to different magnitudes and patterns of shear stress(SS)generated by blood flow could engulf NPs in the blood.However,an unclear understanding of the role of SS on NP uptake is hindering the progress in improving the targeting of NP therapies.Here,the temporal and spatial distribution of SS in vascular ECs and the effect of different SS on NP uptake in ECs are highlighted.The mechanism of SS affecting NP uptake through regulating the cellular ROS level,endothelial glycocalyx and membrane fluidity is summarized,and the molecules containing clathrin and caveolin in the engulfment process are elucidated.SS targeting NPs are expected to overcome the current bottlenecks and change the field of targeting nanomedicine.This assessment on how SS affects the cell uptake of NPs and the marginalization of NPs in blood vessels could guide future research in cell biology and vascular targeting drugs.