Targeting the resolution pathway of inflammation using Ac2–26 peptide-loaded PEGylated lipid nanoparticles for the remission of rheumatoid arthritis

Rheumatoid arthritis(RA)is a common autoimmune disease characterized by joint inflammation and immune dysfunction.Although various therapeutic approaches have been utilized for the treatment of RA in clinical applications,the low responsiveness of RA patients and undesired systemic toxicity are still unresolved problems.Targeting the resolution pathway of inflammation with pro-resolving mediators would evoke the protective actions of patient for combating the inflammation.Ac2–26,a 25-amino acid peptide derived from Annexin A(a pro-resolving mediator),has shown good efficacy in the treatment of inflammatory disorders.However,the low bioavailability of Ac2–26 peptides hinders their efficacy in vivo.In this paper,we formed PEGylated lipid nanoparticles(LDNPs)by the co-assembly of l-ascorbyl palmitate(L-AP)and N-(carbonyl methoxypolyethylene glycol-2000)-1,2-distearoyl-sn–glycero-3-phosphoethanolamine(DSPE-PEG 2 k)to encapsulate and deliver Ac2–26 peptides to the arthritic rats.They showed good stability and biocompatibility.After being intravenously administrated,Ac2–26 peptide-loaded PEGylated lipid nanoparticles(ADNPs)showed the prolonged in vivo circulation time and enhanced accumulation in inflamed sites.In vivo therapeutic evaluations revealed that ADNPs could attenuate synovial inflammation and improve joint pathology.Therefore,the pro-resolving therapeutic strategy using ADNPs is effective in RA treatment.

Numerical simulation of plasma-assisted combustion of methane-air mixtures in combustion chamber

A two-dimensional mathematical model was developed to investigate the effects of dielectric barrier discharge （DBD） plasma on CH4-air mixtures combustion at atmospheric pressure. Considering the physical and chemical processes of plasma-assisted combustion （PAC）, plasma discharge, heat transfer and turbulent were simultaneously coupled into simulation of PAC. This coupling model consists of DBD kinetic model and methane combustion model. By comparing simulations and the original reference＇s results, a high-accuracy of this model was validated. In addition, the effects of PAC actuation parameters on combustion characteristics were studied. Numerical simulations show that with an inlet airflow velocity of 10 m s-1, a CH4-air mixtures＇ equivalence ratio of 0.5, an applied voltage of 10 kV, a frequency of 1200 kHz, compared to conventional combustion （CC）, the highest flame temperature rises by 32 K; outlet temperature distribution coefficient drops by 2.3%; the maximum net reaction rate of CH4 and H20 increase by 11.22% and 12.80% respectively; the maximum CO emission index decreases by 14.61%; the mixing region turbulence mixing time reduces by 89 ms.

Application study on plasma ignition in aeroengine strut–cavity–injector integrated afterburner

To increase the thrust-weight ratio in next-generation military aeroengines,a new integrated afterburner was designed in this study.The integrated structure of a combined strut–cavity–injector was applied to the afterburner.To improve ignition characteristics in the afterburner,a new method using a plasma jet igniter was developed and optimized for application in the integrated afterburner.The effects of traditional spark igniters and plasma jet igniters on ignition processes and ignition characteristics of afterburners were studied and compared with the proposed design.The experimental results show that the strut–cavity–injector combination can achieve stable combustion,and plasma ignition can improve ignition characteristics.Compared with conventional spark ignition,plasma ignition reduced the ignition delay time by 67 ms.Additionally,the ignition delay time was reduced by increasing the inlet velocity and reducing the excess air coefficient.This investigation provides an effective and feasible method to apply plasma ignition in aeroengine afterburners and has potential engineering applications.

A non-viral gene therapy for melanoma by staphylococcal enterotoxin A

Staphylococcal enterotoxin A(SEA)derived from Staphylococcus aureus,as a superantigen,shows potential for cancer immunotherapy,but systemic immunotoxicity restricts its clinical application.Targeted delivery of SEA to tumor site provides a promising option for reducing the systemic toxicity.Here,we constructed an iRGD peptide(H-[Cys-Arg-Gly-Asp-Lys-Gly-Pro-Asp-Cys]-NH_(2))modified nanoparticle(iDPP)to deliver plasmids encoding SEA for melanoma treatment.The iDPP/SEA nanocomplexes efficiently mediated SEA expression in B16-F10 cells in vivo and in vitro and induced the activation of lymphocytes and maturation of murine bone marrow-derived dendritic cells(BMDCs)in vitro.In the subcutaneous B16-F10 melanoma model,the iDPP/SEA nanocomplexes could effectively enhance immune response and T lymphocytes infiltration in tumor site after intravenous administration,thereby considerably decreased melanoma growth.Meanwhile,no obvious adverse effect was observed after intravenous administration of the iDPP/SEA nanocomplexes in vivo.Our findings demonstrated that gene therapy of SEA is a potential candidate for melanoma treatment.

Sulfated peptides and their receptors:Key regulators of plant development and stress adaptation

Four distinct types of sulfated peptides have been identified in Arabidopsis thaliana.These peptides play crucial roles in regulating plant development and stress adaptation.Recent studies have revealed that Xan-thomonas and Meloidogyne can secrete plant-like sulfated peptides,exploiting the plant sulfated peptide signaling pathway to suppress plant immunity.Over the past three decades,receptors for these four types of sulfated peptides have been identified,all of which belong to the leucine-rich repeat receptor-like protein kinase subfamily.A number of regulatory proteins have been demonstrated to play important roles in their corresponding signal transduction pathways.In this review,we comprehensively summarize the discov-eries of sulfated peptides and their receptors,mainly in Arabidopsis thaliana.We also discuss their known biological functions in plant development and stress adaptation.Finally,we put forward a number of ques-tions for reference in future studies.

The influence of radial entrance width of the circular cavity on incident shock wave focusing

Despite the achievement of shock wave focusing with certain reflectors,the influence of the radial entrance width of a circular cavity on the flow field has yet to be addressed.In this study,we systematically investigated the effects of the shock wave focusing process in a cavity based on the radial entrance widths.An experimental system was installed to research the evolution of the flow field under conditions with different radial entrance widths of 3.0,11.1,19.5,and 33.0 mm.A schlieren system was used to photograph the structures of the flow field in the cavity,and a data acquisition system was used to record the dynamic pressure histories of different points.A numerical simulation was carried out to investigate greater details of the shock wave focusing process.A third-order strong stability-preserving Runge-Kutta method,third-order weighed essential non-oscillation scheme,and an adaptive mesh refinement algorithm were adopted to simulate the shock wave reflection,diffraction,and focus process.Good agreement between the experimental and numerical results was observed.By comparing the evolution process of the flow field under the conditions of four different entrance cavity widths,we found that when the entrance width was 19.5 mm,there was the stronger intensity of the shock wave focusing in the focal region,and the larger pressure value at the apex of the cavity than the other three entrance widths,occur.This study improves our understanding of shock wave focusing.

Biomechanical analysis of an osteocyte model by considering bone matrix’s piezoelectricity

Osteocytes,the primary cells in bone,play a crucial role in sensing external load environments and regulating other bone cells.Due to the piezoelectric effect of the mineralized matrix and collagen that make up bone,the mechanical stimulus received is converted into an electrical stimulus to affect the reconstruction of bone.Despite the importance of osteocyte,many studies have focused on the mechanical loading and fluid flow of it,there is still a gap in the study of the piezoelectric effects of various mechanosensors on the microscale.In this paper,we developed a finite element model of osteocytes that incorporates the piezoelectric bone matrix.This model is comprehensive,comprising the osteocyte cell body enclosed by lacuna,osteocyte processes enclosed by canaliculi,and the interposed charged ionic fluid.Additionally,it features mechanosensors such as collagen hillocks and primary cilia.In our study,we subjected the piezoelectric bone matrix model to triaxial displacement,subsequently assessing the electrical signal variations across different mechanosensors within the osteocyte.The observed disparities in mechanical perception by various mechanosensors were primarily attributable to greater liquid velocity changes in the polarization direction as opposed to other directions.Collagen hillocks showed insensitivity to piezoelectric signals,serving predominantly to mechanically transmit signals through solid-to-solid contact.In contrast,processes and primary cilia were highly responsive to piezoelectric signals.Interestingly,the processes oriented in the direction of the electric field demonstrated a differential piezoelectric signal perception compared to those in other directions.Primary cilia were especially sensitive to fluid flow pressure changes,which were influenced both by loading rates and external piezoelectric effects.Overall,our findings illuminate the complexity of mechanical perception within osteocytes in a piezoelectric environment.This adds a new dimension to our understanding and suggests avenues for future research in bone reconstruction and cellular mechanical behavioral transmission.

Experimental study of rotating gliding arc discharge plasma-assisted combustion in an aero-engine combustion chamber

The combustion chamber is the core component of an aero-engine, and affects its reliability and security operation, even the performance of the aircraft. In this work, a Plasma-Assisted Combustion(PAC) test platform was developed to validate the feasibility of using PAC actuators to enhance annular combustor performance. Two plans of PAC(rotating gliding arc discharge plasma) were designed, Assisted Combustion from Primary Holes(ACPH) and Assisted Combustion from Dilution Holes(ACDH). Comparative experiments and analysis between conventional combustion and PAC were conducted to study the effects of ACPH and ACDH on the performances including average outlet temperature, combustion efficiency, pattern factor under four different excessive air coefficients(0.8, 1, 2, and 4), and lean blowout performance at different inlet airflow velocities. Experimental results show that the combustion efficiency is improved after PAC compared with that in normal conditions, and the combustion efficiency of ACPH increases2.45%, 1.49%, 1.04%, and 0.47%, while it increases 2.75%, 1.67%, 1.36%, and 0.36% under ACDH conditions. The uniformity of the outlet temperature field and the lean blowout performance are improved after PAC. Especially for ACPH, the widening of the lean blowout limit is8.3%, 12.4%, 12.8%, and 25% respectively when the inlet velocity ranges from 60 m/s to120 m/s. These results offer new perspectives for using PAC devices to enhance aero-engine combustors' performances.

Research progress of microwave plasma ignition and assisted combustion

As the low temperature non-equilibrium plasma,microwave plasma has the same effects with the plasma produced by the traditional high voltage electrode,which has the function of widening ignition boundary and improving combustion.Microwave has the advantages of uniformity,particle selectivity and no electrode.It can generate a large range of non-equilibrium plasma with relatively low power without electrode ablation.Therefore,how to maximize its effectiveness has become the research hotspot of ignition and combustion in engines.At present,the related research mainly focuses on microwave plasma discharge and microwave assisted spark ignition.The results show that it can broaden lean and rich burn flammability limits,improve combustion efficiency,accelerate flame propagation speed,and reduce pollutant emissions.This paper summarizes the related research at home and abroad in recent years,the main conclusion is that how the microwave plasma affects the turbulence intensity of flow field will be the promising research,and the research trend of microwave plasma ignition and assisted combustion in future will be the research of microwave assisted plasma igniter.

Biomechanical evaluation of two fusion techniques based on finite element analysis:Percutaneous endoscopic and minimally invasive transforaminal lumbar interbody fusion

As a novel minimally invasive technique,percutaneous endoscopic transforaminal lumbar interbody fusion(PETLIF)has been widely used in the treatment of lumbar degenerative diseases.The purpose of this study was to analyze these two operation types’biomechanical performances of PE-TLIF and traditional minimally invasive transforaminal lumbar interbody fusion(MIS-TLIF)using the finite element(FE)method.The intact FE models of L4-L5 were established and validated based on the CT images.On this basis,the FE models of MIS-TLIF and PETLIF were established and analyzed.It is demonstrated that for lumbar interbody fusion with the oblique asymmetrically implanted cage under bilateral pedicle screws and rods fixation,such as MIS-TLIF and PE-TLIF,different degrees of articular process resection have no significant effect on the cage subsidence,and the surgical segment can achieve similar stability.In addition,the maximum stress of the L4 inferior endplate of MIS-TLIF and PE-TLIF is greater than that of the L5 superior endplate,which indicates that MIS-TLIF and PE-TLIF can cause cage subsidence in the L4 inferior endplate.

一种新型设计的个性化椎间融合器及其生物力学分析

椎间融合器在临床上经常用于脊柱感染性和退行性疾病的治疗,然而,进一步的临床应用通常受到一些缺陷的困扰,如应力遮挡和融合器沉降.本研究旨在提出一种新的脊柱融合器个性化设计理念:从微观到宏观的多尺度联合设计方法,创建与腰椎骨终板弹性模量和手术形式皆匹配的脊柱融合器.具体而言,引入三周期极小曲面来模拟聚醚醚酮(PEEK)融合器的多孔结构,通过调整孔隙参数以实现定制的宏观力学性能和孔隙结构的渗透性能。接着,针对经皮内镜下腰椎后路椎间融合术(PE-PLIF)进行多目标(屈伸、弯曲和扭转)拓扑优化,得到二次设计的新型多孔拓扑融合器。最后,将临床常用的钛融合器、PEEK融合器和本文设计的新型融合器进行基于有限元方法的生物力学对比分析。结果表明,与其他两种融合器相比,新型多孔拓扑融合器有着较低的骨-融合器界面应力和较高的内部移植骨应力和应变能密度,证明其有着较低的融合器沉降率和应力屏蔽的风险.总之,新型多孔拓扑融合器由于其良好的生物力学性能成为椎间融合术的理想选择.本文所提出的融合器设计思路和理念也可用于指导其他不同椎间融合术.