AAV-mediated expression of p65shRNA and bone morphogenetic protein 4 synergistically enhances chondrocyte regeneration

BACKGROUND:Adeno-associated virus(AAV)gene therapy has been proven to be reliable and safe for the treatment of osteoarthritis in recent years.However,given the complexity of osteoarthritis pathogenesis,single gene manipulation for the treatment of osteoarthritis may not produce satisfactory results.Previous studies have shown that nuclear factorκB could promote the inflammatory pathway in osteoarthritic chondrocytes,and bone morphogenetic protein 4(BMP4)could promote cartilage regeneration.OBJECTIVE:To test whether combined application of AAV-p65shRNA and AAV-BMP4 will yield the synergistic effect on chondrocytes regeneration and osteoarthritis treatment.METHODS:Viral particles containing AAV-p65-shRNA and AAV-BMP4 were prepared.Their efficacy in inhibiting inflammation in chondrocytes and promoting chondrogenesis was assessed in vitro and in vivo by transfecting AAV-p65-shRNA or AAV-BMP4 into cells.The experiments were divided into five groups:PBS group;osteoarthritis group;AAV-BMP4 group;AAV-p65shRNA group;and BMP4-p65shRNA 1:1 group.Samples were collected at 4,12,and 24 weeks postoperatively.Tissue staining,including safranin O and Alcian blue,was applied after collecting articular tissue.Then,the optimal ratio between the two types of transfected viral particles was further investigated to improve the chondrogenic potential of mixed cells in vivo.RESULTS AND CONCLUSION:The combined application of AAV-p65shRNA and AAV-BMP4 together showed a synergistic effect on cartilage regeneration and osteoarthritis treatment.Mixed cells transfected with AAV-p65shRNA and AAV-BMP4 at a 1:1 ratio produced the most extracellular matrix synthesis(P<0.05).In vivo results also revealed that the combination of the two viruses had the highest regenerative potential for osteoarthritic cartilage(P<0.05).In the present study,we also discovered that the combined therapy had the maximum effect when the two viruses were administered in equal proportions.Decreasing either p65shRNA or BMP4 transfected cells resulted in less collagen II synthesis.This implies that inhibiting inflammation by p65shRNA and promoting regeneration by BMP4 are equally important for osteoarthritis treatment.These findings provide a new strategy for the treatment of early osteoarthritis by simultaneously inhibiting cartilage inflammation and promoting cartilage repair.

Role of microglial polarization in age-related macular degeneration

Microglia,originating from primitive macrophages in the yolk sac,serves as both immune system defenders and regulators of homeostasis.These cells exhibit two primary polarization states:conventionally activated(M1)and alternatively activated(M2).The polarization of microglia plays a crucial role in influencing inflammatory disorders,metabolic imbalances,and neural degeneration.This process is implicated in various aspects of ocular diseases,especially age-related macular degeneration(AMD),including inflammation,oxidative stress and pathological angiogenesis.The distinct functional phenotypes of microglia impact disease progression and prognosis.Thus,regulating the polarization or functional phenotype of microglia at different stages of AMD holds promise for personalized therapeutic approaches.This comprehensive review outlines the involvement of microglia polarization in both physiological and pathological conditions,emphasizing its relevance in AMD.The discussion underscores the potential of polarization as a foundation for personalized treatment strategies for AMD.

Syntheses,crystal structures,and catalytic properties of three zinc(Ⅱ),cobalt(Ⅱ)and nickel(Ⅱ)coordination polymers constructed from 5⁃(4⁃carboxyphenoxy)nicotinic acid

Three zinc(Ⅱ),cobalt(Ⅱ),and nickel(Ⅱ)coordination polymers,namely[Zn(μ^(3-)cpna)(μ-dpea)_(0.5)]_(n)(1),[Co(μ^(3-)cpna)(μ-dpey)_(0.5)]_(n)(2),and[Ni(μ^(3-)cpna)(μ-dpey)_(0.5)(H_(2)O)]_(n)(3),have been constructed hydrothermally using H_(2)cpna(5-(4-carboxyphenoxy)nicotinic acid),dpea(1,2-di(4-pyridyl)ethane),dpey(1,2-di(4-pyridyl)ethylene),and zinc,cobalt,and nickel chlorides at 160℃.The products were isolated as stable crystalline solids and were characterized by IR spectra,elemental analyses,thermogravimetric analyses,and single-crystal X-ray diffraction analyses.Single-crystal X-ray diffraction analyses revealed that three compounds crystallize in the triclinic system,space group P1.Compounds 1-3 show 2D layer structures.The catalytic activities in the Knoevenagel condensation reaction of these compounds were investigated.Compounds 1 and 2 exhibit effective catalytic activities in the Knoevenagel condensa-tion reaction at room temperature.For this reaction,various parameters were optimized,followed by the investiga-tion of the substrate scope.CCDC:2335676,1;2335677,2;2335678,3.

Perfecting HER catalysts via defects:Recent advances and perspectives

Defect engineering has become a promising approach to improve the performance of hydrogen evolution reaction(HER)catalysts.Non-noble transition metal-based catalysts(TMCs)have shown significant promise as effective alternatives to traditional platinum-group catalysts,attracting considerable attention.However,the industrial application of TMCs in electrocatalytic hydrogen production necessitates further optimization to boost both catalytic activity and stability.This review comprehensively examines the types,fabrication methods,and characterization techniques of various defects that enhance catalytic HER activity.Key advancements include optimizing defect concentration and distribution,coupling heteroatoms with vacancies,and leveraging the synergy between bond lengths and defects.In-depth discussions highlight the electronic structure and catalytic mechanisms elucidated through in-situ characterization and density functional theory calculations.Additionally,future directions are identified,exploring novel defect types,emphasizing precision synthesis methods,industrial-scale preparation techniques,and strategies to enhance structural stability and understanding the in-depth catalytic mechanism.This review aims to inspire further research and development in defect-engineered HER catalysts,providing pathways for high efficiency and cost-effectiveness in hydrogen production.

Progresses and future directions on yardangs

Background,aim,and scope Yardang is a kind of typical wind-eroded landform in arid zones both on Earth and other planets.Their geomorphic process records the surface changes and climate,which may play a vital role in exploring the coupled landform-atmosphere system in arid zones.Recently,significant progresses have been made in this research field,and a review is still absent,which is the aim of the paper.Materials and methods Previous studies on the distribution,composition,morphology,and climatic driving force of yardang landform were reviewed.Results Earth yardang’s three evolutionary models were generalized:morphology evolution model,altitude evolution model and climate driven evolution model.Extraterrestrial yardang and its evolution are also summarized:the morphology is dominated by long ridges on Venus and Titan,and three yardang evolution hypotheses and an indirect dating method based on stratigraphic contact have been studied on Mars.Discussion In this study,firstly,the definition and morphology of yardang were described to define its characteristics.Secondly,we argue that yardang evolution has two dimensions:short-term variation and longterm variation.In the short-term variation,the morphological evolution of yardang on earth can be divided into four stages:embryonic stage,juvenile stage,mature stage,and demise stage.In the long-term variation,the evolution of yardang on earth is climate-driven,i.e.,it is controlled by atmospheric circulation changes during glacial-interglacial periods.Thirdly,yardang research on extraterrestrial bodies was also summarized:yardang has been found on Mars,Venus,and Titan,and the research focus by far are on geomorphology only.Conclusions(1)Yardang landform is an erosion landform with alternating ridges and troughs,with main form of whale back shape and fluctuations in the range of aspect ratios;(2)the short-term variation of yardang is manifested in its morphological evolution and height change,while the long-term variation is climate-driven;(3)based on Earth yardang,extraterrestrial yardang research has been carried out on Mars,Venus,and Titan.Recommendations and perspectives We then proposed that:(1)yardang formation ages,due to the erosion characteristics,are difficult to constraint;(2)the wind erosion capacity in the yardang areas might have been severely underestimated,making it essential to re-evaluate the previous paleoclimate reconstruction in the closed basins with limited chronological data;(3)yardang evolution is driven by climate change,but the coupling relationship between the yardang geomorphy and the air circulation is still unclear.Finally,future research directions:(1)more chronological data are needed,as well as the wind erosion capacity for yardang initiation and development;(2)the co-evolution of mid-low latitude landforms involved in yardang long-term variation and its relationship with global atmospheric circulation.

A Prognostic Model Based on Colony Stimulating Factors-related Genes in Triple-negative Breast Cancer

Objective Triple-negative breast cancer(TNBC)is the breast cancer subtype with the worst prognosis,and lacks effective therapeutic targets.Colony stimulating factors(CSFs)are cytokines that can regulate the production of blood cells and stimulate the growth and development of immune cells,playing an important role in the malignant progression of TNBC.This article aims to construct a novel prognostic model based on the expression of colony stimulating factors-related genes(CRGs),and analyze the sensitivity of TNBC patients to immunotherapy and drug therapy.Methods We downloaded CRGs from public databases and screened for differentially expressed CRGs between normal and TNBC tissues in the TCGA-BRCA database.Through LASSO Cox regression analysis,we constructed a prognostic model and stratified TNBC patients into high-risk and low-risk groups based on the colony stimulating factors-related genes risk score(CRRS).We further analyzed the correlation between CRRS and patient prognosis,clinical features,tumor microenvironment(TME)in both high-risk and low-risk groups,and evaluated the relationship between CRRS and sensitivity to immunotherapy and drug therapy.Results We identified 842 differentially expressed CRGs in breast cancer tissues of TNBC patients and selected 13 CRGs for constructing the prognostic model.Kaplan-Meier survival curves,time-dependent receiver operating characteristic curves,and other analyses confirmed that TNBC patients with high CRRS had shorter overall survival,and the predictive ability of CRRS prognostic model was further validated using the GEO dataset.Nomogram combining clinical features confirmed that CRRS was an independent factor for the prognosis of TNBC patients.Moreover,patients in the high-risk group had lower levels of immune infiltration in the TME and were sensitive to chemotherapeutic drugs such as 5-fluorouracil,ipatasertib,and paclitaxel.Conclusion We have developed a CRRS-based prognostic model composed of 13 differentially expressed CRGs,which may serve as a useful tool for predicting the prognosis of TNBC patients and guiding clinical treatment.Moreover,the key genes within this model may represent potential molecular targets for future therapies of TNBC.

不同神经阻滞治疗肩周炎的疗效比较

为探讨肩周炎有效的治疗方法，分别采用四种不同神经阻滞进行比较性研究。106例疼痛门诊病人随机分成四组，Ⅰ组24例，颈部硬膜外阻滞（CEB）；Ⅱ组27例，星状神经节阻滞（SGB）；Ⅲ组26例，肩押上神经阻滞（NSB），Ⅳ组29例，臂丛神经阻滞＋肩周局部神经阻滞（BPB＋LNB）。药物配方：利多卡因509，维生素B12500μg，地塞米松5mg，加生理盐水稀释至10ml（CEB稀释至20ml）。结果：Ⅳ组治愈率高达96．6％，余三组均在73～74％之间，X2检验，有显著差异，P<0.05。结论：BPB＋LNB是治疗肩周炎较理想的方法，CEB、XIB、NSB可视临床症状与体征选择性应用。

刍议Advia-Labcell系统的设备管理措施

检验科是医疗设备高度密集的科室,要求保障设备的高运行率。该研究着重介绍西门子模块化自动系统Adivia-lab-cell的原理和常见故障及该院设备科对该系统采取的管理方法和模式,仅供同行参考。

小鼠脓毒症模型的建立和评价

目的建立小鼠脓毒症模型并进行评价,为研究脓毒症致病机制和开发抗炎药物提供模型动物。方法采用盲肠结扎穿孔法(cecal ligation and puncture,CLP)诱导小鼠脓毒症,通过动物生存、术后小鼠载菌量、血常规和血生化指标、细胞因子水平、组织病理变化等方面对模型进行评价。结果小鼠的死亡率与盲肠结扎部位密切相关,盲肠结扎50%小鼠12 d存活率在40%左右,结扎75%小鼠4 d全部死亡(P<0.01)。与假手术组相比,50%结扎CLP小鼠血液和腹腔中载菌量增加,白细胞下降,差异有显著性(P<0.001)。CLP小鼠肝转氨酶ALT、AST和血清尿素氮BUN水平升高,差异具有显著性(P<0.01),炎症因子IL1α、IL6、IL10、MIP1α、MIP1β、TNFα水平升高。手术后48 h小鼠的肝和肺出现明显组织病理损伤。结论小鼠CLP模型具有典型的脓毒症病理特征,为后期研究抗炎药物的筛选提供了较好的动物模型。

脱氮—混凝气浮—UASB—接触氧化法处理垃圾填埋渗滤液

采用脱氮—混凝气浮—UASB—接触氧化工艺处理高氨氮、高浊度的垃圾渗滤液,使处理后出水的各项指标完全达到国家《污水综合排放标准》(GB8978-1996)二级新扩改标准。对废水处理系统的工艺作了简单介绍,并对系统的调试、运行过程进行了技术总结。

培训体系建设关键点分析及对策建议

随着企业的快速发展,对人力资源开发和培养的要求越来越高,现有的培训管理模式难以满足人才培养的要求,需要建立科学的培训管理体系。本文对培训体系建设的关键点进行分析,并提出对策与建议。

Hydrometallurgical process for recovery of Zn,Pb,Ga and Ge from Zn refinery residues

Zn,Pb,Ga and Ge were separated and recovered from zinc refinery residues by stepwise leaching.In the first stage,by leaching with H2SO4 media,more than 90%of Zn and 99%of Ga were dissolved,leaving 92%of Ge in the leaching residue.In the second stage,by leaching with HCl media,approximately 99%of Pb and less than 2%of Ge were selectively dissolved.Finally,the remaining 90%of Ge was extracted in 1 mol/L NaOH solution by destroying the correlation between SiO2 and Ge.XRD pattern of the leaching residue demonstrated that ZnSO4·H2O,PbSO4 and SiO2 were removed sequentially through the stepwise leaching.The proposed process achieved high recoveries of Zn,Pb,Ga and Ge,thus presenting a potential industrial application.

Flotation performance and adsorption mechanism of novel 1-(2-hydroxyphenyl)hex-2-en-1-one oxime flotation collector to malachite

A novel collector 1-(2-hydroxyphenyl)hex-2-en-1-one oxime(HPHO)was synthesized from 2-hydroxy acetophenone and butyraldehyde.Its flotation performance and adsorption mechanism to malachite were investigated by flotation test,zeta potential,Fourier transform infrared(FTIR)and X-ray photoelectron spectroscopy(XPS)analysis techniques.Compared with benzohydroxamic acid(BA),1-(2-hydroxyphenyl)ethan-1-one oxime(HPEO)and sodium isobutyl xanthate(SIBX),HPHO exhibited excellent collecting power to malachite without additional reagents,such as Na2S regulator and methyl isobutyl carbinol(MIBC)frother.Results of zeta potential indicated that HPHO was coated on malachite surfaces through a chemisorption process.FTIR and XPS data gave clear evidence for the formation of Cu−oxime complex on malachite surfaces after HPHO adsorption through the linkage between C=C,—OH,N—OH group and Cu species.

Preparation of Al2O3 nanowires on 7YSZ thermal barrier coatings against CMAS corrosion

The commonly-employed material for thermal barrier coatings(TBCs)is 7 wt.%Y2O3 ZrO2(7YSZ),generally deposited by electron beam-physical vapor deposition(EB-PVD).Due to the increasing demand for higher operating temperature in aero-derivative gas turbines,a lot of effort has been made to prevent the premature failure of columnar 7YSZ TBCs,which is induced by the microstructure degradation,sintering and spallation after the deposition of infiltrated siliceous mineral(consisting of calcium magnesium aluminum silicate(CaO MgO Al2O3 SiO2,i.e.,CMAS)).A new method called Al-modification for columnar 7YSZ TBCs against CMAS corrosion was present.The Al film was magnetron-sputtered on the surface of the columnar 7YSZ TBCs,followed by performing vacuum heat treatment of the Al-deposited TBCs.During the heat treatment,the molten Al reacted with ZrO2 to formα-Al2O3 overlay that effectively hindered CMAS infiltration.Moreover,the Al film could evaporate and re-nucleate,leading to the generation of Al2O3 nanowires,which further restrained the moving of molten CMAS.

桥梁无损检测及检测信息集成分析技术研究综述

当前桥梁设施的安全问题已成为社会关注的热点,无损检测技术的发展为桥梁结构安全监测提供了有效的技术手段,但是这些检测方法的应用以及信息的分析还较为离散,为桥梁安全诊断带来较大困难。系统阐述了桥梁无损检测技术的发展状况,并探讨了信息集成技术在桥梁无损检测信息综合分析中的应用。

Tensile resistance,microstructures of intermetallic compounds,and fracture modes of welded steel/aluminum joints produced using laser lap welding

The joining of DP780 steel to Al5052 was conducted by laser lap welding,in which the metal vapor and spatters were monitored by a high-speed camera.A universal testing machine was used to test the mechanical properties of the welded joints,and the changing law of lap tensile resistance with the laser welding parameters was analyzed.Optical microscope and scanning electron microscope were used to observe the macro-structure and micro-structure,respectively.Three different intermetallic compounds(IMCs)phases,i.e.banded Fe2Al5,FeAl2 and needle-like FeAl3 were generated at the steel/Al interface on microscopic observation.The aim of this research is to investigate the relationship among the lap tensile resistance,the welding parameters and the failure mode under different energy densities.Experimental results showed that the steel/Al joints have two different fracture modes at low heat input and high heat input.The failures happened along the heat-affected zone of the weld and along the steel/Al joint interface,respectively.And both of the two failure modes are brittle fractures.Additionally,cracks appeared at the fracture interface,and needle-like particle clusters were found in the fracture microstructure.

A highly efficient flower-like cobalt catalyst for electroreduction of carbon dioxide

Electrochemical conversion of CO2 into fuel has been regarded as a promising approach to achieve the global carbon cycle.Herein,we report an efficient cobalt catalyst with a unique flower-like morphology synthesized by a green and facile hydrothermal method,in which n-butylamine is used as the capping agent.The resultant catalyst shows superior electrocatalytic activity toward CO2 electroreduction,which is highly selective for generating formate with a Faraday efficiency of 63.4%.Electrochemical analysis reveals that the oxide on the surface is essential for the electrocatalysis of the CO2 reduction reaction.Cyclic voltammograms further suggest that this catalyst is highly active for the oxidation of reduced product,and can thus be seen as a bifunctional catalyst.

Selective recovery of lithium from spent lithium iron phosphate batteries using oxidation pressure sulfuric acid leaching system

Oxidation pressure leaching was proposed to selectively dissolve Li from spent LiFePO_(4) batteries in a stoichiometric sulfuric acid solution.Using O_(2) as an oxidant and stoichiometric sulfuric acid as leaching agent,above 97% of Li was leached into the solution,whereas more than 99% of Fe remained in the leaching residue,enabling a relatively low cost for one-step separation of Li and Fe.And then,by adjusting the pH of leachate,above 95% of Li was recovered in the form of the Li_(3)PO_(4) product through iron removal and chemical precipitation of phosphate.

Effect of Si and Ti on dynamic recrystallization of high-performance Cu-15Ni-8Sn alloy during hot deformation

Effect of Si and Ti on dynamic recrystallization(DRX)of Cu-15Ni-8 Sn alloy was studied using hot compression tests over deformation temperature range of 750-950℃and strain rate range of 0.001-10 s^-1.The results show that the dynamic recrystallization behavior during hot deformation is significantly affected by the trace elements of Si and Ti.The addition of Si and Ti promotes the formation of Ni16Si7Ti6 particles during hot deformation,which promotes the nucleation of dynamic recrystallization by accelerating the transition from low-angle boundaries(LABs)to high-angle boundaries(HABs).Ni16Si7Ti6 particles further inhibit the growth of recrystallized grains through the pinning effect.Based on the dynamic recrystallization behavior,a processing map of the alloy is built up to obtain the optimal processing parameters.Guided by the processing map,a hot-extruded Cu-15 Ni-8Sn alloy with a fine-grained microstructure is obtained,which shows excellent elongation of 30%and ultimate tensile strength of 910 MPa.