Targeting cholesterol trafficking to mitigate axonal degeneration in hereditary spastic paraplegia

Axonal degeneration underlies many debilitating diseases including hereditary spastic paraplegia(HSP),a genetically and clinically diverse group of disorders characterized by spasticity and weakness of the lower extremities.HSP is one significant cause of chronic neurodisability due to the lack of effective treatments and a wide range of onset ages from early childhood to 70 years.

Research on the Construction of Intellectual Property System and Optimization of Business Environment in China

With the rapid development of globalization and information technology,intellectual property has been one of the key drivers of economic growth,and the construction of intellectual property system has become an important criterion for measuring the quality of business environment.This article is intended to explore the current status of intellectual property system construction in China,the challenges,and its relationship with the business environment,to propose the corresponding countermeasures and suggestions.The study finds that the legal system of intellectual property in China is gradually improving,and judicial and administrative protection are continuously strengthened.However,the challenges still remain such as frequent infringements,rights hard to protect and insufficient international cooperation.These issues not only affect the legitimate rights and interests of innovation entities,but also for the market fairness and the level of the business environment.Therefore,this article proposes that strengthening the perfection of the intellectual property legal system,enhancing intellectual property services and support capabilities,strengthening international cooperation and exchanges,and accelerating the cultivation of composite talents.It aims to provide theoretical references for the construction of intellectual property system and the optimization of the business environment,promote the high-quality development of economy and enhance the global competitiveness of the country.

Genetically modified pigs:Emerging animal models for hereditary hearing loss

Hereditary hearing loss(HHL),a genetic disorder that impairs auditory function,significantly affects quality of life and incurs substantial economic losses for society.To investigate the underlying causes of HHL and evaluate therapeutic outcomes,appropriate animal models are necessary.Pigs have been extensively used as valuable large animal models in biomedical research.In this review,we highlight the advantages of pig models in terms of ear anatomy,inner ear morphology,and electrophysiological characteristics,as well as recent advancements in the development of distinct genetically modified porcine models of hearing loss.Additionally,we discuss the prospects,challenges,and recommendations regarding the use pig models in HHL research.Overall,this review provides insights and perspectives for future studies on HHL using porcine models.

Dual primary gastric and colorectal cancer:The known hereditary causes and underlying mechanisms

In this editorial,I commented on the paper by Lin et al,published in this issue of the World Journal of Gastrointestinal Oncology.The work aimed at analysing the clinicopathologic characteristics and prognosis of synchronous and metachronous cancers in patients with dual primary gastric and colorectal cancer(CRC).The authors concluded the necessity for regular surveillance for metachronous cancer during postoperative follow-up and reported the prognosis is influenced by the gastric cancer(GC)stage rather than the CRC stage.Although surveillance was recommended in the conclusion,the authors did not explore this area in their study and did not include tests used for such surveillance.This editorial focuses on the most characterized gastrointestinal cancer susceptibility syndromes concerning dual gastric and CRCs.These include hereditary diffuse GC,familial adenomatous polyposis,hereditary nonpolyposis colon cancer,Lynch syndrome,and three major hamartomatous polyposis syndromes associated with CRC and GC,namely Peutz-Jeghers syndrome,juvenile polyposis syndrome,and PTEN hamartoma syndrome.Careful assessment of these syndromes/conditions,including inheritance,risk of gastric and colorectal or other cancer development,genetic mutations and recommended genetic investigations,is crucial for optimum management of these patients.

The Economics of Competing Water Uses under a FERC Licensing Agreement: Estimation of Property Value, Recreation, and Hydroelectric Impacts

Reservoirs provide a variety of services with economic values across multiple sectors. As demands for reservoir services continue to grow and precipitation patterns evolve, it becomes ever more important to consider the integrated suite of values and tradeoffs that attend changes in water uses and availability. Section 316 (b) of the Clean Water Act requires that owners of certain water cooled power plants evaluate technologies and operational measures that can reduce their impacts to aquatic organisms. The studies must discuss the social costs and benefits of alternative technologies including cooling towers (79 Fed. Reg. 158, 48300 - 48439). Cooling towers achieve their effect through evaporation. This manuscript estimates the property value, recreation, and hydroelectric generation impacts that could result from the evaporative water loss associated with installing cooling towers at the McGuire Nuclear Generating Station (McGuire) located on Lake Norman, North Carolina. Although this study specifically evaluates the effects of evaporative water loss from cooling towers, its methods are applicable to estimating the economic benefits and costs of a new water user or reduced water input in any complex reservoir system that supports steam electric generation, hydroelectric generation, residential properties, recreation, irrigation, and municipal water use.

Complex heterozygous mutations in hereditary spherocytosis:A case report

BACKGROUND The aim of this study was to investigate the complex heterozygous mutations of ANK1 and SPTA1 in the same individual and improve our understanding of hereditary spherocytosis(HS)in children.We also hope to promote the application of gene detection technology in children with HS,with the goals of identifying more related gene mutations,supporting the acquisition of improved molecular genetic information to further reveal the pathogenesis of HS in children,and providing important guidance for the diagnosis,treatment,and prevention of HS in children.CASE SUMMARY A 1-year and 5-month-old patient presented jaundice during the neonatal period,mild anemia 8 months later,splenic enlargement at 1 year and 5 months,and brittle red blood cell permeability.Genetic testing was performed on the patient,their parents,and sister.Swiss Model software was used to predict the protein structure of complex heterozygous mutations in ANK1 and SPTA1.Genetic testing revealed that the patient harbored a new mutation in the ANK1 gene from the father and a mutation in the SPTA1 gene from the mother.Combined with the clinical symptoms of the children,it is suggested that the newly discovered complex heterozygous mutations of ANK1 and SPTA1 may be the cause,providing important guidance for revealing the pathogenesis,diagnosis,treatment,and promotion of gene detection technology in children with HS.CONCLUSION This case involves an unreported complex heterozygous mutation of ANK1 and SPTA1,which provides a reference for exploring HS.

Machine learning-guided accelerated discovery of structure-property correlations in lean magnesium alloys for biomedical applications

Magnesium alloys are emerging as promising alternatives to traditional orthopedic implant materials thanks to their biodegradability,biocompatibility,and impressive mechanical characteristics.However,their rapid in-vivo degradation presents challenges,notably in upholding mechanical integrity over time.This study investigates the impact of high-temperature thermal processing on the mechanical and degradation attributes of a lean Mg-Zn-Ca-Mn alloy,ZX10.Utilizing rapid,cost-efficient characterization methods like X-ray diffraction and optical microscopy,we swiftly examine microstructural changes post-thermal treatment.Employing Pearson correlation coefficient analysis,we unveil the relationship between microstructural properties and critical targets(properties):hardness and corrosion resistance.Additionally,leveraging the least absolute shrinkage and selection operator(LASSO),we pinpoint the dominant microstructural factors among closely correlated variables.Our findings underscore the significant role of grain size refinement in strengthening and the predominance of the ternary Ca_(2)Mg_(6)Zn_(3)phase in corrosion behavior.This suggests that achieving an optimal blend of strength and corrosion resistance is attainable through fine grains and reduced concentration of ternary phases.This thorough investigation furnishes valuable insights into the intricate interplay of processing,structure,and properties in magnesium alloys,thereby advancing the development of superior biodegradable implant materials.

Mechanical Property and Microstructure of Cement Mortar with Carbonated Recycled Powder

Carbonated recycled powder as cementitious auxiliary material can reduce carbon emissions and realize high-quality recycling of recycled concrete.In this paper,microscopic property of recycled powder with three carbonation methods was tested through XRD and SEM,the mechanical property and microstructure of recycled powder mortar with three replacement rates were studied by ISO method and SEM,and the strengthening mechanism was analyzed.The results showed that the mechanical property of recycled powder mortar decreased with the increasing of replacement rate.It is suggested that the replacement rate of recycled powder should not exceed 20%.The strength index and activity index of carbonated recycled powder mortar were improved,in which the flexural strength was increased by 27.85%and compressive strength was increased by 20%at the maximum.Recycled powder can be quickly and completely carbonated,and the improvement effect of CH pre-soaking carbonation was the best.The activity index of carbonated recycled powder can meet the requirements of Grade II technical standard for recycled powder.Microscopic results revealed the activation mechanism of carbonated recycled powder such as surplus calcium source effect,alkaline polycondensation effect and carbonation enhancement effect.

Adhesion property of AlCrNbSiTi high-entropy alloy coating on zirconium:experimental and theoretical studies

Experimental scratch tests and first-principles calculations were used to investigate the adhesion property of AlCrNbSiTi high-entropy alloy(HEA)coatings on zirconium substrates.AlCrNbSiTi HEA and Cr coatings were deposited on Zr alloy substrates using multi-arc ion plating technology,and scratch tests were subsequently conducted to estimate the adhesion property of the coatings.The results indicated that Cr coatings had better adhesion strength than HEA coatings,and the HEA coatings showed brittleness.The special quasi-random structure approach was used to build HEA models,and Cr/Zr and HEA/Zr interface models were employed to investigate the cohesion between the coatings and Zr substrate using first-principles calculations.The calculated interface energies showed that the cohesion between the Cr coating and the Zr substrate was stronger than that of the HEA coating with Zr.In contrary to Al or Si in the HEA coating,Cr,Nb,and Ti atoms binded strongly with Zr substrate.Based on the calculated elastic constants,it was found that low Cr and high Al content decreased the mechanical performances of HEA coatings.Finally,this study demonstrated the utilization of a combined approach involving first-principles calculations and experimental studies for future HEA coating development.

Transition metal coordination polymers with flexible dicarboxylate ligand:Synthesis,characterization,and photoluminescence property

Under solvothermal conditions,six new coordination polymers(CPs)[Mn(L)(phen)(H_(2)O)]_(n)(1),[Co(L)(phen)(H_(2)O)]_(n)(2),[Cu(L)(phen)(H_(2)O)]_(n)(3),[Zn_(2)(L)_(2)(phen)2(H_(2)O)]_(n)(4),[Zn(L)(phen)]_(n)(5),and[Cd(L)(phen)2]_(n)(6)were synthesized by reactions of dicarboxylate ligand 2,2'-(1,2-phenylenebis(methylene))bis(sulfanediyl)dinobutyric acid(H_(2)L)and 1,10-phenanthroline(phen)with the corresponding metal salts.Complexes 1-6 have been structurally characterized by single-crystal X-ray diffraction analyses,elemental analysis,IR,thermogravimetric analysis,and powder X-ray diffraction.The structures of 1-6 are 1D chains,which are further connected by hydrogen bonding interac-tions to form 3D supramolecular structures.Among them,1 and 2 are isomorphic with L2-of syn-conformation,while L2-shows anti-conformation in 3-6.In addition,the solid-state photoluminescence property of 4-6 was investigated.

Germline pathogenic variants among high hereditary risk patients with breast and ovarian cancer and unaffected subjects in Lebanese Arab women

BACKGROUND The prevalence of germline pathogenic variants in high hereditary risk breast and/or ovarian cancer patients and unaffected subjects referred for testing is an unmet need in low and middle-income countries.AIM To determine the prevalence of germline pathogenic variants in high hereditary risk patients with breast and/or ovarian cancer and unaffected individuals.METHODS We retrospectively reviewed records of patients and unaffected subjects referred for germline pathogenic variant testing due to high hereditary risk between 2010-2020.Data was collected and analyzed on Excel sheet.RESULTS In total,358 individuals were included,including 257 patients and 101 unaffected individuals with relatives with breast or ovarian cancer.The prevalence of breast cancer susceptibility gene(BRCA)1/2 pathogenic variants was 8.63%(19/220)in patients with breast cancer,and 15.1%(5/33)in those with ovarian cancer.Among the 25 of 220 patients with breast cancer tested by next-generation sequencing,3 patients had pathogenic variants other than BRCA1/2.The highest risk was observed in those aged 40 years with breast cancer and a positive family history,where the BRCA1/2 prevalence was 20.1%(9/43).Among the unaffected subjects,31.1%(14/45)had the same BRCA1/2 pathogenic variants in their corresponding relatives.Among the subjects referred because of a positive family history of cancer without known hereditary factors,5.35%(3/56)had pathogenic variants of BRCA1 and BRCA2.The c.131G>T nucleotide change was noted in one patient and two unrelated unaffected subjects with a BRCA1 pathogenic variant.CONCLUSION This study showed a 8.63%prevalence of pathogenic variants in patients with breast cancer and a 15.1%prevalence in patients with ovarian cancer.Among the relatives of patients with BRCA1/2 pathogenic variants,31%tested positive for the same variant,while 5.3%of subjects who tested positive due to a family history of breast cancer had a BRCA pathogenic variant.

Effect of Cryogenic Treatment on Microstructure and Tribological Property Evolution of Electron Beam Melted Ti6Al4V

Cryogenic treatment was used to improve the tribological properties of Ti6Al4V artificial hip joint implants.Cryogenic treatment at-196℃with different holding time were carried out on Ti6Al4V specimens fabricated using electron beam melting(EBM),and their microstructure and tribological properties evolution were systematically analyzed by scanning electron microscopy(SEM),vickers hardness,and wear tests.The experimental results show that the as-fabricated specimen consists of lamellarαphase andβcolumnar crystal.While,the thickness of lamellarαphase decreased after cryogenic treatment.In addition,it can be found that the fineαphase was precipitated and dispersed between the lamellarαphase with the holding time increase.Vickers hardness shows a trend of first increasing and then decreasing.The wear rate of the specimen cryogenic treated for 24 h is the minimum and the average friction coefficient is 0.50,which is reduced by 14.61%compared with the as-fabricated.The wear mechanism of the as-fabricated specimen is severe exfoliation,adhesive,abrasive,and slight fatigue wear.However,the specimen cryogenic treated for 24 h shows slight adhesive and abrasive wear.It can be concluded that it is feasibility of utilizing cryogenic treatment to reduce the wear of EBMed Ti6Al4V.

Capillary Property of Entangled Porous Metallic Wire materials and Its Application in Fluid Buffers:Theoretical Analysis and Experimental Study

Strong impact does serious harm to the military industries so it is necessary to choose reasonable cushioning material and design effective buffers to prevent the impact of equipment.Based on the capillary property entangled porous metallic wire materials(EPMWM),this paper designed a composite buffer which uses EPMWM and viscous fluid as cushioning materials under the low-speed impact of the recoil force device of weapon equipment(such as artillery,mortar,etc.).Combined with the capillary model,porosity,hydraulic diameter,maximum pore diameter and pore distribution were used to characterize the pore structure characteristics of EPMWM.The calculation model of the damping force of the composite buffer was established.The low-speed impact test of the composite buffer was conducted.The parameters of the buffer under low-speed impact were identified according to the model,and the nonlinear model of damping force was obtained.The test results show that the composite buffer with EPMWM and viscous fluid can absorb the impact energy from the recoil movement effectively,and provide a new method for the buffer design of weapon equipment(such as artillery,mortar,etc.).

Fluid property identification of the Lower Cretaceous reservoirs with complex oil-water contacts in Deseo Basin,Chad

Recently,exploration breakthroughs have been made in the Lower Cretaceous sandstone reservoirs in the Doseo Basin,but the identification of reservoir fluid property is difficult due to variable reservoir lithology,complex oil-water contact within and faint responses of the oil zone,which causes the lower accuracy of reservoir fluid property identification with conventional mudlogging and wirelogging techniques.Applying the geochemical logging,fluorescent logging,mud logging and cutting logging technology,in combination with formation test data,this paper distinguishes the crude oil types,analyzes the logging response characteristics of oil zone after water washing,and establishes the interpretation charts and parameter standards for reservoir fluid properties.The crude oil can be divided into two types,namely viscous-heavy and thin-light,based on total hydrocarbon content and component concentration tested by mud logging,features of pyrolysis gas chromatogram and fluorescence spectroscopy.The general characteristics of oil layers experienced water washing include the decrease of total hydrocarbon content and component concentration from mud logging,the decrease of S1 and PS values from geochemical logging,the decrease of hydrocarbon abundance and absence of some light components in pyrolysis gas chromatogram,and the decrease of fluorescence area and intensity from fluorescence logging.According to crude oil types,the cross plots of S1 versus peak-baseline ratio,and the cross plots of rock wettability versus fluorescence area ratio are drawn and used to interpret reservoir fluid property.Meanwhile,the standards of reservoir fluid parameter are established combining with the parameters of PS and the parameters in above charts,and comprehensive multiparameter correlation in both vertical and horizontal ways is also performed to interpret reservoir fluid property.The application in the Doseo Basin achieved great success,improving interpretation ability of fluid property in the reservoir with complex oil-water contact,and also provided technical reference for the efficient exploration and development of similar reservoirs.

Preparation and property of seal coating for gas turbine compressor

Double-layer structure of seal coating which consisted of a Ni5Al bond coating and a Ni25 graphite top coating were prepared on steel substrate of gas turbine compressor cylinder block.Bond coating was prepared by atmospheric plasma spraying and top coating was prepared by flame spraying.The microstructure,mechanical properties and abradability of the coating were characterized by scanning elec-tron microscope(SEM),hardness tester,universal testing machine,thermal shock testing machine and abradability testing machine.The res-ults show that the overall spraying structure of the seal coating is uniform,the nickel metal phase is the skeleton supporting the entire coat-ing,and the coating is well bonded without separation.The seal coating has a bonding strength of not less than 7.7 MPa,excellent thermal stability,and thermal shock resistance cycle numbers at 500℃more than 50;the scratch length,deepest invasion depth and wear amount of the coating increase with rise of test temperature,with almost no coating adhesion,indicating that the seal coating has excellent abradability.

Unveiling the cellular microstructure-property relations in martensitic stainless steel via laser powder bed fusion

Laser powder bed fusion(LPBF)is a widely recognized additive manufacturing technology that can fabricate complex components rapidly through layer-by-layer formation.However,there is a paucity of research on the effect of laser scanning speed on the cellular microstructure and mechanical properties of martensitic stainless steel.This study systematically investigated the influence of laser scanning speed on the cellular microstructure and mechanical properties of a developed Fe11Cr8Ni5Co3Mo martensitic stainless steel produced by LPBF.The results show that increasing the laser scanning speed from 400 to 1000 mm/s does not lead to a noticeable change in the phase fraction,but it reduces the average size of the cellular microstructure from 0.60 to 0.35μm.The scanning speeds of 400 and 1000 mm/s both had adverse effects on performances of sample,resulting in inadequate fusion and keyhole defects respectively.The optimal scanning speed for fabricating samples was determined to be 800 mm/s,which obtained the highest room temperature tensile strength and elongation,with the ultimate tensile strength measured at(1088.3±2.0)MPa and the elongation of(16.76±0.10)%.Furthermore,the mechanism of the evolution of surface morphology,defects,and energy input were clarified,and the relationship between cellular microstructure size and mechanical properties was also established.

Preparation and Anti⁃arc Erosion Property of Ag Matrix Electrical Contact Material Reinforced by Novel Ti_(2)Cd

Due to their outstanding electrical contact properties,Cd-containing silver-matrix electrical contact materials can meet the requirements of high stability and long life for military defense and aerospace applications.In order to further reduce the Cd content under the premise of meeting the high-performance requirements,in this study,high-purity intermediate Ti_(2)Cd powder of MAX phase(Ti_(2)CdC)was synthesized with a pressureless technique and then applied to reinforce the Ag matrix.The Cd content of the as-prepared Ag/Ti_(2)Cd composites was actually reduced by 38.31%compared with conventional Ag/CdO material.Based on the systematic study of the effect of heat treatment temperature on the physical phase,morphology,interface and comprehensive physical properties of Ag/Ti_(2)Cd composites,the preferred samples(heat treated at 400°C for 1 h)showed high density(97.77%),low resistivity(2.34μΩ·cm),moderate hardness(90.8HV),high tensile strength(189.9 MPa),and exhibited good electrical contact performance after 40000 cycles of arc discharging under severe conditions(DC 28 V/20 A).The results of microscopic morphological evolution,phase change and elemental distribution of the electrical contact surface show that the combination of high stability of Ti_(2)Cd reinforcing phase,good interfacial bonding with Ag matrix and improved melt pool viscosity in the primary stage of arc erosion,results in low and stable contact resistance(average value 13.20 mΩ)and welding force(average value 0.6 N),low fluctuation of static force(2.2-2.5 N).The decomposition and absorption energy of Ti_(2)Cd and the arc extinguishing effect of Cd vapor are the main reasons for the stable arcing energy and arcing time of electric contacts in the late stage of arc erosion.

Creep property research of new martensite heat-resistant steel G115

G115 steel was jointly developed by China Iron & Steel Research Institute Group Co.,Ltd.and Baosteel for usage in 600-650 ℃ ultrasupercritical boiler tubes.Using a hot extruded G115 tube,creep tests were conducted under a constant stress of 130 MPa and temperatures of 625,650 and 675 ℃.Comparing creep curves under different temperatures,it is observed that the creep performance of a G115 tube is more sensitive to temperature than stress.Steady-state creep rates of creep specimens are significantly increased by enhancing the temperature.A micro-structural analysis of ruptured creep specimens under a stress of 130 MPa and temperatures of 650 ℃ and 675 ℃ was performed;the fracture mechanism of creep specimens under these two temperatures mainly included the appearance of creep holes on the grain boundary and a decrease in the martensite lath density.

Corrosion and antimicrobial property of TiO_(2)/Cu_(2)O and TiO_(2)/Cu_(2)O@CeO_(2)micro-arc oxidation coatings on Ti-6Al-4V alloys in natural seawater

Microarc oxidation is an effective surface treatment for improving certain properties of metals and their alloys.In this paper,TiO_(2)/Cu_(2)O and TiO_(2)/Cu_(2)O@CeO_(2)coatings were prepared on Ti-6Al-4V by microarc oxidation.Thecoatings exhibited good corrosion resistance and antimicrobial properties.X-ray diffraction(XRD),scanning electronmicroscopy(SEM),and 3D laser confocal were used to characterize the coatings.The properties of TiO_(2)/Cu_(2)O and TiO_(2)/Cu_(2)O@CeO_(2)coatings were analyzed,including microstructure,surface roughness,corrosion resistance,andantimicrobial properties.The electrochemical results showed that the coatings prepared by microarc oxidation hadenhanced corrosion resistance compared to the substrate.The antibacterial properties of TiO_(2)/Cu_(2)O and TiO_(2)/Cu_(2)O@CeO_(2)coating against Pseudomonas aeruginosa were evaluated by fluorescence microscopy and plate counting.The antibacterial rate of TiO_(2)/Cu_(2)O@CeO_(2)coating was up to 99.70%.In summary,the TiO_(2)/Cu_(2)O and TiO_(2)/Cu_(2)O@CeO_(2)coatings prepared by microarc oxidation have a potential application background in the field of marine corrosionprotection and biofouling.

Effect of slow shot speed on externally solidified crystal,porosity and tensile property in a newly developed high-pressure die-cast Al-Si alloy

The effect of slow shot speed on externally solidified crystal(ESC),porosity and tensile property in a newly developed high-pressure die-cast Al-Si alloy was investigated by optical microscopy(OM),scanning electron microscopy(SEM)and laboratory computed tomography(CT).Results showed that the newly developed AlSi9MnMoV alloy exhibited improved mechanical properties when compared to the AlSi10MnMg alloy.The AlSi9MnMoV alloy,which was designed with trace multicomponent additions,displays a notable grain refining effect in comparison to the AlSi10MnMg alloy.Refining elements Ti,Zr,V,Nb,B promote heterogeneous nucleation and reduce the grain size of primaryα-Al.At a lower slow shot speed,the large ESCs are easier to form and gather,developing into the dendrite net and net-shrinkage.With an increase in slow shot speed,the size and number of ESCs and porosities significantly reduce.In addition,the distribution of ESCs is more dispersed and the net-shrinkage disappears.The tensile property is greatly improved by adopting a higher slow shot speed.The ultimate tensile strength is enhanced from 260.31 MPa to 290.31 MPa(increased by 11.52%),and the elongation is enhanced from 3.72%to 6.34%(increased by 70.52%).