Additive manufacturing(AM),with its high flexibility,cost-effectiveness,and customization,significantly accelerates the advancement of nanogenerators,contributing to sustainable energy solutions and the Internet of Th...Additive manufacturing(AM),with its high flexibility,cost-effectiveness,and customization,significantly accelerates the advancement of nanogenerators,contributing to sustainable energy solutions and the Internet of Things.In this review,an in-depth analysis of AM for piezoelectric and triboelectric nanogenerators is presented from the perspectives of fundamental mechanisms,recent advancements,and future prospects.It highlights AM-enabled advantages of versatility across materials,structural topology optimization,microstructure design,and integrated printing,which enhance critical performance indicators of nanogenerators,such as surface charge density and piezoelectric constant,thereby improving device performance compared to conventional fabrication.Common AM techniques for nanogenerators,including fused deposition modeling,direct ink writing,stereolithography,and digital light processing,are systematically examined in terms of their working principles,improved metrics(output voltage/current,power density),theoretical explanation,and application scopes.Hierarchical relationships connecting AM technologies with performance optimization and applications of nanogenerators are elucidated,providing a solid foundation for advancements in energy harvesting,self-powered sensors,wearable devices,and human-machine interaction.Furthermore,the challenges related to fabrication quality,cross-scale manufacturing,processing efficiency,and industrial deployment are critically discussed.Finally,the future prospects of AM for nanogenerators are explored,aiming to foster continuous progress and innovation in this field.展开更多
A novel laser-based additive manufacturing approach of metal additive manufacturing using powder sheets(MAPS)has been introduced recently.The method utilizes polymer-bound powder sheets for metal AM as a feedstock,ins...A novel laser-based additive manufacturing approach of metal additive manufacturing using powder sheets(MAPS)has been introduced recently.The method utilizes polymer-bound powder sheets for metal AM as a feedstock,instead of loose powders.Conventional laser beam powder bed fusion(LPBF)additive manufacturing(AM)is among the most widespread 3D printing technologies.However,LPBF faces challenges related to safety and the impracticality of changing materials due to its reliance on loose powders.Thus,MAPS demonstrates the capability to overcome the limitations of LPBF by offering enhanced safety and the ability to print multi-material structures without the risk of material cross-contamination.As a part of developing processes,we investigate the effects of polymeric binder content on the printability and microstructural characteristics of MAPS-printed stainless steel 316 L.The results indicate that the average layer thickness of solidified material improves as the scanning speed decreases from 1000 mm/s to 50 mm/s across three different polymeric binder contents:10 wt%,20 wt%,and 30 wt%PCL.Additionally,a higher polymeric binder content(i.e.20 wt%and 30 wt%)in the powder sheets reduces the likelihood of crack formation.Electron backscatter diffraction(EBSD)analysis reveals that an increase in scanning speed promotes the formation of more equiaxed grains,while an increase in polymer content results in a reduction in grain size.These findings provide valuable insights into optimizing MAPS configurations for enhanced productivity and functionality in metal component manufacturing.展开更多
The utilization of lunar regolith for construction on the lunar surface presents a critical challenge in-situ resource utilization.This study proposes a lunar regolith manufacturing method that uses a high-performance...The utilization of lunar regolith for construction on the lunar surface presents a critical challenge in-situ resource utilization.This study proposes a lunar regolith manufacturing method that uses a high-performance resin binder characterized by a high regolith content and strong forming capabilities.A combined resin material with both thermosetting and photosetting properties was developed and mixed with lunar regolith to create a slurry.This slurry can be directly molded or additively extruded into green bodies with specific structures.These green bodies can self-cure under the high temperatures and ultraviolet radiation experienced during the lunar day,reducing energy consumption and fulfilling the requirements of lunar construction.The material-forming processes and effects of various additive types and concentrations,regolith mass ratios,and processing parameters on the properties of the slurry and the formed specimens were thoroughly investigated.The mechanical performance and microstructure of the fabricated samples were analyzed.The lunar regolith mass ratio reached 90 wt%(approximately 79 vol%),with the highest compressive strengths exceeding 60 MPa for cast specimens and 30 MPa for printed samples.This technology shows significant potential for enabling in-situ lunar regolith-based construction in future lunar missions.展开更多
At present,the emerging solid-phase friction-based additive manufacturing technology,including friction rolling additive man-ufacturing(FRAM),can only manufacture simple single-pass components.In this study,multi-laye...At present,the emerging solid-phase friction-based additive manufacturing technology,including friction rolling additive man-ufacturing(FRAM),can only manufacture simple single-pass components.In this study,multi-layer multi-pass FRAM-deposited alumin-um alloy samples were successfully prepared using a non-shoulder tool head.The material flow behavior and microstructure of the over-lapped zone between adjacent layers and passes during multi-layer multi-pass FRAM deposition were studied using the hybrid 6061 and 5052 aluminum alloys.The results showed that a mechanical interlocking structure was formed between the adjacent layers and the adja-cent passes in the overlapped center area.Repeated friction and rolling of the tool head led to different degrees of lateral flow and plastic deformation of the materials in the overlapped zone,which made the recrystallization degree in the left and right edge zones of the over-lapped zone the highest,followed by the overlapped center zone and the non-overlapped zone.The tensile strength of the overlapped zone exceeded 90%of that of the single-pass deposition sample.It is proved that although there are uneven grooves on the surface of the over-lapping area during multi-layer and multi-pass deposition,they can be filled by the flow of materials during the deposition of the next lay-er,thus ensuring the dense microstructure and excellent mechanical properties of the overlapping area.The multi-layer multi-pass FRAM deposition overcomes the limitation of deposition width and lays the foundation for the future deposition of large-scale high-performance components.展开更多
Background Post-weaning diarrhea(PWD)in piglets,often caused by F4^(+)enterotoxigenic Escherichia coli(ETEC),poses significant challenges in pig production.Traditional solutions like antibiotics and zinc oxide face in...Background Post-weaning diarrhea(PWD)in piglets,often caused by F4^(+)enterotoxigenic Escherichia coli(ETEC),poses significant challenges in pig production.Traditional solutions like antibiotics and zinc oxide face increasing restrictions due to growing concerns over antibiotic resistance and environmental sustainability.This study investigates the application of bivalent heavy chain variable domain(V_(H)H)constructs(BL1.2 and BL2.2)targeting ETEC virulence factors,administered in feed to mitigate ETEC-induced PWD in weaned piglets.Results The supplementation of BL1.2 and BL2.2 in both mash and pelleted feed significantly reduced the diarrhea incidence and fecal shedding of F4^(+)ETEC in challenged piglets.Pelleted feed containing V_(H)H constructs helped to preserve gut barrier integrity by maintaining levels of the tight junction protein occludin in the small intestine.Additionally,the constructs maintained blood granulocyte counts at a similar level to the non-challenged control group,including neutrophils,and ameliorated the acute phase protein response after challenge.Notably,even at low feed intake immediately after weaning,V_(H)H constructs helped maintain piglet health by mitigating ETEC-induced inflammation and the resulting diarrhea.Conclusions Our findings demonstrated that using V_(H)H constructs as feed additives could serve as an effective strategy to help manage ETEC-associated PWD,by reducing F4^(+)ETEC gut colonization and supporting gut barrier function of weaned piglets.The high stability of these V_(H)H constructs supports their incorporation into industrial feed manufacturing processes,offering a more sustainable preventive strategy compared to traditional antimicrobial interventions,which could contribute to sustainable farming practices.展开更多
Laser additive manufacturing(LAM)has been widely used in high-end manufacturing fields such as aerospace,nuclear power,and shipbuilding.However,it is a grand challenge for direct and continuous observation of complex ...Laser additive manufacturing(LAM)has been widely used in high-end manufacturing fields such as aerospace,nuclear power,and shipbuilding.However,it is a grand challenge for direct and continuous observation of complex laser-matter interaction,melt flow,and defect formation during LAM due to extremely large temperature gradient,fast cooling rate,and small time(millisecond)and space(micron)scales.The emergence of synchrotron radiation provides a feasible approach for in situ observation of the LAM process.This paper outlines the current development in real-time characterization of LAM by synchrotron radiation,including laser-matter interaction,molten pool evolution,solidification structure evolution,and defects formation and elimination.Furthermore,the future development direction and application-oriented research are also discussed.展开更多
Binder jet printing(BJP)is a state-of-the-art additive manufacturing technique for producing porous magnesium structures.Porous MgZn-Zr based BJP samples were assessed for corrosion performance in simulated body fluid...Binder jet printing(BJP)is a state-of-the-art additive manufacturing technique for producing porous magnesium structures.Porous MgZn-Zr based BJP samples were assessed for corrosion performance in simulated body fluids by electrochemical and hydrogen evolution measurements.The corrosion rates of the BJP specimens were significantly higher than solid controls,even after accounting for their larger surface areas,suggesting that the BJP microstructure is detrimental to corrosion performance.X-ray computed tomography revealed nonuniform corrosion within the porous structure,with corrosion products forming on the pore walls.Impregnating the pores with hydroxyapatite or polymers greatly improved the corrosion resistance of the BJP samples.展开更多
SiC is a wave-absorbing material with good dielectric properties,high-temperature resistance,and corrosion resistance,which has great potential for development in the field of high-temperature wave-absorbing.However,S...SiC is a wave-absorbing material with good dielectric properties,high-temperature resistance,and corrosion resistance,which has great potential for development in the field of high-temperature wave-absorbing.However,SiC is limited by its low impedance-matching performance and single wave-absorbing mechanism.Therefore,compatible metamaterial technologies are required to enhance its wave-absorbing performance further.The electromagnetic wave(EMW)absorbing metamaterials can realize perfect absorption of EMWs in specific frequency bands and precise regulation of EMW phase,propagation mode,and absorption frequency bands through structural changes.However,the traditional molding methods for manufacturing complex geometric shapes require expensive molds,involve process complexity,and have poor molding accuracy and other limitations.Therefore,additive manufacturing(AM)technology,through material layered stacking to achieve the processing of materials,is a comprehensive multidisciplinary advanced manufacturing technology and has become the core technology for manufacturing metamaterials.This review introduces the principles and applications of different AM technologies for SiC and related materials,discusses the current status and development trends of various AM technologies for fabricating silicon-carbon-based wave-absorbing metamaterials,summarizes the limitations and technological shortcomings of existing AM technologies for fabricating silicon-carbon-based wave-absorbing metamaterials,and provides an outlook for the future development of related AM technologies.展开更多
In this review,we propose a comprehensive overview of additive manufacturing(AM)technologies and design possibilities in manufacturing metamaterials for various applications in the biomedical field,of which many are i...In this review,we propose a comprehensive overview of additive manufacturing(AM)technologies and design possibilities in manufacturing metamaterials for various applications in the biomedical field,of which many are inspired by nature itself.It describes how new AM technologies(e.g.continuous liquid interface production and multiphoton polymerization,etc)and recent developments in more mature AM technologies(e.g.powder bed fusion,stereolithography,and extrusion-based bioprinting(EBB),etc)lead to more precise,efficient,and personalized biomedical components.EBB is a revolutionary topic creating intricate models with remarkable mechanical compatibility of metamaterials,for instance,stress elimination for tissue engineering and regenerative medicine,negative or zero Poisson’s ratio.By exploiting the designs of porous structures(e.g.truss,triply periodic minimal surface,plant/animal-inspired,and functionally graded lattices,etc),AM-made bioactive bone implants,artificial tissues,and organs are made for tissue replacement.The material palette of the AM metamaterials has high diversity nowadays,ranging from alloys and metals(e.g.cobalt-chromium alloys and titanium,etc)to polymers(e.g.biodegradable polycaprolactone and polymethyl methacrylate,etc),which could be even integrated within bioactive ceramics.These advancements are driving the progress of the biomedical field,improving human health and quality of life.展开更多
1.Introduction.Cold Spray(CS)is a highly advanced solid-state metal depo-sition process that was first developed in the 1980s.This innovative technique involves the high-speed(300-1200 m/s)impact deposition of micron-...1.Introduction.Cold Spray(CS)is a highly advanced solid-state metal depo-sition process that was first developed in the 1980s.This innovative technique involves the high-speed(300-1200 m/s)impact deposition of micron-sized particles(5-50μm)to fabricate coatings[1-3].CS has been extensively used in a variety of coating applications,such as aerospace,automotive,energy,medical,marine,and others,to provide protection against high temperatures,corrosion,erosion,oxidation,and chemicals[4,5].Nowadays,the technical interest in CS is twofold:(i)as a repair process for damaged components,and(ii)as a solid-state additive manufacturing process.Compared to other fusion-based additive manufacturing(AM)technologies,Cold Spray Additive Manufacturing(CSAM)is a new member of the AM family that can enable the fabrication of deposits without undergoing melting.The chemical composition has been largely preserved from the powder to the deposit due to the minimal oxidation.The significant advantages of CSAM over other additive manufacturing processes include a high production rate,unlimited deposition size,high flexibility,and suitability for repairing damaged parts.展开更多
Gas quenching and vacuum quenching process are widely applied to accelerate solvent volatilization to induce nucleation of perovskites in blade-coating method.In this work,we found these two pre-crystallization proces...Gas quenching and vacuum quenching process are widely applied to accelerate solvent volatilization to induce nucleation of perovskites in blade-coating method.In this work,we found these two pre-crystallization processes lead to different order of crystallization dynamics within the perovskite thin film,resulting in the differences of additive distribution.We then tailor-designed an additive molecule named 1,3-bis(4-methoxyphenyl)thiourea to obtain films with fewer defects and holes at the buried interface,and prepared perovskite solar cells with a certified efficiency of 23.75%.Furthermore,this work also demonstrates an efficiency of 20.18%for the large-area perovskite solar module(PSM)with an aperture area of 60.84 cm^(2).The PSM possesses remarkable continuous operation stability for maximum power point tracking of T_(90)>1000 h in ambient air.展开更多
Friction rolling additive manufacturing(FRAM)is a solid-state additive manufacturing technology that plasticizes the feed and deposits a material using frictional heat generated by the tool head.The thermal efficiency...Friction rolling additive manufacturing(FRAM)is a solid-state additive manufacturing technology that plasticizes the feed and deposits a material using frictional heat generated by the tool head.The thermal efficiency of FRAM,which depends only on friction to generate heat,is low,and the thermal-accumulation effect of the deposition process must be addressed.An FRAM heat-balance-control method that combines plasma-arc preheating and instant water cooling(PC-FRAM)is devised in this study,and a temperature field featuring rapidly increasing and decreasing temperature is constructed around the tool head.Additionally,2195-T87 Al-Li alloy is used as the feed material,and the effects of heating and cooling rates on the microstructure and mechanical properties are investigated.The results show that water cooling significantly improves heat accumulation during the deposition process.The cooling rate increases by 11.7 times,and the high-temperature residence time decreases by more than 50%.The grain size of the PC-FRAM sample is the smallest,i.e.,3.77±1.03μm,its dislocation density is the highest,and the number density of precipitates is the highest,the size of precipitates is the smallest,which shows the best precipitation-strengthening effect.The hardness test results are consistent with the precipitation distribution.The ultimate tensile strength,yield strength and elongation of the PC-FRAM samples are the highest(351±15.6 MPa,251.3±15.8 MPa and 16.25%±1.25%,respectively)among the samples investigated.The preheating and water-cooling-assisted deposition simultaneously increases the tensile strength and elongation of the deposited samples.The combination of preheating and instant cooling improves the deposition efficiency of FRAM and weakens the thermal-softening effect.展开更多
This study investigates full liquid phase sintering as a process of fabrication parts from WE43(Mg-4wt.%Y-3wt.%RE-0.7wt.%Zr)alloy using binder jetting additive manufacturing(BJAM).This fabrication process is being dev...This study investigates full liquid phase sintering as a process of fabrication parts from WE43(Mg-4wt.%Y-3wt.%RE-0.7wt.%Zr)alloy using binder jetting additive manufacturing(BJAM).This fabrication process is being developed for use in producing structural or biomedical devices.Specifically,this study focused on achieving a near-dense microstructure with WE43 Mg alloy while substantially reducing the duration of sintering post-processing after BJAM part rendering.The optimal process resulted in microstructure with 2.5%porosity and significantly reduced sintering time.The improved sintering can be explained by the presence of Y_(2)O_(3)and Nd_(2)O_(3)oxide layers,which form spontaneously on the surface of WE43 powder used in BJAM.These layers appear to be crucial in preventing shape distortion of the resulting samples and in enabling the development of sintering necks,particularly under sintering conditions exceeding the liquidus temperature of WE43 alloy.Sintered WE43 specimens rendered by BJAM achieved significant improvement in both corrosion resistance and mechanical properties through reduced porosity levels related to the sintering time.展开更多
The feasibility of manufacturing Ti-6Al-4V samples through a combination of laser-aided additive manufacturing with powder(LAAM_(p))and wire(LAAM_(w))was explored.A process study was first conducted to successfully ci...The feasibility of manufacturing Ti-6Al-4V samples through a combination of laser-aided additive manufacturing with powder(LAAM_(p))and wire(LAAM_(w))was explored.A process study was first conducted to successfully circumvent defects in Ti-6Al-4V deposits for LAAM_(p) and LAAM_(w),respectively.With the optimized process parameters,robust interfaces were achieved between powder/wire deposits and the forged substrate,as well as between powder and wire deposits.Microstructure characterization results revealed the epitaxial prior β grains in the deposited Ti-6Al-4V,wherein the powder deposit was dominated by a finerα′microstructure and the wire deposit was characterized by lamellar α phases.The mechanisms of microstructure formation and correlation with mechanical behavior were analyzed and discussed.The mechanical properties of the interfacial samples can meet the requirements of the relevant Aerospace Material Specifications(AMS 6932)even without post heat treatment.No fracture occurred within the interfacial area,further suggesting the robust interface.The findings of this study highlighted the feasibility of combining LAAM_(p) and LAAM_(w) in the direct manufacturing of Ti-6Al-4V parts in accordance with the required dimensional resolution and deposition rate,together with sound strength and ductility balance in the as-built condition.展开更多
In this study,a binder based 3D-printing technology viz.Fused Granular Fabrication(FGF)technique was used to produce interconnected and open porous Mg-6.3Gd bone scaffolds for compression test analyses.The consolidati...In this study,a binder based 3D-printing technology viz.Fused Granular Fabrication(FGF)technique was used to produce interconnected and open porous Mg-6.3Gd bone scaffolds for compression test analyses.The consolidation of the green parts(as printed scaffolds)was performed using solvent debinding in cyclohexane and subsequent conventional sintering in argon atmosphere.Compression tests were performed on as sintered parts.Additionally,a simulation strategy was developed for modeling the compression behavior of the sintered parts,utilizing the data from the experimental results.The experimental compression test results and the simulation strategy for the compression behavior of the 3D-printed scaffolds demonstrated good agreement.展开更多
To tackle the common issue of green defects in material extrusion(MEX)additive manufacturing(AM)cemented carbides,warm isostatic pressing(WIP)was introduced to eliminate defects of MEX WC-9Co cemented carbide greens,t...To tackle the common issue of green defects in material extrusion(MEX)additive manufacturing(AM)cemented carbides,warm isostatic pressing(WIP)was introduced to eliminate defects of MEX WC-9Co cemented carbide greens,thereby improving both microstructure uniformity and mechanical properties of sintered bodies.The results indicate that WIP reduces defects in MEX greens,thus decreasing the dimensions and numbers of defects,modifying shapes of pores within sintered bodies,while preserving surface quality and shape characteristics.Compared with WC-9Co prepared via MEX followed by debinding and sintering(DS),the hardness of WC-9Co prepared using MEX-WIP-DS does not change significantly,ranging HV_(30)1494-1508,the transverse rupture strength increases by up to 49.3%,reaching 2998-3514 MPa,and the fracture toughness remains high,ranging 14.8-17.0 MPa·m^(1/2).The mechanical properties surpass comparable cemented carbides fabricated through other AM methods and are comparable to those produced by powder metallurgy.The integration of green WIP into MEX-DS broadens the MEX processing window,and improves the overall mechanical properties of MEX AM WC-Co cemented carbides.展开更多
Metal Additive Manufacturing(MAM) technology has become an important means of rapid prototyping precision manufacturing of special high dynamic heterogeneous complex parts. In response to the micromechanical defects s...Metal Additive Manufacturing(MAM) technology has become an important means of rapid prototyping precision manufacturing of special high dynamic heterogeneous complex parts. In response to the micromechanical defects such as porosity issues, significant deformation, surface cracks, and challenging control of surface morphology encountered during the selective laser melting(SLM) additive manufacturing(AM) process of specialized Micro Electromechanical System(MEMS) components, multiparameter optimization and micro powder melt pool/macro-scale mechanical properties control simulation of specialized components are conducted. The optimal parameters obtained through highprecision preparation and machining of components and static/high dynamic verification are: laser power of 110 W, laser speed of 600 mm/s, laser diameter of 75 μm, and scanning spacing of 50 μm. The density of the subordinate components under this reference can reach 99.15%, the surface hardness can reach 51.9 HRA, the yield strength can reach 550 MPa, the maximum machining error of the components is 4.73%, and the average surface roughness is 0.45 μm. Through dynamic hammering and high dynamic firing verification, SLM components meet the requirements for overload resistance. The results have proven that MEM technology can provide a new means for the processing of MEMS components applied in high dynamic environments. The parameters obtained in the conclusion can provide a design basis for the additive preparation of MEMS components.展开更多
Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant...Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.展开更多
Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating ...Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating excitationcontraction(E-C)coupling.Mutations in JPH2 have been associated with hypertrophic cardiomyopathy(HCM),but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus(MORN)repeat motifs remain incompletely understood.This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis.Methods A recombinant N-terminal fragment of mouse JPH2(residues 1-440),encompassing the MORN repeats and an adjacent helical region,was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain.Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features.Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells.In addition,site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations,including R347C,was used to evaluate their effects on membrane interaction and subcellular localization.Results The crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6Å,revealing a compact,elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration,forming a continuous hydrophobic core stabilized by alternating aromatic residues.A C-terminalα-helix further reinforced structural integrity.Conservation analysis identified the inner groove of the MORN array as a highly conserved surface,suggesting its role as a protein-binding interface.A flexible linker segment enriched in positively charged residues,located adjacent to the MORN motifs,was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes.Functional assays demonstrated that mutation of these basic residues impaired membrane association,while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays,despite preserving the overall MORN-Helix fold in structural modeling.Conclusion This study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2,highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions.The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis.These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.展开更多
基金support from the Research Committee of The Hong Kong Polytechnic University(Project codes:RMJK and 4-ZZSJ)supported by a grant from the Research Grants Council of the Hong Kong Special Administrative Region,China(Project No.PolyU15212523).
文摘Additive manufacturing(AM),with its high flexibility,cost-effectiveness,and customization,significantly accelerates the advancement of nanogenerators,contributing to sustainable energy solutions and the Internet of Things.In this review,an in-depth analysis of AM for piezoelectric and triboelectric nanogenerators is presented from the perspectives of fundamental mechanisms,recent advancements,and future prospects.It highlights AM-enabled advantages of versatility across materials,structural topology optimization,microstructure design,and integrated printing,which enhance critical performance indicators of nanogenerators,such as surface charge density and piezoelectric constant,thereby improving device performance compared to conventional fabrication.Common AM techniques for nanogenerators,including fused deposition modeling,direct ink writing,stereolithography,and digital light processing,are systematically examined in terms of their working principles,improved metrics(output voltage/current,power density),theoretical explanation,and application scopes.Hierarchical relationships connecting AM technologies with performance optimization and applications of nanogenerators are elucidated,providing a solid foundation for advancements in energy harvesting,self-powered sensors,wearable devices,and human-machine interaction.Furthermore,the challenges related to fabrication quality,cross-scale manufacturing,processing efficiency,and industrial deployment are critically discussed.Finally,the future prospects of AM for nanogenerators are explored,aiming to foster continuous progress and innovation in this field.
基金supported by PoSAddive–Powder Sheet Additive Manufacturing(co-funded by EIT Raw Materials,Grant No.22021)the AML in Trinity College Dublin.EIT Raw Materials is supported by EIT,a body of the European Union.
文摘A novel laser-based additive manufacturing approach of metal additive manufacturing using powder sheets(MAPS)has been introduced recently.The method utilizes polymer-bound powder sheets for metal AM as a feedstock,instead of loose powders.Conventional laser beam powder bed fusion(LPBF)additive manufacturing(AM)is among the most widespread 3D printing technologies.However,LPBF faces challenges related to safety and the impracticality of changing materials due to its reliance on loose powders.Thus,MAPS demonstrates the capability to overcome the limitations of LPBF by offering enhanced safety and the ability to print multi-material structures without the risk of material cross-contamination.As a part of developing processes,we investigate the effects of polymeric binder content on the printability and microstructural characteristics of MAPS-printed stainless steel 316 L.The results indicate that the average layer thickness of solidified material improves as the scanning speed decreases from 1000 mm/s to 50 mm/s across three different polymeric binder contents:10 wt%,20 wt%,and 30 wt%PCL.Additionally,a higher polymeric binder content(i.e.20 wt%and 30 wt%)in the powder sheets reduces the likelihood of crack formation.Electron backscatter diffraction(EBSD)analysis reveals that an increase in scanning speed promotes the formation of more equiaxed grains,while an increase in polymer content results in a reduction in grain size.These findings provide valuable insights into optimizing MAPS configurations for enhanced productivity and functionality in metal component manufacturing.
基金supported by International Partnership Program of the Chinese Academy of Sciences(Grant No.310GJH2024010GC)National Natural Science Foundation of China(Grant No.52005479)the China Building Materials Federation(Grant No.2023JBGS0401)。
文摘The utilization of lunar regolith for construction on the lunar surface presents a critical challenge in-situ resource utilization.This study proposes a lunar regolith manufacturing method that uses a high-performance resin binder characterized by a high regolith content and strong forming capabilities.A combined resin material with both thermosetting and photosetting properties was developed and mixed with lunar regolith to create a slurry.This slurry can be directly molded or additively extruded into green bodies with specific structures.These green bodies can self-cure under the high temperatures and ultraviolet radiation experienced during the lunar day,reducing energy consumption and fulfilling the requirements of lunar construction.The material-forming processes and effects of various additive types and concentrations,regolith mass ratios,and processing parameters on the properties of the slurry and the formed specimens were thoroughly investigated.The mechanical performance and microstructure of the fabricated samples were analyzed.The lunar regolith mass ratio reached 90 wt%(approximately 79 vol%),with the highest compressive strengths exceeding 60 MPa for cast specimens and 30 MPa for printed samples.This technology shows significant potential for enabling in-situ lunar regolith-based construction in future lunar missions.
基金supported by the National Key Research and Development Program of China(No.2022YFB3404700)the National Natural Science Foundation of China(Nos.52105313 and 52275299)+2 种基金the Research and Development Program of Beijing Municipal Education Commission,China(No.KM202210005036)the Natural Science Foundation of Chongqing,China(No.CSTB2023NSCQ-MSX0701)the National Defense Basic Research Projects of China(No.JCKY2022405C002).
文摘At present,the emerging solid-phase friction-based additive manufacturing technology,including friction rolling additive man-ufacturing(FRAM),can only manufacture simple single-pass components.In this study,multi-layer multi-pass FRAM-deposited alumin-um alloy samples were successfully prepared using a non-shoulder tool head.The material flow behavior and microstructure of the over-lapped zone between adjacent layers and passes during multi-layer multi-pass FRAM deposition were studied using the hybrid 6061 and 5052 aluminum alloys.The results showed that a mechanical interlocking structure was formed between the adjacent layers and the adja-cent passes in the overlapped center area.Repeated friction and rolling of the tool head led to different degrees of lateral flow and plastic deformation of the materials in the overlapped zone,which made the recrystallization degree in the left and right edge zones of the over-lapped zone the highest,followed by the overlapped center zone and the non-overlapped zone.The tensile strength of the overlapped zone exceeded 90%of that of the single-pass deposition sample.It is proved that although there are uneven grooves on the surface of the over-lapping area during multi-layer and multi-pass deposition,they can be filled by the flow of materials during the deposition of the next lay-er,thus ensuring the dense microstructure and excellent mechanical properties of the overlapping area.The multi-layer multi-pass FRAM deposition overcomes the limitation of deposition width and lays the foundation for the future deposition of large-scale high-performance components.
基金financially supported by the Green Development and Demonstration Programme(GUDP)(case number 34009-19-1585)。
文摘Background Post-weaning diarrhea(PWD)in piglets,often caused by F4^(+)enterotoxigenic Escherichia coli(ETEC),poses significant challenges in pig production.Traditional solutions like antibiotics and zinc oxide face increasing restrictions due to growing concerns over antibiotic resistance and environmental sustainability.This study investigates the application of bivalent heavy chain variable domain(V_(H)H)constructs(BL1.2 and BL2.2)targeting ETEC virulence factors,administered in feed to mitigate ETEC-induced PWD in weaned piglets.Results The supplementation of BL1.2 and BL2.2 in both mash and pelleted feed significantly reduced the diarrhea incidence and fecal shedding of F4^(+)ETEC in challenged piglets.Pelleted feed containing V_(H)H constructs helped to preserve gut barrier integrity by maintaining levels of the tight junction protein occludin in the small intestine.Additionally,the constructs maintained blood granulocyte counts at a similar level to the non-challenged control group,including neutrophils,and ameliorated the acute phase protein response after challenge.Notably,even at low feed intake immediately after weaning,V_(H)H constructs helped maintain piglet health by mitigating ETEC-induced inflammation and the resulting diarrhea.Conclusions Our findings demonstrated that using V_(H)H constructs as feed additives could serve as an effective strategy to help manage ETEC-associated PWD,by reducing F4^(+)ETEC gut colonization and supporting gut barrier function of weaned piglets.The high stability of these V_(H)H constructs supports their incorporation into industrial feed manufacturing processes,offering a more sustainable preventive strategy compared to traditional antimicrobial interventions,which could contribute to sustainable farming practices.
基金supported by the National Natural Science Foundation of China-Distinguished Young Scholars(No.52325407)the National Natural Science Foundation of China-Key Program(No.52234010)the Open Research Fund of the State Key Laboratory of Rolling and Automation,Northeastern University(No.2022RALKFKT004).
文摘Laser additive manufacturing(LAM)has been widely used in high-end manufacturing fields such as aerospace,nuclear power,and shipbuilding.However,it is a grand challenge for direct and continuous observation of complex laser-matter interaction,melt flow,and defect formation during LAM due to extremely large temperature gradient,fast cooling rate,and small time(millisecond)and space(micron)scales.The emergence of synchrotron radiation provides a feasible approach for in situ observation of the LAM process.This paper outlines the current development in real-time characterization of LAM by synchrotron radiation,including laser-matter interaction,molten pool evolution,solidification structure evolution,and defects formation and elimination.Furthermore,the future development direction and application-oriented research are also discussed.
基金the first Singapore-Germany Academic-Industry(2+2)international collaboration grant(Grant No.:A1890b0050)Agency for Science,Technology and Research(A^(*)STAR),under the RIE2020 Advanced Manufacturing and Engineering(AME)Programmatic Grant No.A1881b0061support of a scholarship from the A^(*)STAR Graduate Academy。
文摘Binder jet printing(BJP)is a state-of-the-art additive manufacturing technique for producing porous magnesium structures.Porous MgZn-Zr based BJP samples were assessed for corrosion performance in simulated body fluids by electrochemical and hydrogen evolution measurements.The corrosion rates of the BJP specimens were significantly higher than solid controls,even after accounting for their larger surface areas,suggesting that the BJP microstructure is detrimental to corrosion performance.X-ray computed tomography revealed nonuniform corrosion within the porous structure,with corrosion products forming on the pore walls.Impregnating the pores with hydroxyapatite or polymers greatly improved the corrosion resistance of the BJP samples.
基金supported by National Natural Science Foundation of China(Grant No.U2006218)Project of Construction and Support for High-Level Innovative Teams of Beijing Municipal Institutions(Grant No.BPHR20220124).
文摘SiC is a wave-absorbing material with good dielectric properties,high-temperature resistance,and corrosion resistance,which has great potential for development in the field of high-temperature wave-absorbing.However,SiC is limited by its low impedance-matching performance and single wave-absorbing mechanism.Therefore,compatible metamaterial technologies are required to enhance its wave-absorbing performance further.The electromagnetic wave(EMW)absorbing metamaterials can realize perfect absorption of EMWs in specific frequency bands and precise regulation of EMW phase,propagation mode,and absorption frequency bands through structural changes.However,the traditional molding methods for manufacturing complex geometric shapes require expensive molds,involve process complexity,and have poor molding accuracy and other limitations.Therefore,additive manufacturing(AM)technology,through material layered stacking to achieve the processing of materials,is a comprehensive multidisciplinary advanced manufacturing technology and has become the core technology for manufacturing metamaterials.This review introduces the principles and applications of different AM technologies for SiC and related materials,discusses the current status and development trends of various AM technologies for fabricating silicon-carbon-based wave-absorbing metamaterials,summarizes the limitations and technological shortcomings of existing AM technologies for fabricating silicon-carbon-based wave-absorbing metamaterials,and provides an outlook for the future development of related AM technologies.
基金sponsored by the Science and Technology Program of Hubei Province,China(2022EHB020,2023BBB096)support provided by Centre of the Excellence in Production Research(XPRES)at KTH。
文摘In this review,we propose a comprehensive overview of additive manufacturing(AM)technologies and design possibilities in manufacturing metamaterials for various applications in the biomedical field,of which many are inspired by nature itself.It describes how new AM technologies(e.g.continuous liquid interface production and multiphoton polymerization,etc)and recent developments in more mature AM technologies(e.g.powder bed fusion,stereolithography,and extrusion-based bioprinting(EBB),etc)lead to more precise,efficient,and personalized biomedical components.EBB is a revolutionary topic creating intricate models with remarkable mechanical compatibility of metamaterials,for instance,stress elimination for tissue engineering and regenerative medicine,negative or zero Poisson’s ratio.By exploiting the designs of porous structures(e.g.truss,triply periodic minimal surface,plant/animal-inspired,and functionally graded lattices,etc),AM-made bioactive bone implants,artificial tissues,and organs are made for tissue replacement.The material palette of the AM metamaterials has high diversity nowadays,ranging from alloys and metals(e.g.cobalt-chromium alloys and titanium,etc)to polymers(e.g.biodegradable polycaprolactone and polymethyl methacrylate,etc),which could be even integrated within bioactive ceramics.These advancements are driving the progress of the biomedical field,improving human health and quality of life.
基金supported by the National Natural Science Foundation of China(No.52061135101 and 52001078)the German Research Foundation(DFG,No.448318292)+3 种基金the Technology Innovation Guidance Special Foundation of Shaanxi Province(No.2023GXLH-085)the Fundamental Research Funds for the Central Universities(No.D5000240161)the Project of Key areas of innovation team in Shaanxi Province(No.2024RS-CXTD-20)The author Yingchun Xie thanks the support from the National Key R&D Program(No.2023YFE0108000).
文摘1.Introduction.Cold Spray(CS)is a highly advanced solid-state metal depo-sition process that was first developed in the 1980s.This innovative technique involves the high-speed(300-1200 m/s)impact deposition of micron-sized particles(5-50μm)to fabricate coatings[1-3].CS has been extensively used in a variety of coating applications,such as aerospace,automotive,energy,medical,marine,and others,to provide protection against high temperatures,corrosion,erosion,oxidation,and chemicals[4,5].Nowadays,the technical interest in CS is twofold:(i)as a repair process for damaged components,and(ii)as a solid-state additive manufacturing process.Compared to other fusion-based additive manufacturing(AM)technologies,Cold Spray Additive Manufacturing(CSAM)is a new member of the AM family that can enable the fabrication of deposits without undergoing melting.The chemical composition has been largely preserved from the powder to the deposit due to the minimal oxidation.The significant advantages of CSAM over other additive manufacturing processes include a high production rate,unlimited deposition size,high flexibility,and suitability for repairing damaged parts.
基金supported by National Natural Science Foundation of China(62104082)Guangdong Basic and Applied Basic Research Foundation(2022A1515010746,2022A1515011228,and 2022B1515120006)the Science and Technology Program of Guangzhou(202201010458).
文摘Gas quenching and vacuum quenching process are widely applied to accelerate solvent volatilization to induce nucleation of perovskites in blade-coating method.In this work,we found these two pre-crystallization processes lead to different order of crystallization dynamics within the perovskite thin film,resulting in the differences of additive distribution.We then tailor-designed an additive molecule named 1,3-bis(4-methoxyphenyl)thiourea to obtain films with fewer defects and holes at the buried interface,and prepared perovskite solar cells with a certified efficiency of 23.75%.Furthermore,this work also demonstrates an efficiency of 20.18%for the large-area perovskite solar module(PSM)with an aperture area of 60.84 cm^(2).The PSM possesses remarkable continuous operation stability for maximum power point tracking of T_(90)>1000 h in ambient air.
基金supported by the National Natural Science Foundation of China(Nos.52275299,52105313)R&D Program of Beijing Municipal Education Commission(No.KM202210005036)+1 种基金Natural Science Foundation of Chongqing,China(No.CSTB2023NSCQ-MSX0701)National Defense Basic Research Projects of China(No.JCKY2022405C002).
文摘Friction rolling additive manufacturing(FRAM)is a solid-state additive manufacturing technology that plasticizes the feed and deposits a material using frictional heat generated by the tool head.The thermal efficiency of FRAM,which depends only on friction to generate heat,is low,and the thermal-accumulation effect of the deposition process must be addressed.An FRAM heat-balance-control method that combines plasma-arc preheating and instant water cooling(PC-FRAM)is devised in this study,and a temperature field featuring rapidly increasing and decreasing temperature is constructed around the tool head.Additionally,2195-T87 Al-Li alloy is used as the feed material,and the effects of heating and cooling rates on the microstructure and mechanical properties are investigated.The results show that water cooling significantly improves heat accumulation during the deposition process.The cooling rate increases by 11.7 times,and the high-temperature residence time decreases by more than 50%.The grain size of the PC-FRAM sample is the smallest,i.e.,3.77±1.03μm,its dislocation density is the highest,and the number density of precipitates is the highest,the size of precipitates is the smallest,which shows the best precipitation-strengthening effect.The hardness test results are consistent with the precipitation distribution.The ultimate tensile strength,yield strength and elongation of the PC-FRAM samples are the highest(351±15.6 MPa,251.3±15.8 MPa and 16.25%±1.25%,respectively)among the samples investigated.The preheating and water-cooling-assisted deposition simultaneously increases the tensile strength and elongation of the deposited samples.The combination of preheating and instant cooling improves the deposition efficiency of FRAM and weakens the thermal-softening effect.
文摘This study investigates full liquid phase sintering as a process of fabrication parts from WE43(Mg-4wt.%Y-3wt.%RE-0.7wt.%Zr)alloy using binder jetting additive manufacturing(BJAM).This fabrication process is being developed for use in producing structural or biomedical devices.Specifically,this study focused on achieving a near-dense microstructure with WE43 Mg alloy while substantially reducing the duration of sintering post-processing after BJAM part rendering.The optimal process resulted in microstructure with 2.5%porosity and significantly reduced sintering time.The improved sintering can be explained by the presence of Y_(2)O_(3)and Nd_(2)O_(3)oxide layers,which form spontaneously on the surface of WE43 powder used in BJAM.These layers appear to be crucial in preventing shape distortion of the resulting samples and in enabling the development of sintering necks,particularly under sintering conditions exceeding the liquidus temperature of WE43 alloy.Sintered WE43 specimens rendered by BJAM achieved significant improvement in both corrosion resistance and mechanical properties through reduced porosity levels related to the sintering time.
基金financially supported by the Agency for Science,Technology and Research(A*Star),Republic of Singapore,under the Aerospace Consortium Cycle 12“Characterization of the Effect of Wire and Powder Deposited Materials”(No.A1815a0078)。
文摘The feasibility of manufacturing Ti-6Al-4V samples through a combination of laser-aided additive manufacturing with powder(LAAM_(p))and wire(LAAM_(w))was explored.A process study was first conducted to successfully circumvent defects in Ti-6Al-4V deposits for LAAM_(p) and LAAM_(w),respectively.With the optimized process parameters,robust interfaces were achieved between powder/wire deposits and the forged substrate,as well as between powder and wire deposits.Microstructure characterization results revealed the epitaxial prior β grains in the deposited Ti-6Al-4V,wherein the powder deposit was dominated by a finerα′microstructure and the wire deposit was characterized by lamellar α phases.The mechanisms of microstructure formation and correlation with mechanical behavior were analyzed and discussed.The mechanical properties of the interfacial samples can meet the requirements of the relevant Aerospace Material Specifications(AMS 6932)even without post heat treatment.No fracture occurred within the interfacial area,further suggesting the robust interface.The findings of this study highlighted the feasibility of combining LAAM_(p) and LAAM_(w) in the direct manufacturing of Ti-6Al-4V parts in accordance with the required dimensional resolution and deposition rate,together with sound strength and ductility balance in the as-built condition.
基金Alexander von Humboldt Foundation for the award of the Post-Doctoral Fellowship to M.Marvi-Mashhadi to undertake this research workthe support from the Bundesministerium für Bildung und Forschung(BMBF)through Bio Mag3D project code Nr.03VP09852 to undertake this research。
文摘In this study,a binder based 3D-printing technology viz.Fused Granular Fabrication(FGF)technique was used to produce interconnected and open porous Mg-6.3Gd bone scaffolds for compression test analyses.The consolidation of the green parts(as printed scaffolds)was performed using solvent debinding in cyclohexane and subsequent conventional sintering in argon atmosphere.Compression tests were performed on as sintered parts.Additionally,a simulation strategy was developed for modeling the compression behavior of the sintered parts,utilizing the data from the experimental results.The experimental compression test results and the simulation strategy for the compression behavior of the 3D-printed scaffolds demonstrated good agreement.
基金supported by the Key Project of Chinese Academy of Engineering(No.2019-XZ-11)the General Project of Chinese Academy of Engineering(No.2023-XY-18)+1 种基金the Open Fund of National Joint Engineering Research Center for Abrasion Control and Molding of Metal Materials of China(No.HKDNM201907)the Independent Project of State Key Laboratory of Powder Metallurgy,China。
文摘To tackle the common issue of green defects in material extrusion(MEX)additive manufacturing(AM)cemented carbides,warm isostatic pressing(WIP)was introduced to eliminate defects of MEX WC-9Co cemented carbide greens,thereby improving both microstructure uniformity and mechanical properties of sintered bodies.The results indicate that WIP reduces defects in MEX greens,thus decreasing the dimensions and numbers of defects,modifying shapes of pores within sintered bodies,while preserving surface quality and shape characteristics.Compared with WC-9Co prepared via MEX followed by debinding and sintering(DS),the hardness of WC-9Co prepared using MEX-WIP-DS does not change significantly,ranging HV_(30)1494-1508,the transverse rupture strength increases by up to 49.3%,reaching 2998-3514 MPa,and the fracture toughness remains high,ranging 14.8-17.0 MPa·m^(1/2).The mechanical properties surpass comparable cemented carbides fabricated through other AM methods and are comparable to those produced by powder metallurgy.The integration of green WIP into MEX-DS broadens the MEX processing window,and improves the overall mechanical properties of MEX AM WC-Co cemented carbides.
基金funded by the National Natural Science Foundation of China Youth Fund(Grant No.62304022)Science and Technology on Electromechanical Dynamic Control Laboratory(China,Grant No.6142601012304)the 2022e2024 China Association for Science and Technology Innovation Integration Association Youth Talent Support Project(Grant No.2022QNRC001).
文摘Metal Additive Manufacturing(MAM) technology has become an important means of rapid prototyping precision manufacturing of special high dynamic heterogeneous complex parts. In response to the micromechanical defects such as porosity issues, significant deformation, surface cracks, and challenging control of surface morphology encountered during the selective laser melting(SLM) additive manufacturing(AM) process of specialized Micro Electromechanical System(MEMS) components, multiparameter optimization and micro powder melt pool/macro-scale mechanical properties control simulation of specialized components are conducted. The optimal parameters obtained through highprecision preparation and machining of components and static/high dynamic verification are: laser power of 110 W, laser speed of 600 mm/s, laser diameter of 75 μm, and scanning spacing of 50 μm. The density of the subordinate components under this reference can reach 99.15%, the surface hardness can reach 51.9 HRA, the yield strength can reach 550 MPa, the maximum machining error of the components is 4.73%, and the average surface roughness is 0.45 μm. Through dynamic hammering and high dynamic firing verification, SLM components meet the requirements for overload resistance. The results have proven that MEM technology can provide a new means for the processing of MEMS components applied in high dynamic environments. The parameters obtained in the conclusion can provide a design basis for the additive preparation of MEMS components.
基金supported by the National Natural Science Foundation of China(Nos.82171552 and 82170479)the Natural Science Foundation of Shanghai Ctiy(No.21ZR1457500)the Science and Technology Bureau of Shanghai Putuo District(No.ptkwws202102).
文摘Magnolol,a compound extracted from Magnolia officinalis,demonstrates potential efficacy in addressing metabolic dysfunction and cardiovascular diseases.Its biological activities encompass anti-inflammatory,antioxidant,anticoagulant,and anti-diabetic effects.Growth/differentiation factor-15(GDF-15),a member of the transforming growth factorβsuperfamily,is considered a potential therapeutic target for metabolic disorders.This study investigated the impact of magnolol on GDF-15 production and its underlying mechanism.The research examined the pharmacological effect of magnolol on GDF-15 expression in vitro and in vivo,and determined the involvement of endoplasmic reticulum(ER)stress signaling in this process.Luciferase reporter assays,chromatin immunoprecipitation,and in vitro DNA binding assays were employed to examine the regulation of GDF-15 by activating transcription factor 4(ATF4),CCAAT enhancer binding proteinγ(CEBPG),and CCCTC-binding factor(CTCF).The study also investigated the effect of magnolol and ATF4 on the activity of a putative enhancer located in the intron of the GDF-15 gene,as well as the influence of single nucleotide polymorphisms(SNPs)on magnolol and ATF4-induced transcription activity.Results demonstrated that magnolol triggers GDF-15 production in endothelial cells(ECs),hepatoma cell line G2(HepG2)and hepatoma cell line 3B(Hep3B)cell lines,and primary mouse hepatocytes.The cooperative binding of ATF4 and CEBPG upstream of the GDF-15 gene or the E1944285 enhancer located in the intron led to full-power transcription of the GDF-15 gene.SNP alleles were found to impact the magnolol and ATF4-induced transcription activity of GDF-15.In high-fat diet ApoE^(-/-)mice,administration of magnolol induced GDF-15 production and partially suppressed appetite through GDF-15.These findings suggest that magnolol regulates GDF-15 expression through priming of promoter and enhancer activity,indicating its potential as a drug for the treatment of metabolic disorders.
文摘Objective Junctophilin-2(JPH2)is an essential structural protein that maintains junctional membrane complexes(JMCs)in cardiomyocytes by tethering the plasma membrane to the sarcoplasmic reticulum,thereby facilitating excitationcontraction(E-C)coupling.Mutations in JPH2 have been associated with hypertrophic cardiomyopathy(HCM),but the molecular mechanisms governing its membrane-binding properties and the functional relevance of its membrane occupation and recognition nexus(MORN)repeat motifs remain incompletely understood.This study aimed to elucidate the structural basis of JPH2 membrane association and its implications for HCM pathogenesis.Methods A recombinant N-terminal fragment of mouse JPH2(residues 1-440),encompassing the MORN repeats and an adjacent helical region,was purified under near-physiological buffer conditions.X-ray crystallography was employed to determine the structure of the JPH2 MORN-Helix domain.Sequence conservation analysis across species and junctophilin isoforms was performed to assess the evolutionary conservation of key structural features.Functional membrane-binding assays were conducted using liposome co-sedimentation and cell-based localization studies in COS7 and HeLa cells.In addition,site-directed mutagenesis targeting positively charged residues and known HCM-associated mutations,including R347C,was used to evaluate their effects on membrane interaction and subcellular localization.Results The crystal structure of the mouse JPH2 MORN-Helix domain was resolved at 2.6Å,revealing a compact,elongated architecture consisting of multiple tandem MORN motifs arranged in a curved configuration,forming a continuous hydrophobic core stabilized by alternating aromatic residues.A C-terminalα-helix further reinforced structural integrity.Conservation analysis identified the inner groove of the MORN array as a highly conserved surface,suggesting its role as a protein-binding interface.A flexible linker segment enriched in positively charged residues,located adjacent to the MORN motifs,was found to mediate direct electrostatic interactions with negatively charged phospholipid membranes.Functional assays demonstrated that mutation of these basic residues impaired membrane association,while the HCM-linked R347C mutation completely abolished membrane localization in cellular assays,despite preserving the overall MORN-Helix fold in structural modeling.Conclusion This study provides structural insight into the membrane-binding mechanism of the cardiomyocyte-specific protein JPH2,highlighting the dual roles of its MORN-Helix domain in membrane anchoring and protein interactions.The findings clarify the structural basis for membrane targeting via a positively charged linker and demonstrate that disruption of this interaction—such as that caused by the R347C mutation—likely contributes to HCM pathogenesis.These results not only enhance current understanding of JPH2 function in cardiac E-C coupling but also offer a structural framework for future investigations into the assembly and regulation of JMCs in both physiological and disease contexts.
