The Earliest Discovery of the Role of Magnesium Ions on Stabilizing the Tertiary Structure of the Transfer RNA and Its Biological Significance —A Short Memoir

In early of 1960s, I was a graduate student studying on tRNA biochemistry. In the course of the research, the magnesium ions stabilized the tertiary structure of tRNA, resulting in its resistance to enzymatic degradation was discovered independently. The experiment of deaminated (denatured) tRNA obtained from native tRNA was designed and conducted and further proved the validity of this finding. It was found that magnesium ions could stabilize the tertiary structure of the natrive tRNA but could not stabilize structure of the deaminated tRNA. In term of the methodology, this stabilization technique has been widely applied in sequencing analysis of RNA and has greatly promoted the progress in the study of primary structure of RNA. More importantly, the stabilization of the tertiary structure of RNA by magnesium ions plays a key role both in the processing of messenger RNAs and the ribozyme activity. After our first article in Chinese was published in 1963, a paper of Nishimura & Novelli came into our note. The received date of their paper was March 22 of 1963, only 4 days earlier than that of our first paper. Thus, we and Nishimura & Novelli made almost at the same time the earliest discovery of the role of magnesium ions on stabilizing the tertiary structure of the transfer RNA and thus resulted in resistance of tRNA degradation by enzymes. However, this discovery was not initially appreciated for a period of time but was finally “visualized” and proved by X-ray crystal structure of yeast phenylalanine tRNA, which has provided more accurate information on the geometry of the magnesium-binding sites in tRNA.

Bio-cementation for tidal erosion resistance improvement of foreshore slopes based on microbially induced magnesium and calcium precipitation

In most coastal and estuarine areas,tides easily cause surface erosion and even slope failure,resulting in severe land losses,deterioration of coastal infrastructure,and increased floods.The bio-cementation technique has been previously demonstrated to effectively improve the erosion resistance of slopes.Seawater contains magnesium ions(Mg^(2+))with a higher concentration than calcium ions(Ca^(2+));therefore,Mg^(2+)and Ca^(2+)were used together for bio-cementation in this study at various Mg^(2+)/Ca^(2+)ratios as the microbially induced magnesium and calcium precipitation(MIMCP)treatment.Slope angles,surface strengths,precipitation contents,major phases,and microscopic characteristics of precipitation were used to evaluate the treatment effects.Results showed that the MIMCP treatment markedly enhanced the erosion resistance of slopes.Decreased Mg^(2+)/Ca^(2+)ratios resulted in a smaller change in angles and fewer soil losses,especially the Mg^(2+)concentration below 0.2 M.The decreased Mg^(2+)/Ca^(2+)ratio achieved increased precipitation contents,which contributed to better erosion resistance and higher surface strengths.Additionally,the production of aragonite would benefit from elevated Mg^(2+)concentrations and a higher Ca^(2+)concentration led to more nesquehonite in magnesium precipitation crystals.The slopes with an initial angle of 53°had worse erosion resistance than the slopes with an initial angle of 35°,but the Mg^(2+)/Ca^(2+)ratios of 0.2:0.8,0.1:0.9,and 0:1.0 were effective for both slope stabilization and erosion mitigation to a great extent.The results are of great significance for the application of MIMCP to improve erosion resistance of foreshore slopes and the MIMCP technique has promising application potential in marine engineering.

Intelligent microneedle patch with prolonged local release of hydrogen and magnesium ions for diabetic wound healing

Diabetes mellitus,an epidemic with a rapidly increasing number of patients,always leads to delayed wound healing associated with consistent pro-inflammatory M1 polarization,decreased angiogenesis and increased reactive oxygen species(ROS)in the microenvironment.Herein,a poly(lactic-co-glycolic acid)(PLGA)-based microneedle patch loaded with magnesium hydride(MgH_(2))(MN-MgH_(2))is manufactured for defeating diabetic wounds.The application of microneedle patch contributes to the transdermal delivery and the prolonged release of MgH_(2) that can generate hydrogen(H_(2))and magnesium ions(Mg^(2+))after reaction with body fluids.The released H_(2) reduces the production of ROS,transforming the pathological microenvironment induced by diabetes mellitus.Meanwhile,the released Mg^(2+)promotes the polarization of pro-healing M2 macrophages.Consequently,cell proliferation and migration are improved,and angiogenesis and tissue regeneration are enhanced.Such intelligent microneedle patch provides a novel way for accelerating wound healing through steadily preserving and releasing of H_(2) and Mg^(2+)locally and sustainably.

Multidimensional defects tailoring local electron and Mg^(2+) diffusion channels for boosting magnesium storage performance of WO_(3)/MoO_(2)

Defect engineering presents great promise in addressing lower specific capacity,sluggish diffusion kinetics and poor cycling life issues in energy storage devices.Herein,multidimensional(0D/2D/3D) structural defects are constructed in WO_(3)/MoO_(2) simultaneously via competing for and sharing with O atoms during simple hydrothermal process.OD and 2D defects tailor local electron,activating more sites and generating built-in electric fields to yield ion reservoir,meanwhile,3D defect owning lower anisotropic property tailors Mg^(2+) diffusion channels to fully exploit Mg^(2+) adsorbed sites induced by OD and 2D defects,enhance the kinetics and maintain structural stability.Benefitted from synergistic effect of 0D/2D/3D structural defects,the designed WO_(3)/MoO_(2) shows the higher specific capacity(112.8 mA h g^(-1) at 50 mA g^(-1) with average attenuation rate per cycle of 0.068%),superior rate capability and excellent cycling stability(specific capacity retention of 80% after 1500 cycles at 1000 mA g^(-1)).This strategy provides design ideas of introducing multidimensional structural defects for tailoring local electron and microstructure to improve energy storage property.

Effect of magnesium ions/Type I collagen promote the biological behavior of osteoblasts and its mechanism

Type I collagen(Col I)is a main component of extracellular matrix(ECM).Its safety,biocompatibility,hydrophilicity and pyrogen immunogenicity make it suitable for tissues engineering applications.Mg2t also control a myriad of cellular processes,including the bone development by enhancing the attachment and differentiation of osteoblasts and accelerating mineralization to enhance bone healing.In our studies,Mg2t bind collagen to promote the proliferation and differentiation of osteoblasts through the expression of integrins and downstream signaling pathways.In order to clarify the biological behavior effect of 10mM Mg2t/Col I coating,we performed 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT),alkaline phosphatase(ALP),406-diamidino-2-phenylindole(DAPI),Alizarin red staining and Rhodamine B-isothiocyanate(RITC)-labeled phalloidin experiments and found that 10mM Mg2t group,Col I-coating group,10mM Mg2t/Col I-coating group,respectively,promoted the proliferation and differentiation of osteoblasts,especially 10mM Mg2t/Col I-coating group.We detected the mRNA expression of osteogenic-related genes(Runx2,ALP and OCN,OPN and BMP-2)and the protein expression of signaling pathway(integrin a2,integrin b1,FAK and ERK1/2),these results indicated that 10mM Mg2t/Col I coating play an critical role in up-regulating the MC3T3-E1 cells activity.The potential mechanisms of this specific performance may be through activating via integrin a2b1-FAK-ERK1/2 protein-coupled receptor pathway.

Effect of Magnesium on the C-S-H Nanostructure Evolution and Aluminate Phases Transition in Cement-Slag Blend

The microstructural study was conducted on cement and cement-slag pastes immersed in different concentrations of Mg（NO3）2 solutions utilizing ^29Si, ^27Al NMR spectroscopy and XRD techniques. The results show that the hydration of both the cement and cement-slag pastes is delayed when the pastes are cured in Mg（NO3）2 solutions as compared to the pastes cured in water. Moreover, Mg^2＋ ions also exhibit an decalcifying and dealuminizing effect on the C-A-S-H in cement and cement-slag pastes, and thereby decrease Ca/Si and Al[4]/Si ratios of the C-A-S-H. The dealuminization of C-A-S-H is mitigated for cement-slag paste as compared to pure cement paste. The depolymerized calcium and aluminum ions from C-A-S-H gel mainly enter the pore solution to maintain the pH value and form Al^[6] in TAH, respectively. On the other hand, Mg^2＋ ions exert an impact on the intra-transition between Al^[6] species, from AFm and hydrogarnet to hydrotalcite-like phase. NO3^-ions are interstratified in the layered Mg-Al structure and formed nitrated hydrotalcite-like phase（Mg1-xAlx（OH）2（NO3）x·nH2O）. Results from both ^27Al NMR and XRD data show that ettringite seems not to react with Mg^2＋ ions.

Emerging rechargeable aqueous magnesium ion battery

Recently,aqueous rechargeable batteries have played an essential role in developing renewable energy due to the merits of low cost,high security,and high energy density.Among various aqueous-based batteries,aqueous magnesium ion batteries(AMIBs)have rich reserves and high theoretical specific capacity(3833 mAh cm3).However,for future industrialization,AMIBs still face many scientific issues to be solved,such as the slow diffusion of magnesium ions in the material structure,the desolvation penalty at electrode-electrolyte interfaces,the cost of water-in-salt electrolyte,the low voltage of traditional aqueous electrolyte,etc.And yet a comprehensive summary of the components of AMIBs is lacking in the research community.This review mainly introduces the exploration and development of AMIB systems and related components.We conduct an in-depth study of the cathode materials appropriate for magnesium ion batteries from their crystal structures,focusing primarily on layered structures,spinel structures,tunnel structures,and three-dimensional framework structures.We also investigate the anode materials,ranging from inorganic materials to organic materials,as well as the electrolyte materials(from the traditional electrolyte to water-in-salt electrolyte).Finally,some perspectives on ensuing optimization design for future research efforts in the AMIBs field are summarized.

Exploration of amino trimethylene phosphonic acid to eliminate the adverse effect of seawater in molybdenite flotation

In this investigation,a chelating agent of amino trimethylene phosphonic acid(ATMP) was introduced to eliminate the adverse effect of seawater in molybdenite flotation.Microflotation results presented that high flotation recovery of molybdenite was achieved in freshwater using kerosene as the collector,but it was significantly decreased in the presence of seawater when pH> 9.5.Among the main ions in seawater,magnesium and calcium ions played a more detrimental role than others.After the addition of ATMP,molybdenite floatability can restore in seawater.Zeta potential distribution and solution chemistry calculation results illustrated that the decreased molybdenite floatability was attributed to the interaction of positive Mg(OH)_(2)(s)(major) and CaOH^(+)(minor) components with the molybdenite surface.The magnesium/calcium ions of positive components of Mg(OH)_(2)(s) and CaOH^(+) interacted with the ionized species of ATMP and then produced ATMP-calcium/magnesium complex,leading to the electrostatic repulsion between molybdenite and ATMP-calcium/magnesium complex that was restoring the molybdenite flotation.Hence,the ATMP can be utilized as an appropriate reagent to improve molybdenite flotation in seawater.

Changes of calcitonin gene-related peptide and other serological indicators in vestibular migraine patients

Objective:It aims to evaluate the diagnostic ability of CGRP and other blood indicators in vestibular migraine(VM)patients,and to explain the potential pathological effects of these biomarkers.The hypothesis of VM being a variant of migraine was examined.Methods:A total of 32 VM patients,35 migraine patients,and 30 healthy control subjects(HC)were selected for this cross-sectional study.Detailed statistics on demographic data,clinical manifestations,calcitonin gene-related peptide(CGRP)and common clinical laboratory indicators were measured within 24 hours from the onset of the conditions.Receptor operating characteristic(ROC)curve and area under the curve(AUC)were analyzed for biomarkers.The risk factors of VM and migraine were determined through univariate and multivariate analyses.Results:Compared with HC,serum CGRP levels(p(VM)=0.012,p(Migraine)=0.028)increased and Mg^(2+)levels(p(VM)<0.001,p(Migraine)<0.001)deceased in VM patients and migraine patients.In multiple logistic regression,VM was correlated with CGRP[odds ratio(OR)=1.07;95%confidence interval(CI),1.02-1.12;P=0.01]and Mg^(2+)[odds ratio(OR)=0.03;95%CI,0.07-0.15;P<0.001].Migraine was correlated with CGRP[odds ratio(OR)=1.07;95%CI,1.02-1.12;P=0.01]and Mg^(2+)[odd ratio(OR=0.01;95%CI,0-0.02;P<0.001)].Mg^(2+)discriminated good differentiation between VM and migraine groups,with AUC of 0.649(95%CI,0.518 to 0.780).The optimal threshold for Mg^(2+)to diagnose VM was 0.805.Conclusions:This study demonstrated that CGRP and Mg^(2+)may be promising laboratory indicators to discriminate HC from VM/migraine,while Mg^(2+)may be uded as a discriminator between VM and migraine.

Fabrication of magnesium-doped porous polylactic acid microsphere for bone regeneration

Biodegradable polymer microspheres that can be used as drug carriers are of great importance in biomedical applications,however,there are still challenges in controllable preparation of microsphere surface morphology and improvement of bioactivity.In this paper,firstly,poly(L-lactic acid)(PLLA)was synthesised by ring-opening polymerisation under anhydrous anaerobic conditions and further combined with the emulsion method,biodegradable PLLA microspheres(PM)with sizes ranging from 60-100μm and with good sphericity were prepared.In addition,to further improve the surface morphology of PLLA microspheres and enhance their bioactivity,functionalised porous PLLA microspheres loaded with magnesium oxide(MgO)/magnesium carbonate(MgCO_(3))(PMg)were also prepared by the emulsion method.The results showed that the loading of MgO/MgCO_(3)resulted in the formation of a porous structure on the surface of the microspheres(PMg)and the dissolved Mg^(2+)could be released slowly during the degradation of microspheres.In vitro cellular experiments demonstrated the good biocompatibility of PM and PMg,while the released Mg^(2+)further enhanced the anti-inflammatory effect and osteogenic activity of PMg.Functionalised PMg not only show promise for controlled preparation of drug carriers,but also have translational potential for bone regeneration.

Exosome-functionalized magnesium-organic framework-based scaffoldswith osteogenic, angiogenic and anti-inflammatory properties foraccelerated bone regeneration

Exosomes derived from human adipose-derived stem cells (hADSCs-Exos) have shown potential as an effectivetherapeutic tool for repairing bone defects. Although metal-organic framework (MOF) scaffolds are promisingstrategies for bone tissue regeneration, their potential use for exosome loading remains unexplored. In this study,motivated by the potential advantages of hADSCs-Exos and Mg-GA MOF, we designed and synthesized anexosome-functionalized cell-free PLGA/Mg-GA MOF (PLGA/Exo-Mg-GA MOF) scaffold, taking using of thebenefits of hADSCs-Exos, Mg2+, and gallic acid (GA) to construct unique nanostructural interfaces to enhanceosteogenic, angiogenic and anti-inflammatory capabilities simultaneously. Our in vitro work demonstrated thebeneficial effects of PLGA/Exo-Mg-GA MOF composite scaffolds on the osteogenic effects in human bonemarrow-derived mesenchymal stem cells (hBMSCs) and angiogenic effects in human umbilical endothelial cells(HUVECs). Slowly released hADSCs-Exos from composite scaffolds were phagocytosed by co-cultured cells,stabilized the bone graft environment, ensured blood supply, promoted osteogenic differentiation, and acceleratedbone reconstruction. Furthermore, our in vivo experiments with rat calvarial defect model showed thatPLGA/Exo-Mg-GA MOF scaffolds promoted new bone formation and satisfactory osseointegration. Overall, weprovide valuable new insights for designing exosome-coated nanocomposite scaffolds with enhanced osteogenesisproperty.

Regulation of extracellular bioactive cations in bone tissue microenvironment induces favorable osteoimmune conditions to accelerate in situ bone regeneration

The design of orthopedic biomaterials has gradually shifted from“immune-friendly”to“immunomodulatory,”in which the biomaterials are able to modulate the inflammatory response via macrophage polarization in a local immune microenvironment that favors osteogenesis and implant-to-bone osseointegration.Despite the well-known effects of bioactive metallic ions on osteogenesis,how extracellular metallic ions manipulate immune cells in bone tissue microenvironments toward osteogenesis and subsequent bone formation has rarely been studied.Herein,we investigate the osteoimmunomodulatory effect of an extracellular bioactive cation(Mg^(2+))in the bone tissue microenvironment using custom-made poly lactic-co-glycolic acid(PLGA)/MgO-alendronate microspheres that endow controllable release of magnesium ions.The results suggest that the Mg^(2+)-controlled tissue microenvironment can effectively induce macrophage polarization from the M0 to M2 phenotype via the enhancement of anti-inflammatory(IL-10)and pro-osteogenic(BMP-2 and TGF-β1)cytokines production.It also generates a favorable osteoimmune microenvironment that facilitates the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells.The in vivo results further verify that a large amount of bony tissue,with comparable bone mineral density and mechanical properties,has been generated at an early post-surgical stage in rat intramedullary bone defect models.This study demonstrates that the concept of in situ immunomodulated osteogenesis can be realized in a controlled magnesium tissue microenvironment.

Stepwise 3D-spatio-temporal magnesium cationic niche: Nanocomposite scaffold mediated microenvironment for modulating intramembranous ossification

The fate of cells and subsequent bone regeneration is highly correlated with temporospatial coordination of chemical,biological,or physical cues within a local tissue microenvironment.Deeper understanding of how mammalian cells react to local tissue microenvironment is paramount important when designing next generation of biomaterials for tissue engineering.This study aims to investigate that the regulation of magnesium cationic(Mg^2+)tissue microenvironment is able to convince early-stage bone regeneration and its mechanism undergoes intramembranous ossification.It was discovered that moderate Mg^2+content niche(~4.11 mM)led to superior bone regeneration,while Mg^2+-free and strong Mg^2+content(~16.44 mM)discouraged cell adhesion,proliferation and osteogenic differentiation,thereby bone formation was rarely found.When magnesium ions diffused into free Mg zone from concentrated zone in late time point,new bone formation on free Mg zone became significant through intramembranous ossification.This study successfully demonstrates that magnesium cationic microenvironment serves as an effective biochemical cue and is able to modulate the process of bony tissue regeneration.The knowledge of how a Mg^2+cationic microenvironment intertwines with cells and subsequent bone formation gained from this study may provide a new insight to develop the next generation of tissuerepairing biomaterials.

Potassium ion pre‑intercalated MnO_(2)for aqueous multivalent ion batteries

Manganese dioxide(MnO_(2)),as a cathode material for multivalent ion(such as Mg^(2+)and Al^(3+))storage,is investigated due to its high initial capacity.However,during multivalent ion insertion/extraction,the crystal structure of MnO_(2)partially collapses,leading to fast capacity decay in few charge/discharge cycles.Here,through pre-intercalating potassium-ion(K+)intoδ-MnO_(2),we synthesize a potassium ion pre-intercalated MnO_(2),K_(0.21)MnO_(2)·0.31H_(2)O(KMO),as a reliable cathode material for multivalent ion batteries.The as-prepared KMO exhibits a high reversible capacity of 185 mAh/g at 1 A/g,with considerable rate performance and improved cycling stability in 1 mol/L MgSO_(4)electrolyte.In addition,we observe that aluminum-ion(Al^(3+))can also insert into a KMO cathode.This work provides a valid method for modifcation of manganesebased oxides for aqueous multivalent ion batteries.