Bioprocess-inspired Actin Biomineralized Hematite Mesocrystals for Energy Storage

Biomineralization is a biological process of synthesizing inorganic minerals within organisms.It has been found that intracellular proteins are involved in the room temperature synthesis process of anatase Ti O2in living mussels.Here,we used intracellular actin to synthesize hematite by biomineralization.Biomineralized hematite has a nano spindle structure with a particle size of approximately 150 nm.The microstructure indicates that the prepared hematite is a mesocrystals composed of ordered arrangement and assembly of primary nanoparticles.In addition,hematite mesocrystals exhibit good lithium storage performance as electrode materials for lithium batteries.The discharge specific capacity of the battery remained at 560.7 m Ah·g^(-1)after 130 cycles at a current density of 200 m A·g^(-1).This work expands the synthesis methods of hematite by biomineralization,and provides a new strategy for preparing inorganic materials by intracellular proteins.

A Study of Chromium Adsorption on Natural Goethite Biomineralized with Iron Bacteria

Goethite, especially biogenic goethite, has high specific surface area and great capacity for the adsorption of many contaminants including metal ions and organic chelates. Chromium is a redox actively toxic metal ion that exists as either Cr^Ⅲ or Cr^Ⅵ in nature, and as such it is essential to understand its behavior of adsorption on natural goethite mineralized by iron bacteria, as Gallionella and Leptothrix in water body. The adsorption of Cr^3＋ and Cr^Ⅵ on naturally biomineralized goethite is studied in this paper. The results show that both Langmuir and Freundlich adsorption isothermal models are able to accurately describe the adsorption of these two ions. Investigation of SEM/EDS, TEM/EDS indicates that the two ions do not adsorb homogeneously on goethite owing to the different microstructures of goethite, and that the microspherical goethite has a greater adsorption capacity for chromium ions than the helical one. XPS data show that redox reaction of chromium on the surface of biomineralized goethite takes place in the adsorption of both Cr^3＋ and Cr^Ⅵ. The CrvI adsorbed on biogoethite is much easier to transform into CrIII than the oxidization of Cr^Ⅲ on the bio-goethite.

Cementomimetics——constructing a cementum-like biomineralized microlayer via amelogenin-derived peptides

Cementum is the outer-, mineralized-tissue covering the tooth root and an essential part of the system of periodontal tissue that anchors the tooth to the bone. Periodontal disease results from the destructive behavior of the host elicited by an infectious biofilm adhering to the tooth root and left untreated, may lead to tooth loss. We describe a novel protocol for identifying peptide sequences from native proteins with the potential to repair damaged dental tissues by controlling hydroxyapatite biomineralization. Using amelogenin as a case study and a bioinformatics scoring matrix, we identified regions within amelogenin that are shared with a set of hydroxyapatite-binding peptides （HABPs） previously selected by phage display. One 22-amino acid long peptide regions referred to as amelogenin-derived peptide 5 （ADP5） was shown to facilitate cell-free formation of a cementum-like hydroxyapatite mineral layer on demineralized human root dentin that, in turn, supported attachment of periodontal ligament cells in vitro. Our findings have several implications in peptide-assisted mineral formation that mimic biomineralization. By further elaborating the mechanism for protein control over the biomineral formed, we afford new insights into the evolution of protein-mineral interactions. By exploiting small peptide domains of native proteins, our understanding of structure-function relationships of biomineralizing proteins can be extended and these peptides can be utilized to engineer mineral formation. Finally, the cementomimetic layer formed by ADP5 has the potential clinical application to repair diseased root surfaces so as to promote the regeneration of periodontal tissues and thereby reduce the morbiditv associated with tooth loss.

Biomineralized nanoparticles for the immobilization and degradation of crude oil-contaminated soil

Accidental oil leaks and spills often cause server soil pollution,and in situ remediation is a powerful and economical treatment technology.While during in situ remediation process,unpredicted migration of petroleum hydrocarbon in heterogeneous soil will lead to a long-term source of persistent aquifer contamination.To reduce the migration of petroleum hydrocarbon and effectively improve the in situ remediation efficiency,herein,fungal biomineralization strategy was proposed for the immobilization of petroleum contaminants.A ureolytic fungi strain with crude oil-degradation ability was screened and identified as Chaetomium globosum.When incubated in medium containing Ca2+and crude oil,a mineral corona with spiny nanoparticles was formed at the edge of oil and the interface characters were analyzed using fluorescent pH and dissolved oxygen(DO)sensing films,respectively.Results indicated that biominerals preferred to aggregate around the edge of crude oil,providing favorable microenvironment for fungal growth and then leading to the increase of pH in the microenvironment,eventually accompanied by the formation of mineral corona.The mineral corona with numerous nanoparticles may act as a solid and stable shell,limiting or reducing the mobility of crude oil,and providing enough time for fungal biodegradation.After 28 days incubation,oilcontaminated soil treated with fungal biomineralization showed better immobilization ability for total petroleum hydrocarbon(TPH)under simulated acid-rain condition and higher TPH removal efficiency.This is the first demonstration for the immobilization of oil through fungal biomineralized nanoparticles,thus providing a novel strategy for the in situ remediation of oilcontaminated sites.

Copper carbonate nanoparticles as an effective biomineralized carrier to load macromolecular drugs for multimodal therapy

Macromolecular drugs have attracted great interest as biotherapy to cure previously untreatable diseases.For clinical translation,biomacromolecules encounter several common druggability difficulties,such as in vivo instability and poor penetration to cross physiologic barriers,thus requiring sophisticated systems for drug delivery.Inspired by the natural biomineralization via interaction between inorganic ions and biomacromolecules,herein we rationally screened biocompatible transition metals to biomineralize with carbonate for macromolecules loading.Among the metal ions,Cu^(2+)was found to be the best candidate,and its superiority over the widely studied Ca^(2+)minerals was also demonstrated.Capitalized on this finding,copper carbonate nanoparticles were prepared via a simple mixing process to co-load glucose oxidase(GOx)and a HIF-αDNAzyme(DZ),achieving ultra-high loading capacity of 61%.Upon encapsulation into nanoparticles,enzymatic activity of both drugs was passivated to avoid potential side-effects during circulation,while the drugs could be rapidly released within 1 h in response to acidic p H to fully recover their activities.The nanoparticles could accumulate into tumor via intravenous injection,facilitate the cell membrane penetration,and release the payloads of GOx,DZ and Cu^(2+)inside cells to exert a series of anti-tumor effects.GOx caused tumor starvation by catalytic glucose consumption,and the concomitantly generated H_(2)O_(2)byproduct boosted the Cu^(2+)-mediated chemodynamic therapy(CDT).Meanwhile,the DZ silenced HIF-αexpression to sensitize both starvation therapy and CDT.As a result,a synergistic tumor growth inhibition was achieved.This work provides a simple method to prepare biomineralized nanoparticles,and offers a general approach for macromolecular drugs delivery via Cu^(2+)-based biomineralization.

MV-mediated biomineralization mechanisms and treatments of biomineralized diseases

As the quality of life improves,people pay more and more attention to health.They are concerned about the causes of diseases,and seek better treatments.The most common diseases are biomineralized diseases,four different kinds of typical examples among which are selected to elaborate their mechanisms and existing treatments.Whether it is tooth and bone in physiological mineralization or cartilage and blood vessel in pathological mineralization,they are all related to matrix vesicle(MV)-mediated biomineralization.MV-mediated biomineralization is the initial stage of biomineralization and the nucleation site mediating collagen mineralization.Definition,composition,biogenesis,and action mechanism of MVs are refined and expounded,especially a novel biomineralization pathway similar to exosome(EX)origin.Four differences are summarized to distinguish MVs and EXs.A series of treatments using MVs to solve biomineralized diseases such as tooth and bone defects,osteoarthritis and atherosclerosis are proposed,and the experimental extraction steps of MVs are summarized.

Human osteoclast formation and resorptive function on biomineralized collagen

Biomineralized collagen composite materials pose an intriguing alternative to current synthetic bone graft substitutes by offering a biomimetic composition that closely resembles native bone.We hypothesize that this composite can undergo cellular resorption and remodeling similar to natural bone.We investigate the formation and activity of human osteoclasts cultured on biomineralized collagen and pure collagen membranes in comparison to cortical bone slices.Human monocytes/macrophages from peripheral blood differentiate into multinucleated,tartrate-resistant alkaline phosphatase(TRAP)-positive osteoclast-like cells on all substrates.These cells form clear actin rings on cortical bone,but not on biomineralized collagen or pure collagen membranes.Osteoclasts form resorption pits in cortical bone,resulting in higher calcium ion concentration in cell culture medium;however,osteoclast resorption of biomineralized collagen and collagen membranes does not measurably occur.Activity of osteoclast enzymes-TRAP,carbonic anhydrase II(CA-II),and cathepsin-K(CTS-K)-is similar on all substrates,despite phenotypic differences in actin ring formation and resorption.The mesh-like structure,relatively low stiffness,and lack of RGD-containing binding domains are likely the factors responsible for preventing formation of stable actin rings on and resorption of(biomineralized)collagen membranes.This insight helps to guide further research toward the optimized design of biomineralized collagen composites as a more biomimetic bone-graft substitute.

Comparative Transcriptome Analysis of Shell-Matrix-Protein Genes and Observation of the Shell Microstructure in the Deep-Sea Clam Calyptogena marissinica

The deep-sea clam Calyptogena marissinica is widely distributed in the Haima cold seep ecosystem on the northwes-tern slope of the South China Sea with low pH values,low temperature and high pressure.Limited information is available on the biomineralization of this species.In this research,we generated a comprehensive transcript dataset of C.marissinica’s mantle tissue,and a total of 19821 unigenes were assembled.Fourteen shell matrix proteins(SMP)-related genes were identified.The qPCR results showed that four out of six prismatic matrix genes(MSP2,MSP5,prisilkin-39,and shematrin),four out of the six nacreous matrix genes(perlucin,pif,pif97,and papilin),and two extrapallial fluid proteins(SPARC and calmodulin)were significantly expressed in the mantle.Both the nacreous and the prismatic layers are chrysanthemum-shaped,which are stacked on the top of each other to form a laminated nacreous structure.The alignment and phylogenetic analysis of MSP-5,Prisilkin-39,Perlucin,and Pif homologues showed that some amino acids of C.marissinica that differed from those detected in other molluscs may cause the different shape of the nacreous and prismatic layers,but do not lead to a change in the species’evolutionary status.These results indicated the conservation of the functions of SMP-related genes in C.marissinica,and the specific shape of the prismatic and nacreous layers of this deep-sea mollusc,which will contribute to the research on the molecular regulation mechanisms of biomineralization in C.marissinica and provide a new perspective to investigate biomineralization in deep-sea clams in general.

Enhanced Photocatalytic Activity of Z-scheme Meso-BiVO_(4)-Au-CdS for Degradation of Rhodamine B

We synthesized BiVO_(4)mesocrystals with ordered assembly structure,and studied the structural order and the relationship between the photodegradation of Rhodamine B.Au nanoparticles(NPs)were successfully loaded onto Meso-BiVO_(4)by light-assisted induction,and Cd nanoparticles were further selected to be deposited on Au nanoparticles to form Z-scheme photocatalyst Meso-BiVO_(4)-Au-CdS heterostructures.We try and propose to analyze its ordered assembly structure by XRD for the first time.The results show that Meso-BiVO_(4)is a mesocrystal with highly exposed(001)plane and directional assembly structure.The charge separation efficiency of all samples was studied by PL spectroscopy.The results show that the Z-scheme Meso-BiVO_(4)-Au-CdS can promote the charge separation and obtain the best carrier separation efficiency.Thus,it has the best photocatalytic activity in the experiment of photocatalytic degradation of rhodamine B.The main active species in the degradation process were confirmed by free radical trapping experiment,and the degradation mechanism was put forward.

Biomineralization of soil with crude soybean urease using different calcium salts

Calcium salt is an important contributing factor for calcium-based biomineralization.To study the effect of calcium salt on soil biomineralization using crude soybean urease,the calcium salts,including the calcium chloride (CaCl_(2)),calcium acetate ((CH_(3)COO)_(2)Ca) and calcium nitrate (Ca(NO_(3))_(2)),were used to prepare the biotreatment solution to carry out the biomineralization tests in this paper.Two series of biomineralization tests in solution and sand column,respectively,were conducted.Scanning electron microscopy (SEM) and X-ray diffraction (XRD) were performed to determine the microscopic characteristics of the precipitated calcium carbonate (CaCO_(3)) crystals.The experimental results indicate that the biomineralization effect is the best for the CaCl2 case,followed by (CH_(3)COO)_(2)Ca,and worst for Ca(NO_(3))_(2) under the test conditions of this study (i.e.1 mol/L of calcium salt-urea).The mechanism for the effect of the calcium salt on the biomineralization of crude soybean urease mainly involves: (1) inhibition of urease activity,and (2) influence on the crystal size and morphology of CaCO_(3).Besides Ca^(2+) ,the anions in solution can inhibit the activity of crude soybean urease,and NO_(3)− has a stronger inhibitory effect on the urease activity compared with both CH_(3)COO^(−) and Cl^(−) .The co-inhibition of Ca^(2+) and NO_(3)− on the activity of urease is the key reason for the worst biomineralization of the Ca(NO_(3))_(2) case in this study.The difference in biomineralization between the CaCl_(2) and (CH_(3)COO)_(2) Ca cases is strongly correlated with the crystal morphology of the precipitated CaCO_(3).

Biomimetic biomineralization nanoplatform-mediated differentiation therapy and phototherapy for cancer stem cell inhibition and antitumor immunity activation

Growing evidence suggests that the presence of cancer stem cells(CSCs)is a major challenge in current tumor treatments,especially the transition from non-CSCs to differentiation of CSCs for evading conventional therapies and driving metastasis.Here we propose a therapeutic strategy of synergistic differentiation therapy and phototherapy to induce differentiation of CSCs into mature tumor cells by differentiation inducers and synergistic elimination of them and normal cancer cells through phototherapy.In this work,we synthesized a biomimetic nanoplatform loaded with IR-780 and all-trans retinoic acid(ATRA)via biomineralization.This method can integrate aluminum ions into small-sized protein carriers to form nanoclusters,which undergo responsive degradation under acidic conditions and facilitate deep tumor penetration.With the help of CSC differentiation induced by ATRA,IR-780 inhibited the self-renewal of CSCs and cancer progression by generating hyperthermia and reactive oxygen species in a synergistic manner.Furthermore,ATRA can boost immunogenic cell death induced by phototherapy,thereby strongly causing a systemic anti-tumor immune response and efficiently eliminating CSCs and tumor cells.Taken together,this dual strategy represents a new paradigm of targeted eradication of CSCs and tumors by inducing CSC differentiation,improving photothermal therapy/photodynamic therapy and enhancing antitumor immunity.

Recent progress in microbial cell surface display systems and their application on biosensors

Microbial cell surface display technology is a recombinant technology to express target proteins on the cell membrane,which can be used to redesign the cell surface with functional proteins and peptides.Bacterial and yeast surface display systems are the most common cell surface display systems of prokaryotic and eukaryotic proteins,that are widely applied as the core elements in the field of biosensors due to their advantages,including enhanced stability,high yield,good safety,expression of larger and more complex proteins.To further promote the performance of biosensors,the biomineralized microbial surface display technology was proposed.This review summarized the different microbial surface display systems and the biomineralized surface display systems,where the mechanisms of surface display and biomineralization were introduced.Then we described the recent progress of their applications on biosensors for different types of detection targets.Finally,the outlooks and tendencies were discussed and forecasted with the expectation to provide some general functions and enlightenments to this aspect of research.

Biologically Inspired Self-assembling Synthesis of Bone-like Nano-hydroxyapatite/PLGA-(PEG-ASP)_n Composite: A New Biomimetic Bone Tissue Engineering Scaffold Material

A new biomimetic bone tissue engineering scaffold material, nano-HAI PLGA-（ PEG-Asp ）n composite, was synthesized by a biologically inspired self-assembling approach. A novel biodegradable PLGA- （ PEG-Asp ）n copolymer with pendant amine functional groups and enhanced hydrophilicity woo synthesized by bulk ring-opening copolymerization by DL-lactide（ DLLA） and glycolide（ GA ） with Aspartic acid （ Asp ）-Polyethylene glycol（PEG） alt-prepolymer. A Three-dimensional, porous scaffold of the PLGA-（ PEG- Asp）n copolymer was fabricated by a solvent casting , particulate leaching process. The scaffold woo then incubated in modified simulated body fluid （naSBF）. Growth of HA nanocrystals on the inner pore surfaces of the porous scaffold is confirmed by calcium ion binding analyses, SEM , mass increooe meoourements and quantification of phosphate content within scaffolds. SEM analysis demonstrated the nucleation and growth of a continuous bonelike, low crystalline carbonated HA nanocrystals on the inner pore surfaces of the PLGA- （ PEG-Asp ）n scaffolds. The amount of calcium binding, total mass and the mass of phosphate on experimental PLGA- （ PEG-Asp ） n scaffolds at different incubation times in mSBF was significantly greater than that of control PLGA scaffolds. This nano-HA/ PLGA-（ PEG- Asp ）n composite stunts some features of natural bone both in main composition and hierarchical microstrueture. The Asp- PEG alt-prepolymer modified PleA copolymer provide a controllable high surface density and distribution of anionic functional groups which would enhance nucleation and growth of bonelike mineral following exposure to mSBF. This biomimetic treatment provides a simple method for surface functionalization and sabsequent mineral nucleation and self-oosembling on bodegradable polymer scaffolds for tissue engineering.

Characterization of calcium deposition induced by Synechocystis sp. PCC6803 in BG11 culture medium

Calcium carbonate （CaCO3） crystals in their preferred orientation were obtained in BG11 culture media inoculated with Synechocystis sp. PCC6803 （inoculated BG11）. In this study, the features of calcium carbonate deposition were investigated. Inoculated BGll in different calcium ion concentrations was used for the experimental group, while the BGll culture medium was used for the control group. The surface morphologies of the calcium carbonate deposits in the experimental and control groups were determined by scanning and transmission electron microscopy. The deposits were analyzed by electronic probe micro-analysis, Fourier transform infrared spectrum, X-ray diffraction, thermal gravimetric analysis and differential scanning calorimetry. The results show that the surfaces of the crystals in the experimental group were hexahedral in a scaly pattern. The particle sizes were micrometer-sized and larger than those in the control group. The deposits of the control group contained calcium （Ca）, carbon （C）, oxygen （O）, phosphorus （P）, iron （Fe）, copper （Cu）, zinc （Zn）, and other elements. The deposits in the experimental group contained Ca, C, and O only. The deposits of both groups contained calcite. The thermal decomposition temperature of the deposits in the control group was lower than those in the experimental group. It showed that the CaCO3 deposits of the experimental group had higher thermal stability than those of the control group. This may be due to the secondary metabolites produced by the algae cells, which affect the carbonate crystal structure and result in a close-packed structure. The algae cells that remained after thermal weight loss were heavier in higher calcium concentrations in BGll culture media. There may be more calcium- containing crystals inside and outside of these cells. These results shall be beneficial for understanding the formation mechanism of carbonate minerals.

Biomineralization of Uranium: A Simulated Experiment and Its Significance

A simulated experimental reduction of and the synthesis of uraninite by a sulfate-reducing bacteria, Desulfovibrio desulfuricans DSM 642, are first reported. The simulated physicochemical experimental conditions were: 35°C, pH=7.0-7.4, corresponding to the environments of formation of the sandstone-hosted interlayer oxidation-zone type uranium deposits in Xinjiang, NW China. Uraninite was formed on the surface of the host bacteria after a one-week's incubation. Therefore, sulfate-reducing bacteria, which existed extensively in Jurassic sandstone-producing environments, might have participated in the biomineralization of this uranium deposit. There is an important difference in the order- disorder of the crystalline structure between the uraninite produced by Desulfovibrio desulfuricans and naturally occurring uraninite. Long time and slow precipitation and growth of uraninite in the geological environment might have resulted in larger uraninite crystals, with uraninite nanocrystals arranged in order, whereas the experimentally produced uraninite is composed of unordered uraninite nanocrystals which, in contrast, result from the short time span of formation and rapid precipitation and growth of uraninite. The discovery has important implications for understanding genetic significance in mineralogy, and also indicates that in-situ bioremediation of U-contaminated environments and use of biotechnology in the treatment of radioactive liquid waste is being contemplated.

Microstructure and surface texture driven improvement in in-vitro response of laser surface processed AZ31B magnesium alloy

The present work explored effects of laser surface melting on microstructure and surface topography evolution in AZ31B magnesium alloy.Thermokinetic effects experienced by the material during laser surface melting were simulated using a multiphysics finite element model.Microstructure and phase evolution were examined using scanning electron microscopy,X-ray diffraction,and electron back scatter diffraction.Surface topography was evaluated using white light interferometry.The interaction of surface melted samples with simulated body fluid was monitored by contact angle measurements and immersion studies up to 7 days.Laser surface melting led to formation of a refined microstructure with predominantly basal crystallographic texture.Concurrently,the amount ofβphase(Mg_(17)Al_(12))increased with an increase in the laser fluence.βphase preferentially decorated the cell boundaries.In terms of topography,the surface became progressively rougher with an increase in laser fluence.As a result,upon immersion in simulated body fluid,the laser surface melted samples showed an improved wettability,corrosion resistance,and precipitation of mineral having composition closer to the hydroxyapatite bone mineral compared to the untreated sample.

Growth of Hydroxyapatite Crystal in the Presence of Origanic Film

The growth of hydroxyapatite (HAp) crystal in the presence of hexadecylamine was investigated. Due to its high polarity and high charge density, the organic film could increase the ion supersaturation on its surface. Therefore the growth of pure HAp crystals was accelerated. Moreover, the positive headgroups of the organic film could act as recognized nucleation sites and orient the growth of HAp crystals along the <0001> direction.

High efficient removal and mineralization of Cr(VI)from water by functionalized magnetic fungus nanocomposites

A hydroxyl-functionalized magnetic fungus nanocomposite(MFH@GO)was prepared by a simple one-pot method for the removal of Cr(VI)from wastewater.The adsorption behavior of MFH@GO to Cr(VI)in wastewater was discussed in detail.At pH of 5.0 and temperature of 323.15 K,MFH@GO had higher adsorption capacity to Cr(VI)(58.4 mg/g)than the unmodified fungus and GO.Fourier transform infrared spectroscopy(FTIR),X-ray diffraction(XRD),thermogravimetry and differential thermal analysis(TG-DTA),scanning electron microscopy and energy dispersive X-Ray spectroscopy(SEM-EDX)were employed to determine the characteristics of MFH@GO.Results showed that magnetic graphene oxide nanoparticles significantly enhanced the physiochemical properties of the fungi.In addition,the adsorption mechanisms analyses show that Cr(VI)could be reduced and mineralized into ferric chromate in residues.These results suggested that MFH@GO could be used as an promising and alternative biosorbent for removal of Cr(VI)from industrial wastewater.

Does acid pickling of Mg-Ca alloy enhance biomineralization?

The mechanical and physical properties of biodegradable magnesium(Mg)alloys make them suitable for temporary orthopaedic implants.The success of these alloys depends on their performance in the physiological environment.In the present work,surface modification of Mg-Ca binary alloy by acid pickling for better biomineralization and controlled biodegradation is explored.The corrosion rates of nitric and phosphoric acid treated samples were analysed by conducting electrochemical corrosion tests.In vitro degradation behaviour was studied using immersion test in simulated body fluid(SBF).The sample surfaces were characterized using scanning electron microscope(SEM),energy dispersive X-ray spectroscopy(EDS),Fourier transform infrared spectroscopy(FTIR)and X-ray photoelectron spectroscopy(XPS).It is seen that acid pickling leads to significant improvement in biomineralization and develop in situ calcium phosphate(Ca P)coating on the sample surfaces.In addition,the treated samples recorded a reduced degradation rate in the SBF compared to untreated samples.Thus,acid pickling is suggested as an effective surface treatment method to tailor the biomineralization and degradation behaviour of the Mg-Ca alloy in the physiological environment.

Redox control of magnetosome biomineralization

Magnetotactic bacteria can orientate in the Earth’s magnetic field to search for their preferred microoxic environments,which is achieved by their unique organelles,the magnetosomes.Magnetosomes contain nanometer-sized crystal particles of magnetic iron minerals,which are only synthesized in lowoxygen environments.Although the mechanism of aerobic repression for magnetosome biomineralization has not yet fully understood,a series of studies have verified that redox modulation is pivotal for magnetosome formation.In this review,these advances in redox modulation for magnetosome biosynthesis are highlighted,mainly including respiration pathway enzymes,specific magnetosome-associated redox proteins,and oxygen-or nitrate-sensing regulators.Furthermore,their relationship during magnetosome biomineralization is discussed to give insight into redox control and biomineralization and inspire potential solutions for the application of respiration pathways to improve the yields of magnetosome.