Uniting tensile ductility with ultrahigh strength via composition undulation.

Metals with nanocrystalline grains have ultrahigh strengths approaching two gigapascals. However, such extreme grain-boundary strengthening results in the loss of almost all tensile ductility, even when the metal has a face-centred-cubic structure-the most ductile of all crystal structures1-3. Here we demonstrate that nanocrystalline nickel-cobalt solid solutions, although still a face-centred-cubic single phase, show tensile strengths of about 2.3 gigapascals with a respectable ductility of about 16 per cent elongation to failure. This unusual combination of tensile strength and ductility is achieved by compositional undulation in a highly concentrated solid solution. The undulation renders the stacking fault energy and the lattice strains spatially varying over length scales in the range of one to ten nanometres, such that the motion of dislocations is thus significantly affected. The motion of dislocations becomes sluggish, promoting their interaction, interlocking and accumulation, despite the severely limited space inside the nanocrystalline grains. As a result, the flow stress is increased, and the dislocation storage is promoted at the same time, which increases the strain hardening and hence the ductility. Meanwhile, the segment detrapping along the dislocation line entails a small activation volume and hence an increased strain-rate sensitivity, which also stabilizes the tensile flow. As such, an undulating landscape resisting dislocation propagation provides a strengthening mechanism that preserves tensile ductility at high flow stresses.

Scalable production of high-performing woven lithium-ion fibre batteries.

Fibre lithium-ion batteries are attractive as flexible power solutions because they can be woven into textiles, offering a convenient way to power future wearable electronics1-4. However, they are difficult to produce in lengths of more than a few centimetres, and longer fibres were thought to have higher internal resistances3,5 that compromised electrochemical performance6,7. Here we show that the internal resistance of such fibres has a hyperbolic cotangent function relationship with fibre length, where it first decreases before levelling off as length increases. Systematic studies confirm that this unexpected result is true for different fibre batteries. We are able to produce metres of high-performing fibre lithium-ion batteries through an optimized scalable industrial process. Our mass-produced fibre batteries have an energy density of 85.69 watt hour per kilogram (typical values8 are less than 1 watt hour per kilogram), based on the total weight of a lithium cobalt oxide/graphite full battery, including packaging. Its capacity retention reaches 90.5% after 500 charge-discharge cycles and 93% at 1C rate (compared with 0.1C rate capacity), which is comparable to commercial batteries such as pouch cells. Over 80 per cent capacity can be maintained after bending the fibre for 100,000 cycles. We show that fibre lithium-ion batteries woven into safe and washable textiles by industrial rapier loom can wirelessly charge a cell phone or power a health management jacket integrated with fibre sensors and a textile display.

Structure of hepcidin-bound ferroportin reveals iron homeostatic mechanisms.

The serum level of iron in humans is tightly controlled by the action of the hormone hepcidin on the iron efflux transporter ferroportin. Hepcidin regulates iron absorption and recycling by inducing the internalization and degradation of ferroportin1. Aberrant ferroportin activity can lead to diseases of iron overload, such as haemochromatosis, or iron limitation anaemias2. Here we determine cryogenic electron microscopy structures of ferroportin in lipid nanodiscs, both in the apo state and in complex with hepcidin and the iron mimetic cobalt. These structures and accompanying molecular dynamics simulations identify two metal-binding sites within the N and C domains of ferroportin. Hepcidin binds ferroportin in an outward-open conformation and completely occludes the iron efflux pathway to inhibit transport. The carboxy terminus of hepcidin directly contacts the divalent metal in the ferroportin C domain. Hepcidin binding to ferroportin is coupled to iron binding, with an 80-fold increase in hepcidin affinity in the presence of iron. These results suggest a model for hepcidin regulation of ferroportin, in which only ferroportin molecules loaded with iron are targeted for degradation. More broadly, our structural and functional insights may enable more targeted manipulation of the hepcidin-ferroportin axis in disorders of iron homeostasis.

Nanozyme Catalytic Performance Enhancement through Defect and Electronic Structure Regulation of Metal-Doped NiCo2O4@Pd.

Spinel oxides have emerged as a promising candidate in the realm of nanozymes with variable oxidation states, while their limited active sites and low conductivity hinder further application. In this work, we synthesize a series of metal-doped NiCo2O4 nanospheres decorated with Pd, which are deployed as highly efficient nanozymes for the detection of cancer biomarkers. Through meticulous modulation of the molar ratio between NiCo2O4 and Pd, we orchestrated precise control over the oxygen vacancies and electronic structure within the nanozymes, a key factor in amplifying the catalytic prowess. Leveraging the superior H2O2 reduction catalytic properties of Fe-NiCo2O4@Pd, we have successfully implemented its application in the electrochemical detection of biomarkers, achieving unparalleled analytical performance, much higher than that of Pd/C and other reported nanozymes. This research paves the way for innovative electron modification strategies in the design of high-performance nanozymes, presenting a formidable tool for clinical diagnostic analyses.

Cobalt(II)-Substituted Cysteamine Dioxygenase Oxygenation Proceeds through a Cobalt(III)-Superoxo Complex.

We investigated the metal-substituted catalytic activity of human cysteamine dioxygenase (ADO), an enzyme pivotal in regulating thiol metabolism and contributing to oxygen homeostasis. Our findings demonstrate the catalytic competence of cobalt(II)- and nickel(II)-substituted ADO in cysteamine oxygenation. Notably, Co(II)-ADO exhibited superiority over Ni(II)-ADO despite remaining significantly less active than the natural enzyme. Structural analyses through X-ray crystallography and cobalt K-edge excitation confirmed successful metal substitution with minimal structural perturbations. This provided a robust structural basis, supporting a conserved catalytic mechanism tailored to distinct metal centers. This finding challenges the proposed high-valent ferryl-based mechanism for thiol dioxygenases, suggesting a non-high-valent catalytic pathway in the native enzyme. Further investigation of the cysteamine-bound or a peptide mimic of N-terminus RGS5 bound Co(II)-ADO binary complex revealed the metal center's high-spin (S = 3/2) state. Upon reaction with O2, a kinetically and spectroscopically detectable intermediate emerged with a ground spin state of S = 1/2. This intermediate exhibits a characteristic 59Co hyperfine splitting (A = 67 MHz) structure in the EPR spectrum alongside UV-vis features, consistent with known low-spin Co(III)-superoxo complexes. This observation, unique for protein-bound thiolate-ligated cobalt centers in a protein, unveils the capacities for O2 activation in such metal environments. These findings provide valuable insights into the non-heme iron-dependent thiol dioxygenase mechanistic landscape, furthering our understanding of thiol metabolism regulation. The exploration of metal-substituted ADO sheds light on the intricate interplay between metal and catalytic activity in this essential enzyme.

Biomimetic-Structured Cobalt Nanocatalyst Suppresses Aortic Dissection Progression by Catalytic Antioxidation.

As one of the most lethal cardiovascular diseases, aortic dissection (AD) is initiated by overexpression of reactive oxygen species (ROS) in the aorta that damages the vascular structure and finally leads to massive hemorrhage and sudden death. Current drugs used in clinics for AD treatment fail to efficiently scavenge ROS to a large extent, presenting undesirable therapeutic effect. In this work, a nanocatalytic antioxidation concept has been proposed to elevate the therapeutic efficacy of AD by constructing a cobalt nanocatalyst with a biomimetic structure that can scavenge pathological ROS in an efficient and sustainable manner. Theoretical calculations demonstrate that the antioxidation reaction is catalyzed by the redox transition between hydroxocobalt(III) and oxo-hydroxocobalt(V) accompanied by inner-sphere proton-coupled two-electron transfer, forming a nonassociated activation catalytic cycle. The efficient antioxidation action of the biomimetic nanocatalyst in the AD region effectively alleviates oxidative stress, which further modulates the aortic inflammatory microenvironment by promoting phenotype transition of macrophages. Consequently, vascular smooth muscle cells are also protected from inflammation in the meantime, suppressing AD progression. This study provides a nanocatalytic antioxidation approach for the efficient treatment of AD and other cardiovascular diseases.

Bioinspired Heterocoordination in Adaptable Cobalt Metal-Organic Framework for DNA Epigenetic Modification Detection.

Metal-organic frameworks (MOFs) show unique advantages in simulating the dynamics and fidelity of natural coordination. Inspired by zinc finger protein, a second linker was introduced to affect the homogeneous MOF system and thus facilitate the emergence of diverse functionalities. Under the systematic identification of 12 MOF species (i.e., metal ions, linkers) and 6 second linkers (trigger), a dissipative system consisting of Co-BDC-NO2 and o-phenylenediamine (oPD) was screened out, which can rapidly and in situ generate a high photothermal complex (η = 36.9%). Meanwhile, both the carboxylation of epigenetic modifications and metal ion (Fe3+, Ni2+, Cu2+, Zn2+, Co2+ and Mn2+) screening were utilized to improve the local coordination environment so that the adaptable Co-MOF growth on the DNA strand was realized. Thus, epigenetic modification information on DNA was converted to an amplified metal ion signal, and then oPD was further introduced to generate bimodal dissipative signals by which a simple, high-sensitivity detection strategy of 5-hydroxymethylcytosine (LOD = 0.02%) and 5-formylcytosine (LOD = 0.025‰) was developed. The strategy provides one low-cost method (< 0.01 $/sample) for quantifying global epigenetic modifications, which greatly promotes epigenetic modification-based early disease diagnosis. This work also proposes a general heterocoordination design concept for molecular recognition and signal transduction, opening a new MOF-based sensing paradigm.

A Programmable Microfluidic Paper-Based Analytical Device for Simultaneous Colorimetric and Photothermal Visual Sensing of Multiple Enzyme Activities.

New strategies for the simultaneous and portable detection of multiple enzyme activities are highly desirable for clinical diagnosis and home care. However, the methods developed thus far generally suffer from high costs, cumbersome procedures, and heavy reliance on large-scale instruments. To satisfy the actual requirements of rapid, accurate, and on-site detection of multiple enzyme activities, we report herein a smartphone-assisted programmable microfluidic paper-based analytical device (µPAD) that utilizes colorimetric and photothermal signals for simultaneous, accurate, and visual quantitative detection of alkaline phosphatase (ALP) and butyrylcholinesterase (BChE). Specifically, the operation of this µPAD sensing platform is based on two sequential steps. Cobalt-doped mesoporous cerium oxide (Co-m-CeO2) with remarkable peroxidase-like activities under neutral conditions first catalytically decomposes H2O2 for effectively converting colorless 3,3',5,5'-tetramethylbenzidine (TMB) into blue oxidized TMB (oxTMB). The subsequent addition of ALP or BChE to their respective substrates produces a reducing substance that can somewhat inhibit the oxTMB transformation for compromised colorimetric and photothermal signals of oxTMB. Notably, these two-step bioenzyme-nanozyme cascade reactions strongly support the straightforward and excellent processability of this platform, which exhibit lower detection limits for ALP and BChE with a detection limit for BChE an order of magnitude lower than those of the other reported paper-based detection methods. The practicability and efficiency of this platform are further demonstrated through the analysis of clinical serum samples. This innovative platform exhibits great potential as a facile yet robust approach for simultaneous, accurate, and on-site visual detection of multiple enzyme activities in authentic samples.

Highly Electroactive Co2+-Based Metal-Organic Frameworks as an Efficient Coreaction Accelerator for Amplifying Near-Infrared Electrochemiluminescence of Gold Nanoclusters in Biomarkers Immunoassay.

Metal nanoclusters (NCs) as a new kind of luminophore have acquired sufficient interest, but their widespread application is restricted on account of their relatively low electrochemiluminescence (ECL) efficiency. Then, aqueous metal NCs with high ECL efficiency were strongly anticipated, especially for the ultrasensitive analysis of biomarkers. Herein, a near-infrared (NIR) ECL biosensing strategy for the test of neuron-specific enolase (NSE) was proposed by utilizing N-acetyl-l-cysteine (NAC)- and cysteamine (Cys)-stabilized gold NCs (NAC/Cys-AuNCs) as ECL emitters with the NIR ECL emission around 860 nm and a metal-organic framework/palladium nanocubes (ZIF-67/PdNCs) hybrid as the coreaction accelerator through their admirable electrocatalytic activity. The NIR emission would reduce photochemical injury to the samples and even realize nondestructive analysis with highly strong susceptibility and suitability. Furthermore, the utilization of ZIF-67/PdNCs could improve the ECL response of NAC/Cys-AuNCs by facilitating the oxidation of the coreactant triethylamine (TEA), leading to the production of a larger quantity of reducing intermediate radical TEA•+. Consequently, NAC/Cys-AuNCs with ZIF-67/PdNCs displayed 2.7 fold enhanced ECL emission compared with the single NAC/Cys-AuNCs using TEA as the coreactant. In addition, HWRGWVC (HWR), a heptapeptide, was introduced to immobilize antibodies for the specially binding Fc fragment of the antibodies, which improved the binding efficiency and sensitivity. As a result, a "signal-on" immunosensor for NSE analysis was obtained with an extensive linear range of 0.1 to 5 ng/mL and a low limit of detection (0.033 fg/mL) (S/N = 3). This study provides a wonderful method for the development of an efficient nondestructive immunoassay.

Innovative Colorimetric NQO1 Detection Strategy via Substrate Competitive and Biomimetic Cascade Reactions with a Highly Active NADH Oxidase Mimic.

NAD(P)H: quinone oxidoreductase-1 (NQO1) plays critical roles in antioxidation and abnormally overexpresses in tumors. Developing a fast and sensitive method of monitoring NQO1 will greatly promote cancer diagnosis in clinical practice. This study introduces a transformative colorimetric detection strategy for NQO1, harnessing an innovative competitive substrate mechanism between NQO1 and a new NADH oxidase (NOX) mimic, cobalt-nitrogen-doped carbon nanozyme (CoNC). This method ingeniously exploits the differential consumption of NADH in the presence of NQO1 to modulate the generation of H2O2 from CoNC catalysis, which is then quantified through a secondary, peroxidase-mimetic cascade reaction involving Prussian blue (PB) nanoparticles. This dual-stage reaction framework not only enhances the sensitivity of NQO1 detection, achieving a limit of detection as low as 0.67 µg mL-1, but also enables the differentiation between cancerous and noncancerous cells by their enzymatic activity profiles. Moreover, CoNC exhibits exceptional catalytic efficiency, with a specific activity reaching 5.2 U mg-1, significantly outperforming existing NOX mimics. Beyond mere detection, CoNC serves a dual role, acting as both a robust mimic of cytochrome c reductase (Cyt c) and a cornerstone for enzymatic regeneration, thereby broadening the scope of its biological applications. This study not only marks a significant step forward in the bioanalytical application of nanozymes but also sets the stage for their expanded use in clinical diagnostics and therapeutic monitoring.

Hybrid Organic-Inorganic Copper and Cobalt Complexes for Antimicrobial Potential Applications.

BACKGROUND/AIMS: The naturally occurring phenolic chemical curcumin (CUR), which was derived from the Curcuma longa plant, has a variety of biological actions, including anti-inflammatory, antimicrobial, antioxidant, and anticancer activities. Curcumin is known for its restricted bioavailability due to its hydrophobicity, poor intestinal absorption, and quick metabolism. To boost the biological effects of these bioactive molecules, it is necessary to raise both their bioavailability and their solubility in water. Aim: The aim of this study is to synthesize and characterize hybrid organic-inorganic complexes of copper and cobalt, and to evaluate their antimicrobial potential against a range of pathogenic microorganisms. METHODS: The synthesis of metal curcumin complexes (Cu-CUR and Co-CUR) was achieved by mixing curcumin with copper acetate monohydrate. The solid residue was isolated, filtered, and dried in an oven. X-ray diffraction analysis was used to identify the structure and phase of the prepared samples. FTIR spectra were recorded using a Shimadzu 2200 module. The antimicrobial activity of the prepared complexes was evaluated against four bacterial strains and two Candida species. The chemical materials were dissolved in DMSO to a final concentration of 20%, and the plates were incubated at 37°C for 24 hours. The results showed that the prepared complexes had antimicrobial activity against the tested microorganisms. RESULTS: The study compared the Powder X-ray diffraction (XRD) patterns of prepared copper and cobalt complexes to pure curcumin, revealing new, isostructural complexes. The FTIR analysis showed that the Cu-CUR and Co-CUR complexes varied in their inhibitory effect against microorganisms, with Co-CUR being more effective. The results are consistent with previous studies showing the cobalt-curcumin complex was effective against various bacterial genera, with inhibition activity varying depending on the species and strains of microorganisms. CONCLUSION: Copper and cobalt curcumin complexes, synthesized at room temperature, exhibit high crystallinity and antimicrobial activity. Co-CUR, with its superior antibacterial potential, outperforms pure curcumin in inhibiting microbes. Further investigation is needed to understand their interaction mechanisms with bacteria and fungi.

A novel closed-loop biotechnology for recovery of cobalt from a lithium-ion battery active cathode material.

In recent years, the demand for lithium-ion batteries (LIBs) has been increasing rapidly. Conventional recycling strategies (based on pyro- and hydrometallurgy) are damaging for the environment and more sustainable methods need to be developed. Bioleaching is a promising environmentally friendly approach that uses microorganisms to solubilize metals. However, a bioleaching-based technology has not yet been applied to recover valuable metals from waste LIBs on an industrial scale. A series of experiments was performed to improve metal recovery rates from an active cathode material (LiCoO2; LCO). (i) Direct bioleaching of ≤0.5 % LCO with two prokaryotic acidophilic consortia achieved >80 % Co and 90 % Li extraction. Significantly lower metal recovery rates were obtained at 30 °C than at 45 °C. (ii) In contrast, during direct bioleaching of 3 % LCO with consortia adapted to elevated LCO levels, the 30 °C consortium performed significantly better than the 45 °C consortium, solubilizing 73 and 93 % of the Co and Li, respectively, during one-step bioleaching, and 83 and 99 % of the Co and Li, respectively, during a two-step process. (iii) The adapted 30°C consortium was used for indirect leaching in a low-waste closed-loop system (with 10 % LCO). The process involved generation of sulfuric acid in an acid-generating bioreactor (AGB), 2-3 week leaching of LCO with the biogenic acid (pH 0.9), selective precipitation of Co as hydroxide, and recirculation of the metal-free liquor back into the AGB. In total, 58.2 % Co and 100 % Li were solubilized in seven phases, and >99.9 % of the dissolved Co was recovered after each phase as a high-purity Co hydroxide. Additionally, Co nanoparticles were generated from the obtained Co-rich leachates, using Desulfovibrio alaskensis, and Co electrowinning was optimized as an alternative recovery technique, yielding high recovery rates (91.1 and 73.6% on carbon felt and roughened steel, respectively) from bioleachates that contained significantly lower Co concentrations than industrial hydrometallurgical liquors. The closed-loop system was highly dominated by the mixotrophic archaeon Ferroplasma and sulfur-oxidizing bacteria Acidithiobacillus caldus and Acidithiobacillus thiooxidans. The developed system achieved high metal recovery rates and provided high-purity solid products suitable for a battery supply chain, while minimizing waste production and the inhibitory effects of elevated concentrations of dissolved metals on the leaching prokaryotes. The system is suitable for scale-up applications and has the potential to be adapted to different battery chemistries.

Hollow CoFe Nanozymes Integrated with Oncolytic Peptides Designed via Machine-Learning for Tumor Therapy.

Developing novel substances to synergize with nanozymes is a challenging yet indispensable task to enable the nanozyme-based therapeutics to tackle individual variations in tumor physicochemical properties. The advancement of machine learning (ML) has provided a useful tool to enhance the accuracy and efficiency in developing synergistic substances. In this study, ML models to mine low-cytotoxicity oncolytic peptides are applied. The filtering Pipeline is constructed using a traversal design and the Autogluon framework. Through the Pipeline, 37 novel peptides with high oncolytic activity against cancer cells and low cytotoxicity to normal cells are identified from a library of 25,740 sequences. Combining dataset testing with cytotoxicity experiments, an 80% accuracy rate is achieved, verifying the reliability of ML predictions. Peptide C2 is proven to possess membranolytic functions specifically for tumor cells as targeted by Pipeline. Then Peptide C2 with CoFe hollow hydroxide nanozyme (H-CF) to form the peptide/H-CF composite is integrated. The new composite exhibited acid-triggered membranolytic function and potent peroxidase-like (POD-like) activity, which induce ferroptosis to tumor cells and inhibits tumor growth. The study suggests that this novel ML-assisted design approach can offer an accurate and efficient paradigm for developing both oncolytic peptides and synergistic peptides for catalytic materials.

A Potential Antidote for Both Azide and Cyanide Poisonings.

There do not appear to be any established therapeutics for treating azide poisoning at this time, and presently available antidotes to cyanide poisoning are far from ideal, being particularly impractical for use if multiple victims present. The cobalt (II/III) complex of the Schiff-base ligand trans-[14]-diene (5,7,7,12,14,14-hexamethyl-1,4,8,11-tetraazacyclotetradeca-4,11-diene (CoN4[14]) is shown to act as an effective antidote to both azide and cyanide toxicity in mice. Groups of animals challenged with an LD40 dose of NaCN (100 µmol/kg i.p.) exhibited significantly faster recovery from knockdown and fewer (zero) deaths if given CoN4[14] (50 µmol/kg i.p.) 2 minutes after the toxicant. Groups of animals challenged with an essentially lethal dose of NaCN (1.5 x LD50 = 150 µmol/kg i.p.) all survived if given the CoN4[14] (75 µmol/kg i.p.) 5 minutes before the toxicant dose. These data represent improved antidotal capability over the Food and Drug Administration-approved cobalt-based cyanide antidote hydroxocobalamin. Recovery of animals challenged sublethally with NaN3 (415 µmol/kg i.p.) was assessed employing a modified pole-climbing test. Mice given the CoN4[14] antidote (70 µg/kg i.p.) 5 minutes after the toxicant dose recovered twice as fast as the controls given no antidote. The interactions of cyanide and azide with CoN4[14] in vitro (buffered aqueous solutions) have been further investigated by a combination of spectroscopic approaches. The Co(II) form of the complex is able to bind two CN- anions while only binding a single N3 -, providing a reasonable explanation for the difference between their therapeutic abilities. SIGNIFICANCE STATEMENT: The Schiff-base complex CoN4[14] is shown to be an effective antidote to cyanide in mice, with improved therapeutic capabilities compared to the Food and Drug Administration-approved cobalt-containing hydroxocobalamin. CoN4[14] is also antidotal in mice toward azide poisoning, for which there is seemingly no approved therapy currently available. The activity toward cyanide involves a "redox-switching" mechanism that could be a common, but largely unrecognized, feature of all cobalt-based cyanide antidotes in use and under development.

Exploring the Role of Metal in the Biointeraction of Metallacarboranes with C. elegans Embryos.

Cobaltabis(dicarbollides), ferrabis(dicarbollide), and their halogenated derivatives are the most studied metallacarboranes with great medical potential. These versatile compounds and their iodinated derivatives can be used in chemotherapy, radiotherapy, particle therapy, and bioimaging when isotopes are used. These metallacarboranes have been evaluated in vitro and recently in vivo with complex animal models. Lately, these studies have been complemented using the invertebrate Caenorhabditis elegans (C. elegans), a nematode largely used in toxicology. When evaluated at the L4 stage, cobaltabis(dicarbollides), ([o-COSAN]- and [8,8'-I2 -o-COSAN]- ), exhibited a higher mean lethal dose (LD50 ) than ferrabis(dicarbollides) ([o-FESAN]- and [8,8'-I2 -o-FESAN]- ). In this work, we used the C. elegans embryos since they are a complex biological barrier with concentric layers of polysaccharides and proteins that protect them from the environment. We assessed if the metal atom changes their biointeraction with the C. elegans embryos. First, we assessed the effects on embryo development for metallacarboranes and their di-iodinated derivatives. We observed changes in color and in their surface structure. An exhaustive physicochemical characterization was performed to understand better this interaction, revealing a stronger interaction of ferrabis(dicarbollide) compounds with C. elegans embryos than the cobaltabis(dicarbollide) molecules. Unveiling the biological interaction of these compounds is of great interest for their future biomedical applications.

Co(II) Substitution Enhances the Esterase Activity of a de Novo Designed Zn(II) Carbonic Anhydrase.

Carbonic Anhydrases (CAs) have been a target for de novo protein designers due to the simplicity of the active site and rapid rate of the reaction. The first reported mimic contained a Zn(II) bound to three histidine imidazole nitrogens and an exogenous water molecule, hence closely mimicking the native enzymes' first coordination sphere. Co(II) has served as an alternative metal to interrogate CAs due to its d7 electronic configuration for more detailed solution characterization. We present here the Co(II) substituted [Co(II)(H2O/OH-)]N(TRIL2WL23H)3 n+ that behaves similarly to native Co(II) substituted human-CAs. Like the Zn(II) analogue, the cobalt-derivative at slightly basic pH is incapable of hydrolyzing p-nitrophenylacetate (pNPA); however, as the pH is increased a significant activity develops, which at pH values above 10 eventually yields a catalytic efficiency that exceeds that of the [Zn(II)(OH-)]N(TRIL2WL23H)3 + peptide complex. X-ray absorption analysis is consistent with an octahedral species at pH 7.5 that converts to a 5-coordinate species by pH 11. UV-vis spectroscopy can monitor this transition, giving a pKa for the conversion of 10.3. We assign this conversion to the formation of a 5-coordinate Co(II)(Nimid)3(OH)(H2O) species. The pH dependent kinetic analysis indicates the maximal rate (kcat), and thus the catalytic efficiency (kcat/Km), follow the same pH profile as the spectroscopic conversion to the pentacoordinate species. This correlation suggests that the chemically irreversible ester hydrolysis corresponds to the rate determining process.

Metal-Organic Framework PCN-224 Combined Cobalt Oxide Nanoparticles for Hypoxia Relief and Synergistic Photodynamic/Chemodynamic Therapy.

Photodynamic therapy (PDT) and chemodynamic therapy (CDT) are promising tumor treatments mediated by reactive oxygen species (ROS), which have the advantages of being minimally invasive. However, the hypoxia of tumor microenvironment and poor target ability often reduce the therapeutic effect. Here we propose a tumor targeted nanoplatform PCN-224@Co3O4-HA for enhanced PDT and synergistic CDT, constructed by hyaluronate-modified Co3O4 nanoparticles decorated metal-organic framework PCN-224. Co3O4 can catalyze the decomposition of highly expressed H2O2 in tumor cells to produce oxygen and alleviate the problem of hypoxia. It can also produce hydroxyl radicals according to the Fenton-like reaction for chemical dynamic therapy, significantly improving the therapeutic effect. The cell survival experiment showed that after in vitro treatment, 4T1 and MCF-7 cancer cells died in a large area under the anaerobic state, while the survival ability of normal cell L02 was nearly unchanged. This result effectively indicated that PCN-224@Co3O4-HA could effectively relieve tumor hypoxia and improve the effect of PDT and synergistic CDT. Cell uptake experiments showed that PCN-224@Co3O4-HA had good targeting properties and could effectively aggregate in tumor cells. In vivo experiments on mice, PCN-224@Co3O4-HA presented reliable biosafety performance, and can cooperate with PDT and CDT therapy to prevent the growth of tumor.

Cholesterol vs Ergosterol: Influence on the Dynamic and Structural Properties of the Cobalt-Based Metallosomal Bilayer Membrane.

Sterol derivatives are a crucial part of liposomes, as their concentration and nature can induce significant alternations in their characteristic features. For natural liposomal-based (phospholipid-based) studies, the bulk literature is already present depicting the role of the concentration or nature of different sterol derivatives in modulation of membrane properties. However, the studies aiming at evaluating the effect of sterol derivatives on synthetic liposomal assemblies are limited to cholesterol (Chl), and a comparative effect with other sterol derivatives, such as ergosterol (Erg), has never been studied. To fill this research gap, through this work, we intend to provide insights into the concentration-dependent effect of two sterol derivatives (Chl and Erg) on a synthetic liposomal assembly (i.e., metallosomes) prepared via thin film hydration route using a double-tailed metallosurfactant fabricated by modifying cetylpyridinium chloride with cobalt (Co) (i.e., Co:CPC II). The morphological evaluations with cryogenic-transmission electron microscopy (cryo-TEM), atomic force microscopy (AFM), and field emission-scanning electron microscopy (FE-SEM) indicated that metallosomes retained their spherical morphology irrespective of the nature and concentration of sterol derivatives. However, the size, ζ-potential, and lamellar width values were significantly modified with the incorporation of sterol derivatives in a concentration-dependent manner. In-depth studies affirmed that the extent of modulation of the bilayer in terms of hydrophobicity, fluidity, and rigidity was more severe with Chl than Erg. Such differences in the membrane properties lead to their contrasting behavior in the delivery of the broad-spectrum active compound "curcumin". From entrapment to in vitro behavior, the metallosomes demonstrated dissimilar behavior as even though Erg-modified metallosomes (at higher concentrations of Erg) exhibited low entrapment efficiency, they still could easily release >80% of the entrapped drug. In vitro studies conducted with Staphylococcus aureus bacterial cultures further revealed an interesting pattern of activity as the incorporation of Chl reduced the toxicity of the self-assembly, whereas their Erg-modified counterparts yielded slightly augmented toxicity toward these bacterial cells. Furthermore, Chl- and Erg-modified assemblies also exhibited contrasting behavior in their interaction studies with bacterial DNA.

Alloyed Trimetallic Nanocomposite as an Efficient and Recyclable Solid Matrix for Ideonella sakaiensis Lipase Immobilization.

In this work, a trimetallic (Ni/Co/Zn) organic framework (tMOF), synthesized by a solvothermal method, was calcinated at 400 and 600 °C and the final products were used as a support for lipase immobilization. The material annealed at 400 °C (Ni-Co-Zn@400) had an improved surface area (66.01 m2/g) and pore volume (0.194 cm3/g), which showed the highest enzyme loading capacity (301 mg/g) with a specific activity of 0.196 U/mg, and could protect the enzyme against thermal denaturation at 65 °C. The optimal pH and temperature for the lipase were 8.0 and 45 °C but could tolerate pH levels 7.0-8.0 and temperatures 40-60 °C. Moreover, the immobilized enzyme (Ni-Co-Zn@Lipase, Ni-Co-Zn@400@Lipase, or Ni-Co-Zn@600@Lipase) could be recovered and reused for over seven cycles maintaining 80, 90, and 11% of its original activity and maintained a residual activity >90% after 40 storage days. The remarkable thermostability and storage stability of the immobilized lipase suggest that the rigid structure of the support acted as a protective shield against denaturation, while the improved pH tolerance toward the alkaline range indicates a shift in the ionization state attributed to unequal partitioning of hydroxyl and hydrogen ions within the microenvironment of the active site, suggesting that acidic residues may have been involved in forming an enzyme-support bond. The high enzyme loading capacity, specific activity, encouraging stability, and high recoverability of the tMOF@Lipase indicate that a multimetallic MOF could be a better platform for efficient enzyme immobilization.

Oxygen Vacancy-Enriched CoFe2O4 for Electrochemically Sensitive Detection of the Breast Cancer CD44 Biomarker.

Enhancing the selectivity of detection methods is essential to distinguish breast cancer biomarker cluster of differentiation 44 (CD44) from other species and reduce false-positive or false-negative results. Here, oxygen vacancy-enriched CoFe2O4 (CoFe2O4-x) was crafted, and its implementation as an electrochemical electrode for the detection of CD44 biomarkers has been scrutinized. This unique electrode material offers significant benefits and novel features that enhance the sensitivity and selectivity of the detection process. The oxygen vacancy density of CoFe2O4-x was tuned by adjusting the mass ratios of iron to cobalt precursors (iron-cobalt ratio) and changing annealing atmospheres. Electrochemical characterization reveals that, when the iron-cobalt ratio is 1:0.54 and the annealing atmosphere is nitrogen, the as-synthesized CoFe2O4-x electrode manifests the best electrochemical activity. The CoFe2O4-x electrode demonstrates high sensitivity (28.22 µA (ng mL)-1 cm-2), low detection limit (0.033 pg mL-1), and robust stability (for 11 days). Oxygen vacancies can not only enhance the conductivities of CoFe2O4 but also provide better adsorption of -NH2, which is beneficial for stability and electrochemical detection performance. The electrochemical detection signal can be amplified using CoFe2O4-x as a signal probe. Additionally, it is promising to know that the CoFe2O4-x electrode has shown good accuracy in real biological samples, including melanoma cell dilutions and breast cancer patient sera. The electrochemical detection results are comparable to ELISA results, which indicates that the CoFe2O4-x electrode can detect CD44 in complex biological samples. The utilization of CoFe2O4-x as the signal probe may expand the application of CoFe2O4-x in biosensing fields.