Molybdenum, a trace element essential for micro-organisms, plants, and animals, was discovered in 1778 by a Swedish chemist named Karl Scheele. Initially mistaken for lead, molybdenum was named after the Greek work molybdos, meaning lead-like. In the 1930s, it was recognized that ingestion of forage with high amounts of molybdenum by cattle caused a debilitating condition. In the 1950s, the essentiality of molybdenum was established with the discovery of the first molybdenum-containing enzymes. In humans, only 4 enzymes requiring molybdenum have been identified to date: sulfite oxidase, xanthine oxidase, aldehyde oxidase, and mitochondrial amidoxime-reducing component (mARC). Sulfite oxidase, an enzyme found in mitochondria, catalyzes oxidation of sulfite to sulfate, the final step in oxidation of sulfur amino acids (cysteine and methionine). Xanthine oxidase converts hypoxanthine to xanthine, and further converts xanthine to uric acid, preventing hypoxanthine, formed from spontaneous deamination of adenine, from leading to DNA mutations if paired with cytosine in place of thymine. Aldehyde oxidase is abundant in the liver and is an important enzyme in phase 1 drug metabolism. Finally, mARC, discovered less than a decade ago, works in concert with cytochrome b5 type B and NAD(H) cytochrome b5 reductase to reduce a variety of N-hydroxylated substrates, although the physiologic significance is still unclear. In the case of each of the molybdenum enzymes, activity is catalyzed via a tricyclic cofactor composed of a pterin, a dithiolene, and a pyran ring, called molybdenum cofactor (MoCo) (1).

About 80% of all molybdenum mined in the world (not including units recovered via recycling) is used as an alloying element in iron and steel. In general, the intensity of molybdenum use in China is still lower than in more highly developed regions such as the USA and Europe. This difference is manifest in both carbon steels and stainless steels, suggesting a significant opportunity for more widespread use of molybdenum in the future as China follows its self-reliance policy, calling for more sophisticated materials. Active market development, as being pursued by the International Molybdenum Association (IMOA), is a key asset in that respect. This article summarizes some key facts on molybdenum mining, use and market development in China.

Selective laser melting (SLM) of pure molybdenum encounters all the difficulties of SLM metals due to its intrinsic properties (high melting point, high ductile-to-brittle transition temperature and high surface tension). In this work, we studied the influence of key factors such as powder morphology and processing parameters on SLM fabricated pure molybdenum. Pure molybdenum with a relative density of 99.1% was fabricated by SLM using optimized processing parameters. The formation mechanisms for densification behavior and crack growth behaviors are systematically analyzed. Electron backscattered diffraction analysis indicates that the interlocking grain boundary structure and stretch columnar grains can increase bonding force and inhibit crack growth. The balling and cracking can be reduced by adding support structure and suppressing oxygen content. The hardness of SLM-fabricated molybdenum exceeding 260 HV, which is 30–37% higher than Mo prepared by conventional manufacturing methods, mainly attributed to the fine grains and dislocation strengthening in the SLM process. The bending strength of SLM-ed Mo reached 280 ± 52 Mpa. The fracture mode of SLM Mo was intergranular. This study provides a new route for the fabrication of refractory metals with a complex structure.

Powder bed fusion (PBF) is recognized as one of the most common additive manufacturing technologies because of its attractive capability of fabricating complex geometries using many possible materials. However, the quality and reliability of parts produced by this technology are observed to be crucial aspects. In addition, the challenges of PBF-produced parts are hot issues among stakeholders because parts are still insufficient to meet the strict requirements of high-tech industries. This paper discusses the present state of the art in PBF and technological challenges, with a focus on selective laser melting (SLM). The review work focuses mainly on articles that emphasize the status and challenges of PBF metal-based AM, and the study is primarily limited to open-access sources, with special attention given to the process parameters and flaws as a determining factor for printed part quality and reliability. Moreover, the common defects due to an unstrained process parameter of SLM and those needed to monitor and sustain the quality and reliability of components are encompassed. From this review work, it has been observed that there are several factors, such as laser parameters, powder characteristics, material properties of powder and the printing chamber environments, that affect the SLM printing process and the mechanical properties of printed parts. It is also concluded that the SLM process is not only expensive and slow compared with conventional manufacturing processes, but it also suffers from key drawbacks, such as its reliability and quality in terms of dimensional accuracy, mechanical strength and surface roughness.

Preheating is an essential process step in electron beam powder bed fusion. It has the purpose of establishing a sintered powder bed and maintaining an elevated temperature. The sintered powder bed reduces the risk of smoke and in combination with the elevated temperature improves the processability. Today, the line-ordering preheating scheme is widely used. This scheme does not take the previously built layers into account and results in an inhomogeneous elevated temperature and consequently in a variety of sinter degrees, which is disadvantageous for the process. The main challenge is now to modify this scheme to establish a homogeneous temperature distribution. This study addresses this challenge and analyses as well as optimises this scheme. A GPU-parallelised thermal model reveals a heterogeneous temperature distribution during preheating because of varying thermal conditions within a build job. In addition, a work-of-sintering model predicts that the sinter degree of the current powder layer on top of previously consolidated material is smaller than on top of the surrounding powder bed. This work aims to invert this trend to improve powder re-usage and material consolidation. Consequently, this work proposes an extension of the current scheme, compensating for the specific energy loss with local adjustments to the energy input. This adaption results in a uniform temperature distribution and advantageous sintering. Applying the proposed numerical model proves to be an effective method to analyse the evolving process conditions and tailor the local energy input, thereby improving the efficiency of the preheating step.

A hallmark of low-temperature plasticity in body-centered cubic (BCC) metals is its departure from Schmid’s law. One aspect is that non-glide stresses, which do not produce any driving force on the dislocations, may affect the yield stress. We show here that this effect is due to a variation of the relaxation volume of the $$1/2\\langle 111\\rangle$$1∕2⟨111⟩ screw dislocations during glide. We predict quantitatively non-glide effects by modeling the dislocation core as an Eshelby inclusion, which couples elastically to the applied stress. This model explains the physical origin of the generalized yield criterion classically used to include non-Schmid effects in constitutive models of BCC plasticity. We use first-principles calculations to properly account for dislocation cores and use tungsten as a reference BCC metal. However, the methodology developed here applies to other BCC metals, other energy models and other solids showing non-glide effects.

Without post-manufacture HIPing the fatigue life of electron beam melting (EBM) additively manufactured parts is currently dominated by the presence of porosity, exhibiting large amounts of scatter. Here we have shown that the size and location of these defects is crucial in determining the fatigue life of EBM Ti-6Al-4V samples. X-ray computed tomography has been used to characterise all the pores in fatigue samples prior to testing and to follow the initiation and growth of fatigue cracks. This shows that the initiation stage comprises a large fraction of life (>70%). In these samples the initiating defect was often some way from being the largest (merely within the top 35% of large defects). Using various ranking strategies including a range of parameters, we found that when the proximity to the surface and the pore aspect ratio were included the actual initiating defect was within the top 3% of defects ranked most harmful. This lays the basis for considering how the deposition parameters can be optimised to ensure that the distribution of pores is tailored to the distribution of applied stresses in additively manufactured parts to maximise the fatigue life for a given loading cycle.

Recently, molybdenum (Mo) has been recognized a promising biodegradable metal, however, it is difficult to be processed through traditional deformation or machining due to its high strength & hardness. Additive manufacturing is a good way to get rid of this dilemma. Here, Mo components were directly fabricated with fine Mo powder through selective laser melting (SLM). Microstructure, in-vitro corrosion behaviors and biocompatibility of the as-obtained Mo were thoroughly investigated. Compared to Mo fabricated through rotary swaging (RS), ineluctable hot cracks were found in SLMed bulk Mo, and those defects accelerated the initial ion release rate (1.31 μg·mL·d during the first week, one order of magnitude higher than that of RSed Mo). The unique SLMed microstructure resulted in different surface chemical components, constituent phases and corrosion layer structures, thus leading to a different corrosion mode and corrosion evolution along with time. SLMed Mo exhibited good hemocompatibility, and mouse/rat-derived mesenchymal stem cells have certain tolerance to soluble Mo in the sample extracts. However, the deteriorative surface condition on SLMed Mo impaired its biocompatibility to directly attached cells. Cells could adhere onto SLMed Mo, however their proliferation and spreading were impaired along with further corrosion. Additive manufacturing is a powerful tool to fabricate Mo based structural parts, however, the issue of microstructural defects should be well resolved. Close attention should be paid to the hot-cracks and accompanied fast & non-uniform corrosion. STATEMENT OF SIGNIFICANCE: Additive manufacturing is a good way to fabricate implants based on refractory and un-processable biodegradable metals. Here, Mo components were directly fabricated with Mo powder through selective laser melting (SLM). Microstructure, in-vitro corrosion behaviors and biocompatibility of the as-obtained Mo were thoroughly investigated. Compared to Mo fabricated through traditional rotary swaging (RS), the unique SLMed microstructure resulted in different corrosion mode and corrosion evolution along with time. Localized corrosion appeared at the micro-cracks in SLMed samples, thus leading to a 10-fold ion release at week 1. Cells could adhere onto SLMed Mo, however their proliferation and spreading were impaired along with further corrosion. Close attention should be paid to the hot-cracks and accompanied fast & non-uniform corrosion.Copyright © 2024. Published by Elsevier Ltd.

The objectives of this study were to determine physiologic adaptations that occur when humans are exposed to a wide range of molybdenum intake levels and to identify the pathways that are influenced by dietary intake. Four males consumed each of 5 daily molybdenum intakes of 22, 72, 121, 467, and 1490 microg/d (0.23, 0.75, 1.3, 4.9, and 15.5 micromol/d) for 24 d each. During each treatment period, oral and intravenous doses of (100)Mo and (97)Mo were administered. Serial plasma, urine, and fecal samples were analyzed for labeled and unlabeled molybdenum. Compartmental modeling was used to determine rates of distribution and elimination at each dietary intake level. Three pathways were sensitive to daily molybdenum intake. With increasing intake, absorption and urinary molybdenum excretion increased, whereas the fraction deposited in tissues decreased. Kinetic analysis suggested a daily intake of 115-120 microg/d (1.20-1.25 micromol/d) would maintain initial plasma molybdenum levels at their prestudy values and that their prestudy dietary intake was well above the Recommended Dietary Allowance of 45 microg/d. The physiological adaptations to changing intake that the model demonstrated may help prevent molybdenum deficiency and toxicity.

Mammalian aldehyde oxidases (AOXs; EC1.2.3.1) are a group of conserved proteins belonging to the family of molybdo-flavoenzymes along with the structurally related xanthine dehydrogenase enzyme. AOXs are characterized by broad substrate specificity, oxidizing not only aromatic and aliphatic aldehydes into the corresponding carboxylic acids, but also hydroxylating a series of heteroaromatic rings. The number of AOX isoenzymes expressed in different vertebrate species is variable. The two extremes are represented by humans, which express a single enzyme (AOX1) in many organs and mice or rats which are characterized by tissue-specific expression of four isoforms (AOX1, AOX2, AOX3, and AOX4). In vertebrates each AOX isoenzyme is the product of a distinct gene consisting of 35 highly conserved exons. The extant species-specific complement of AOX isoenzymes is the result of a complex evolutionary process consisting of a first phase characterized by a series of asynchronous gene duplications and a second phase where the pseudogenization and gene deletion events prevail. In the last few years remarkable advances in the elucidation of the structural characteristics and the catalytic mechanisms of mammalian AOXs have been made thanks to the successful crystallization of human AOX1 and mouse AOX3. Much less is known about the physiological function and physiological substrates of human AOX1 and other mammalian AOX isoenzymes, although the importance of these proteins in xenobiotic metabolism is fairly well established and their relevance in drug development is increasing. This review article provides an overview and a discussion of the current knowledge on mammalian AOX.

Hepatic lipid peroxidation has been implicated in the pathogenesis of alcohol-induced liver injury, but the mechanism(s) by which ethanol metabolism or resultant free radicals initiate lipid peroxidation is not fully defined. The role of the molybdenum-containing enzymes aldehyde oxidase and xanthine oxidase in the generation of such free radicals was investigated by measuring alkane production (lipoperoxidation products) in isolated rat hepatocytes during ethanol metabolism. Inhibition of aldehyde oxidase and xanthine oxidase (by feeding tungstate at 100 mg/day per kg) decreased alkane production (80-95%), whereas allopurinol (20 mg/kg by mouth), a marked inhibitor of xanthine oxidase, inhibited alkane production by only 35-50%. Addition of acetaldehyde (0-100 microM) (in the presence of 50 microM-4-methylpyrazole) increased alkane production in a dose-dependent manner (Km of aldehyde oxidase for acetaldehyde 1 mM); menadione, an inhibitor of aldehyde oxidase, virtually inhibited alkane production. Desferrioxamine (5-10 microM) completely abolished alkane production induced by both ethanol and acetaldehyde, indicating the importance of catalytic iron. Thus free radicals generated during the metabolism of acetaldehyde by aldehyde oxidase may be a fundamental mechanism in the initiation of alcohol-induced liver injury.

In an attempt to define a tolerable daily intake (TDI) for molybdenum based on a toxicological risk analysis approach, a large literature survey was conducted. In man, absorption of molybdenum after oral intake is in the range of 28-77% and urinary excretion is 17-80% of the total dose. A low order of toxicity of molybdenum compounds has been observed in humans. However, with the available data, it is not possible to calculate any dose-response or dose-effect relationships. Because molybdenum toxicity is associated with copper intake or depleted copper stores in the body, humans who have an inadequate intake of dietary copper or some dysfunction in their copper metabolism that makes them copper-deficient could be at greater risk of molybdenum toxicity. In the absence of relevant human studies, animal studies were evaluated for the derivation of the TDI. Effects of Mo on reproduction and foetal development were found to be critical effects observed in rats and mice. A dose-response relationship was observed in a study by Fungwe et al., with a 'no observed adverse effect' level (NOAEL) and a 'lowest observed adverse effect' level (LOAEL) of 0.9 and 1.6 mg Mo kg(-1) day(-1), respectively. Applying uncertainty factors of 10 for intraspecies and 10 for interspecies differences to the NOAEL, a TDI of 0.009 mg Mo kg(-1) day(-1) was calculated. The TDI is given a medium confidence rating. This TDI is more than double the upper limit of adequate intake for adolescents and adults that was derived from the Mo content of the average diet in the USA.

Chronic oral administration of ammonium molybdate in rats markedly retarded the growth rate of rats and high protein diet could partially reverse this condition. The activities of several enzymes viz. acid phosphatase, alkaline phosphatase, glucose-6-phosphatase, succinic dehydrogenase, glutamate oxaloacetate transaminase, inorganic pyrophosphatase and acetylcholinesterase in different tissues and serum levels of luteinizing hormone, follicle stimulating hormone, prolactin and cortisol are altered due to the toxicity conditions and high protein diet fed group of animals showed almost normal values in respect of a few of these parameters. Normal histological pattern of both liver and kidney tissues were altered under molybdenum toxicity condition. Significant increase of basophilic substances are observed in the cytoplasm of the liver cells of the toxic group of animals which is counteracted by feeding high protein diet.

In this study we investigated the effect of two molybdenum (Mo) doses (40 and 80 mg/kg/d) on renal function. Neither dose of Mo was able to induce significant hypertension in treated animals. Subchronic exposure to high doses of Mo resulted in a delay in body weight gain associated with mild renal failure marked by a decrease in glomerular filtration. An increase in diuresis and urinary kallikrein excretion associated with unchanged glycosuria and proximal tubular enzymuria (alanine aminopeptidase and gamma-glutamyl transpeptidase) evoked a preferential mild effect at the distal tubule.

The link between environmental chemicals and human health has emerged, but has not been completely examined in terms of its risk factors. Therefore, we aimed to study the relationships of different sets of urinary environmental chemical concentrations and high blood pressure (BP) in a national, population-based study. Data were retrieved from the United States National Health and Nutrition Examination Surveys, 2009-2012, including demographics, BP readings and urinary environmental chemical concentrations. Analyses included χ(2)-test, t-test, survey-weighted logistic regression models and population attributable risk estimation. Urinary cesium (odds ratio (OR) 1.52, 95% confidence interval (CI) 1.06-2.18, P=0.026), molybdenum (OR 1.45, 95% CI 1.04-2.02, P=0.029), lead (OR 1.49, 95% CI 1.12-1.98, P=0.009), platinum (OR 1.66, 95% CI 1.14-2.21, P=0.002), antimony (OR 1.44, 95% CI 1.12-1.86, P=0.008) and tungsten (OR 1.48, 95% CI 1.22-1.79, P<0.001) concentrations were observed to be associated with high BP. Similar results were observed for mono-2-ethyl-5-carboxypentyl (OR 1.29, 95% CI 1.04-1.59, P=0.024), mono-n-butyl (OR 1.36, 95% CI 1.11-1.67, P=0.005), mono-2-ethyl-5-hydroxyhexyl (OR 1.21, 95% CI 1.01-1.46, P=0.041), mono-n-methyl (OR 1.24, 95% CI 1.01-1.46, P=0.014), mono-2-ethyl-5-oxohexyl (OR 1.21, 95% CI 1.01-1.45, P=0.036), mono-benzyl (OR 1.41, 95% CI 1.15-1.74, P=0.002), dimethylarsonic acid (OR 1.38, 95% CI 1.08-1.76, P=0.012) and trimethylarsine oxide (OR 2.56, 95% CI 1.29-5.07, P=0.010) concentrations. Each chemical could account for 3-19% of the population attributable risk for high BP. A small sex difference was found. However, there are no associations between environmental parabens and pesticides and high BP. Urinary heavy metal, phthalate and arsenic concentrations were associated with high BP, although a causal effect cannot be established. Elimination of environmental chemical exposure in humans still needs to be pursued.

Oxidative stress represents excessive intracellular levels of reactive oxygen species (ROS), which plays a major role in the pathogenesis of cardiovascular disease. Besides having a critical impact on the development and progression of vascular pathologies including atherosclerosis and diabetic vasculopathy, oxidative stress also regulates physiological signaling processes. As a cell permeable ROS generated by cellular metabolism involved in intracellular signaling, hydrogen peroxide (HO) exerts tremendous impact on cardiovascular pathophysiology. Under pathological conditions, increased oxidase activities and/or impaired antioxidant systems results in uncontrolled production of ROS. In a pro-oxidant environment, vascular smooth muscle cells (VSMC) undergo phenotypic changes which can lead to the development of vascular dysfunction such as vascular inflammation and calcification. Investigations are ongoing to elucidate the mechanisms for cardiovascular disorders induced by oxidative stress. This review mainly focuses on the role of HO in regulating physiological and pathological signals in VSMC.Copyright © 2016. Published by Elsevier B.V.

Nitric oxide contrasts with most intercellular messengers because it diffuses rapidly and isotropically through most tissues with little reaction but cannot be transported through the vasculature due to rapid destruction by oxyhemoglobin. The rapid diffusion of nitric oxide between cells allows it to locally integrate the responses of blood vessels to turbulence, modulate synaptic plasticity in neurons, and control the oscillatory behavior of neuronal networks. Nitric oxide is not necessarily short lived and is intrinsically no more reactive than oxygen. The reactivity of nitric oxide per se has been greatly overestimated in vitro because no drain is provided to remove nitric oxide. Nitric oxide persists in solution for several minutes in micromolar concentrations before it reacts with oxygen to form much stronger oxidants like nitrogen dioxide. Nitric oxide is removed within seconds in vivo by diffusion over 100 microns through tissues to enter red blood cells and react with oxyhemoglobin. The direct toxicity of nitric oxide is modest but is greatly enhanced by reacting with superoxide to form peroxynitrite (ONOO-). Nitric oxide is the only biological molecule produced in high enough concentrations to out-compete superoxide dismutase for superoxide. Peroxynitrite reacts relatively slowly with most biological molecules, making peroxynitrite a selective oxidant. Peroxynitrite modifies tyrosine in proteins to create nitrotyrosines, leaving a footprint detectable in vivo. Nitration of structural proteins, including neurofilaments and actin, can disrupt filament assembly with major pathological consequences. Antibodies to nitrotyrosine have revealed nitration in human atherosclerosis, myocardial ischemia, septic and distressed lung, inflammatory bowel disease, and amyotrophic lateral sclerosis.

The role of reactive oxygen species in the vascular pathology associated with atherosclerosis was examined by testing the hypothesis that impaired vascular reactivity results from the reaction of nitric oxide (.NO) with superoxide (O2-), yielding the oxidant peroxynitrite (ONOO-). Contractility studies were performed on femoral arteries from rabbits fed a cholesterol-supplemented diet. Cholesterol feeding shifted the EC50 for acetylcholine (ACh)-induced relaxation and impaired the maximal response to ACh. We used pH-sensitive liposomes to deliver CuZn superoxide dismutase (SOD; superoxide:superoxide oxidoreductase, EC 1.15.1.1) to critical sites of.NO reaction with O2-. Intravenously injected liposomes (3000 units of SOD per ml) augmented ACh-induced relaxation in the cholesterol-fed group to a greater extent than in controls. Quantitative immunocytochemistry demonstrated enhanced distribution of SOD in both endothelial and vascular smooth muscle cells as well as in the extracellular matrix. SOD activity in vessel homogenates of liposome-treated rabbits was also increased. Incubation of beta very low density lipoprotein with ONOO- resulted in the rapid formation of conjugated dienes and thiobarbituric acid-reactive substances. Our results suggest that the reaction of O2- with.NO is involved in the development of atherosclerotic disease by yielding a potent mediator of lipoprotein oxidation, as well as by limiting.NO stimulation of vascular smooth muscle guanylate cyclase activity.

Oxidized low density lipoprotein (LDL) may be of central importance in triggering atherosclerosis. One potential pathway involves the production of nitric oxide (NO) by vascular wall endothelial cells and macrophages. NO reacts with superoxide to form peroxynitrite (ONOO-), a potent agent of LDL oxidation in vitro. ONOO- nitrates the aromatic ring of free tyrosine to produce 3-nitrotyrosine, a stable product. To explore the role of reactive nitrogen species such as ONOO- in the pathogenesis of vascular disease, we developed a highly sensitive and specific method involving gas chromatography and mass spectrometry to quantify 3-nitrotyrosine levels in proteins. In vitro studies demonstrated that 3-nitrotyrosine was a highly specific marker for LDL oxidized by ONOO-. LDL isolated from the plasma of healthy subjects had very low levels of 3-nitrotyrosine (9 +/- 7 micromol/mol of tyrosine). In striking contrast, LDL isolated from aortic atherosclerotic intima had 90-fold higher levels (840 +/- 140 micromol/mol of tyrosine). These observations strongly support the hypothesis that reactive nitrogen species such as ONOO- form in the human artery wall and provide direct evidence for a specific reaction pathway that promotes LDL oxidation in vivo. The detection of 3-nitrotyrosine in LDL isolated from vascular lesions raises the possibility that NO, by virtue of its ability to form reactive nitrogen intermediates, may promote atherogenesis, counteracting the well-established anti-atherogenic effects of NO.

Concentrations of uric acid in carotid endarterectomy specimens in men and women were measured using high-performance liquid chromatography in comparison wo nonatherosclerotic control specimens.

Atherosclerosis is a chronic inflammatory disease due to lipid deposition in the arterial wall. Multiple mechanisms participate in the inflammatory process, including oxidative stress. Xanthine oxidase (XO) is a major source of reactive oxygen species (ROS) and has been linked to the pathogenesis of atherosclerosis, but the underlying mechanisms remain unclear. Here, we show enhanced XO expression in macrophages in the atherosclerotic plaque and in aortic endothelial cells in ApoE(-/-) mice, and that febuxostat, a highly potent XO inhibitor, suppressed plaque formation, reduced arterial ROS levels and improved endothelial dysfunction in ApoE(-/-) mice without affecting plasma cholesterol levels. In vitro, febuxostat inhibited cholesterol crystal-induced ROS formation and inflammatory cytokine release in murine macrophages. These results demonstrate that in the atherosclerotic plaque, XO-mediated ROS formation is pro-inflammatory and XO-inhibition by febuxostat is a potential therapy for atherosclerosis.

Biodegradable stents have tremendous theoretical potential as an alternative to bare metal stents and drug-eluting stents for the treatment of obstructive coronary artery disease. Any bioresorbable or biodegradable scaffold material needs to possess optimal mechanical properties and uniform degradation behavior that avoids local and systemic toxicity. Recently, molybdenum (Mo) has been investigated as a potential novel biodegradable material for this purpose. With its proven moderate degradation rate and excellent mechanical properties, Mo may represent an ideal source material for clinical cardiac and vascular applications. The present study was performed to evaluate the mechanical performance of metallic Mo and the biodegradation properties. The results demonstrated favorable mechanical behavior and a uniform degradation profile as desired for a new generation ultra-thin degradable endovascular stent material. Moreover, Mo implants in mouse arteries avoided the typical cellular response that contributes to restenosis. There was minimal neointimal hyperplasia over 6 months, an absence of excessive smooth muscle cell (SMC) proliferation or inflammation near the implant, and avoidance of significant harm to regenerating endothelial cells (EC). Qualitative inspection of kidney sections showed a potentially pathological remodeling of kidney Bowman's capsule and glomeruli, indicative of impaired filtering function and development of kidney disease, although quantifications of these morphological changes were not statistically significant. Together, the results suggest that the products of Mo corrosion may exert beneficial or inert effects on the activities of inflammatory and arterial cells, while exerting potentially toxic effects in the kidneys that warrant further investigation.© 2021 The Authors.

Measuring vital physiological pressures is important for monitoring health status, preventing the buildup of dangerous internal forces in impaired organs, and enabling novel approaches of using mechanical stimulation for tissue regeneration. Pressure sensors are often required to be implanted and directly integrated with native soft biological systems. Therefore, the devices should be flexible and at the same time biodegradable to avoid invasive removal surgery that can damage directly interfaced tissues. Despite recent achievements in degradable electronic devices, there is still a tremendous need to develop a force sensor which only relies on safe medical materials and requires no complex fabrication process to provide accurate information on important biophysiological forces. Here, we present a strategy for material processing, electromechanical analysis, device fabrication, and assessment of a piezoelectric Poly-l-lactide (PLLA) polymer to create a biodegradable, biocompatible piezoelectric force sensor, which only employs medical materials used commonly in Food and Drug Administration-approved implants, for the monitoring of biological forces. We show the sensor can precisely measure pressures in a wide range of 0-18 kPa and sustain a reliable performance for a period of 4 d in an aqueous environment. We also demonstrate this PLLA piezoelectric sensor can be implanted inside the abdominal cavity of a mouse to monitor the pressure of diaphragmatic contraction. This piezoelectric sensor offers an appealing alternative to present biodegradable electronic devices for the monitoring of intraorgan pressures. The sensor can be integrated with tissues and organs, forming self-sensing bionic systems to enable many exciting applications in regenerative medicine, drug delivery, and medical devices.

Chronic wounds, particularly those associated with diabetes mellitus, represent a growing threat to public health, with additional notable economic impacts. Inflammation associated with these wounds leads to abnormalities in endogenous electrical signals that impede the migration of keratinocytes needed to support the healing process. This observation motivates the treatment of chronic wounds with electrical stimulation therapy, but practical engineering challenges, difficulties in removing stimulation hardware from the wound site, and absence of means to monitor the healing process create barriers to widespread clinical use. Here, we demonstrate a miniaturized wireless, battery-free bioresorbable electrotherapy system that overcomes these challenges. Studies based on a splinted diabetic mouse wound model confirm the efficacy for accelerated wound closure by guiding epithelial migration, modulating inflammation, and promoting vasculogenesis. Changes in the impedance provide means for tracking the healing process. The results demonstrate a simple and effective platform for wound site electrotherapy.

Molybdenum (Mo) alloys with different La2O3 particle additions (0.6, 0.9, 1.5 wt.%) were prepared by powder metallurgy to investigate the effect of La2O3 particles on microstructural evolution and creep behavior of the alloy. Pure Mo, annealed at 1500 °C for 1 h, presented a fully recrystallized microstructure characterized by equiaxed grains. The alloys doped with La2O3 particles (Mo-La2O3 alloys), on the other hand, exhibited fibrous grains elongated in the rolling direction of the plate. In contrast to the shape of the grains, the average grain size of the alloys was found to be insensitive to the addition of La2O3 particles. Nanosized La2O3 particles with diameters ranging from 65 to 75 nm were distributed within the grain interior. Tensile creep tests showed that dislocation creep was the predominant deformation mode at intermediate creep rate (10−7 s−1-10−4 s−1) in the present alloys. The creep stress exponent and activation energy were found to decrease with increasing temperature, particularly within the low creep rate regime (< 10−7 s−1). The Mo-La2O3 alloys exhibited remarkably greater apparent stress exponent and activation energy than pure Mo. A creep constitutive model based on the interaction between particles and dislocations was utilized to rationalize the nanoparticle-improved creep behavior. It was demonstrated that low relaxed efficiency of dislocation line energy, which is responsible for an enhanced climb resistance of dislocations, is the major creep strengthening mechanism in the Mo-La2O3 alloys. In addition, the area reduction and creep fracture mode of the Mo-La2O3 alloys were found to be a function of the creep rate and temperature, which can be explained by the effect of the two parameters on the creep and fracture mechanisms.

\n Molybdenum and its alloys are known for their superior strength among body-centered cubic materials. However, their widespread application is hindered by a significant decrease in ductility at lower temperatures. In this study, we demonstrate the achievement of exceptional ductility in a Mo alloy containing rare-earth La\n 2\n O\n 3\n nanoparticles through rotary-swaging, a rarity in Mo-based materials. Our analysis reveals that the large ductility originates from substantial variations in the electronic density of states, a characteristic intrinsic to rare-earth elements. This characteristic can accelerate the generation of oxygen vacancies, facilitating the amorphization of the oxide-matrix interface. This process promotes vacancy absorption and modification of dislocation configurations. Furthermore, by inducing irregular shapes in the La\n 2\n O\n 3\n nanoparticles through rotary-swaging, incoming dislocations interact with them, creating multiple dislocation sources near the interface. These dislocation sources act as potent initiators at even reduced temperatures, fostering diverse dislocation types and intricate networks, ultimately enhancing dislocation plasticity.\n

When osteochondral tissues suffer from focal or degenerative lesions caused by trauma or disorders, it is a tough challenge to regenerate them because of the limited self-healing capacity of articular cartilage. In this study, a series of Mo-doped bioactive glass ceramic (Mo-BGC) scaffolds were prepared and then systematically characterized. The released MoO ions from 7.5Mo-BGC scaffolds played a vital role in regenerating articular cartilage and subchondral bone synchronously. The Mo-BGC scaffolds were fabricated through employing both a sol-gel method and 3D printing technology. SEM, EDS, HRTEM, XRD, ICPAES and mechanical strength tests were respectively applied to analyze the physicochemical properties of Mo-BGC scaffolds. The proliferation and differentiation of rabbit chondrocytes (RCs) and human bone mesenchymal stem cells (HBMSCs) cultured with dilute solutions of 7.5Mo-BGC powder extract were investigated. The co-culture model was established to explore the possible mechanism of stimulatory effects of MoO ions on the RCs and HBMSCs The efficacy of regenerating articular cartilage and subchondral bone using 7.5Mo-BGC scaffolds was evaluated. The incorporation of Mo into BGC scaffolds effectively enhanced the compressive strength of scaffolds owing to the improved surface densification. The MoO ions released from the 7.5Mo-BGC powders remarkably promoted the proliferation and differentiation of both RCs and HBMSCs. The MoO ions in the co-culture system significantly stimulated the chondrogenic differentiation of RCs and meanwhile induced the chondrogenesis of HBMSCs. The chondrogenesis stimulated by MoO ions happened through two pathways: 1) MoO ions elicited anabolic responses through activating the HIF-1α signaling pathway; 2) MoO ions inhibited catabolic responses and protected cartilage matrix from degradation. The study showed that 7.5Mo-BGC scaffolds were able to significantly promote cartilage/bone regeneration when implanted into rabbit osteochondral defects for 8 and 12 weeks, displaying bi-lineage bioactivities. The 3D-printed Mo-BGC scaffolds with bi-lineage bioactivities and activated anabolic responses could offer an effective strategy for cartilage/bone interface regeneration.

The positive regulation of bone-forming osteoblast activity and the negative feedback regulation of osteoclastic activity are equally important in strategies to achieve successful alveolar bone regeneration. Here, a molybdenum (Mo)-containing bioactive glass ceramic scaffold with solid-strut-packed structures (Mo-scaffold) was printed, and its ability to regulate pro-osteogenic and anti-osteoclastogenic cellular responses was evaluated in vitro and in vivo. We found that extracts derived from Mo-scaffold (Mo-extracts) strongly stimulated osteogenic differentiation of bone marrow mesenchymal stem cells and inhibited differentiation of osteoclast progenitors. The identified comodulatory effect was further demonstrated to arise from Mo ions in the Mo-extract, wherein Mo ions suppressed osteoclastic differentiation by scavenging reactive oxygen species (ROS) and inhibiting mitochondrial biogenesis in osteoclasts. Consistent with the in vitro findings, the Mo-scaffold was found to significantly promote osteoblast-mediated bone formation and inhibit osteoclast-mediated bone resorption throughout the bone healing process, leading to enhanced bone regeneration. In combination with our previous finding that Mo ions participate in material-mediated immunomodulation, this study offers the new insight that Mo ions facilitate bone repair by comodulating the balance between bone formation and resorption. Our findings suggest that Mo ions are multifunctional cellular modulators that can potentially be used in biomaterial design and bone tissue engineering.

The high-temperature stability and mechanical properties of refractory molybdenum alloys are highly desirable for a wide range of critical applications. However, a long-standing problem for these alloys is that they suffer from low ductility and limited formability. Here we report a nanostructuring strategy that achieves Mo alloys with yield strength over 800 MPa and tensile elongation as large as ~ 40% at room temperature. The processing route involves a molecular-level liquid-liquid mixing/doping technique that leads to an optimal microstructure of submicrometre grains with nanometric oxide particles uniformly distributed in the grain interior. Our approach can be readily adapted to large-scale industrial production of ductile Mo alloys that can be extensively processed and shaped at low temperatures. The architecture engineered into such multicomponent alloys offers a general pathway for manufacturing dispersion-strengthened materials with both high strength and ductility.