Inhibition of signaling protein ERN1 increases the sensitivity of serine synthesis gene expressions to glucose and glutamine deprivations in U87MG glioblastoma cells.

Objective. Glucose and glutamine supply as well as serine synthesis and endoplasmic reticulum (ER) stress are important factors of glioblastoma growth. Previous studies showed that the knockdown of ERN1 (ER to nucleus signaling 1) suppressed glioblastoma cell proliferation and modified the sensitivity of numerous gene expressions to nutrient deprivations. The present study is aimed to investigate the impact of glucose and glutamine deprivations on the expression of serine synthesis genes in U87MG glioblastoma cells in relation to ERN1 knockdown with the intent to reveal the role of ERN1 signaling pathway on the ER stress-dependent regulation of these gene expressions. Clarification of the regulatory mechanisms of serine synthesis is a great significance for glioblastoma therapy. Methods. The control U87MG glioblastoma cells (transfected by empty vector) and ERN1 knockdown cells (transfected by dominant-negative ERN1) were exposed under glucose and glutamine deprivation conditions for 16 h. RNA was extracted from cells and reverse transcribed. The expression level of PHGDH (phosphoglycerate dehydrogenase), PSAT1 (phosphoserine amino-transferase 1), PSPH (phosphoserine phosphatase), ATF4 (activating transcription factor 4), and SHMT1 (serine hydroxymethyltransferase 1) genes was studied by real-time qPCR and normalized to ACTB. Results. It was found that the expression level of genes responsible for serine synthesis such as PHGDH, PSAT1, PSPH, and transcription factor ATF4 was up-regulated in U87MG glioblastoma cells under glucose and glutamine deprivations. Furthermore, inhibition of ERN1 significantly enhances the impact of glucose and especially glutamine deprivations on these gene expressions. At the same time, the expression of the SHMT1 gene, which is responsible for serine conversion to glycine, was down-regulated in both nutrient deprivation conditions with more significant changes in ERN1 knockdown glioblastoma cells. Conclusion. Taken together, the results of present study indicate that the expression of genes responsible for serine synthesis is sensitive to glucose and glutamine deprivations in gene-specific manner and that suppression of ERN1 signaling significantly modifies the impact of both glucose and glutamine deprivations on PHGDH, PSAT1, PSPH, ATF4, and SHMT1 gene expressions and reflects the ERN1-mediated genome reprograming introduced by nutrient deprivation condition.

The influence of hot isostatic pressing on precipitates, mechanical properties of Mg-12Gd-0.8Zn-0.4Zr (wt.%) alloy manufactured by sand casting.

Microstructures and mechanical properties of Mg-12Gd-0.8Zn-0.4Zr (GZ1208K, wt.%) alloy under different treatments (as-cast: signed as nonHIP-GZ1208K, hot isostatic pressing (HIP): signed as HIP-GZ1208K) were characterized. Based on microstructure characterization, two prismatic precipitates, ß' and ß1 precipitates, and one basal precipitate, γ' precipitate, formed in both of nonHIP-GZ1208K and HIP-GZ1208K alloy. According to analysis, the area number density and the size of ß' precipitate could be adjusted through HIP treatment. The area number density of ß' precipitate increased after HIP treatment when aged at 32 h, and the size of ß' precipitate refined in both of the HIP-GZ1208K alloy aged at 8 h and 32 h. Except the influence of HIP treatment on microstructures, the ultimate tensile strength (UTS) and elongation of nonHIP-GZ1208K alloy also improved after HIP treatment. The UTS of the GZ1208K alloy aged at 8 h increased from 348 MPa (nonHIP-) to 371 MPa (HIP-) and the elongation increased from 2.6% to 4.7%. The density of the nonHIP-GZ1208K alloy increased after HIP treatment, that is to say the casting defects could be eliminated and the compactness of microstructures could be increased under the high pressure of HIP treatment.

3D Printing of a Porous Zn-1Mg-0.1Sr Alloy Scaffold: A Study on Mechanical Properties, Degradability, and Biosafety.

In recent years, the use of zinc (Zn) alloys as degradable metal materials has attracted considerable attention in the field of biomedical bone implant materials. This study investigates the fabrication of porous scaffolds using a Zn-1Mg-0.1Sr alloy through a three-dimensional (3D) printing technique, selective laser melting (SLM). The results showed that the porous Zn-1Mg-0.1Sr alloy scaffold featured a microporous structure and exhibited a compressive strength (CS) of 33.71 ± 2.51 MPa, a yield strength (YS) of 27.88 ± 1.58 MPa, and an elastic modulus (E) of 2.3 ± 0.8 GPa. During the immersion experiments, the immersion solution showed a concentration of 2.14 ± 0.82 mg/L for Zn2+ and 0.34 ± 0.14 mg/L for Sr2+, with an average pH of 7.61 ± 0.09. The porous Zn-1Mg-0.1Sr alloy demonstrated a weight loss of 12.82 ± 0.55% and a corrosion degradation rate of 0.36 ± 0.01 mm/year in 14 days. The Cell Counting Kit-8 (CCK-8) assay was used to check the viability of the cells. The results showed that the 10% and 20% extracts significantly increased the activity of osteoblast precursor cells (MC3T3-E1), with a cytotoxicity grade of 0, which indicates safety and non-toxicity. In summary, the porous Zn-1Mg-0.1Sr alloy scaffold exhibits outstanding mechanical properties, an appropriate degradation rate, and favorable biosafety, making it an ideal candidate for degradable metal bone implants.

Ratiometric fluorescence platform for the ultrasensitive detection of kanamycin based on split aptamer co-recognition triggers Mg2+-DNAzyme-driven DNA walker systems.

In this work, a novel 3D-DNA walker signal amplification strategy was designed to construct a fluorescent aptasensor for the detection of kanamycin (KAN). The aptasensor utilizes split aptamers for the synergistic recognition of KAN. The presence of KAN induces the split aptamers recombination to form the Mg2+-DNAzyme structure, which is activated by Mg2+ to drive the 3D-DNA walker process for cascading signal amplification. Employing gold nanoflowers (AuNFs) as walking substrate material increases the local DNA concentration to enhance the walker efficiency. The prepared fluorescent aptasensor achieved efficient and sensitive detection of KAN with satisfactory results in the concentration range of 1 × 10-8 - 1 × 10-3 µg/kg and the detection limit of 5.63 fg/kg. Meanwhile, the designed fluorescent aptasensor exhibited favorable specificity, anti-interference, storage stability and reproducibility, and verified the feasibility of its application in milk samples. The present work provides an effective tool for the regulation of KAN contamination in animal-derived foods with promising prospects.

Li-Site Defects Induce Formation of Li-Rich Impurity Phases: Implications for Charge Distribution and Performance of LiNi0.5-xMxMn1.5O4 Cathodes (M = Fe and Mg; x = 0.05-0.2).

An understanding of the structural properties that allow for optimal cathode performance, and their origin, is necessary for devising advanced cathode design strategies and accelerating the commercialisation of next-generation cathodes. High-voltage, Fe- and Mg-substituted LiNi0.5Mn1.5O4 cathodes offer a low-cost and cobalt-free, yet energy-dense alternative to commercial cathodes. In this work, we explore the effect of substituents on several important structure properties including Ni/Mn ordering, charge distribution and extrinsic defects. In the cation-disordered samples studied, we observe a correlation between increased Fe/Mg substitution, Li-site defects and Li-rich impurity phase formation - the concentrations of which are greater for Mg-substituted samples. We attribute this to the lower formation energy of MgLi defects when compared to FeLi defects. Li-site defect-induced impurity phases consequently alter the charge distribution of the system, resulting in increased [Mn3+] with Fe/Mg substitution. In addition to impurity phases, other charge compensators were also investigated to explain the origin of Mn3+ (extrinsic defects, [Ni3+], oxygen vacancies and intrinsic off-stoichiometry), although their effects were found to be negligible. This article is protected by copyright. All rights reserved.

Data analysis of the influence of microstructure, composition, and loading conditions on stress corrosion cracking behavior of Mg alloys.

Stress corrosion cracking (SCC) can be a crucial problem in applying rare earth (RE) Magnesium alloys in environments where mechanical loads and electrochemical driven degradation processes interact. It has been proven already that the SCC behavior is associated with microstructural features, compositions, loading conditions, and corrosive media, especially in-vivo. However, it is still unclear when and how mechanisms acting on multiple scales and respective system descriptors predictable contribute to SCC for the wide set of existing Mg alloys. In the present work, suitable literature data along SCC of Mg alloys has been analyzed to enable the development of a reliable SCC model for MgGd binary alloys. Pearson correlation coefficient and linear fitting are utilized to describe the contribution of selected parameters to corrosion and mechanical properties. Based on our data analysis, a parameter ranking is obtained, providing information on the SCC impact with regard to ultimate tensile strength (UTS) and fracture elongation of respective materials. According to the analyzed data, SCC susceptibility can be grouped and mapped onto Ashby type diagrams for UTS and elongation of respective base materials tested in air and in corrosive media. The analysis reveals the effect of secondary phase content as a crucial materials descriptor for our analyzed materials and enables better understanding towards SCC model development for Mg-5Gd alloy based implant.

MG53/GMs/HA-Dex neural scaffold promotes the functional recovery of spinal cord injury by alleviating neuroinflammation.

The adverse microenvironment, including neuroinflammation, hinders the recovery of spinal cord injury (SCI). Regulating microglial polarization to alleviate neuroinflammation at the injury site is an effective strategy for SCI recovery. MG53 protein exerts obvious repair ability on multiple tissues damage, but with short half-life. In this study, we composited an innovative MG53/GMs/HA-Dex neural scaffold using gelatin microspheres (GMs), hyaluronic acid (HA), and dextran (Dex) loaded with MG53 protein. This novel neural scaffold could respond to MMP-2/9 protein and stably release MG53 protein with good physicochemical properties and biocompatibility. In addition, it significantly improved the motor function of SCI mice, suppressed M1 polarization of microglia and neuroinflammation, and promoted neurogenesis and axon regeneration. Further mechanistic experiments demonstrated that MG53/GMs/HA-Dex hydrogel inhibited the JAK2/STAT3 signaling pathway. Thus, this MG53/GMs/HA-Dex neural scaffold promotes the functional recovery of SCI mice by alleviating neuroinflammation, which provides a new intervention strategy for the neural regeneration and functional repair of SCI.

Recommendations and good practices for dissolved organic carbon (DOC) analyses at low concentrations.

Numerous protocols for dissolved organic carbon (DOC) measurements on natural water are used in the literature. An ISO protocol for the determination of DOC exists since 2018, but it is certified for DOC values ≥ 1 mg L-1, while many publications report DOC values much lower. In addition, this ISO protocol does not include indications on vials cleaning, filtering material, and type of caps and septa to be used. The purpose of this study was to evaluate protocols for measurements of low DOC concentrations (≤ 1 mg L-1). The effect of the sample container, type of septum, filtration material, nature of acid used for storage, and matrix effects on DOC concentration were evaluated.•The use of glass vials decontaminated at 450 °C or 500 °C for at least 1 h, 0.45 µm hydrophilic polytetrafluoroethylene (PTFE) membranes previously rinsed with 20 mL ultra-pure water and HCl acidification gives the lowest DOC contamination,•Sulfides (ΣH2S), sodium (Na+) or calcium (Ca2+) do not induce high matrix effect for the analysis (≤ 10%),•At low DOC concentrations (≤ 1 mg L-1), the use of pierced PTFE septa with acidified samples induce slight DOC contamination after storage at 4 °C, and dramatic contamination after storage at -18 °C.

Microstructural characterization and corrosion-resistance behavior of friction stir-welded A390/10 wt% SiC composites-AA2024 Al alloy joints.

This study examined the effect of traverse speed on the mechanical properties, corrosion-resistance behavior, and microstructure of friction stir-welded A390/10 wt% SiC composites-AA2024 Al alloy joints. The laminar flow of both materials was found to diminish in the stir zone (SZ) when the traverse speed of the tool increased from 40 to 80 mm/min, lowering their mixing rate. Large aspect ratio Si particles are broken by the tool pin-induced applied plastic strain, which turns them into refined equiaxed particles. Their aspect ratio remains unchanged in the SZ, despite their decreasing size. SiC and Si particles progressively come into view when moving from the AA2024 alloy's SZ to the composite workpieces. These changes happen abruptly as traverse speed increases due to the lack of an interfacial layer structure. The advancing side (AS)'s SZ grain size drops from 4.2 ± 0.3 µm to 1.2 ± 0.2 µm as the traverse speed drops from 80 to 40 mm/min. Increased traverse speed from 40 to 80 mm/min will result in a 5.8% decrease in elongation percentage (EP) and 8.4%, 36%, and 10.3% increases in the ultimate tensile strength (UTS), corrosion resistance, and yield strength, respectively.

Efficient phosphate removal by Mg-La binary layered double hydroxides: synthesis optimization, adsorption performance, and inner mechanism.

Layered double hydroxides (LDH) hold great promise as phosphate adsorbents; however, the conventional binary LDH exhibits low adsorption rate and adsorption capacity. In this study, Mg and La were chosen as binary metals in the synthesis of Mg-La LDH to enhance phosphate efficient adsorption. Different molar ratios of Mg to La (2:1, 3:1, and 4:1) were investigated to further enhance P adsorption. The best performing Mg-La LDH, with Mg to La ratio is 4:1 (LDH-4), presented a larger adsorption capacity and faster adsorption rate than other Mg-La LDH. The maximum adsorption capacity (87.23 mg/g) and the rapid adsorption rate in the initial 25 min of LDH-4 (70 mg/(g·h)) were at least 1.6 times and 1.8 times higher than the others. The kinetics, isotherms, the effect of initial pH and co-existing anions, and the adsorption-desorption cycle experiment were studied. The batch experiment results proved that the chemisorption progress occurred on the single-layered LDH surface and the optimized LDH exhibited strong anti-interference capability. Furthermore, the structural characteristics and adsorption mechanism were further investigated by SEM, BET, FTIR, XRD, and XPS. The characterization results showed that the different metal ratios could lead to changes in the metal hydroxide layer and the main ions inside. At lower Mg/La ratios, distortion occurred in the hydroxide layer, resulting in lower crystallinity and lower performance. The characterization results also proved that the main mechanisms of phosphate adsorption are electrostatic adsorption, ion exchange, and inner-sphere complexation. The results emphasized that the Mg-La LDH was efficient in phosphate removal and could be successfully used for this purpose.

Tracing the impact of CO2 on the electrochemical and charge-discharge behavior for Al-Mg alloy in KOH and LiOH electrolytes for battery applications.

For the first time, it has been found that the electrochemical performance of the Al-Mg alloy as an anode in alkaline batteries has been markedly enhanced in the presence of CO2 and LiOH as an electrolyte. This work compares the electrochemical performance of an Al-Mg alloy used as an anode in Al-air batteries in KOH and LiOH solutions, both with and without CO2. Potentiodynamic polarization (Tafel), charging-discharging (galvanostatic) experiments, and electrochemical impedance spectroscopy (EIS) are used. X-ray diffraction spectroscopy (XRD) and a scanning electron microscope (SEM) outfitted with an energetic-dispersive X-ray spectroscope (EDX) were utilized for the investigation of the products on the corroded surface of the electrode. Findings revealed that the examined electrode's density of corrosion current (icorr.) density in pure LiOH is significantly lower than in pure KOH (1 M). Nevertheless, in the two CO2-containing solutions investigated, icorr. significantly decreased. The corrosion rate of the examined alloy in the two studied basic solutions with and without CO2 drops in the following order: KOH > LiOH > KOH + CO2 > LiOH + CO2. The obtained results from galvanostatic charge-discharge measurements showed excellent performance of the battery in both LiOH and KOH containing CO2. The electrochemical findings and the XRD, SEM, and EDX results illustrations are in good accordance.

Effects of Simvastatin on Gene Expression and Alkaline Phosphatase Activity in the MG-63 Cell Line Treated With Hyperglycemia for Bone Regeneration.

Background Dental implants have become a widespread treatment option for replacing missing teeth. Adequate bone is required for the placement of dental implants, in the absence of which, augmentation by bone regeneration is done. Antiresorptive drugs are used as treatment procedures for bone regeneration. One such antiresorptive drug is simvastatin (SV), a 3-hydroxy-3-methylglutaryl coenzyme used to manage hyperlipidemia. It reduces serum cholesterol levels and has an advantageous effect on new bone formation. Various studies establish that SV stimulates bone morphogenetic protein (BMP)-2 expression and leads to bone formation. SV prevents the production of isoprenoids and mevalonate, which are essential for osteoclastogenesis and contribute to the bone-sparing effect.  Aim The aim of the study was to investigate the osteoregenerative activity of SV in the osteoblast-like cell models, MG-63 cell line, with hyperglycemic conditions. Methodology MG-63 cultures were established under high glucose concentrations during the experiments and cultured with SV concentrations of 1 µM and 3 µM. The quantification of the expression of the genes, namely, BMP-2 and osteocalcin (OCN) was done by real-time quantitative polymerase chain reaction (RTqPCR). The measurement of alkaline phosphatase activity in the SV-treated cells was also determined. Results According to the results of the study, SV had osteoprotective properties resulting from the inhibition of osteoclast stimulation and osteoinductive properties, facilitated by BMP-2 and OCN. In addition, SV at concentrations of 1 µM and 3 µM increased the gene expression of BMP-2 and OCN in the MG-63 cell line. Conclusion The results of this study demonstrated that SV had a significant and direct effect on osteogenesis in osteoblasts in vitro.

Environmental magnesium ion affects global gene expression, motility, biofilm formation and virulence of Vibrio parahaemolyticus.

Vibrio parahaemolyticus is widely distributed in marine ecosystems. Magnesium ion (Mg2+) is the second most abundant metal cation in seawater, and plays important roles in the growth and gene expression of V. parahaemolyticus, but lacks the detailed mechanisms. In this study, the RNA sequencing data demonstrated that a total of 1494 genes was significantly regulated by Mg2+. The majority of the genes associated with lateral flagella, exopolysaccharide, type III secretion system 2, type VI secretion system (T6SS) 1, T6SS2, and thermostable direct hemolysin were downregulated. A total of 18 genes that may be involved in c-di-GMP metabolism and more than 80 genes encoding putative regulators were also significantly and differentially expressed in response to Mg2+, indicating that the adaptation process to Mg2+ stress may be strictly regulated by complex regulatory networks. In addition, Mg2+ promoted the proliferative speed, swimming motility and cell adhesion of V. parahaemolyticus, but inhibited the swarming motility, biofilm formation, and c-di-GMP production. However, Mg2+ had no effect on the production of capsular polysaccharide and cytoxicity against HeLa cells. Therefore, Mg2+ had a comprehensive impact on the physiology and gene expression of V. parahaemolyticus.

Injectable, self-healing hydrogels based on gelatin, quaternized chitosan, and laponite as localized celecoxib delivery system for nucleus pulpous repair.

Utilization of injectable hydrogels stands as a paradigm of minimally invasive intervention in the context of intervertebral disc degeneration treatment. Restoration of nucleus pulposus (NP) function exerts a profound influence in alleviating back pain. This study introduces an innovative class of injectable shear-thinning hydrogels, founded on quaternized chitosan (QCS), gelatin (GEL), and laponite (LAP) with the capacity for sustained release of the anti-inflammatory drug, celecoxib (CLX). First, synthesis of Magnesium-Aluminum-Layered double hydroxide (LDH) was achieved through a co-precipitation methodology, as a carrier for celecoxib and a source of Mg ions. Intercalation of celecoxib within LDH layers (LDH-CLX) was verified through a battery of analytical techniques, including FTIR, XRD, SEM, EDAX, TGA and UV-visible spectroscopy confirmed a drug loading efficiency of 39.22 ± 0.09 % within LDH. Then, LDH-CLX was loaded in the optimal GEL-QCS-LAP hydrogel under physiological conditions. Release behavior (15 days profile), mechanical properties, swelling ratio, and degradation rate of the resulting composite were evaluated. A G* of 15-47 kPa was recorded for the hydrogel at 22-40 °C, indicating gel stability in this temperature range. Self-healing properties and injectability of the composite were proved by rheological measurements. Also, ex vivo injection into intervertebral disc of sheep, evidenced in situ forming and NP cavity filling behavior of the hydrogel. Support of GEL-QCS-LAP/LDH-CLX (containing mg2+ ions) for viability and proliferation (from ~94 % on day 1 to ~134 % on day 7) of NP cells proved using MTT assay, DAPI and Live/Dead assays. The hydrogel could significantly upregulate secretion of glycosaminoglycan (GAG, from 4.68 ± 0.1 to 27.54 ± 1.0 µg/ml), when LHD-CLX3% was loaded. We conclude that presence of mg2+ ion and celecoxib in the hydrogel can lead to creation of a suitable environment that encourages GAG secretion. In conclusion, the formulated hydrogel holds promise as a minimally invasive candidate for degenerative disc repair.

In vitro corrosion and cytocompatibility of Mg-Zn-Ca alloys coated with FHA.

In the field of orthopedics, it's crucial to effectively slow down the degradation rate of Mg alloys. This study aims to improve the degradation behavior of Mg-Zn-Ca alloys by electrodepositing fluorohydroxyapatite (FHA). We investigated the microstructure and bond strength of the deposition, as well as degradation and cellular reactions. After 15-30 days of degradation in Hanks solution, FHA deposited alloys showed enhanced stability and less pH change. The strong interfacial bond between FHA and the Mg-Zn-Ca substrate was verified through scratch tests (Critical loads: 10.73 ± 0.014 N in Mg-Zn-0.5Ca alloys). Cellular studies demonstrated that FHA-coated alloys exhibited good cytocompatibility and promoted the growth of MC3T3-E1 cells. Further tests showed FHA-coated alloys owed improved early bone mineralization and osteogenic properties, especially in Mg-Zn-0.5Ca. This research highlighted the potential of FHA-coated Mg-Zn-0.5Ca alloys in orthopedics applications.

Large-Scale Integration of the Ion-Reinforced Phytic Acid Layer Stabilizing Magnesium Metal Anode.

Rechargeable magnesium batteries (RMBs) have garnered significant attention for their potential in large-scale energy storage applications. However, the commercial development of RMBs has been severely hampered by the rapid failure of large-sized Mg metal anodes, especially under fast and deep cycling conditions. Herein, a concept proof involving a large-scale ion-reinforced phytic acid (PA) layer (100 cm × 7.5 cm) with an excellent water-oxygen tolerance, high Mg2+ conductivity, and favorable electrochemical stability is proposed to enable rapid and uniform plating/stripping of Mg metal anode. Guided by even distributions of Mg2+ flux and electric field, the as-prepared large-sized PA-Al@Mg electrode (5.8 cm × 4.5 cm) exhibits no perforation and uniform Mg plating/stripping after cycling. Consequently, an ultralong lifespan (2400 h at 3 mA cm-2 with 1 mAh cm-2) and high current tolerance (300 h at 9 mA cm-2 with 1 mAh cm-2) of the symmetric cell using the PA-Al@Mg anode could be achieved. Notably, the PA-Al@Mg//Mo6S8 full cell demonstrates exceptional stability, operating for 8000 cycles at 5 C with a capacity retention of 99.8%, surpassing that of bare Mg (3000 cycles, 74.7%). Moreover, a large-sized PA-Al@Mg anode successfully contributes to the stable pouch cell (200 and 750 cycles at 0.1 and 1 C), further confirming its significant potential for practical utilization. This work provides valuable theoretical insights and technological support for the practical implementation of RMBs.

Topological Electronic Transition Contributing to Improved Thermoelectric Performance in p-Type Mg3Sb2- xBix Solid Solutions.

Topological electronic transition is the very promising strategy for achieving high band degeneracy (NV) and for optimizing thermoelectric performance. Herein, this work verifies in p-type Mg3Sb2- xBix that topological electronic transition could be the key mechanism responsible for elevating the NV of valence band edge from 1 to 6, leading to much improved thermoelectric performance. Through comprehensive spectroscopy characterizations and theoretical calculations of electronic structures, the topological electronic transition from trivial semiconductor is unambiguously demonstrated to topological semimetal of Mg3Sb2- xBix with increasing the Bi content, due to the strong spin-orbit coupling of Bi and the band inversion. The distinct evolution of Fermi surface configuration and the multivalley valence band edge with NV of 6 are discovered in the Bi-rich compositions, while a peculiar two-step band inversion is revealed for the first time in the end compound Mg3Bi2. As a result, the optimal p-type Mg3Sb0.5Bi1.5 simultaneously obtains a positive bandgap and high NV of 6, and thus acquires the largest thermoelectric power factor of 3.54 and 6.93 µW cm-1 K-2 at 300 and 575 K, respectively, outperforming the values in other compositions. This work provides important guidance on improving thermoelectric performance of p-type Mg3Sb2- xBix utilizing the topological electronic transition.

Influence of implant base material on secondary bone healing: an in silico study.

The implant material at the fracture site influences fracture healing not only from biological perspective but also from mechanical perspective. Biodegradable implants such as magnesium (Mg) based alloys have shown faster secondary bone healing properties as compared to bioinert implants such as titanium (Ti). The general reasoning behind this is the benefit of Mg from biocompatibility perspectives. We studied the effect of Ti and Mg as base materials for implants from mechanical perspectives, where we focused on the displacements at the fracture site of the tibia and their influence on the stimulus for bone healing. We found out that in comparison to Ti, Mg implants have minimal stress shielding problem, only which led to better mechanical stimulus at the fracture site.

Transmembrane Protein TMEM230, Regulator of Glial Cell Vascular Mimicry and Endothelial Cell Angiogenesis in High-Grade Heterogeneous Infiltrating Gliomas and Glioblastoma.

High-grade gliomas (HGGs) and glioblastoma multiforme (GBM) are characterized by a heterogeneous and aggressive population of tissue-infiltrating cells that promote both destructive tissue remodeling and aberrant vascularization of the brain. The formation of defective and permeable blood vessels and microchannels and destructive tissue remodeling prevent efficient vascular delivery of pharmacological agents to tumor cells and are the significant reason why therapeutic chemotherapy and immunotherapy intervention are primarily ineffective. Vessel-forming endothelial cells and microchannel-forming glial cells that recapitulate vascular mimicry have both infiltration and destructive remodeling tissue capacities. The transmembrane protein TMEM230 (C20orf30) is a master regulator of infiltration, sprouting of endothelial cells, and microchannel formation of glial and phagocytic cells. A high level of TMEM230 expression was identified in patients with HGG, GBM, and U87-MG cells. In this study, we identified candidate genes and molecular pathways that support that aberrantly elevated levels of TMEM230 play an important role in regulating genes associated with the initial stages of cell infiltration and blood vessel and microchannel (also referred to as tumor microtubule) formation in the progression from low-grade to high-grade gliomas. As TMEM230 regulates infiltration, vascularization, and tissue destruction capacities of diverse cell types in the brain, TMEM230 is a promising cancer target for heterogeneous HGG tumors.

Development of Upper Extremity Deep Vein Thrombosis in a Patient With Seronegative Myasthenia Gravis: A Case Report and Review of Literature.

We present the case report of a patient with seronegative myasthenia gravis (MG) who was admitted for metabolic encephalopathy and acute on chronic hypoxic respiratory failure secondary to an MG crisis three days after an intravenous immunoglobulin treatment. In the intensive care unit, her MG was managed with intravenous immunoglobulin, plasmapheresis, prednisone, and pyridostigmine. During the course of her visit, she had urosepsis along with a left chest port that had cultured positive for Pseudomonas aeruginosa and developed a right upper extremity deep vein thrombosis (UEDVT) and superficial thrombosis in the left upper extremity despite being on heparin therapy. She had a transient drop in platelets to below 150,000 that resolved within a day. We analyzed the variables of this case report and reviewed the literature of similar cases to elucidate the factors that may have led to the development of the UEDVTs. The patient had many factors in her past medical history that could have contributed to her thrombosis including morbid obesity and prior history of pulmonary embolisms. It is hypothesized that MG disturbs the endothelial cell lining through an increased inflammatory state that could also be a causative factor. There is no definitive way we could link MG as a causative factor due to a lack of testing to assess alteration in the integrity or functionality of her endothelium. A case report we reviewed showed a presentation of UEDVT in an MG patient due to a thymoma compressing the subclavian vein. However, this is not the case in this example due to the patient having a history of thymectomy. She was also at risk due to her hospital stay which led to immobility and placement of a central venous catheter. We conclude the formation of the UEDVT was likely a combination of these factors.