Herbo-Mineral Medicine, Lithom Exhibits Anti-Nephrolithiasis Activity in Rat Model of Hyperoxaluria by Attenuating Calcium Oxalate Crystal Formation and Oxidative Stress.

BACKGROUND: Calcium oxalate monohydrate (COM) forms the most common type of kidney stones observed in clinics, elevated levels of urinary oxalate being the principal risk factor for such an etiology. The objective of the present study was to evaluate the anti-nephrolithiatic effect of herbo-mineral formulation, Lithom. METHODS: The in vitro biochemical synthesis of COM crystals in the presence of Lithom was performed and observations were made by microscopy and Scanning Electron Microscope (SEM) based analysis for the detection of crystal size and morphology. The phytochemical composition of Lithom was evaluated by Ultra-High-Performance Liquid Chromatography (UHPLC). The in vivo model of Ethylene glycol-induced hyperoxaluria in Sprague-Dawley rats was used for the evaluation of Lithom. The animals were randomly allocated to 5 different groups namely Normal control, Disease control (ethylene glycol (EG), 0.75%, 28 days), Allopurinol (50 mg/kg, q.d.), Lithom (43 mg/kg, b.i.d.), and Lithom (129 mg/kg, b.i.d.). Analysis of crystalluria, oxalate, and citrate levels, oxidative stress parameters (malondialdehyde (MDA), catalase, myeloperoxidase (MPO)), and histopathology by hematoxylin and eosin (H&E) and Von Kossa staining was performed for evaluation of Lithom. RESULTS: The presence of Lithom during COM crystals synthesis significantly reduced the average crystal area, feret's diameter, and area-perimeter ratio, in a dose-dependent manner. SEM analysis revealed that COM crystals synthesized in the presence of 100 and 300 µg/mL of Lithom exhibited a veritable morphological transition from irregular polygons with sharp edges to smoothened smaller cuboid polygons. UHPLC analysis of Lithom revealed the presence of Trigonelline, Bergenin, Xanthosine, Adenosine, Bohoervinone B, Vanillic acid, and Ellagic acid as key phytoconstituents. In EG-induced SD rats, the Lithom-treated group showed a decrease in elevated urinary oxalate levels, oxidative stress, and renal inflammation. Von Kossa staining of kidney tissue also exhibited a marked reduction in crystal depositions in Lithom-treated groups. CONCLUSION: Taken together, Lithom could be a potential clinical-therapeutic alternative for management of nephrolithiasis.

Biotransformation of ethylene glycol by engineered Escherichia coli.

There has been extensive research on the biological recycling of PET waste to address the issue of plastic waste pollution, with ethylene glycol (EG) being one of the main components recovered from this process. Therefore, finding ways to convert PET monomer EG into high-value products is crucial for effective PET waste recycling. In this study, we successfully engineered Escherichia coli to utilize EG and produce glycolic acid (GA), expecting to facilitate the biological recycling of PET waste. The engineered E. coli, able to utilize 10 g/L EG to produce 1.38 g/L GA within 96 h, was initially constructed. Subsequently, strategies based on overexpression of key enzymes and knock-out of the competing pathways are employed to enhance EG utilization along with GA biosynthesis. An engineered E. coli, characterized by the highest GA production titer and substrate conversion rate, was obtained. The GA titer increased to 5.1 g/L with a yield of 0.75 g/g EG, which is the highest level in the shake flake experiments. Transcriptional level analysis and metabolomic analysis were then conducted, revealing that overexpression of key enzymes and knock-out of the competing pathways improved the metabolic flow in the EG utilization. The improved metabolic flow also leads to accelerated synthesis and metabolism of amino acids.

Cymbopogon proximus and Petroselinum crispum seed ethanolic extract/Gum Arabic nanogel emulsion: Preventing ethylene glycol and ammonium chloride-induced urolithiasis in rats.

Urolithiasis is a prevalent urological disorder that contributes significantly to global morbidity. This study aimed to assess the anti-urolithic effects of Cymbopogon proximus (Halfa Bar) and Petroselinum crispum (parsley) seed ethanolic extract /Gum Arabic (GA) emulsion, and its nanogel form against ethylene glycol (EG) and ammonium chloride (AC)-induced experimental urolithiasis in rats. Rats were divided into four groups: group 1 served as the normal control, group 2 received EG with AC in drinking water for 14 days to induce urolithiasis, groups 3 and 4 were orally administered emulsion (600 mg/kg/day) and nanogel emulsion (600 mg/kg/day) for 7 days, followed by co-administration with EG and AC in drinking water for 14 days. Urolithiatic rats exhibited a significant decrease in urinary excreted magnesium, and non-enzymic antioxidant glutathione and catalase activity. Moreover, they showed an increase in oxalate crystal numbers and various urolithiasis promoters, including excreted calcium, oxalate, phosphate, and uric acid. Renal function parameters and lipid peroxidation were intensified. Treatment with either emulsion or nanogel emulsion significantly elevated urolithiasis inhibitors, excreted magnesium, glutathione levels, and catalase activities. Reduced oxalate crystal numbers, urolithiasis promoters' excretion, renal function parameters, and lipid peroxidation while improving histopathological changes. Moreover, it decreased renal crystal deposition score and the expression of Tumer necrosis factor-α (TNF-α) and cleaved caspase-3. Notably, nanogel emulsion showed superior effects compared to the emulsion. Cymbopogon proximus (C. proximus) and Petroselinum crispum (P. crispum) seed ethanolic extracts/GA nanogel emulsion demonstrated protective effects against ethylene glycol induced renal stones by mitigating kidney dysfunction, oxalate crystal formation, and histological alterations.

Optimization of Interleukin-10 incorporation for dendritic cells embedded in Poly(ethylene glycol) hydrogels.

Translational research in biomaterials and immunoengineering is leading to the development of novel advanced therapeutics to treat diseases such as cancer, autoimmunity, and viral infections. Dendritic cells (DCs) are at the center of these therapeutics given that they bridge innate and adaptive immunity. The biomaterial system developed herein uses a hydrogel carrier to deliver immunomodulatory DCs for amelioration of autoimmunity. This biomaterial vehicle is comprised of a poly (ethylene glycol)-4 arm maleimide (PEG-4MAL) hydrogels, conjugated with the immunosuppressive cytokine, interleukin-10, IL-10, and cross-linked with a collagenase-degradable peptide sequence for the injectable delivery of immunosuppressive DCs to an anatomical disease-relevant site of the cervical lymph nodes, for intended application to treat multiple sclerosis. The amount of IL-10 incorporated in the hydrogel was optimized to be 500 ng in vitro, based on immunological endpoints. At this concentration, DCs exhibited the best viability, most immunosuppressive phenotype, and protection against proinflammatory insult as compared with hydrogel-incorporated DCs with lower IL-10 loading amounts. Additionally, the effect of the degradability of the PEG-4MAL hydrogel on the release rate of incorporated IL-10 was assessed by varying the ratio of degradable peptides: VPM (degradable) and DTT (nondegradable) and measuring the IL-10 release rates. This IL-10-conjugated hydrogel delivery system for immunosuppressive DCs is set to be assessed for in vivo functionality as the immunosuppressive cytokine provides a tolerogenic environment that keeps DCs in their immature phenotype, which consequently enhances cell viability and optimizes the system's immunomodulatory functionality.

Ethylene Glycol-Choline Chloride Based Hydrated Deep Eutectic Electrolytes Enabled High-Performance Zinc-Ion Battery.

Aqueous rechargeable zinc-ion batteries (ARZIBs) are considered as an emerging energy storage technology owing to their low cost, inherent safety, and reasonable energy density. However, significant challenges associated with electrodes, and aqueous electrolytes restrict their rapid development. Herein, ethylene glycol-choline chloride (Eg-ChCl) based hydrated deep-eutectic electrolytes (HDEEs) are proposed for RZIBs. Also, a novel V10O24·nH2O@rGO composite is prepared and investigated in combination with HDEEs. The formulated HDEEs, particularly the composition of 1 ml of EG, 0.5 g of ChCl, 4 ml of H2O, and 2 M ZnTFS (1-0.5-4-2 HDEE), not only exhibit the lowest viscosity, highest Zn2+ conductivity (20.38 mS cm-1), and the highest zinc (Zn) transference number (t+ = 0.937), but also provide a wide electrochemical stability window (>3.2 V vs ZnǁZn2+) and enabledendrite-free Zn stripping/plating cycling over 1000 hours. The resulting ZnǁV10O24·nH2O@rGO cell with 1-0.5-4-2 HDEE manifests high reversible capacity of ≈365 mAh g-1 at 0.1 A g-1, high rate-performance (delivered ≈365/223 mAh g-1 at 0.1/10 mA g-1) and enhanced cycling performance (≈63.10% capacity retention in the 4000th cycle at 10 A g-1). Furthermore, 1-0.5-4-2 HDEE support feasible Zn-ion storage performance across a wide temperature range (0-80 °C) FInally, a ZnǁV10O24·nH2O@rGO pouch-cell prototype fabricated with 1-0.5-4-2 HDEE demonstrates good flexibility, safety, and durability.

Effect of Poly(ethylene glycol) Configuration on Microbubble Pharmacokinetics.

Microbubbles (MBs) hold substantial promise for medical imaging and therapy; nonetheless, knowledge gaps persist between composition, structure, and in vivo performance, especially with respect to pharmacokinetics. Of particular interest is the role of the poly(ethylene glycol) (PEG) layer, which is thought to shield the MB against opsonization and rapid clearance but is also known to cause an antibody response upon multiple injections. The goal of this study was, therefore, to elucidate the role of the PEG layer in circulation persistence of MBs in the naïve animal (prior to an adaptive immune response). Here, we directly observe the number and size of individual MBs obtained from blood samples, unifying size and concentration into the microbubble volume dose (MVD) parameter. This approach enables direct evaluation of the pharmacokinetics of intact MBs, comprising both the lipid shell and gaseous core, rather than separately assessing the lipid or gas components. We examined the in vivo circulation persistence of 3 µm diameter phospholipid-coated MBs with three different mPEG2000 content: 2 mol % (mushroom), 5 mol % (intermediate), and 10 mol % (brush). MB size and concentration in the blood were evaluated by a hemocytometer analysis over 30 min following intravenous injections of 20 and 40 µL/kg MVD in Sprague-Dawley rats. Interestingly, pharmacokinetic analysis demonstrated that increasing PEG concentration on the MB surface resulted in faster clearance. This was evidenced by a 1.6-fold reduction in half-life and area under the curve (AUC) (p < 0.05) in the central compartment. Conversely, the AUC in the peripheral compartment increased with PEG density, suggesting enhanced MB trapping by the mononuclear phagocyte system. This was supported by an in vitro assay, which showed a significant rise in complement C3a activation with a higher PEG content. In conclusion, a minimal PEG concentration on the MB shell (mushroom configuration) was found to prolong circulation and mitigate immunogenicity.

Nonlinear Elastic Bottlebrush Polymer Hydrogels Modulate Actomyosin Mediated Protrusion Formation in Mesenchymal Stromal Cells.

The nonlinear elasticity of many tissue-specific extracellular matrices is difficult to recapitulate without the use of fibrous architectures, which couple strain-stiffening with stress relaxation. Herein, bottlebrush polymers are synthesized and crosslinked to form poly(ethylene glycol)-based hydrogels and used to study how strain-stiffening behavior affects human mesenchymal stromal cells (hMSCs). By tailoring the bottlebrush polymer length, the critical stress associated with the onset of network stiffening is systematically varied, and a unique protrusion-rich hMSC morphology emerges only at critical stresses within a biologically accessible stress regime. Local cell-matrix interactions are quantified using 3D traction force microscopy and small molecule inhibitors are used to identify cellular machinery that plays a critical role in hMSC mechanosensing of the engineered, strain-stiffening microenvironment. Collectively, this study demonstrates how covalently crosslinked bottlebrush polymer hydrogels can recapitulate strain-stiffening biomechanical cues at biologically relevant stresses and be used to probe how nonlinear elastic matrix properties regulate cellular processes. This article is protected by copyright. All rights reserved.

Improvement in Crystallization, Thermal, and Mechanical Properties of Flexible Poly(L-lactide)-b-poly(ethylene glycol)-b-poly(L-lactide) Bioplastic with Zinc Phenylphosphate.

Poly(L-lactide)-b-poly(ethylene glycol)-b-poly(L-lactide) (PLLA-PEG-PLLA) shows promise for use in bioplastic applications due to its greater flexibility over PLLA. However, further research is needed to improve PLLA-PEG-PLLA's properties with appropriate fillers. This study employed zinc phenylphosphate (PPZn) as a multi-functional filler for PLLA-PEG-PLLA. The effects of PPZn addition on PLLA-PEG-PLLA characteristics, such as crystallization and thermal and mechanical properties, were investigated. There was good phase compatibility between the PPZn and PLLA-PEG-PLLA. The addition of PPZn improved PLLA-PEG-PLLA's crystallization properties, as evidenced by the disappearance of the cold crystallization temperature, an increase in the crystallinity, an increase in the crystallization temperature, and a decrease in the crystallization half-time. The PLLA-PEG-PLLA's thermal stability and heat resistance were enhanced by the addition of PPZn. The PPZn addition also enhanced the mechanical properties of the PLLA-PEG-PLLA, as demonstrated by the rise in ultimate tensile stress and Young's modulus. We can conclude that the PPZn has potential for use as a multi-functional filler for the PLLA-PEG-PLLA composite due to its nucleating-enhancing, thermal-stabilizing, and reinforcing ability.

Effect of Plasticization/Annealing on Thermal, Dynamic Mechanical, and Rheological Properties of Poly(Lactic Acid).

This study investigates the use of low molecular weight poly(ethylene glycol) (PEG) as a plasticizer for poly(lactic acid) (PLA). PLA/PEG blend films were prepared using the solvent casting method with varying mixing ratios. The films were analyzed using differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and dynamic rheological analysis. The results indicate that the addition of PEG as a plasticizer affects the thermal and mechanical properties of the PLA/PEG blend films. The study found that the glass transition and cold crystallization temperatures decreased with increasing PEG content up to 20 wt%, while the crystallinity and crystallization rate increased. The blends with up to 20 wt% PEG were miscible, but phase separation occurred when the plasticizer content was increased to 30 wt%. Subsequently, amorphous samples of neat PLA and PLA plasticized with 10 wt% of PEG underwent annealing at various temperatures (Ta = 80-120 °C) for durations ta of 1 and 24 h. The samples were then analyzed using DSC and DMA. The addition of PEG to PLA altered the content of α' and α crystalline forms compared to neat PLA at a given (Ta; ta) and favored the formation of a mixture of α' and α crystals. The crystallinity achieved upon annealing increased with increasing Ta or ta and with the incorporation of PEG.

A comparative transcriptomics analysis reveals ethylene glycol derivatives of squalene ameliorate excessive lipogenesis and inflammatory response in 3T3-L1 preadipocytes.

Squalene (SQ) is a natural compound with anti-inflammatory, anti-cancer, and anti-oxidant effects, but due to its low solubility, its biological properties have been greatly underestimated. This study aims to explore the differences in gene expression patterns of four newly synthesized amphipathic ethylene glycol (EG) derivatives of SQ by whole-genome transcriptomics analysis using DNA microarray to examine the mRNA expression profile of adipocytes differentiated from 3T3-L1 cells treated with SQ and its EG derivatives. Enrichment analyses of the transcriptional data showed that compared with SQ, its EG derivatives exerted different, in most cases desirable, biological responses. EG derivatives showed increased enrichment of mitochondrial functions, lipid and glucose metabolism, and inflammatory response. Mono-, di-, and tetra-SQ showed higher enrichment of the cellular component-ribosome. Histological staining showed EG derivatives prevented excessive lipid accumulation. Additionally, mitochondrial transcription factors showed upregulation in tetra-SQ-treated cells. Notably, EG derivatives showed better anti-inflammatory effects. Further, gene-disease association analysis predicted substantial improvement in the bioactivities of SQ derivatives in metabolic diseases. Cluster analyses revealed di- and tetra-SQ had more functional similarities than others, reflected in their scanning electron microscopy images; both di- and tetra-SQ self-organized into similar sizes and shapes of vesicles, subsequently improving their cation binding activities. Protein-protein interaction networks further revealed that cation binding activity might explain a major part, if not all, of the differences observed in functional analyses. Altogether, the addition of EG derivatives may improve the biological responses of SQ and thus may enhance its health-promoting potential.

Aqueous Processed All-Polymer Solar Cells with High Open-Circuit Voltage Based on Low-Cost Thiophene-Quinoxaline Polymers.

Eco-friendly solution processing and the low-cost synthesis of photoactive materials are important requirements for the commercialization of organic solar cells (OSCs). Although varieties of aqueous-soluble acceptors have been developed, the availability of aqueous-processable polymer donors remains quite limited. In particular, the generally shallow highest occupied molecular orbital (HOMO) energy levels of existing polymer donors limit further increases in the power conversion efficiency (PCE). Here, we design and synthesize two water/alcohol-processable polymer donors, poly[(thiophene-2,5-diyl)-alt-(2-((13-(2,5,8,11-tetraoxadodecyl)-2,5,8,11-tetraoxatetradecan-14-yl)oxy)-6,7-difluoroquinoxaline-5,8-diyl)] (P(Qx8O-T)) and poly[(selenophene-2,5-diyl)-alt-(2-((13-(2,5,8,11-tetraoxadodecyl)-2,5,8,11-tetraoxatetradecan-14-yl)oxy)-6,7-difluoroquinoxaline-5,8-diyl)] (P(Qx8O-Se)) with oligo(ethylene glycol) (OEG) side chains, having deep HOMO energy levels (∼-5.4 eV). The synthesis of the polymers is achieved in a few synthetic and purification steps at reduced cost. The theoretical calculations uncover that the dielectric environmental variations are responsible for the observed band gap lowering in OEG-based polymers compared to their alkylated counterparts. Notably, the aqueous-processed all-polymer solar cells (aq-APSCs) based on P(Qx8O-T) and poly[(N,N'-bis(3-(2-(2-(2-methoxyethoxy)-ethoxy)ethoxy)-2-((2-(2-(2-methoxyethoxy)ethoxy)ethoxy)-methyl)propyl)naphthalene-1,4,5,8-bis(dicarboximide)-2,6-diyl)-alt-(2,5-thiophene)] (P(NDIDEG-T)) active layer exhibit a PCE of 2.27% and high open-circuit voltage (VOC) approaching 0.8 V, which are among the highest values for aq-APSCs reported to date. This study provides important clues for the design of low-cost, aqueous-processable polymer donors and the fabrication of aqueous-processable OSCs with high VOC.

One-pot Synthesis of PdCuAg and CeO2 Nanowires Hybrid with Abundant Heterojunction Interface for Ethylene Glycol Electrooxidation.

Introducing CeO2 into Pd-based nanocatalysts for electrocatalytic reactions is a good way to solve the intermediate toxicity problem and improve the catalytic performance. Here we reported a simple strategy to synthesize the PdCuAg and CeO2 nanowires hybrid via a one-pot synthesis process under strong nanoconfined effect of specific surfactant as templates. Owing to the structural (ultrathin nanowires, abundant heterojunction/interfaces between metal and metal oxide) and compositional (Pd, Cu, Ag, CeO2) advantages, the hybrid showed significantly enhanced catalytic activity (6.06 A mgPd -1) and stability, accelerated reaction rate, and reduced activation energy toward electrocatalytic ethylene glycol oxidation reaction.

Reflections on a Copenhagen-Minneapolis Axis in Bioorganic Chemistry.

The international peptide community rejoiced when one of its most distinguished members, Morten Meldal of Denmark, shared the 2022 Nobel Prize in Chemistry. In fact, the regiospecific solid-phase "copper(I)-catalyzed 1,3-dipolar cycloaddition of terminal alkynes to azides" (CuACC) reaction-that formed the specific basis for Meldal's recognition-was reported first at the 17th American Peptide Symposium held in San Diego in June 2001. The present perspective outlines intertwining conceptual and experimental threads pursued concurrently in Copenhagen and Minneapolis, sometimes by the same individuals, that provided context for Meldal's breakthrough discovery. Major topics covered include orthogonality in chemistry; the dithiasuccinoyl (Dts) protecting group for amino groups in α-amino acids, carbohydrates, and monomers for peptide nucleic acids (PNA); and poly(ethylene glycol) (PEG)-based solid supports such as PEG-PS, PEGA, and CLEAR [and variations inspired by them] for solid-phase peptide synthesis (SPPS), solid-phase organic synthesis (SPOS), and combinatorial chemistry that can support biological assays in aqueous media.

Broadening the Voltage Window of 3D-Printed MXene Micro-Supercapacitors with a Hybridized Electrolyte.

The burgeoning demand for miniaturized energy storage devices compatible with the miniaturization trend of electronic technologies necessitates advancements in micro-supercapacitors (MSCs) that promise safety, cost efficiency, and high-speed charging capabilities. However, conventional aqueous MSCs face a significant limitation due to their inherently narrow electrochemical potential window, which restricts their operational voltage and energy density compared to their organic and ionic liquid counterparts. In this study, we introduce an innovative aqueous NaCl/H2O/EG hybrid gel electrolyte (comprising common salt (NaCl), H2O, ethylene glycol (EG), and SiO2) for Ti3C2Tx MXene MSCs that substantially widens the voltage window to 1.6 V, a notable improvement over traditional aqueous system. By integrating the hybrid electrolyte with 3D-printed MXene electrodes, we realized MSCs with remarkable areal capacitance (1.51 F cm-2) and energy density (675 µWh cm-2), significantly surpassing existing benchmarks for aqueous MSCs. The strategic formulation of the hybrid electrolyte-a low-concentration NaCl solution with EG-ensures both economic and environmental viability while enabling enhanced electrochemical performance. Furthermore, the MSCs fabricated via 3D printing technology exhibit exceptional flexibility and are suitable for modular device integration, offering a promising avenue for the development of high-performance, sustainable energy storage devices. This advancement not only provides a tangible solution to the challenge of limited voltage windows in aqueous MXene MSCs but also sets a new precedent for the design of next-generation MSCs that align with the needs of an increasingly microdevice-centric world.

Lignin-Based Hydrogels for the Delivery of Bioactive Chaga Mushroom Extract.

Lignin-poly(ethylene)glycol diglycidyl ether hydrogels were synthesized from lignin fractions readily extracted during the hot-water treatment of angiosperms: hardwoods, sugar maple and energy-crop willow, monocotyledons, grasses, miscanthus and agriculture residues, and wheat straw. These lignins represent a broad range of chemical structures and properties as a comparative analysis of their suitability to produce the hydrogels as a novel carrier of chaga-silver nanoparticles. The formation of hydrogels was assessed via attenuated total reflectance Fourier-transformed infrared spectroscopy. Then, the hydrogels were observed via scanning electron microscopy and evaluated for their free-absorbency capacity and moduli of compression. Furthermore, a hydrogel produced from kraft lignin and two commercial hydrogels was evaluated to benchmark the effectiveness of our hydrogels. Chaga extracts were prepared via the hot-water extraction of chaga mushroom, a method selected for its relatively higher yields and preserved antioxidizing activities. Hydrogels synthesized with lignins of monocotyledons, wheat straw, and miscanthus were found to be suitable carriers for chaga-silver nanoparticles due to their favorable absorption and release behaviors.

Tailoring the Degradation Time of Polycationic PEG-Based Hydrogels toward Dynamic Cell Culture Matrices.

Poly(ethylene glycol)-based (PEG) hydrogels provide an ideal platform to obtain well-defined and tailor-made cell culture matrices to enhance in vitro cell culture conditions, although cell adhesion is often challenging when the cells are cultivated on the substrate surface. We herein demonstrate two approaches for the synthesis of polycationic PEG-based hydrogels which were modified to enhance cell-matrix interactions, to improve two-dimensional (2D) cell culture, and catalyze hydrolytic degradation. While the utilization of N,N-(bisacryloxyethyl) amine (BAA) as cross-linker for in situ gelation provides degradable scaffolds for dynamic cell culture, the incorporation of short segments of poly(N-(3-(dimethylamino)propyl)acrylamide) (PDMAPAam) provides high local cationic charge density leading to PEG-based hydrogels with high selectivity for fibroblastic cell lines. The adsorption of transforming growth factor (TGF-ß) into the hydrogels induced stimulation of fibrosis and thus the formation of collagen as a natural ECM compound. With this, these dynamic hydrogels enhance in vitro cell culture by providing a well-defined, artificial, and degradable matrix that stimulates cells to produce their own natural scaffold within a defined time frame.

Fomepizole use reported to United States Poison Centers from 2010 to 2021.

BACKGROUND: The diagnosis of toxic alcohol poisoning is often based on clinical presentation and nonspecific surrogate laboratory studies due to limited testing availability. Fomepizole is the recommended antidote and often administered empirically. The objective of this study is to identify substances that mimic toxic alcohols and compare key clinical factors between toxic alcohol and non-toxic alcohol exposures when fomepizole was administered. METHODS: This study was a retrospective evaluation using the National Poison Data System from January 1, 2010 through December 31, 2021. Exposures were included if fomepizole was administered. Toxic alcohol exposures had ethylene glycol or methanol as a coded substance. For exposures not coded as a toxic alcohol, the first substance was described. Paracetamol (acetaminophen) exposures from 2020 and 2021 were excluded. RESULTS: Fomepizole was reportedly used 25,110 times over 12 years. Use increased from 1,955 in 2010 to 2,710 in 2021. Most administrations were for reported toxic alcohol poisoning (60 percent) but use in reported non-toxic alcohol poisoning was greater starting in 2020. Toxic alcohol exposures were older (43.3 versus 39.8 years; P < 0.001) and more likely male (65.7 percent versus 58.2 percent). Level of care was mostly a critical care unit (67.7 percent), which was less common in toxic alcohol (63.3 percent) than non-toxic alcohol exposures (74.2 percent). The most common non-toxic alcohol substances were ethanol (24.9 percent) or an unknown drug (17.5 percent). Acidosis, increased creatinine concentration, anion gap, and osmolal gap, and kidney failure were coded in a lower proportion of toxic alcohol exposures than non-toxic alcohol exposures (P < 0.001). DISCUSSION: The inability to provide rapid clinical confirmation of toxic alcohol poisoning results in the empiric administration of fomepizole to many patients who will ultimately have other diagnoses. Although fomepizole is relative well tolerated we estimated that this practice costs between $1.5 to $2.5 million. The major limitations of this work include the biases associated with retrospective record review, and the inability to confirm the exposures which may have resulted in allocation error. CONCLUSION: Most fomepizole use was for a presumed toxic alcohol. This recently shifted to greater use in likely non-toxic alcohol poisoning. Key difference between the groups suggest fomepizole administration was likely due to the difficulty in diagnosis of toxic alcohol poisoning along with the efficacy and safety of fomepizole. Increased toxic alcohol laboratory testing availability could improve timely diagnosis, reserving fomepizole use for toxic alcohol poisoning.

Successful vitrification of equine embryos >300 microns without puncture or aspiration.

BACKGROUND: Equine embryos >300 µm require puncture before vitrification. Protocols that do not require pre-puncture would make vitrification easier and allow for its widespread use. OBJECTIVES: To design a successful vitrification protocol for embryos >300 µm without puncture as a pre-treatment. STUDY DESIGN: Experimental in vivo study. METHODS: Thirty-eight embryos were divided into 3 groups (G1: ≤300 µm, n = 11; G2: >300-500 µm, n = 20; G3: >500 µm, n = 7). Embryos were vitrified using a human vitrification kit. Following a 15 min exposure to equilibration solution (ES; 7.5% DMSO +7.5% ethylene glycol [EG] in a base medium [BM] of M199 HEPES-buffered medium [H199] + hydroxypropyl cellulose + gentamycin), embryos were exposed for ≤90 s to a vitrification solution (15% DMSO +15% EG + 0.5 M trelahose in BM), loaded onto a Cryolock and plunged into LN2. Warming was undertaken by plunging the Cryolock tip into 1 mL of H199 + 20% FBS + pen/strep +1 M sucrose at 42°C for 1 min. The embryos were then moved to a 0.5 M sucrose solution for 4 min, then placed in Vigro Hold for 4 min prior to transfer to a recipient. RESULTS: Pregnancy rates were 81.8% (9/11) for G1, 80% (16/20) for G2, and 0% (0/7) for G3. The largest embryo to survive was 480 µm. MAIN LIMITATIONS: Limited numbers and only one pregnancy was followed to term. CONCLUSIONS: Equine embryos ≤480 µm can be successfully vitrified using a protocol with a longer exposure time to the ES. This does not appear to have a negative effect on early embryonic development.

Cu-MSNs and ZnO nanoparticles incorporated poly(ethylene glycol) diacrylate/sodium alginate double network hydrogel for simultaneous enhancement of osteogenic differentiation.

In this study, a double network (DN) hydrogel was synthesized using poly(ethylene glycol) diacrylate (PEGDA) and sodium alginate (SA), incorporating copper-doped mesoporous silica nanospheres (Cu-MSNs) and zinc oxide nanoparticles (ZnO NPs). The blending of PEGDA and SA (PS) facilitates the double network and improves the less porous microstructure of pure PEGDA hydrogel. Furthermore, the incorporation of ZnO NPs and Cu-MSNs into the hydrogel network (PS@ZnO/Cu-MSNs) improved the mechanical properties of the hydrogel (Compressive strength = ⁓153 kPa and Young's modulus = ⁓ 1.66 kPa) when compared to PS hydrogel alone (Compressive strength = ⁓ 103 kPa and Young's modulus = ⁓ 0.95 kPa). In addition, the PS@ZnO/Cu-MSNs composite hydrogel showed antibacterial activities against Staphylococcus aureus and Escherichia coli. Importantly, the PS@ZnO/Cu-MSNs hydrogel demonstrated excellent biocompatibility, enhanced MC3T3-E1 cell adhesion, proliferation, and significant early-stage osteoblastic differentiation, as evidenced by increased alkaline phosphatase (ALP), and improved calcium mineralization, as evidenced by increased alizarin red staining (ARS) activities. These findings point to the possible use of the PS@ZnO/Cu-MSNs composite hydrogel in bone tissue regeneration.

Transition from active motion to anomalous diffusion for Bacillus subtilis confined in hydrogel matrices.

We investigate the motility of B. subtilis under different degrees of confinement induced by transparent porous hydrogels. The dynamical behavior of the bacteria at short times is linked to characteristic parameters describing the hydrogel porosity. Mean squared displacements (MSDs) reveal that the run-and-tumble dynamics of unconfined B. subtilis progressively turns into sub-diffusive motion with increasing confinement. Correspondingly, the median instantaneous velocity of bacteria decreases and becomes more narrowly distributed, while the reorientation rate increases and reaches a plateau value. Analyzing single-trajectories, we show that the average dynamical behavior is the result of complex displacements, in which active, diffusive and sub-diffusive segments coexist. For small and moderate confinements, the number of active segments reduces, while the diffusive and sub-diffusive segments increase. The alternation of sub-diffusion, diffusion and active motion along the same trajectory can be described as a hopping ad trapping motion, in which hopping events correspond to displacements with an instantaneous velocity exceeding the corresponding mean value along a trajectory. Different from previous observations, escape from local trapping occurs for B. subtilis through active runs but also diffusion. Interestingly, the contribution of diffusion is maximum at intermediate confinements. At sufficiently long times transport coefficients estimated from the experimental MSDs under different degrees of confinement can be reproduced using a recently proposed hopping and trapping model. Finally, we propose a quantitative relationship linking the median velocity of confined and unconfined bacteria through the characteristic confinement length of the hydrogel matrix. Our work provides new insights for the bacterial motility in complex media that mimic natural environments and are relevant to important problems like sterilization, water purification, biofilm formation, membrane permeation and bacteria separation.