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Ozonation (O3) is a widely used advanced oxidation process (AOP) for the treatment of wastewater, while its drawbacks include high energy consumption and poor solubility must be reduced or eliminated. Hence, a combined catalytic ozonation process with H2O2 and S2O82- was employed to degrade mono ethylene glycol (MEG) and eliminate ecological risks during the treatment of gas refinery wastewater. In this study, the reduction of chemical oxygen demand (COD) and MEG from wastewater by O3, O3/H2O2, O3/Na2 S2O8, O3/GAC, O3/GAC/S2O82- and O3/GAC/H2O2 oxidation treatment systems were investigated. The optimal treatment conditions were obtained as O3 dosage of 0.81 g h−1, H2O2 (0.15 mol L−1), S2O82- (2 g L−1), GAC (7 g L−1), pH of 11 and 60 min reaction time. The results revealed that the highest rate of degradation of MEG, COD reduction and the minimum electrical energy per order from the wastewater were 87.6%, 78.1% and 1.01 kWh/m3 respectively for O3/GAC/S2O82- process and 91.0%, 82.5% and 0.877 kWh/m3 respectively for O3/GAC/H2O2 process. The MEG degradation rate constant by O3/GAC/H2O2 system about 6.2 times and O3/GAC/S2O82- system over 5.3 times were higher than O3. After calculation, the synergy factors in O3/GAC with H2O2/S2O82- systems are more than 4.7, demonstrating that both systems have a strong synergistic effect. The finding related to the OH° trapping agent illustrates that indirect oxidation by OH° plays a vital role in the degradation of MEG. The performance of GAC stability was checked and resulted in the GAC also showing good stable catalytic activity in five consecutive cycles of use. The degradation pathways of MEG in the O3/GAC with H2O2 or S2O82- system were proposed based on intermediate analysis. The main intermediates found in MEG oxidation include glycolaldehyde, glycolic acid, glyoxal, glyoxylic acid, oxalic acid and formic acid. Finally, modification of wastewater treatment suggested that the burping phenomenon and the glycol foaming tendency were not observed. [ABSTRACT FROM AUTHOR]

The iron oxide nanoparticles (IONs), coated with different materials, are synthesized and utilized as nucleating agents to prepare magnetic multi‐modal porous scaffolds of poly (lactic‐co‐glycolic acid)/IONs using the supercritical carbon dioxide (ScCO2) foaming process. The effects of the modification materials, including citric acid, polycaprolactone, and polyvinyl acetate, on the foaming process and properties of the magnetic scaffolds are systematically investigated. The results indicate that the solubility and diffusion ability of CO2 in the foaming materials played a vital role in the foaming process. The use of CO2‐philic materials and high pressure proves beneficial in generating micropores. The scaffolds with multi‐modal porous structures can be obtained at relatively low pressure for the ScCO2 foaming systems evaluated in this study. Furthermore, the prepared scaffolds exhibit high porosity and a good compressive modulus (higher than 0.4 MPa), satisfying the requirements of tissue engineering for soft tissue scaffolds. [ABSTRACT FROM AUTHOR]

Polyoxovanadium glycolates (NH4)3[V6O6(glyc)6V(μ-OH)6]·10H2O (1-V7) (H2glyc = glycolic acid) and its derivatives added with ammonium sulfates (NH4)3[V6O6(glyc)6M(μ-OH)6][(NH4)2SO4]2·xH2O (M = Cr, x = 6, 2-CrV6; M = Fe, x = 7, 3-FeV6; M = Al, x = 6, 4-AlV6) were obtained through self-assembly and fully characterized. Compounds 1–4 are composed of the same fully reduced cyclic {V IV6 O6} unit bridged by six glycolate ligands. The framework encapsulated an octahedral metal(III) hydroxide {M(OH)6} (M = V3+, Cr3+, Fe3+, and Al3+) in the center, forming an iso- or hetero-heptanuclear Anderson-type structure. Moreover, two sulfate anions capped the two sides of cyclic {V6O6} units in compounds 2–4. Each sulfate formed a strong triple hydrogen bond (2.657–2.829 Å) with the μ3-OH group of the hydroxide. The sulfate anions played important roles in the formation of layered structures in 2–4, while the clusters were stacked compactly through strong hydrogen bonds in 1-V7. Because of the different central metals, these heptanuclear clusters exhibited distinct electronic structures as well as redox and magnetic properties. Magnetic studies showed that compounds 1–3 exhibited weak antiferromagnetic interactions in decreasing order with Fe3+, V3+ and Cr3+, while 4-AlV6 displayed weak ferromagnetic interactions. Their relationships with the local environment of the FeV-cofactor in V-nitrogenase are also discussed. [ABSTRACT FROM AUTHOR]

We developed a semiconductor photocatalyst, Pd–Pt alloy nanoparticle-loaded, Al-doped SrTiO3 (PdPt/STO:Al), for photoreduction of unsaturated carboxylic acids. Due to the cooperative STO:Al surface and Pd–Pt alloy nanoparticles, the catalyst dispersed in water provided highly redox-selective photoreduction against oxidative degradation of starting materials/products and against reductive evolution of H2, where minimal glycolic acid worked as an efficient electron-donating fuel. [ABSTRACT FROM AUTHOR]

Bone marrow stem cells (BMSCs)‐engineered cartilage (BEC) shows promise for clinically repairing cartilage defects. However, when implanted in immunocompetent large animals, BEC becomes susceptible to ossification due to inflammatory infiltration. To address this, a nanofilm isolation approach is developed to enhance BEC's chondrogenic stability. Tacrolimus (FK506), known for its immunosuppressive effect, is integrated into adipic dihydrazide (ADH)‐modified hyaluronic acid (HA), creating an acid‐responsive macromolecular prodrug called FK506@HA‐ADH. This prodrug is then blended with poly(lactic‐co‐glycolic acid) (PLGA) to form electrospun FK506@HA/PLGA nanofilm. Goat‐derived BMSCs are induced in vitro to form BEC, which is enclosed within the FK506@HA/PLGA nanofilm and subcutaneously implanted in autologous goats. The nanofilm acted as a physical barrier, preventing immunocyte infiltration. Additionally, in response to the acidic environment triggered by inflammation and the gradual degradation of PLGA, the FK506@HA‐ADH prodrug is cleaved, releasing FK506 as needed. The released FK506 effectively countered inflammatory cytokines and promoted cartilaginous maturity. These combined mechanisms significantly inhibited BEC hypertrophy and improved its chondrogenic stability within an immunocompetent goat model. This nanofilm‐based isolation strategy established an immunosuppressive niche, successfully preventing endochondral ossification and promoting stable cartilage formation in BEC. These advancements are crucial for translating stem cell‐based therapies into clinical use for cartilage repair. [ABSTRACT FROM AUTHOR]

This study investigates the development of a biopolymer blend electrolyte composed of alginate and poly (vinyl alcohol) (PVA), doped with glycolic acid (GA) to enhance H+ conductivity. The addition of GA significantly impacts the biopolymer blend's physicochemical properties and ionic conduction performance. Fourier transform infrared (FTIR) spectroscopy verified the intricate interactions and hydrogen bonding between the alginate-PVA matrix and GA. The addition of GA was shown to increase the amorphous phase, as observed through X-ray diffraction (XRD) and scanning electron microscopy (SEM) analysis. This increase in the amorphous phase was found to enhance the thermal stability. Impedance analysis demonstrated a significant increase in ionic conductivity from approximately ∼10⁻⁸ S cm⁻1 for the undoped blend to 3.45 × 10⁻⁵ S cm⁻1 with 30 wt% GA (sample GA-30). The enhanced H+ conduction behaviour was consistent across various temperatures, adhering to the Arrhenius rule. These findings suggest that the alginate-PVA-GA system is a promising candidate for efficient proton transport applications. • A bio-based polymer blend electrolyte composed of alginate-PVA containing H + carriers has been successfully prepared. • Amorphous Structure : GA doping transforms alginate-PVA into a highly amorphous, ion-conductive structure. • Strong Hydrogen Bonding : FTIR shows enhanced hydrogen bonding, aiding proton conduction via Grotthuss mechanism. • Thermal Stability : TGA confirms GA-doped alginate-PVA maintains thermal stability and boosts proton conductivity. • Enhanced Proton Conductivity : Glycolic acid-doped alginate-PVA boosts conductivity to 3.45 × 10⁻⁵ S cm⁻1. [ABSTRACT FROM AUTHOR]

Overexpression of permeability-glycoprotein (P-gp) transporter leads to multidrug resistance (MDR) through cellular exclusion of chemotherapeutics. Co-administration of P-gp inhibitors and chemotherapeutics is a promising approach for improving the efficacy of therapy. Nevertheless, problems in pharmacokinetics, toxicity and solubility limit the application of P-gp inhibitors. Herein, we developed a novel all-in-one hybrid nanoparticle system to overcome MDR in doxorubicin (DOX)-resistant breast cancer. First, folic acid-modified DOX-loaded mesoporous silica nanoparticles (MSNs) were prepared and then loaded into PEGylated poly(lactic-co-glycolic acid) (PLGA) nanoparticles along with a P-gp inhibitor, elacridar. This hybrid nanoparticle system had high drug loading capacity, enabled both passive and active targeting of tumour tissues, and exhibited sequential and pH-triggered release of drugs. In vitro and in vivo studies in DOX-resistant breast cancer demonstrated the ability of the hybrid nanoparticles to reverse P-gp-mediated drug resistance. The nanoparticles were efficiently taken up by the breast cancer cells and delivered elacridar, in vitro. Biodistribution studies demonstrated substantial accumulation of the folate receptor-targeted PLGA/MSN hybrid nanoparticles in tumour-bearing mice. Moreover, deceleration of the tumour growth was remarkable in the animals administered with the DOX and elacridar co-loaded hybrid nanoparticles when compared to those treated with the marketed liposomal DOX (Caelyx®) or its combination with elacridar. [ABSTRACT FROM AUTHOR]

The selection of quality excipients is a crucial step in peptide formulation development. Apart from excipient incompatibility, process-related impurities or degradants of an excipient can interact with peptide-active pharmaceutical ingredients, forming the interaction products. The formaldehyde has been reported as an impurity of excipient in polyethylene glycol, glycerol, magnesium stearate, microcrystalline cellulose, mannitol, etc. The peptide contains various amino acids such as histidine, lysine, and arginine having free amine groups. These amine groups act as strong nucleophile and can increase the reactivity of peptides. PLGA is the most widely used biodegradable polymer in sustained-release formulations. The hydrolysis of PLGA generates glycolic acid and lactic acid impurities, which can form the interaction product with the amines of peptides. During the formulation development of Liraglutide, we have found few interaction products. The systematic characterization and mechanistic understanding of these interaction products lead us to imidazopyrimidine, glycolyl, and lactolyl moieties. These interaction products have been characterized thoroughly with the use of LC-HRMS, MS/MS, and hydrogen-deuterium exchange mass studies. The study revealed that the reactivity of N-terminal histidine must be considered for formulation development. Moreover, the quality of excipients with respect to presence of impurities must be considered as critical material attributes. [ABSTRACT FROM AUTHOR]

Background: The hands are one of the areas where skin aging is most noticeable, alongside the face, but limited studies used dermoscopic evaluation on hand aging. The Dermoscopy Photoaging Scale (DPAS) is frequently used to assess face aging but is never used for hand aging. Treating skin aging using chemical peeling is a commonly used method to rejuvenate the skin on the hands, as it is relatively affordable. Using multiple chemical peels may yield more significant results. Aims: To determine the effectiveness of a chemical peeling combination in retarding hand aging and to assess the utility of DPAS in this process. Methods: This study involved 69 Fitzpatrick skin types III–IV volunteers aged 20–69. One hand of each participant was treated with 20% glycolic acid (GA), while the other received a combination of peels consisting of 20% GA and 15% trichloroacetic acid (TCA). The hands were clinically examined before and after the treatments, and dermoscopic examinations were performed using a modified DPAS. Results: Four treatments improved clinical and dermoscopic characteristics in both hands. The combined peeling considerably improved pigmentation intensity on the dorsal hand compared to the GA peel (p < 0.001). Post‐chemical peeling patient satisfaction increased significantly. Conclusions: The modified DPAS is a valuable instrument to assess the signs of hand aging. The combination of GA and TCA effectively improves skin aging of the hands and offers an accessible and economical option for addressing skin aging. [ABSTRACT FROM AUTHOR]

Amid rising environmental concerns, attempts have been made to produce glycolic acid (GA) using microbial processes with renewable carbon resources instead of using chemicals. The Dahms pathway for GA production uses xylose as a substrate and consists of relatively simple enzymatic steps. However, employing it leads to a decrease in cell growth and GA productivity. Systematically identifying and addressing metabolic bottlenecks in the Dahms pathway are essential for efficient glycolic acid (GA) production have not yet been performed. Through metabolic flux balance analysis, we found that insufficient aldehyde dehydrogenase (AldA) activity lowers GA production and negatively affects cell growth due to reduced energy production. Thus, we discovered a novel AldA isolated from Buttiauxella agrestis (BaAldA) demonstrated a 1.69-fold lower KM and a 1.49-fold higher turnover rate (kcat/KM) than AldA from Escherichia coli (EcAldA). GA production in E. coli harboring BaAldA was 1.59 times higher than in the original strain. Fed-batch fermentation of E. coli harboring BaAldA produced 22.70 g/L GA with a yield of 0.497 g/gxylose (98.2% of the theoretical maximum yield in the Dahms pathway), showing a higher final yield for GA than previously reported in E. coli. Our novel BaAldA enzyme shows great potential for the production of GA using microorganisms or enzymes. Furthermore, our approach to identifying metabolic bottlenecks using flux balance analysis could be utilized to enhance the microbial production of various desirable products in future studies. [ABSTRACT FROM AUTHOR]

In this work, MBi2O4‐P25 (M = Cu, Ni, Co, Zn) composites are successfully synthesized by a simple ball milling method by varying some parameters (rotation speed, rotation time, metal/TiO2 ratio) to optimize the preparation conditions. The noble metal‐free TiO2‐based photocatalysts are used to carry out the partial oxidation of glucose and glycerol with the simultaneous H2 production under simulated solar light irradiation. Starting from glucose, 2.6 mmol of H2 are obtained with a conversion of 34%, along with arabinose, formic acid and gluconic acid as main intermediates. By using glycerol, 3.2 mmol of H2 are produced, with 17% conversion and the production of dihydroxyacetone and glycolic acid. The composites exhibit higher activity than pure P25 and CuBi2O4 (CBO). The produced H2 amount is comparable to that reported in the literature by using Pt–TiO2 photocatalysts. This study offers a paradigm for the future design of bifunctional photocatalysts for simultaneous noble metal‐free H2 production and biomass valorization under environmentally friendly conditions with a possible scale up of the process. [ABSTRACT FROM AUTHOR]

The physical microtopography, in an effective and stable manner, can powerfully confer biomaterials with enhanced osteoconduction for the repair of critical‐sized bone defects. However, the realization of the osteoconductive microtopography within a 3D porous scaffold is still unmet. Herein, this work presents a stone‐cottage‐inspired printing strategy to build microsphere patterned scaffolds with a tunable microtopography for accelerated bone regeneration. The customized composite inks of poly (lactic‐co‐glycolic acid) microspheres as “Stone” and alginate hydrogels as “Mortar” endow the fibers of as‐printed scaffolds with a stable and tunable groove‐ridge microstructure. Owing to this microtopography, microsphere patterned scaffolds significantly promote cell recruitment, immune response, angiogenesis, and osteogenesis. Meanwhile, compared to 55 and 85 µm, 25 µm width of groove‐ridge microstructure displays the most osteoconduction for repair of critical bone defects. Mechanistically, while cells prefer to adhere to microstructure with a bigger width and higher modulus in the early phase, this microstructure should also act as a barrier for cell growth and its smaller width is more beneficial for cell communication and differentiation in the later phase. Overall, it provides a robust strategy to fabricate the osteoconductive microtopography within a 3D scaffold, broadening the manipulation of physical morphology in tissue engineering. [ABSTRACT FROM AUTHOR]

Creating interconnected macropores in calcium phosphate cement (CPC) is an effective strategy to promote its degradation and osteogenesis. However, little attention has been given to the osteogenic effect of the CPC scaffolds with pre-forming and in-situ forming interconnected macropores. Herein, two types of CPC scaffolds were prepared by infiltrating CPC pastes into 3D-printed polycaprolactone (PCL) and poly(lactic-co-glycolic acid) (PLGA) networks. Meanwhile, the sacrificial PCL network within CPC was dissolved to obtain the CPC scaffold with approximately 300 μm macropores, whereas the PLGA network was retained within the CPC to obtain the PLGA/CPC scaffold. The results indicated that the PLGA/CPC scaffold showed higher degradation rate and compressive strength compared to the CPC scaffold with pre-forming interconnected macropores. However, the proliferation rate and alkaline phosphatase activity of mouse bone mesenchymal stem cells cultured with the CPC scaffold were superior to those cultured with the PLGA/CPC scaffold. In addition, greater formation of new bone and material degradation in the CPC scaffold compared to the PLGA/CPC scaffold after implanted in the rabbit femoral defects. [ABSTRACT FROM AUTHOR]

Recently, cases of antifreeze poisoning in companion animals, particularly cats, have surged in the Republic of Korea. Ethylene glycol (EG), the toxic primary component of antifreeze, is metabolized into glycolic acid (GA), leading to severe metabolic acidosis, acute kidney injury, and death. Traditional detection methods, although effective, are often time-consuming owing to complex sample preparation. This study involved a novel analytical method utilizing GC-MS for EG and LC-MS/MS for GA detection, which streamlined the detection process by eliminating the need for derivatization. The method was validated for accuracy and reliability, enabling the rapid and precise identification of EG and GA in biological samples. This study also included the successful application of this method in a case where initial exposure to antifreeze was not apparent, which highlighted the effectiveness of this method in diagnosing poisoning even in cases where clinical history is unclear. The development of this rapid diagnostic approach addresses the urgent need for the efficient detection of antifreeze poisoning, improving animal welfare and supporting forensic investigations. [ABSTRACT FROM AUTHOR]

In this study, we developed an injectable DNA vaccine targeting the aopB gene of Aeromonas hydrophila, encapsulated within poly(lactic‐co‐glycolic acid) (PLGA) nanoparticles, for use in common carp. Juvenile common carp were divided into six groups with three replicates each. Groups A and B received intramuscular injections of the plasmid containing the target gene (pCDNA3.1‐aopB) with or without encapsulation, respectively. Groups C and D received the plasmid lacking the target gene via the same route. Group E received PLGA, while Group F (control) received phosphate‐buffered saline. Sampling occurred on days 0, 30, and 60, and hematological and immunological indices were compared among the groups. On day 60, all groups were challenged with Aeromonas hydrophila, and cumulative mortality rates were assessed. Our results indicated successful detection of the target gene in various tissues of vaccinated fish. Notably, vaccinated groups exhibited a significant decrease in cumulative mortality (p < 0.05). Immunological indices, such as serum antibody titer and nonspecific immune responses, significantly improved in vaccinated groups, particularly those receiving the DNA vaccine with PLGA encapsulation (p < 0.05). Overall, the DNA vaccine, especially when nanoencapsulated with PLGA, demonstrated efficacy and immunogenicity against A. Hydrophila in common carp, suggesting its potential as a vaccination strategy against this infection. Further research could optimize its effectiveness and applicability. [ABSTRACT FROM AUTHOR]

Biomass feedstock ethylene glycol (EG) can be anodically oxidized to the high‐value glycolic acid (GA), which is widely considered as one critical raw material of biodegradable plastics. Developing low‐cost electrocatalyst to economically produce GA with high selectivity still meeting challenges. Herein, a non‐precious Co‐Ni bimetal catalysts are developed for controllable electrooxidizing EG to GA (EGOR). Through regulating the generation of key intermediate (CH2OH‐CO*) on the low‐cost catalyst surface, a successive electrooxidation from EG to GA has been achieved with high selective (96.3%) and conversion rate (>85%) at current density of 150 mA cm−2, which is on par with the reported precious metal catalysts. Through coupling with hydrogen evolution reaction (EGOR‐HER), 2.759 mmol H2 and 7.48 mmol of GA are generated at 80 mA cm−2, which also can save 27% energy comparing with a water splitting system. The synergistic effect between Co and Ni in the bimetallic catalyst has been exploited: high‐valent CoOOH sites catalyzed the generation of CH2OH‐CO* and reduce the energy barrier during GA formation; Whereas, Ni sites can effectively facilitate the formation of CoOOH and improve the adsorption of EG. [ABSTRACT FROM AUTHOR]

Electroreduction of oxalic acid (OX) to glyoxylic acid (GO) is an extremely important and promising application in organic electrosynthesis. Pb cathodes, which exhibits good selectivity, need to be replace due to the severe deactivation and harmful to the environment. Herein, self‐doped titanium dioxide nanotube arrays (H‐TiO2NTs‐2) are synthesized as an alternative cathode for OX electroreduction to GO. Benefiting from two‐step anodization, the synthesized nanotube arrays are highly ordered with oriented openings. The ordered structure promotes the mass transfer of both OX and GO to ensure efficiently providing OX reactants for the diffusion‐controlled OX electroreduction and removal of GO products from the electrode to prevent the over‐reduction to glycolic acid. Additionally, the electroreduction treatment introduces more Ti3+ active sites and modulates the conduction band position of H‐TiO2NTs‐2, thereby enhancing the reduction driving force. Owing to the unique structural advantages, the Faraday efficiency of generating GO from OX reaches up to 81.3 % in an oxalic acid saturated electrolyte at 20 °C with a current density of 1500 A m−2. This designed H‐TiO2NTs‐2 holds broad application prospects in OX electroreduction. [ABSTRACT FROM AUTHOR]

Objectives: The study explores the potential of various deep eutectic solvents (DESs) to serve as drug delivery systems and pharmaceutical excipients. The research focuses on two primary objectives: evaluating the ability of the selected DES systems to enhance the solubility of two poorly water-soluble model drugs (IBU and MFA), and evaluating their physicochemical properties, including density, viscosity, flow behavior, surface tension, thermal stability, and water dilution effects, to determine their suitability for pharmaceutical applications. Methods: A range of DES systems containing pharmaceutically acceptable constituents was explored, encompassing organic acid-based, sugar- and sugar alcohol-based, and hydrophobic systems, as well as menthol (MNT)-based DES systems with common pharmaceutical excipients. MNT-based DESs exhibited the most significant solubility enhancements. Results: IBU solubility reached 379.69 mg/g in MNT: PEG 400 (1:1) and 356.3 mg/g in MNT:oleic acid (1:1), while MFA solubility peaked at 17.07 mg/g in MNT:Miglyol 812®N (1:1). In contrast, solubility in hydrophilic DES systems was significantly lower, with choline chloride: glycerol (1:2) and arginine: glycolic acid (1:8) showing the best results. While demonstrating lower solubility compared to the MNT-based systems, sugar-based DESs exhibited increased tunability via water and glycerol addition both in terms of solubility and physicochemical properties, such as viscosity and surface tension. Conclusions: Our study introduces novel DES systems, expanding the repertoire of pharmaceutically acceptable DES formulations and opening new avenues for the rational design of tailored solvent systems to overcome solubility challenges and enhance drug delivery. [ABSTRACT FROM AUTHOR]

In the study, a new strategy is presented to make PLGA (poly lactic‐co‐glycolic acid) and POEGMEMA (poly(oligo(ethylene glycol) methyl ether methacrylate)) based biodegradable and biocompatible tissue scaffold via a new physical cross‐linking method. The advantage of brushed structure of POEGMEMA polymer and the hydrophobic character of PLGA polymer is taken to make physically entangled network in aqueous media. The hydrophobic nature of PLGA allows to get scaffolds even at low ratio of PLGA (25%, w/w) when using POEGMEMA (yield: 86%). This strategy gives robust polymeric networks in aqueous media without using chemical reactions through high hydrophilic polymer content. Scaffolds with high POEGMEMA ratio (75%, w/w) show two times higher water uptake ratio (≈300%) and two times lower compression strength (19 kPa) compared to the ones with lower POEGMEMA content (50%, w/w). They also show desired degradation profiles in various aqueous solutions. While the scaffolds prepared with 25% and 50% PLGA are almost stable in first 20 days, they completely degrade in 40–50 days. Both scaffold formulations (25% PLGA‐75% POEGMEMA and 50% PLGA‐50% POEGMEMA) have similar proliferative properties for fibroblast cells. The scaffolds also do not show toxicity compared to control group according to live‐dead assay. [ABSTRACT FROM AUTHOR]

α‐ketoglutarate (AKG), a key component of the tricarboxylic acid cycle, has attracted attention for its antiaging properties. In the recent study, it is indicated that locally delivered cell‐permeable AKG significantly promotes osteogenic differentiation and mouse bone regeneration. However, the cytotoxicity and rapid hydrolysis of the metabolite limit its application. In this study, novel AKG‐based polymeric microparticles (PAKG MPs) are synthesized for sustained release. In vitro data suggest that the chemical components, hydrophilicity, and size of the MPs can significantly affect their cytotoxicity and pro‐osteogenic activity. Excitingly, these biodegradable PAKG MPs are highly phagocytosable for nonphagocytic pre‐osteoblasts MC3T3‐E1 and primary bone marrow mesenchymal stem cells, significantly promoting their osteoblastic differentiation. RNA‐Sequencing (RNA‐Seq) data suggest that PAKG MPs strongly activate Wnt/β‐catenin and PI3K–Akt pathways for osteogenic differentiation. Moreover, PAKG enables poly(L‐lactic acid) and poly(lactic‐co‐glycolic acid) MPs (PLGA MPs) for efficient phagocytosis. In this data, it is indicated that PLGA–PAKG‐MPs‐mediated intracellular drug delivery can significantly promote stronger osteoblastic differentiation compared to PLGA‐MPs‐delivered phenamil. Notably, PAKG MPs significantly improve large bone regeneration in a mouse cranial bone defect model. Thus, the novel PAKG‐based MPs show great promise to improve osteogenic differentiation and bone regeneration and enable efficient intracellular drug delivery for broad regenerative medicine. [ABSTRACT FROM AUTHOR]

Cancer is ranked among the top causes of mortality throughout the world. Conventional therapies are associated with toxicity and undesirable side effects, rendering them unsuitable for prolonged use. Additionally, there is a high occurrence of resistance to anticancer drugs and recurrence in certain circumstances. Hence, it is essential to discover potent anticancer drugs that exhibit specificity and minimal unwanted effects. Curcumin, a polyphenol derivative, is present in the turmeric plant (Curcuma longa L.) and has chemopreventive, anticancer, radio-, and chemo-sensitizing activities. Curcumin exerts its anti-tumor effects on cancer cells by modulating the disrupted cell cycle through p53-dependent, p53-independent, and cyclin-dependent mechanisms. This review provides a summary of the formulations of curcumin based on nanospheres, since there is increasing interest in its medicinal usage for treating malignancies and tumors. Nanospheres are composed of a dense polymeric matrix, and have a size ranging from 10 to 200 nm. Lactic acid polymers, glycolic acid polymers, or mixtures of them, together with poly (methyl methacrylate), are primarily used as matrices in nanospheres. Nanospheres are suitable for local, oral, and systemic delivery due to their minuscule particle size. The majority of nanospheres are created using polymers that are both biocompatible and biodegradable. Previous investigations have shown that the use of a nanosphere delivery method can enhance tumor targeting, therapeutic efficacy, and biocompatibility of different anticancer agents. Moreover, these nanospheres can be easily taken up by mammalian cells. This review discusses the many curcumin nanosphere formulations used in cancer treatment. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is considered one of the biggest threats to public health worldwide. Methicillin-resistant S. aureus is the causative agent of a number of infections and lung colonization in people suffering from cystic fibrosis. Moreover, a growing body of evidence links the microbiome to the development of cancer, as well as to the success of the treatment. In this view, the development of novel antibiotics is of critical importance, and SV7, a novel antibiotic active against MRSA at low concentrations, represents a promising candidate. However, the low aqueous solubility of SV7 hampers its therapeutic translation. In this study, SV7 was encapsulated in poly(lactic- co -glycolic acid) (PLGA) nanoparticles (NPs) to improve the solubility profile, to ensure sustained release and eventually support deposition in the airways. Furthermore, PLGA NPs were formulated as dry powder to extend their shelf-life and were shown to efficiently target intracellular infections. After identifying a formulation with suitable physico-chemical characteristics, SV7-loaded NPs were investigated in vitro in terms of inhibitory activity against MRSA, and their safety profile in lung epithelial cells. Subsequently, the activity against MRSA intracellular infections was investigated in a co-culture model of MRSA and macrophages. To test the translatability of our findings, SV7-loaded NPs were tested in vivo in a Galleria mellonella infection model. In conclusion, SV7-loaded NPs showed a safe profile and efficient inhibitory activity against MRSA at low concentrations. Furthermore, their activity against intracellular infections was confirmed, and was retained in vivo , rendering them a promising candidate for treatment of MRSA lung infections. [Display omitted] [ABSTRACT FROM AUTHOR]

Microbial production of glycolic acid (GA) from ethylene glycol is extensively used in a variety of industries because ethylene glycol is not only an inexpensive raw material but also the main component of industrial wastes. In this study, we produced GA from ethylene glycol using Escherichia coli overexpressing the endogenous 1,2-propanediol oxidoreductase (fucO) and lactaldehyde dehydrogenase (aldA) genes. To increase GA productivity, we screened a random mutant library generated using an error-prone polymerase chain reaction of fucO and obtained FucO mutants MF2-9 and MF6-9 with enhanced GA production in Lysogeny Broth medium containing 800 mM ethylene glycol. MF2-9 contained three amino acid substitutions (D23E, E222K, and G363S) and two synonymous mutations (coding DNA [c.] 93G > A and c.1131T > C) in fucO. MF6-9 contained one amino acid substitution (L377H) in FucO. An amino acid substitution (L377H) and a single synonymous mutation (c.1131T > C) in fucO contributed to the enhancement in GA production. Notably, cell lysates from E. coli harboring a synonymous mutation (c.1131T > C) or amino acid substitution (L377H) in fucO showed that only AldA activity was 1.3-fold higher than that of the cell lysate from E. coli harboring the wild-type fucO. We confirmed that c.1131T > C and L377H mutations increased aldA expression in E. coli. Analysis of mRNA levels and simulation of mRNA stabilization indicated that base substitutions at positions c.1130T, which corresponds to L377H amino acid substitution, and c.1131T increased aldA expression due to partial destabilization of the mRNA. These findings will be useful for the large-scale microbial production of GA from industrial waste. [ABSTRACT FROM AUTHOR]

Background/Objectives: Neutrophils are emerging as promising candidates for cell-based nanodrug delivery to tumors due to their unique biological properties. This study aims to investigate the mechanisms of nanoparticle internalization by neutrophils, specifically focusing on liposomes, poly(lactic-co-glycolic acid) (PLGA), and magnetite nanoparticles. Understanding these mechanisms could enhance the efficiency of neutrophil-based nanodrug delivery for cancer treatment. Methods: Neutrophils were isolated from the peripheral blood of mice bearing 4T1 mammary adenocarcinoma. Confocal microscopy, transmission electron microscopy, and flow cytometry were employed to evaluate the uptake of liposomes, PLGA, and magnetite nanoparticles by neutrophils. The effects of cultivation conditions, such as the presence or absence of plasma in the growth medium, were also examined. Additionally, the roles of immunoglobulins (IgG/IgM) and cell surface receptors (Fc and scavenger receptors) in nanoparticle internalization were explored. Results: All types of nanoparticles were successfully internalized by neutrophils, though the mechanisms of uptake varied. Plasma presence in the medium significantly influenced nanoparticle binding, particularly for PLGA nanoparticles. Internalization of PLGA nanoparticles was found to depend on the presence of IgG/IgM in the medium and Fc receptors on neutrophil surfaces, while scavenger receptors were not involved. Conclusions: Understanding the distinct endocytosis pathways for different nanoparticles can improve the efficacy of neutrophil loading with nanodrugs, potentially advancing the development of neutrophil-based cancer therapies. The findings underscore the importance of the extracellular environment in modulating nanoparticle uptake. [ABSTRACT FROM AUTHOR]

Biomaterial-based implantable scaffolds capable of promoting physical and functional reconnection of injured spinal cord and nerves represent the latest frontier in neural tissue engineering. Here, we report the fabrication and characterization of self-standing, biocompatible and bioresorbable substrates endowed with both controlled nanotopography and electroactivity, intended for the design of transient implantable scaffolds for neural tissue engineering. In particular, we obtain conductive and nano-modulated poly(D,L-lactic acid) (PLA) and poly(lactic- co -glycolic acid) free-standing films by simply iterating a replica moulding process and coating the polymer with a thin layer of poly(3,4-ethylendioxythiophene) polystyrene sulfonate. The capability of the substrates to retain both surface patterning and electrical properties when exposed to a liquid environment has been evaluated by atomic force microscopy, electrochemical impedance spectroscopy and thermal characterizations. In particular, we show that PLA-based films maintain their surface nano-modulation for up to three weeks of exposure to a liquid environment, a time sufficient for promoting axonal anisotropic sprouting and growth during neuronal cell differentiation. In conclusion, the developed substrates represent a novel and easily-tunable platform to design bioresorbable implantable devices featuring both topographic and electrical cues. [ABSTRACT FROM AUTHOR]

Ahmad Abdulrahman Almeman Department of Pharmacology, College of Medicine, Qassim University, Burydah, Qassim, Saudi ArabiaCorrespondence: Ahmad Abdulrahman Almeman, Department of Pharmacology, College of Medicine, P.O.Box 6688, Burydah, Al-mulaida, Qassim, Saudi Arabia, Email meman@qu.edu.sa; ahmadalmeman@gmail.comAbstract: The global market for alpha-hydroxy acids (AHAs) is undergoing significant expansion, propelled by increasing demand for skincare products that address aging and environmental damage. This review focuses on the dermatological applications of AHAs, particularly in cosmetic formulations like chemical peels. We have identified that AHAs, such as glycolic and lactic acids, enhance skin rejuvenation by promoting apoptosis in skin cells, boosting collagen and elastin synthesis, and improving skin texture and luminosity. Our comprehensive analysis reveals a nuanced understanding of AHAs’ effectiveness across various skin types and conditions, demonstrating their broad utility in treating conditions like acne, hyperpigmentation, and photoaging. However, the optimal concentrations for therapeutic efficacy with minimal side effects are yet to be precisely defined, necessitating further research. Regulatory compliance is underscored as essential for the safe application of AHAs in cosmetics, with international guidelines recommending specific concentrations and pH levels to minimize potential skin irritation. In Conclusion, the review highlights the effectiveness of AHAs in cosmetic dermatology, emphasizing the necessity for continued research and rigorous regulatory adherence to maximize their safe and beneficial application worldwide.Keywords: chemical peels, alpha hydroxy acids, practice guidelines, glycolic acid

The electrocatalytic valorization of polyethylene terephthalate-derived ethylene glycol to valuable glycolic acid offers considerable economic and environmental benefits. However, conventional methods face scalability issues due to rapid activity decay of noble metal electrocatalysts. We demonstrate that a dynamic potential cycling approach, which alternates the electrode potential between oxidizing and reducing values, significantly mitigates surface deactivation of noble metals during electrochemical oxidation of ethylene glycol. This method enhances catalyst activity by 20 times compared to a constant-potential approach, maintaining this performance for up to 60 h with minimal deactivation. In situ Raman and X-ray absorption spectroscopy show that this effectiveness results from efficient removal of surface oxide during the reaction. The strategy is applicable to polyethylene terephthalate hydrolysates and various noble metals, such as palladium, gold, and platinum, with palladium showing a high conversion rate in recent studies. Our approach offers an efficient and durable method for electrochemical upcycling of biomass-derived compounds. The value-added electrochemical conversion of ethylene glycol using noble metal catalysts is often hindered by rapid deactivation. In this study, the authors present a dynamic potential cycling method that effectively suppresses oxide-induced deactivation and enhances both catalyst activity and stability. [ABSTRACT FROM AUTHOR]

AbstractUrsolic acid (UA) is an abundant natural product and has shown great promise for treating diseases related to the appearance of new blood vessels. However, its clinical use is limited due to its low solubility in aqueous media, resulting in reduced bioavailability. The present study aimed to synthetize poly(lactic-co-glycolic acid) nanoparticles loaded with UA by nanoprecipitation method and to evaluate the toxicity and anti-angiogenic activity using the in vivo chorioallantoic model. The nanoparticles were obtained in the size range that varied from 103.0 to 169.3 nm, they presented a uniform distribution (polydispersity index <0.2), and a negatively charged surface, with an encapsulation efficiency close to 50%. The release profile of the developed nanoformulation showed an initial burst in the first 2 h and demonstrated no acute toxicity (irritation index <0.9). Moreover, the chorioallantoic assay showed a significant reduction in both geometrical and topological parameters compared to saline control (p < .05). In conclusion, the study revealed a quick and simple way to obtain poly(lactic-co-glycolic) acid nanoparticles, a drug delivery system to UA, which showed potential antiangiogenic action and can be used to treat diseases involving neovascularisation. [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Methods Results Conclusion The lipid‐lowering simvastatin (SIM) has been shown to be an effective inhibitor of keloid proliferation. However, due to its low water solubility and short half‐life, simvastatin aggregates to the liver and does not reach the skin lesions after oral administration, which restricts its widespread clinical use. The development of nanomedicine provides the possibility for us to break through this bottleneck problem clinically. The objective of this study was to investigate the feasibility of using complex nanocontrolled delivery system (CNDS), simvastatin‐loaded polyethylene glycol‐poly lactic‐co‐glycolic acid (PEG‐PLGA), in the treatment of keloids.In the in vitro study, the release of simvastatin in fibroblasts by CNDS@Simvastatin and its effect on inhibition of the proliferation of fibroblasts, Col Ι, and CTGF by the slow release of simvastatin were assessed. The efficacy of CNDS@Simvastatin in improving keloids and the biocompatibility and safety of CNDS@Simvastatin were examined in vivo by establishing a murine ear keloid model.CNDS@Simvastatin showed sustained and uniform inhibition of the proliferation of fibroblasts, Col Ι, and CTGF via the gradual release of simvastatin over 72 h. It was efficient in the treatment of the murine ear keloid with no observable toxic side effects on various organs.Simvastatin‐loaded copolymer acid‐sensitive nanocarriers, CNDS@Simvastatin nanospheres, were successfully developed in this study, and these were characterized by favorable physicochemical properties and biocompatibility. [ABSTRACT FROM AUTHOR]

This study investigated the effects of dietary resveratrol (RES) and β-Hydroxy-β-methyl butyric acid (HMB) on immune, oxidative, and morphological changes in the livers of Tibetan sheep using transcriptomics and metabolomics. One hundred and twenty male Tibetan lambs of a similar initial weight (15.5 ± 0.14 kg) were randomly divided into four groups with thirty lambs per treatment: (1) H group (basal diet without RES or HMB); (2) H-RES group (1.5 g/day of RES); (3) H-HMB group (1250 mg/day of HMB); (4) H-RES-HMB group (1.5 g/day of RES and 1250 mg/day of HMB). The experiment was conducted for 100 days, including a pre-test period of 10 days and a formal period of 90 days. The results showed significantly increased concentrations of glutathione peroxidase, superoxide dismutase, and IgM in the H-RES-HMB group (p < 0.05), while the malondialdehyde levels were significantly decreased (p < 0.05). The glycolytic indices including creatinine kinase (CK), malate dehydrogenase (MDH), and succinate dehydrogenase (SDH) were significantly increased in the H-RES-HMB group compared with the others (p < 0.05). A histological analysis showed that the hepatic plate tissue in the H-RES-HMB group appeared normal with multiple cells. The transcriptomic analysis showed that the expression of genes associated with the calcium signaling pathway (MYLK2, CYSLTR2, ADCY1, HRH1, ATP2B2, NOS2, HRC, ITPR1, and CAMK2B) and the NF-κB signaling pathway (BCL2 and CARD14) in the H-RES-HMB group were upregulated. The key differential metabolites (d-pyroglutamic acid, DL-serine, DL-threonine, fumarate, and glyceric acid) were enriched in the pathways associated with D-amino acid metabolism, the citrate cycle (TCA cycle), and carbon metabolism. The combined transcriptomic and non-targeted metabolomic analyses showed the co-enrichment of differential genes (NOS2 and GLUD1) and metabolites (fumarate) in arginine biosynthesis-regulated glycolytic activity, whereas the differential genes (ME1, SCD5, FABP2, RXRG, and CPT1B) and metabolites (Leukotriene b4) co-enriched in the PPAR signaling pathway affected the immune response by regulating the PI3K/AKT and cGMP/PKG signaling. In conclusion, the dietary RES and HMB affected the hepatic antioxidant capacity, immune response, and glycolytic activity through modulating the transcriptome (BCL2, CAMK2B, ITPR1, and IL1R1) and metabolome (DL-serine, DL-threonine, fumaric acid, and glycolic acid). [ABSTRACT FROM AUTHOR]

The presented experiments aimed to synthesize multi-targeted polymeric antibody-microparticles for the treatment of CD19+/CD20+ cancers. It is hypothesized that (1) targeting multiple tumor specific antigen (TSA) improves drug delivery by increasing binding in patients with low TSA expression and (2) polymeric drug encapsulation enables controlled drug release. Protein-bound paclitaxel was successfully entrapped in biotin-avidin-antibody coated poly(lactic-co-glycolic acid) (PLGA). Targeting layers and antibody attachment did not negatively impacted drug release in vitro. Cell viability was reduced after administration in target cell lines. The presented technology forms a foundation for further investigation of multi-targeted polymeric antibody-microparticle conjugates capable of optimizing cancer treatment. [ABSTRACT FROM AUTHOR]

A bifunctional thiourea‐amine‐based organocatalyst (Takemoto's catalyst), employing a metal‐free approach, is presented for the regioselective ring‐opening polymerization (ROP) of optically active (D and L) methyl glycolide (MG). In this study, a chiral version of Takemoto's catalyst efficiently promotes the ROP of MG at room temperature, yielding poly(lactic‐co‐glycolic acids) (PLGAs) with predicted molecular weights and narrow polydispersity indices (PDI≤1.2). These PLGAs exhibit highly alternating structures without transesterification, as confirmed by 1H NMR, SEC, and MALDI‐TOF analyses. Additionally, various macromolecular architectures, including linear and star‐shaped PLGAs, were successfully synthesized using the corresponding multi‐functional alcohol initiators while maintaining the same alternating structures and regioselectivity with PLGA obtained from benzyl alcohol as initiator. Computational studies were conducted to elucidate the mechanism of alternating PLGA formation, revealing two key transition states (TSs): TS‐1, which implicates the nucleophilic attack of the hydroxyl group of the initiator or propagating chain on the carbonyl carbon of MG, and TS‐2, which involves the subsequent ring‐opening of the cyclic ester. The results indicate that ring‐opening occurs at both the glycolyl and lactyl sites, with a preference for the glycolyl site, as supported by experimental results. The resulting atactic PLGAs are amorphous, rendering them suitable for drug delivery applications. [ABSTRACT FROM AUTHOR]

[Objectives] This paper aimed to explore the quality traits of ‘Chardonnay' and ‘Viognier', two winemaking white grape varieties in Rushan area, in order to provide certain theoretical basis for the utilization, introduction and promotion of white winemaking varieties. [Methods] ‘Chardonnay' and ‘Viognier' were used as the test materials, and the quality traits of fruits were analyzed in the veraison stage and maturity stage, and the transcriptome sequencing was performed on the fruits in the veraison stage and maturity stage. [Results]At the maturity stage, ‘Viognier' was higher in grain weight, transverse diameter, longitudinal diameter, total phenolic content, soluble sugar content and total soluble solids (TSS) content, and ‘Chardonnay' was higher in total organic acid content. From the veraison stage to maturity stage, the soluble sugar, TSS and total phenol contents in ‘Viognier' changed more rapidly than ‘Chardonnay'. Among the sugar fractions, fructose and glucose content changed more rapidly, while other traits showed similar changes. The results of transcriptome analysis showed that the number of differentially expressed genes (DEG) was higher in ‘Viognier' than in ‘Chardonnay' from the veraison stage to maturity stage. Both differentially expressed genes were most distributed on chromosome 18 and least distributed on chromosome 15. In addition, the metabolic pathways of genes related to glycolate metabolism were screened by GO functional analysis and KEGG metabolic pathway analysis of differentially expressed genes. [Conclusions] There were differences in fruit quality between two white grape varieties in different periods, mainly in terms of total organic acid content, soluble sugar content, TSS content, total phenol contents and transverse and longitudinal diameter of the fruit. From the veraison stage to maturity stage, the development of fruit traits in ‘Viognier' was faster than that of ‘Chardonnay'. The differences in the expression levels of related genes in the glycolic acid anabolic pathway between two varieties might be the reason for the differences in fruit quality traits between two white grape varieties. [ABSTRACT FROM AUTHOR]

Docetaxel (DTX) and betulinic acid (BA) co-encapsulated poly-lactic co-glycolic acid (PLGA) nanoparticles (NPs) were developed for enhanced lung cancer activity in vitro. Poly (lactic-co-glycolic acid) (PLGA) was used as an encapsulating polymer along with polyvinyl alcohol (PVA) as a stabilizing base to formulate NPs with the double-emulsion solvent evaporation method to study the size and potential, along with the surface morphology and in vitro release, of NPs. Cell culture studies like in vitro cellular uptake, apoptosis, and cell cycle arrest were performed in an in vitro cytotoxicity study to access the NP's effect in the A549 human lung cancer cell line. The emulsification solvent evaporation technique produced smooth spherical nanoparticles of small sizes with a relatively narrow size distribution (147.2 ± 12.29 nm). On the A549 cell line, the formulation showed higher cytotoxicity (6.43 ± 0.11, 4.21 ± 0.32, and 1.17 ± 0.23 µmol for 24, 48, and 72 h, respectively) compared to the free drug due to an increase in vitro cellular uptake. Apoptosis and cell cycle analysis also confirmed the effectiveness of the prepared NPs. In vitro studies have proven the tumor-targeting potential of DTX-BA-NPs in A549 cell lines and could be future medication for lung cancer treatment. [ABSTRACT FROM AUTHOR]

The distribution equilibria of Am(III) and Cm(III) between the organic phase of bis(2,4,4-trimethylpentyl)dithiophosphonic acid (purified Cyanex301, HA) in xylene and aqueous solutions containing varying concentrations of formic acid or glycolic acid have been investigated aiming at the separation of the two actinides from each other after the groups separation of Am(III)/Cm(III) from Ln(III) ions. The apparent extraction constants for Am(III) and Cm(III) in the Cyanex301-xylene system are determined to be −8.84 and −9.37, respectively, at 0.01 M ionic strength. The specific ion interaction method (SIT) is used to obtain the stability constants of Am(III) and Cm(III) with nitrate and glycolate for calculating the speciation of the ions in extraction at 25°C and I = 0.01 M. The separation of Cm(III) from Am(III) loaded in 0.5 M HA in xylene can be considerably improved by emplying 0.01 to 0.05 M formic acid or glycolic acid as selective stripping reagents favoring complexation with Cm(III). Specifically, with 0.01 M formic acid or glycolic acid in the aqueous phase, the separation factor (SF) for Am(III) over Cm(III) is improved from 3.61 to 5.87 and 5.26, respectively. Hence, both separations of An(III) from Ln(III) and then Am(III) from Cm(III) are achieved by a selective extraction process at first and then a selective stripping process in one simple efficient system using purified Cyanex301 as extractant in organic phase and carboxylic acids as stripping chelates in aqueous. [ABSTRACT FROM AUTHOR]

Toxicological analyses often necessitate the identification of compounds belonging to diverse functional groups. For GC–MS analyses, derivatization of compounds belonging to different functional groups can pose a challenge and requires the development of comprehensive methods of analysis. One example could be ethylene glycol, whose widespread use is related to possible unintentional or suicidal intoxications. This fact clearly indicates the need to develop sensitive methods for the determination of ethylene glycol and its metabolites in biological material, as only such complex analysis allows for proper toxicological expertise. A simultaneous GC–QqQ–MS/MS method for the determination of ethylene glycol together with its metabolites, glyoxal and glycolic acid, as well as the detection of glyoxylic acid and oxalic acid, was developed and fully validated. A novel approach for simultaneous derivatization of substances from different groups (alcohols, aldehydes, and carboxylic acids) was established. Sample preparation included the addition of three internal standards (BHB-d4, ethylene glycol-d4 and methylglyoxal), precipitation with acetonitrile and subsequent derivatization with N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide (MTBSTFA), as well as pentafluorophenylhydrazine (PFPH). Detection was carried out with the use of triple quadrupole mass spectrometer. The ionization method was electron impact, and quantitative analysis was carried out in multiple reaction monitoring mode. The lower limit of quantification was 1 μg/mL, 0.1 μg/mL, and 500 μg/mL for ethylene glycol, glyoxal, and glycolic acid, respectively. The presented method was applied in three authentic postmortem cases of ethylene glycol intoxication. [ABSTRACT FROM AUTHOR]

The use of biodegradable materials combined with natural metabolites in wound dressings has received much attention. Flavonoids (FLs) from green cocoons, as metabolites, have antibacterial, antioxidant, anti-inflammatory, and other pharmacological effects. In this study, composite membranes of FL-loaded polylactic glycolic acid (PLGA)/silk fibroin (SF) were prepared by an electrospinning method. The prepared membranes, including SF, exhibited a good slow-release effect and cytocompatibility. An in vitro evaluation of the FL-loaded PLGA/SF membranes demonstrated good antioxidant, antibacterial, and anti-inflammatory properties. Animal experiments showed that the wound healing rate of PLGA/SF-2.5FL membranes within 15 days was 97.3%, and that of the control group was 72.5%. The PLGA/SF-2.5FL membranes shortened the inflammatory period of a full-layer wound model and promoted skin regeneration and wound healing by downregulating expression of the pro-inflammatory cytokines IL-1β and TNF-α and promoting expression of the growth factors VEGF, TGF-β, and EGF. In summary, the PLGA/SF-2.5FL composite nanofibre membrane with anti-inflammatory properties is an ideal wound dressing to promote acute wound healing. [ABSTRACT FROM AUTHOR]

The treatment landscape for opioid use disorder (OUD) faces challenges stemming from the limited efficacy of existing medications, poor adherence to prescribed regimens, and a heightened risk of fatal overdose post-treatment cessation. Therefore, there is a pressing need for innovative therapeutic strategies that enhance the effectiveness of interventions and the overall well-being of individuals with OUD. This study explored the therapeutic potential of nor-Levo-α-acetylmethadol (nor-LAAM) to treat OUD. We developed sustained release nor-LAAM-loaded poly (lactic- co -glycolic acid) (PLGA) microparticles (MP) using a hydrophobic ion pairing (HIP) approach. The nor-LAAM-MP prepared using HIP with pamoic acid had high drug loading and exhibited minimal initial burst release and sustained release. The nor-LAAM-MP was further optimized for desirable particle size, drug loading, and release kinetics. The lead nor-LAAM-MP (F4) had a relatively high drug loading (11 wt%) and an average diameter (19 μm) and maintained a sustained drug release for 4 weeks. A single subcutaneous injection of nor-LAAM-MP (F4) provided detectable nor-LAAM levels in rabbit plasma for at least 15 days. We further evaluated the therapeutic efficacy of nor-LAAM-MP (F4) in a well-established fentanyl-addiction rat model, and revealed a marked reduction in fentanyl choice and withdrawal symptoms in fentanyl-dependent rats. These findings provide insights into further developing long-acting nor-LAAM-MP for treating OUD. It has the potential to offer a new effective medication to the existing sparse armamentarium of products available to treat OUD. [Display omitted] [ABSTRACT FROM AUTHOR]

The purpose of the present study was to create resorbable nanoparticles (NPs) using poly(lactic-co-glycolic acid) (PLGA) to develop novel antibacterial therapeutics for the treatment of chronic wound infections that are susceptible to recurrent infections. By first performing a release study, it was possible to predict the behavior of the different PLGA NP formulations and assess the efficacy of the nanocomposite drug delivery system. These PLGA NP formulations consisted of varying ratios of PLGA without polyvinyl alcohol (PVA) and PLGA with PVA (PLGA-PVA) (i.e. 25:75[PLGA25], 50:50[PLGA50], and 75:25[PLGA75]). Then, different antibiotics (i.e. ciprofloxacin and gentamicin) were incorporated into the PLGA NP formulations to test the antibacterial efficacy of these antimicrobial NPs against different pathogens (i.e. methicillin-resistant Staphylococcus aureus USA300 [MRSA], Pseudomonas aeruginosa FRD1, and Acinetobacter baumannii BAA1605). Of particular interest was testing against the MRSA strain USA300 and the P. aeruginosa strain FRD1. This was possible by measuring the zone of inhibition. A 3-day period was used to monitor the antibacterial efficacy of the different PLGA NP formulations (i.e. PLGA25, PLGA50, and a 1:1 combination of PLGA25:PLGA50) against A. baumannii BAA1605 , MRSA, and P aeruginosa FRD1. Throughout the study, A. baumannii was a negative control and was resistant to all the PLGA NP formulations loaded with ciprofloxacin and gentamicin. At the end of the 3-day period, the PLGA and PLGA50 ciprofloxacin-loaded formulations produced zones of inhibition of 27 mm and 23 mm, respectively, against P. aeruginosa FRD1. This indicated that P. aeruginosa FRD1 was susceptible to both formulations. The mixed formulations with equal parts PLGA25:PLGA50 loaded with ciprofloxacin produced a zone of inhibition (i.e. 25 mm). This again indicated that P. aeruginosa FRD1 was susceptible to ciprofloxacin. The formulations tested against MRSA showed that only gentamicin-loaded formulations produced intermediate results, and that ciprofloxacin-loaded formulations were ineffective. The PLGA25 and the PLGA50 NP formulations loaded with gentamicin both produced zones of inhibition of 13 mm. This indicated that MRSA was intermediate to both the formulations. The PLGA25:PLGA50 loaded with gentamicin produced a zone of inhibition of 14 mm, which again showed that MRSA was intermediate to this formulation. Overall, these PLGA NP formulations showed the sustained antibacterial potential of a burst release, followed by a sustained release of antibiotics from antibiotics loaded PLGA NPs in a controlled manner. In the future, this can help prevent the emergence of recurrent infections in the treatment of chronic wounds and reduce the number of medical dressing changes. [ABSTRACT FROM AUTHOR]

In recent studies we have reported on the near-UV light-induced degradation of iron complexes of various pharmaceutical excipients, such as Fe(III)-citrate and Fe(III)-amino acid complexes. Mechanistic studies revealed a common photo-degradation pattern, i.e. the formation of carbon dioxide radical anion, a potent reducing agent, via an alkoxyl/amino radical intermediate generated by light-induced ligand-to-metal charge transfer (LMCT) involving α-hydroxycarboxylates or amino acids. Herein, we confirm the proposed general photo-degradation pathways through the study of the iron complexes of other α-hydroxycarboxylates that may be present in protein formulations, such as lactate and glycolate. The results indicate that lactate generates even higher yields of •CO 2 − as compared to citrate, suggesting a significant potential of lactate for the promotion of photo-degradation in pharmaceutical formulations. [Display omitted] [ABSTRACT FROM AUTHOR]

Gluconic acid and sorbitol are among the value-added chemicals that can be derived from biomass. Nowadays, these compounds are typically produced through biotechnological processes, but electrochemical methods offer numerous advantages over alternative approaches. While studies have extensively explored metals like copper, palladium, gold, and platinum, nickel has received relatively limited attention in this context. Notably, nickel exhibits electrochemical activity suitable for organic electrosynthesis. This work has been achieved with 5-h long-term electrolysis, glucose as a reactant, utilizing modified nickel electrodes in a KOH solution. While these studies achieved substantial conversion rates, the selectivities and Faraday efficiencies toward gluconic acid and sorbitol remained comparatively low. The long-term electrolysis of glucose using modified nickel electrodes resulted in the identification of various side products. These include formic acid, oxalic acid, glycolic acid, tartronic acid, glyceric acid, and arabinose. [ABSTRACT FROM AUTHOR]

Sulfur-containing organic compounds (SOCs) and nitrogen-containing organic compounds (NOCs) play critical roles in regulating the physical and chemical properties of organic aerosols (OA), while the understanding of them remains limited. Here, the high-resolution real-time measurements of submicron aerosols were conducted in urban Beijing, mainly to investigate wet scavenging effects on the potential formation and evolution mechanism of OA, especially SOCs and NOCs. OA composition transitioned from being primarily SOCs before wet processes to NOCs after wet processes. Further molecular fragments identification suggested SOCs mainly comprised glycolic acid sulfate formed by aqueous-phase processing during the entire observation, and aromatic- and monoterpene-derived SOCs formed by photochemical processing before snowfall. NOCs species were diverse and dominated by highly oxidized amides and amino acids mainly produced by photochemical processing. This study provided an in-depth insight into the potential formation and evolution pathways of SOCs and NOCs in OA in the urban atmosphere. [ABSTRACT FROM AUTHOR]

Objective: Prototype cosmetic formulations containing short-chain acids and alcohols intended to be applied in the proximity of the eyes are sometimes evaluated for ocular irritation potential using the validated Bovine Corneal Opacity and Permeability Assay (OECD TG 437). We evaluated the eye irritation potential of nine experimental cosmetic formulations designed and prepared by Avon Global Reserach and Development to differ only in the concentrations of Ethanol, Glycolic Acid and Salicylic Acid. Methods: We analysed the data generated using the BCOP assay. The opacity and permeability values obtained following the exposure of bovine corneas to experimental cosmetic formulations were combined into a single In Vitro Irritancy Score used to rank eye irritation potential. Histopathological examination of treated corneas was used to provide additional information about the depth and degree of the injury and to support the prediction of eye irritation potential of each experimental cosmetic formulation. Results: The In Vitro Irritancy Scores and histopathological analysis showed that experimental formulations containing only Ethanol, Glycolic Acid, or Salicylic Acid alone had, at most, a mild ocular irritation potential. The experimental formulations containing both Ethanol and Glycolic Acid had a mild ocular irritation potential, while the experimental formulations containing both Ethanol and Salicylic Acid had a moderate ocular irritation potential. Severe ocular irritation potential was induced by an experimental formulation containing a combination of Glycolic Acid and Salicylic Acid and it was further accentuated by the addition of Ethanol to the formulation. Our data indicate a possible synergistic effect on eye irritation potential of Ethanol, Glycolic Acid and Salicylic Acid in at least some experimental cosmetic formulations. Further, our results provide insight on an apparent concentration-dependent ocular irritation potential effect of combinations of Glycolic Acid, Salicylic Acid and Ethanol in at least one experimental cosmetic formulation. Conclusions: The results presented herein emphasise the need to consider in vitro testing of prototype cosmetic formulations containing combinations of Ethanol, Glycolic Acid and Salicylic Acid rather than relying on any predicted additive effect on ocular irritation based solely on previously generated results of similar formulations containing Ethanol, Glycolic Acid or Salicylic Acid alone. Further work is required to understand the significance of these observations and to elucidate the mechanisms responsible for the apparent synergistic effects of Glycolic Acid, Salicylic Acid and Ethanol and eye irritation potential suggested by our results. [ABSTRACT FROM AUTHOR]

Background: Tea polyphenols (TPs), prominent constituents of green tea, possess remarkable antioxidant and anti-inflammatory properties. However, their therapeutic potential is limited due to low absorption and poor bioavailability. To address this limitation and enhance their efficacy, we developed a biomimetic nanoplatform by coating platelet membrane (PM) onto poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) to create targeted delivery vehicles for TPs (PM@TP/NPs) to the inflamed tissues in asthma. Methods: After synthesizing and characterizing PM@TP/NPs, we assessed their biocompatibility and biosafety through cell viability assays, hemolysis tests, and inflammation analysis in vivo and in vitro. The therapeutic effect of PM@TP/NPs on asthma was then evaluated using a mouse model of HDM-induced asthma. Additionally, PM@TP/NPs-mediated reactive oxygen species (ROS) scavenging capacity, as well as the activation of signaling pathways, were analyzed in HBE cells and asthmatic mice via flow cytometry, RT-qPCR, and western blotting. Results: Compared with free TPs, PM@TP/NPs demonstrated excellent biocompatibility and safety profiles in both in vitro and in vivo, as well as enhanced retention in inflamed lungs. In HDM-induced mouse asthma model, inhaled PM@TP/NPs largely attenuated lung inflammation and reduced the secretion of type 2 pro-inflammatory cytokines in the lungs compared to free TPs. The therapeutic effects of PM@TP/NPs on asthma might be associated with an enhanced ROS scavenging capacity, increased activation of the Nrf2/HO-1 pathway, and decreased activation of the CCL2/MAPK and TLR4/NF-κB pathway in the lungs. Conclusions: Our findings demonstrate that inhalation of PM@TP/NPs largely attenuated lung inflammation in HDM-induced asthmatic mice. These results suggest that PM@TP/NPs might be a novel therapeutic strategy for asthma. [ABSTRACT FROM AUTHOR]

We previously reported that a pathogenic abnormality in the barrier and water-holding functions of the stratum corneum (SC) in the skin of patients with atopic dermatitis (AD) is mainly attributable to significantly decreased levels of total ceramides in the SC. That decrease is mediated by the abnormal expression of a novel ceramide-reducing enzyme, sphingomyelin/glucosylceramide deacylase (SGDase), which is the β-subunit (ASAH1b) of acid ceramidase. In this study, we determined whether mice overexpressing ASAH1b in their epidermis develop AD-like skin symptoms. We generated transgenic (TG) mice overexpressing ASAH1b, regulated by the involucrin promoter, to localize its expression in the upper epidermis. After hair removal using a depilatory cream containing glycolic acid, the TG mice without any visible skin inflammation at 8 weeks of age had increased levels of ASAH1b and decreased levels of SC ceramide, with disrupted barrier functions measured by trans-epidermal water loss compared to the wild-type (WT) mice. Interestingly, enzymatic assays revealed that SGDase activity was not detectable in the skin of the TG mice compared to WT mice. Immunological staining revealed that there was an increased expression level of IL-33 in the epidermis and an accumulation of macrophages in the dermis of TG mice compared to WT mice, which are phenotypic characteristics of AD, that were exacerbated by tape-stripping of the skin. In the skin of the TG mice, the mRNA levels of IL-5, CCL11, IL-22, CXCL10, and IFNγ were significantly upregulated compared to the WT mice, and tape-stripping significantly increased the mRNA levels of IL-4, IL-33, CXCL1, CXCL12, TLR9, and CD163 compared to WT mice. These findings strongly indicate that the skin of the depilatory cream-treated TG mice exists in an atopic dry skin condition that is highly sensitive to various environmental stimuli. The sum of our results suggests that ASAH1b itself, even in the absence of its enzymatic activity, is a major etiologic factor for atopic dry skin symptoms via an unknown mechanism. [ABSTRACT FROM AUTHOR]