Microorganisms produce diverse polymers for various purposes such as storing genetic information, energy, and reducing power, and serving as structural materials and scaffolds. Among these polymers, ...polyhydroxyalkanoates (PHAs) are microbial polyesters synthesized and accumulated intracellularly as a storage material of carbon, energy, and reducing power under unfavorable growth conditions in the presence of excess carbon source. PHAs have attracted considerable attention for their wide range of applications in industrial and medical fields. Since the first discovery of PHA accumulating bacteria about 100 years ago, remarkable advances have been made in the understanding of PHA biosynthesis and metabolic engineering of microorganisms toward developing efficient PHA producers. Recently, nonnatural polyesters have also been synthesized by metabolically engineered microorganisms, which opened a new avenue toward sustainable production of more diverse plastics. Herein, the current state of PHAs and nonnatural polyesters is reviewed, covering mechanisms of microbial polyester biosynthesis, metabolic pathways, and enzymes involved in biosynthesis of short‐chain‐length PHAs, medium‐chain‐length PHAs, and nonnatural polyesters, especially 2‐hydroxyacid‐containing polyesters, metabolic engineering strategies to produce novel polymers and enhance production capabilities and fermentation, and downstream processing strategies for cost‐effective production of these microbial polyesters. In addition, the applications of PHAs and prospects are discussed.
Polyhydroxyalkanoates (PHAs) are biodegradable and bio‐based polymers that can substitute petroleum‐based plastics currently in use. A comprehensive overview of the mechanisms and metabolism of PHA biosynthesis, and strategies for strain development, fermentation, and downstream processing toward the cost‐effective production of natural and nonnatural polyesters having diverse material properties is provided. Additionally, applications of PHAs and future prospects are discussed.
Polyhydroxyalkanoates (PHAs) are natural polyesters synthesized by numerous microorganisms as energy and reducing power storage materials, and have attracted much attention as substitutes for ...petroleum‐based plastics. Here, we report the first crystal structure of Ralstonia eutropha PHA synthase at 1.8 Å resolution and structure‐based mechanisms for PHA polymerization. RePhaC1 contains two distinct domains, the N‐terminal (RePhaC1ND) and C‐terminal domains (RePhaC1CD), and exists as a dimer. RePhaC1CD catalyzes polymerization via non‐processive ping‐pong mechanism using a Cys‐His‐Asp catalytic triad. Molecular docking simulation of 3‐hydroxybutyryl‐CoA to the active site of RePhaC1CD reveals residues involved in the formation of 3‐hydroxybutyryl‐CoA binding pocket and substrate binding tunnel. Comparative analysis with other polymerases elucidates how different classes of PHA synthases show different substrate specificities. Furthermore, we attempted structure‐based protein engineering and developed a RePhaC1 mutant with enhanced PHA synthase activity.
Polyhydroxyalkanoates (PHAs) are bacterial polyesters and have attracted substantial attention as substitutes for the petroleum‐based plastics. In this study, the authors report the crystal structure of C‐terminal domain of PHA synthase from Ralstonia eutropha, the best studied bacterium for PHA production, and the structural basis for the detailed molecular mechanisms of PHA biosynthesis. The structural information with reaction mechanisms will be useful for the rational engineering of PHA synthases to produce designer bioplastics from various monomers more efficiently.
The efficient evolution of gaseous hydrogen and oxygen from water is required to realize sustainable energy conversion systems. To address the sluggish kinetics of the multielectron transfer ...reaction, bifunctional catalyst materials for both the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER) should be developed. Herein, a tailored combination of atomically minimized iridium catalysts and highly conductive black WO3‐x nanofiber supports are developed for the bifunctional electrolyzer system. Atomic Ir catalysts, particularly those that activate the OER, minimize the utilization of precious metals. The oxygen‐deficient black WO3‐x NF support, which boosts the HER, offers increased electronic conductivity and favorable nucleation sites for Ir loading. The Ir‐black WO3‐x NFs exhibit increased double‐layer capacitance, a significantly reduced onset potential, lower Tafel slope, and stable cyclability for both the OER and HER, compared to large‐sized Ir catalysts loaded on white WO3 nanofibers. This study offers a strategy for developing an optimal catalyst material with suitable supports for high‐performance and economical water electrolysis systems for achieving carbon‐negative targets.
Black WO3‐x nanofiber (NF) supports attached to Ir nanoparticle catalysts (Ir‐black WO3‐x NFs) are introduced as bifunctional catalysts in water electrolysis systems. The structural and chemical features of Ir‐black WO3‐x and Ir‐white WO3 NFs are compared. Ir‐black WO3‐x nanofibers exhibit excellent catalytic activities and durability for both O2 and H2 evolution reactions, superior to those of Ir‐white WO3 NFs.
Cinnamon essential oil (CEO) has antibacterial properties, but its ability to suppress the formation of multi-species oral biofilms has not been fully elucidated. This study evaluated the ...antibacterial and antibiofilm activities of cinnamon essential oil nanoemulsion (CEON) against oral biofilms formed using a microcosm biofilm model. The biofilms were formed on bovine enamel specimens over a 7-day period, during which all specimens were treated with one of three solutions: 5% CEON (n = 35), 0.5% cocamidopropyl betaine (n = 35), or 0.12% chlorhexidine gluconate (CHX; n = 35). Antibacterial and antibiofilm activities were determined by the red/green ratios (R/G values) of 7-day-old mature biofilms photographed with quantitative light-induced fluorescence-digital, the number of aciduric bacterial colony-forming units (CFUs) within each biofilm, and the absorbance of bacterial suspensions. One-way and repeated-measures analysis of variance were performed to compare differences among the three solutions. R/G values were lowest in the 0.12% CHX group, but not significantly differ from the 5% CEON group. The number of CFUs and absorbance were lowest in the 5% CEON group. This study showed that nanoemulsified CEO inhibited the maturation of multi-species oral biofilms and the growth of oral microorganisms in biofilms, including aciduric bacteria that cause dental caries.
To introduce a prospective cohort for rheumatoid arthritis (RA) patients with interstitial lung disease (ILD) and to identify their clinical features in comparison with RA patients without ILD.
Using ...a multidisciplinary collaborative approach, a single-center cohort for RA patients with ILD (RA-ILD) was established in May 2017, and enrolment data from May 2017 to March 2021 were used to compare the clinical features of RA patients without ILD (RA-non ILD). Multivariable logistic regression analysis was used to identify factors associated with ILD in RA patients.
Among 148 RA-ILD and 410 RA-non ILD patients, participants in the RA-ILD group were older (65.8 ± 9.9 vs. 58.0 ± 10.4 years, P < 0.001) and included more males (35.8% vs. 14.6%, P < 0.001) than in the RA-non ILD group. The RA-ILD group had a higher proportion of late-onset RA patients (age ≥ 60 years) than in the comparator group (43.9% vs. 14.2%, P < 0.001). Multivariable logistic regression analysis showed that higher age at RA onset (OR 1.056, 95% CI 1.021-1.091), higher body mass index (BMI; OR 1.65, 95% CI 1.036-2.629), smoking history (OR 2.484, 95% CI 1.071-5.764), and oral glucocorticoid use (OR 3.562, 95% CI 2.160-5.874) were associated with ILD in RA patients, whereas methotrexate use was less likely to be associated with ILD (OR 0.253, 95% CI 0.155-0.412).
Higher age at RA onset, smoking history, and higher BMI were associated with the presence of ILD among RA patients. Oral glucocorticoids were more frequently used whereas methotrexate was less likely to be used in RA-ILD patients.
What is known and objective
Medication reconciliation is recommended to be performed at every transition of medical care to prevent medication errors or adverse drug events. This study investigated ...the impact of pharmacy‐led medication reconciliation on medication discrepancies and potential adverse drug events in the ED to assess the benefits of pharmacy services.
Methods
The systematic review and meta‐analysis was performed according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses statement. The PubMed, Ovid Embase and Cochrane library databases were searched up from inception to 1 July 2018. Studies comparing the effectiveness of the medication reconciliation service performed by pharmacy personnel to usual care (nurses or physicians) in the ED were included. Duplicated studies, non‐clinical studies, studies with ineligible comparators or study designs were excluded.
Results and discussion
Eleven studies were eligible for qualitative analysis, and 8 studies were included in meta‐analysis. Pharmacy‐led medication reconciliation substantially reduced medication discrepancies in the ED. The most common medication discrepancies included medication omission and incorrect/omitted dose or frequency. Unlike usual care, pharmacy‐led medication reconciliation significantly reduced the proportion of patients with medication discrepancies by 68% (response rate 0.32; 95% confidence interval (CI): 0.19‐0.53, P < .0001) and the number of medication discrepancy events by 88% (response rate 0.12; 95% CI 0.06‐0.26, P < .00001). Intervention decreased the number of discrepancies per patient by 3.08 (mean difference −3.08; 95% CI: −4.76 to −1.39, P = .0003). Subgroup analysis revealed no differences between pharmacists and pharmacy technicians in medication reconciliation performance pertaining to medication discrepancies. The patients with several comorbidities or those administered numerous medications received marked benefits related to reduced medication discrepancies from pharmacy‐led medication reconciliation. Moreover, a randomized controlled trial revealed decreased risk of potential adverse drug events by pharmacy‐led medication reconciliation in patients receiving care in the ED.
What is new and conclusion
Pharmacy‐led medication reconciliation significantly decreased the number of medication discrepancies. However, only one study investigated potential adverse drug events in patients receiving care in the ED. Therefore, further studies investigating the direct clinical impact of decreased medication discrepancies are required.
This meta‐analysis investigated the impact of pharmacy‐led medication reconciliation on medication discrepancies and potential adverse drug events in the ED. Pharmacy‐led medication reconciliation significantly reduced the proportion of patients with medication discrepancies and the number of medication discrepancy events.
Nonalcoholic fatty liver disease (NAFLD) is frequently observed in obese and aged individuals. Peroxisome proliferator-activated receptors (PPARs) play a role in regulating hepatic lipid ...accumulation, a hallmark of NAFLD development. A PPAR pan agonist, 2-(4-(5,6-methylenedioxybenzodthiazol-2-yl)-2-methylphenoxy)-2-methylpropanoic acid (MHY2013) has been shown to prevent fatty liver formation and insulin resistance in obese mice (db/db) model. However, the beneficial effects of MHY2013 in aged model remain unknown. In this study, we investigated whether MHY2013 alleviates hepatic lipid accumulation in aged Sprague–Dawley (SD) rats. We confirmed that MHY2013 increased the activities of three PPAR subtypes in HepG2 cells using luciferase assay. When administered orally in aged SD rats, MHY2013 markedly decreased the hepatic triglyceride levels without changes in body weight. Regarding underlying mechanisms, MHY2013 increased the mRNA levels of lipid oxidation-related genes, including carnitine palmitoyltransferase 1 (CPT1) and peroxisomal acyl-CoA oxidase 1 (ACOX1), without apparent change in the mRNA expression of lipogenesis-related genes. Furthermore, MHY2013 significantly increased systemic fibroblast growth factor 21 (FGF21) and adiponectin levels and suppressed inflammatory mRNA expression in the liver. In conclusion, MHY2013 alleviated age-related hepatic lipid accumulation, in part by upregulating β-oxidation signaling and suppressing inflammation in the liver. Therefore, MHY2013 is a potential pharmaceutical agent for treating age-related hepatic lipid accumulation.
The retinal pigment epithelium (RPE), situated upon Bruch's membrane, plays multiple roles in the ocular system by interacting with photoreceptors and. Therefore, dysfunction of the RPE causes ...diseases related to vision loss, such as age-related macular degeneration (AMD). Despite AMD being a global cause of blindness, the pathogenesis remains unclear. Understanding the pathogenesis of AMD is the first step for its prevention and treatment. This review summarizes the common pathways of RPE dysfunction and their effect in AMD. Potential treatment strategies for AMD based on targeting the RPE have also been discussed.
Polyhydroxyalkanoates (PHAs) are natural polyesters synthesized by numerous microorganisms as energy and reducing power storage materials, and have attracted much attention as substitutes for ...petroleum‐based plastics. In an accompanying paper, the authors reported the crystal structure of the C‐terminal domain of Ralstonia eutropha PHA synthase (PhaC1). Here, the authors report the 3D reconstructed model of full‐length of R. eutropha PhaC1 (RePhaC1F) by small angle X‐ray scattering (SAXS) analysis. The catalytic C‐terminal domain of RePhaC1 (RePhaC1CD) dimer is located at the center of RePhaC1F, and the N‐terminal domain of RePhaC1 (RePhaC1ND) is located opposite the dimerization subdomain of RePhaC1CD, indicating that RePhaC1ND is not directly involved in the enzyme catalysis. The localization studies using RePhaC1F, RePhaC1ND and RePhaC1CD revealed that RePhaC1ND plays important roles in PHA polymerization by localizing the enzyme to the PHA granules and stabilizing the growing PHA polymer near the active site of RePhaC1CD. The serial truncation study on RePhaC1ND suggested that the predicted five α‐helices (N‐α3 to N‐α7) are required for proper folding and granule binding function of RePhaC1ND. In addition, the authors also report the SAXS 3D reconstructed model of the RePhaC1F/RePhaMΔC complex (RePhaMΔC, PAKKA motif‐truncated version of RePhaM). RePhaM forms a complex with RePhaC1 by interacting with RePhaC1ND and activates RePhaC1 by providing a more extensive surface area for interaction with the growing PHA polymer.
The polyhydroxyalkanoates (PHAs) are bacterial polyesters and have drawn much attention as substitutes of petroleum‐based plastics. In PHA biosynthesis, PHA synthase (PhaC) is a key polymerase enzyme. In this study, the authors first demonstrate the 3D reconstructed models of PHA synthase from Ralstonia eutropha and the complex with PhaM, a PHA granule associated protein. In addition, the authors reveal the role of N‐terminal domain of PhaC and the interaction with PhaM. This work provides deep understanding of PHA biosynthesis and basis of enzyme engineering for tailor‐made bio‐plastic production.
Water Electrolysis
The efficient evolution of gaseous hydrogen and oxygen from water is required to realize sustainable water electrolyzing systems. In article number 2401858, Won‐Hee Ryu and ...co‐workers developed a tailored combination of atomically minimized Ir catalysts and highly conductive black WO3‐x nanofiber supports as a symmetric catalyst design for a bifunctional electrolyzer system.
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