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Diols are important platform chemicals with a wide range of applications in the fields of chemical and pharmaceutical industries, food, feed and cosmetics. In particular, 1,3-propandiol (PDO), 1,4-butanediol (1,4-BDO) and 1,3-butanediol (1,3-BDO) are appealing monomers for producing industrially important polymers and plastics. Therefore, the commercialization of bio-based diols is highly important for supporting the growth of biomanufacturing for the fiber industry. This review focuses primarily on the microbial production of PDO, 1,4-BDO and 1,3-BDO with respect to different microbial strains and biological routes. In addition, metabolic platforms which are designed to produce various diols using generic bioconversion strategies are reviewed for the first time. Finally, we also summarize and discuss recent developments in the downstream processing of PDO according to their advantages and drawbacks, which is taken as an example to present the prospects and challenges for industrial separation and purification of diols from microbial fermentation broth.

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1,4-Butanediol ether (BDDE) is widely used as a cross-linker for hyaluronic acid in dermal fillers. The purpose of this scoping review was to determine the state of knowledge about the behaviour of cross-linked substances and safety of BDDE application. The rationale behind the review came from the clinical experience of one of the authors (KS), who noticed adverse reactions after BDDE-linked hyaluronan application. The scoping review was conducted according to PRISMA-ScR guidelines. Out of 399 articles, 52 met the inclusion criteria. Data on study design, sample/population, aims, methodology, outcomes and funding were extracted. Results were charted according to 6 subtopics: rheological properties, hydrogel stability, BDDE toxicity, immunogenicity, tissue interactions and clinical studies. In vitro, cross-linked hydrogels were characterized as effective fillers in terms of viscosity and elasticity; however, previously uncharacterized by-products of the cross-linking reaction were found. Most in vivo studies reported increased dermis regeneration, vascularization and anti-inflammatory cytokine release after implantation of BDDE-cross-linked substances. In clinical studies, BDDE was shown to sensitize subjects to 1,6-hexanediol ether and other substances found in epoxy resin systems. Occupational dermatitis and hypersensitivity reactions were documented. Our review shows that BDDE may have long-term adverse effects, which are overlooked in the safety assessment of fillers. Reviews on BDDE conducted so far have mostly been sponsored by the industry, potentially leading to incomplete reporting of adverse effects. A review of the occurrence of allergic reactions after commercial dermal filler use and analysis of possibly harmful by-products of BDDE hyaluronan degradation are needed.Level of Evidence III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

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Electrorefinery of polybutylene terephthalate (PBT) waste plastic, specifically conversion of a PBT-derived 1,4-butanediol (BDO) monomer into value-added succinate coupled with H2 production, emerges as an auspicious strategy to mitigate severe plastic pollution. Herein, we report the synthesis of Mn-doped NiNDA nanosheets (NDA: 2,6-naphthalenedicarboxylic acid), a metal-organic framework (MOF) through a ligand exchange method, and its utilization for electrocatalytic BDO oxidation to succinate. Interestingly, the transformation of doped layered-hydroxide (d-LH) precursors to MOF promotes BDO oxidation while hindering the competitive oxygen evolution reaction. Experimental and theoretical results indicate that the MOF has a higher affinity (i.e., alcoholophilic) for BDO than the d-LH, while Mn doping into NiNDA results in electron accumulation at Ni sites with an upward shift in the d-band center and convenient spin-dependent charge transfer, which are all beneficial for BDO oxidation. The as-constructed two-electrode membrane-electrode assembly (MEA) flow cell, by coupling BDO oxidation and hydrogen evolution reaction, attains an industrial current density of 1.5 A cm-2@1.82 V at 50 °C, corresponding to a specific energy consumption of 3.68 kWh/Nm3 H2. This represents an energy saving of >25% for hydrogen production on an industrial scale compared to conventional water electrolysis (∼5 kWh/Nm3 H2) in addition to the production of valuable chemicals.

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CONTEXT: Poly(butylene adipate-co-terephthalate) (PBAT) is a biodegradable plastic. It was introduced to the plastics market in 1998 and since then has been widely used around the world. The main idea of this research is to perform quantum chemical calculations to study the potential toxicity of PBAT and its degradation products. We analyzed the electron transfer capacity to determine its potential toxicity. We found that biodegradable products formed with benzene rings are as good electron acceptors as PBAT and OOH•. Our results indicate that the biodegradation products are potentially as toxic as PBAT. This might explain why biodegradation products alter the photosynthetic system of plants and inhibit their growth. From this and other previous investigations, we can think that biodegradable plastics could represent a potential environmental risk. METHODS: All DFT computations were performed using the Gaussian16 at M062x/6-311 + g(2d,p) level of theory without symmetry constraints. Electro-donating (ω-) and electro-accepting (ω +) powers were used as response functions.

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The widespread attention towards 1,4-butanediol (BDO) as a key chemical raw material stems from its potential in producing biodegradable plastics. However, the efficiency of its biosynthesis via current bioprocesses is limited. In this study, a dual-pathway approach for 1,4-BDO production from succinic acid was developed. Specifically, a double-enzyme catalytic pathway involving carboxylic acid reductase and ethanol dehydrogenase was proposed. Optimization of the expression levels of the pathway enzymes led to a significant 318 % increase in 1,4-BDO titer. Additionally, the rate-limiting enzyme MmCAR was engineered to enhance the kcat/KM values by 50 % and increase 1,4-BDO titer by 46.7 %. To address cofactor supply limitations, an NADPH and ATP cycling system was established, resulting in a 48.9 % increase in 1,4-BDO production. Ultimately, after 48 hours, 1,4-BDO titers reached 201 mg/L and 1555 mg/L in shake flask and 5 L fermenter, respectively. This work represents a significant advancement in 1,4-BDO synthesis from succinic acid, with potential applications in the organic chemical and food industries.

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The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 10 alkane diol ingredients as used in cosmetics. The alkane diols are structurally related to each other as small diols, and most are reported to function in cosmetics as solvents. The Panel reviewed the relevant data for these ingredients, and concluded that seven alkane diols are safe in cosmetics in the present practices of use and concentration described in this safety assessment, but that the available data are insufficient to make a determination of safety for three ingredients, namely 1,4-Butanediol, 2,3-Butanediol, and Octanediol.

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Gamma-hydroxybutyrate (GHB), along with its precursors, 1,4-butanediol (1,4-BD) and gamma-butyrolactone (GBL), are potent central depressant agents widely illicitly used for their euphoric and relaxant effects. The article presents a review of the literature on the 1,4-BD misuse, the clinical picture of intoxication, development of addiction and delirium. The available evidence shows that 1,4-BD is a substance with its own psychoactive effects, a high addiction potential and potentially severe withdrawal symptoms.

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One of the main branches of regenerative medicine is biomaterials research, which is designed to develop and study materials for regenerative therapies, controlled drug delivery systems, wound dressings, etc. Research is continually being conducted to find biomaterials-especially polymers-with better biocompatibility, broader modification possibilities and better application properties. This study describes a potential biomaterial, poly(1,4-butanediol citrate). The gelation time of poly(1,4-butanediol citrate) was estimated. Based on this, the limiting reaction time and temperature were determined to avoid gelling of the reaction mixture. Experiments with different process conditions were carried out, and the products were characterised through NMR spectra analysis. Using statistical methods, the functions were defined, describing the dependence of the degree of esterification of the acid groups on the following process parameters: temperature and COOH/OH group ratio. Polymer films from the synthesised polyester were prepared and characterised. The main focus was assessing the initial biocompatibility of the materials.

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High-quality genome-scale metabolic models (GEMs) could play critical roles on rational design of microbial cell factories in the classical Design-Build-Test-Learn cycle of synthetic biology studies. Despite of the constant establishment and update of GEMs for model microorganisms such as Escherichia coli and Saccharomyces cerevisiae, high-quality GEMs for non-model industrial microorganisms are still scarce. Zymomonas mobilis subsp. mobilis ZM4 is a non-model ethanologenic microorganism with many excellent industrial characteristics that has been developing as microbial cell factories for biochemical production. Although five GEMs of Z. mobilis have been constructed, these models are either generating ATP incorrectly, or lacking information of plasmid genes, or not providing standard format file. In this study, a high-quality GEM iZM516 of Z. mobilis ZM4 was constructed. The information from the improved genome annotation, literature, datasets of Biolog Phenotype Microarray studies, and recently updated Gene-Protein-Reaction information was combined for the curation of iZM516. Finally, 516 genes, 1389 reactions, 1437 metabolites, and 3 cell compartments are included in iZM516, which also had the highest MEMOTE score of 91% among all published GEMs of Z. mobilis. Cell growth was then predicted by iZM516, which had 79.4% agreement with the experimental results of the substrate utilization. In addition, the potential endogenous succinate synthesis pathway of Z. mobilis ZM4 was proposed through simulation and analysis using iZM516. Furthermore, metabolic engineering strategies to produce succinate and 1,4-butanediol (1,4-BDO) were designed and then simulated under anaerobic condition using iZM516. The results indicated that 1.68 mol/mol succinate and 1.07 mol/mol 1,4-BDO can be achieved through combinational metabolic engineering strategies, which was comparable to that of the model species E. coli. Our study thus not only established a high-quality GEM iZM516 to help understand and design microbial cell factories for economic biochemical production using Z. mobilis as the chassis, but also provided guidance on building accurate GEMs for other non-model industrial microorganisms.

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Photocatalytic 2-iodoethanol (IEO) coupling provides 1,4-butanediol (BDO) of particular interest to produce degradable polyesters. However, the reduction potential of IEO is too negative (-1.9 vs NHE) to be satisfied by most of the semiconductors, and the kinetics of transferring one electron for IEO coupling is slow. Here we design a catalytic Ni complex, which works synergistically with TiO2 , realizing reductive coupling of IEO powered by photo-energy. Coordinating by terpyridine stabilizes Ni2+ from being photo-deposited to TiO2 , thereby retaining the steric configuration beneficial for IEO coupling. The Ni complex can rapidly extract electrons from TiO2 , generating a low-valent Ni capable of reducing IEO. The photocatalytic IEO coupling thus provides BDO in 72 % selectivity. By a stepwise procedure, BDO is obtained with 70 % selectivity from ethylene glycol. This work put forward a strategy for the photocatalytic reduction of molecules requiring strong negative potential.

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1,4-Butanediol (1,4-BDO) is a valuable industrial chemical that is primarily produced via several energy-intensive petrochemical processes based on fossil-based raw materials, leading to issues related to: non-renewability, environmental contamination, and high production costs. 1,4-BDO is used in many chemical reactions to develop a variety of useful, valuable products, such as: polyurethane, Spandex intermediates, and polyvinyl pyrrolidone (PVP), a water-soluble polymer with numerous personal care and pharmaceutical uses. In recent years, to satisfy the growing need for 1,4-BDO, there has been a major shift in focus to sustainable bioproduction via microorganisms using: recombinant strains, metabolic engineering, synthetic biology, enzyme engineering, bioinformatics, and artificial intelligence-guided algorithms. This article discusses the current status of the development of: various chemical and biological production techniques for 1,4-BDO, advances in biological pathways for 1,4-BDO biosynthesis, prospects for future production strategies, and the difficulties associated with environmentally friendly and bio-based commercial production strategies.

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Biotransformation of plastics or their depolymerization monomers as raw materials would offer a better end-of-life solutions to the plastic waste dilemma. 1,4-butanediol (BDO) is one of the major depolymerization monomers of many plastics polymers. BDO valorization presents great significance for waste plastic up-recycling and fermenting feedstock exploitation. In the present study, atmospheric pressure room temperature plasma (ARTP)-induced mutation combined with adaptive laboratory evolution (ALE) was used to improve the BDO utilization capability of Pseudomonas putida KT2440. The excellent mutant P. putida NB10 was isolated and stored in the China Typical Culture Preservation Center (CCTCC) with the deposit number M 2021482. Whole-genome resequencing and transcriptome analysis revealed that the BDO degradation process consists of ß-oxidation, glyoxylate carboligase (GCL) pathway, glyoxylate cycle and gluconeogenesis pathway. The imbalance between the two key intermediates (acetyl-CoA and glycolyl-CoA) and the accumulation of cytotoxic aldehydes resulted in the weak metabolism performance of KT2440 in the utilization of BDO. The balance of the carbon flux and enhanced tolerance to cytotoxic intermediates endow NB10 with great BDO degradation capability. This study deeply revealed the metabolic mechanism behind BDO degradation and provided an excellent chassis cell for BDO further up-cycling to high-value chemicals. IMPORTANCE Plastic waste represents not only a global pollution problem but also a carbon-rich, low-cost, globally renewable feedstock for industrial biotechnology. BDO is the basic material for polybutylene terephthalate (PBT), poly butylene adipate-co-terephthalate (PBAT), poly (butylene succinate) (PBS), etc. Herein, the construction of BDO valorization cell factory presents great significance for waste plastic up-recycling and novel fermentation feedstock exploitation. However, BDO is hard to be metabolized and its metabolic pathway is unclear. This study presents a P. putida mutant NB10, obtained through the integration of ARTP and ALE, displaying significant growth improvement with BDO as the sole carbon source. Further genome resequencing, transcriptome analysis and genetic engineering deeply revealed the metabolic mechanism behind BDO degradation in P. putida, this study offers an excellent microbial chassis and modification strategy for plastic waste up-cycling.

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Bio-based C3 and C4 bi-functional chemicals are useful monomers in biopolymer production. This review describes recent progresses in the biosynthesis of four such monomers as a hydroxy-carboxylic acid (3-hydroxypropionic acid), a dicarboxylic acid (succinic acid), and two diols (1,3-propanediol and 1,4-butanediol). The use of cheap carbon sources and the development of strains and processes for better product titer, rate and yield are presented. Challenges and future perspectives for (more) economical commercial production of these chemicals are also briefly discussed.

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In order to extract sulforaphane (SFN) from broccoli via green and efficient ways, a novel method based on salting-out assisted deep eutectic solvent (DES) has been developed. Compared to known organic solvent- (such as dichloromethane, ethyl acetate, n-hexane, etc.) based liquid-liquid extraction, this new N8881Cl-based DES method exhibited excellent extraction efficiency for SFN, including a significant improvement due to the salting-out effect of KH2PO4. Under optimal conditions, 97.77 % of SFN was extracted by N8881Cl-EG DES and more than 82.5 % of SFN was recovered by activated carbon from DES. In addition, further studies with Kamlet-Taft parameters and density functional theory showed that the H-bond accepting capacity of hydrophobic DES, the existing vdW interaction, and the electrostatic interaction between N8881Cl-EG DES all contributed to efficient extraction of SFN. This is the first time that the underlying mechanism for SFN extraction by DES was revealed.

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RATIONALE: Regular consumption of gamma-hydroxybutyrate (GHB) may result in a dependence syndrome that can lead to withdrawal symptoms. There are limited data on medications to manage GHB withdrawal. OBJECTIVES: To examine characteristics associated with delirium and discharge against medical advice (DAMA), in the context of implementing a GHB withdrawal management protocol at an inner-city hospital in 2020. METHODS: We retrospectively reviewed records (01 January 2017-31 March 2021), and included admissions that were ≥ 18 years of age, admitted for GHB withdrawal, and with documented recent GHB use. Admissions were assessed for demographics, medications administered, features of delirium, ICU admission, and DAMA. Exploratory analyses were conducted to examine factors associated (p < 0.2) with features of delirium and DAMA. RESULTS: We identified 135 admissions amongst 91 patients. Medications administered included diazepam (133 admissions, 98.5%), antipsychotics (olanzapine [70 admissions, 51.9%]), baclofen (114 admissions, 84%), and phenobarbital (8 admissions, 5.9%). Features of delirium were diagnosed in 21 (16%) admissions. Delirium was associated with higher daily GHB consumption prior to admission, while duration of GHB use, time from presentation to first dose of diazepam, and concomitant methamphetamine use were inversely associated with delirium. DAMA occurred amongst 41 (30%) admissions, and was associated with a longer time from presentation to first dose of baclofen, while being female and receiving a loading dose of diazepam were inversely associated. CONCLUSIONS: This study adds to the literature in support of the safety and feasibility of diazepam and baclofen for the management of GHB withdrawal. Prospective, randomised trials are required.

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Halomonas bluephagenesis has been engineered to produce flexible copolymers P34HB or poly(3-hydroxybutyrate-co-4-hydroxybutyrate) from glucose and petrol-chemical precursor, γ-butyrolactone. Herein, gene cluster aldD-dhaT was constructed in recombinant H. bluephagenesis for catalyzing 1,4-butanediol (BDO) into 4-hydroxybutyrate, which could grow to 86 g L-1 dry cell mass (DCM) containing 77 wt% P(3HB-co-14 mol% 4HB) in 7-L bioreactor fed with glucose and bio-based BDO. Furthermore, 4HB monomer ratio could be increased to 16 mol% by engineered H. bluephagenesis TDH4-WZY254 with defected outer-membrane. Upon deletion of 4HB degradation pathway, followed by aldD-dhaT integration, the resulted H. bluephagenesis TDB141ΔAC was grown to 95 g L-1 DCM containing 79 wt% P(3HB-co-14 mol% 4HB) with a BDO conversion efficiency of 86% under fed-batch fermentation. Notably, 4HB molar ratio can be significantly improved to 21 mol% with negligible effects on cell growth and P34HB synthesis by adding 50% more BDO. This study successfully demonstrated a fully bio-based P34HB effectively produced by H. bluephagenesis.

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The excessive inflammation, oxidative stress, and impaired angiogenesis are major factors leading to difficulties in chronic wound healing. To develop bioactive materials with intrinsic antioxidant and anti-inflammatory properties, we prepared hydrogels for the first time using paramylon secreted by Euglena gracilis which is a polysaccharide has been approved by FDA as food additive. Results showed that the paramylon hydrogel has favourable anti-inflammatory effects and the ability to scavenge reactive oxygen species (ROS) through free radical destruction, deoxygenation, and singlet oxygen quenching, and inhibit ROS production by chelating the metal ions required for the formation of ROS. We found that the paramylon hydrogel could effectively reduce wound inflammation and promote angiogenesis to facilitate wound repair. Furthermore, for the first time, we found that paramylon hydrogel could promote the formation of blood vessels via the HIF-1α-VEGF pathway. These results indicated that the highly bioactive paramylon could be the preferred material for wound healing.

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HYPOTHESIS: The crystallisation of biosourced ferulic acid derivatives - Bis-O-feruloyl-1,4-butanediol (BDF) - in a polylactic acid (PLA) matrix produces thermoplastic elastomeric blends that are transparent and biodegradable. Elastomeric and transparency are controlled by the domain size. PLA-BDF blends up to a threshold BDF concentration providing elastomeric properties show no evidence of BDF crystallisation. Heat treatment weakens the PLA-BDF interaction, give BDF molecules mobility to interact with nearby BDF molecules, leading to BDF nano-crystallisation. EXPERIMENTS: PLA-BDF blends were synthesised by hot-melt processing by mixing pure PLA with different concentrations of BDF (0-40 wt%) at 180 °C for 13 min. One set of blends was annealed at 50 °C for 24 h and compared with the unannealed set. The BDF crystallisation in the blends is studied by combining SAXS, SEM, XRD and Polarised Optical Microscopy. Monte-Carlo simulations were performed to validate SAXS data analysis. FINDINGS: Unannealed PLA-BDF blends of up to the threshold of 20 wt% BDF are dominated by the semicrystalline behaviour of PLA, without any trace of BDF crystallisation. Surprisingly, the PLA-BDF 40 wt% blend shows BDF crystallisation in the form of large and nanoscale structures bonded together by weak interparticle interaction. At concentrations up to 20 wt%, the BDF molecules are homogenously dispersed and bonded with PLA. Increasing BDF to 40 wt% brings the BDF molecules close enough to crystallise at room temperature, as the BDF molecules are still bonded with the PLA network. Annealing of PLA-BDF blends led to BDF nanocrystallisation and self-assembling in the PLA network. Both BDF nanoparticle size and interparticle distance decrease as the BDF concentration increases. However, the number density of BDF nanocrystals increases. The formed BDF nanocrystals have size ranging between 100 and 380 Å with interparticle distance of 120-180 Å. The structure factor and potential mean force confirm the strong interparticle interaction at the higher BDF concentration. Heat treatment weakens the PLA -BDF interaction, which provides mobility to the BDF molecules to change conformation and interact with the nearby BDF molecules, leading to BDF crystallisation. This novel BDF crystallisation and self-assembly mechanism can be used to develop biodegradable shape memory PLA blends for biomedical, shape memory, packaging and energy applications.

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1,4-Butanediol (1,4-BDO), a significant commodity chemical, is currently manufactured exclusively from a host of energy-intensive processes, accompanied by severe environmental issues, such as the greenhouse effect and air pollution. As a result of the ever-increasing global market demands and increasing applications of 1,4-BDO, attention has turned to the sustainable bioproduction of 1,4-BDO, and several bio-based approaches for 1,4-BDO production have been successfully established in engineered Escherichia coli, including de novo biosynthesis and biocatalysis. Recent achievements in enhancing the accumulation of 1,4-BDO have been achieved by metabolic engineering strategies, such as improving precursor supply, enhancing activities of critical enzymes, and fewer byproduct synthesis. Here, we summarize the primary advances of the biological pathway for 1,4-BDO synthesis and put forward the future development prospect of bio-based 1,4-BDO production.

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The aim of the present study was to obtain a better and safer galactomannan-based material for drug release applications. A novel epoxy-crosslinked galactomannan hydrogel (EGH) was prepared from guar gum using 1,4-butanediol diglycidyl ether as a crosslinking agent. The diffusion rate constant of water molecules in freeze-dried EGH positively correlated with water uptake/equilibrium swelling rate (WU/ESR), and the water molecules participated in Fickian diffusion. The ESR, WU/ESR, and bovine serum albumin (BSA) loading capacity of a customized EGH with a crosslinking density of 48.9% were 48.7 ± 0.15 g/g, 95.3%, and 56.4 mg/g, respectively. The release of BSA from freeze-dried EGH was affected by the WU/ESR and the pH; the release equilibrium time was ~40 h at pH 1.2, decreasing to ~24 h at pH 7.4. Furthermore, the cumulative release rate increased from 63.5% to 80.7% and the t50 decreased from 59 to 41 min upon changing from the acidic to basic pH. The release process conformed to the Ritger-Peppas and Hixson-Crowell models, and represented Fickian diffusion and chain relaxation. The EGH showed no cytotoxicity toward HeLa cells. Together, these results demonstrate the properties of a novel galactomannan-based hydrogel that can potentially be employed as a vehicle for drug delivery.

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