Acid Mixture Research Articles

Amino acid surface modified bioglass: A candidate biomaterial for bone tissue engineering1.

Bioglasses are solid materials consisted of sodium oxide, calcium oxide, silicon dioxide and phosphorus in various proportions and have used in bone tissue engineering. There have been ongoing efforts to improve the surface properties of bioglasses to increase biocompatibility and performance. The aim of the present study is to modify the bioglass surface with an amino acid mixture consisting of arginine, aspartic acid, phenylalanine, cysteine, histidine and lysine, to characterize the surface, and to evaluate the performance and biocompatibility in vitro and in vivo. The untreated bioglass, bioglass kept in simulated body fluid (SBF), and modified bioglass were used in further evaluation. After confirmation of the surface modification with FT-IR analyses and SEM analyses, MC3T3-E1 preosteoblasts adhesion on the surface was also revealed by SEM. The modified bioglass had significantly higher ALP activity in colorimetric measurement, rate of calcium accumulations in Alizarin red s staining, lower rate of cell death in Annexin-V/PI staining to determine apoptosis and necrosis. Having higher cell viability rate in MTT test and absence of genotoxicity in micronucleus test (OECD 487), the modified bioglass was further confirmed for biocompatibility in vitro. The results of the rat tibial defect model revealed that the all bioglass treatments had a significantly better bone healing score compared to the untreated negative control. However, the modified bioglass exhibited significantly better bone healing efforts especially during the first and the second months compared to the other bioglass treatment treatments. As a result, the amino acid surface modification of bioglasses improves the surface biocompatibility and osteogenic performance that makes the amino acid modified bioglass a better candidate for bone tissue engineering. RESEARCH HIGHLIGHTS: Bioglass surface modification with amino acids contributes to bioglass-tissue interaction with an improved cell attachment. Modified bioglass increases in vitro Alp activity and calcium accumulation, and also positively affects cell behavior by supporting cell adaptation. Bioglass exerts osteogenic potential in vivo especially during early bone healing.

Ecofriendly treatments to improve pomegranate trees production and tolerance to climate change

BackgroundPomegranate is capable of growing in different agro-climatic conditions ranging from tropical to sub-tropical. Where vegetative growth, nutritional and physiological status of pomegranate plants oscillate at high temperatures waves in the summer season. While we can overcome the cracking and sunburn of fruits, which are the main problems confronting pomegranate cultivars due to their significant impact on the quality of fruits.MethodsThe present research was conducted over the course of two consecutive seasons in 2021 and 2022. The study focused on ten-year-old trees that were cultivated in sandy soil inside a private orchard situated 70 km away from Cairo on the Cairo-Alexandria desert road in Egypt (30o13′31.4″N30o39′09″E). The aim of the present work was to evaluate the effect of foliar spraying of Wonderful pomegranate trees with some nutrients (B, Zn, Fe, Mn, Ca and Cu), amino acids and irradiated licorice on vegetative growth, fruit physical, quality and chemical and leaf chemical parameters. A randomized full-block design with three duplicates was employed in the study. Using the recently computed least significant difference values at the 5% level, averages were compared.ResultsThe results indicated that foliar spraying with nutrients, amino acids and licorice extract (irradiated or not) alone or in combination significantly increased the vegetative growth and leaf total chlorophyll content compared to the control. Also, they significantly increased fruit length, diameter, weight, and number/tree and thus yield. As compared to the control, all treatments significantly reduced the number of sunburned and cracked fruits leading to decrease the percentage of un-marketable fruits. The juice content of anthocyanin, total sugars and total soluble solids increased significantly in response to all treatments compared to the control while the acidity% greatly reduced. When these treatments were used instead of the control, the content of N, P, K, Fe, Zn, and Mn in the leaves was also positively increased.ConclusionsIn conclusion, foliar spraying of “Wonderful” pomegranate trees with a mixture of nutrients (B, Zn, Fe, Mn, Ca, Cu) and amino acids or irradiated licorice extract can be considered as a suitable management of the problem of sunburned or cracked fruits while improving the physical and chemical fruit quality with increased productivity.

Efficient dark-fermentation biohydrogen production by Shigella flexneri SPD1 from biowaste-derived sugars through green solvents approach

This study evaluated the dark-fermentative hydrogen (H2) production potential of isolated and identified Shigella flexneri SPD1 from various pure (glucose, fructose, sucrose, lactose, and galactose) and biowastes (coconut coir, cotton fiber, groundnut shells, rice-, and wheat-straws)-derived sugars. Among sugars, S. flexneri SPD1 exhibited high H2 production of up to 3.20 mol/mole of hexose using glucose (5.0 g/L). The pre-treatment of various biowastes using green solvents (choline chloride and lactic acid mixture) and enzymatic hydrolysis resulted in the generation of up to 36.0 g/L of sugars. The maximum H2 production is achieved up to 2.92 mol/mol of hexose using cotton-hydrolysate. Further, the upscaling of bioprocess up to 5 L of capacity resulted in a maximum yield of up to 3.06 mol/mol of hexose. These findings suggested that S. flexneri SPD1, a novel H2-producer, can be employed to develop a circular economy-based approach to produce clean energy.

Preparation of a colorimetric hydrogel indicator reinforced with modified aramid nanofiber employing natural anthocyanin to monitor shrimp freshness.

The pH-responsive hydrogels have potential applications in food visualization detection, but their fragile mechanical properties limit their applicability. The excellent mechanical properties and thermal stability of aramid nanofibers (ANFs) can improve the structural stability of hydrogels. In this study, the surface properties of ANFs were enhanced through modification to improve their surface activity. The modified ANFs, designated as ANF-SN, were produced following treatment with a mixture of sulfuric acid (H2SO4) and nitric acid (HNO3), which led to increased reactivity and dispersibility of the ANFs due to the proliferation of active groups on their nanofiber surface. The preferred anthocyanin extract from purple sweet potatoes (purple sweet potato extract [PSPE]) had significant color responses to pH (2-12) and ammonia vapor. A stable dual-network colorimetric hydrogel was fabricated by combining ANF-SN, polyvinyl alcohol/sodium alginate (PVA/SA), and PSPE through a two-step method (freeze-thawing and staining). Characterization analysis showed that the strong acid modification of ANFs effectively improved their chemical reactivity. ANF-SN was better than ANF in promoting the formation of hydrogen bond networks, enhancing hydrogel network structures, and improving the viscoelasticity of hydrogels. The optimal hydrogel indicator PVA/SA/ANF-SN/PSPE had good color responsiveness and sensitivity to ammonia. It can also be used to further determine shrimp freshness value using a smartphone and RGB color-picking software.

Carbon type and quantity regulate soil free-living nitrogen fixation through restructuring diazotrophic community

Free-living nitrogen fixation (FLNF) is a ubiquitous and significant source of new nitrogen in ecosystems. This process requires a substantial amount of energy, and as a result, the input of labile carbon to soils may enhance FLNF. Here, we aim to explore the precise influence of different types and quantities of carbon on FLNF. We conducted experiments where sugars, carboxylic acids, and amino acids (common labile carbon inputs via root exudates) were added to cropland and forest soils. We monitored the changes in FLNF rate and diazotrophic community in response to these additions. Our findings revealed that sugars and carboxylic acids significantly stimulated FLNF rate, with an increase of up to three orders of magnitude, while amino acids either restricted FLNF or had no effect. When a mixture of sugars and carboxylic acids was added, the stimulation of FLNF was not observed until a threshold quantity of carbon was reached, indicating competition between diazotrophs and other microbes. Furthermore, the enhanced FLNF rate following carbon addition was attributable to shifts in diazotrophic community composition (e.g., increased abundance of Paenibacillus, a genus frequently used as biofertilizers), rather than to changes in the overall abundance of diazotrophs (reflected by nifH gene copy number). Our findings highlight the significant role of carbon type and quantity in regulating soil FLNF, partly through restructuring the diazotrophic community. The results have implications for predicting the response of rhizosphere FLNF to shifts in root exudation under environmental changes and can contribute to the application of diazotrophic biofertilizers in sustainable agriculture.

Three-phase crystallization for purification of acrylic acid from acrylic/propionic acid mixture

A new separation technology, three-phase crystallization (TPC), was utilized to purify acrylic acid (AA) from a binary liquid mixture comprising AA and propionic acid (PA). The solid–liquid equilibrium data of AA/PA mixture reported in the literature were adopted to recover the activity coefficients of the liquid mixture; and, subsequently, the vapor–liquid equilibrium conditions of AA/PA mixture were predicted using Raoult’s law and the Wilson equations for the recovered activity coefficients. The reported solid–liquid equilibrium data and the predicted vapor–liquid equilibrium conditions were coupled to determine the three-phase transformation conditions of AA/PA mixture, which were employed to conduct the batch TPC experiments. Upon conclusion of the TPC, the yield and purity were measured to estimate the amount of the AA crystals and volume of the liquid mixture retained in the overall final product, respectively.

Functional and metabolic effects of omega-3 polyunsaturated fatty acid supplementation and the role of β-hydroxy-β-methylbutyrate addition in chronic obstructive pulmonary disease: A randomized clinical trial

IntroductionShort-term (4 weeks) supplementation with n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has recently been shown to improve protein metabolism in a dose dependent way in normal weight patients with Chronic Obstructive Pulmonary Disease (COPD). Furthermore, EPA/DHA supplementation was able to increase extremity lean soft tissue but not muscle function. No studies are available combining n-3 PUFAs and the leucine metabolite β-hydroxy-β-methylbutyrate (HMB) supplementation in chronic clinical conditions. Whether adding HMB to daily EPA/DHA supplementation for 10 weeks enhances muscle and brain health, daily functional performance, and quality of life of patients with COPD by further improving their protein and amino acid homeostasis remains unknown. MethodsPatients with COPD (GOLD: II-IV, n=46) received daily for 10 weeks, according to a randomized double-blind placebo-controlled three-group design, EPA/DHA (n=16), EPA/DHA to which HMB was added (n=14), or placebo (n=16). The daily dose of 2.0 g of EPA/DHA or soy + corn oil as the placebo was provided via gel capsules, and 3.0 g of Ca-HMB or maltodextrin as placebo as powders. At pre- and post-intervention, a pulse mixture of multiple amino acids was administered to measure postabsorptive net protein breakdown (netPB as primary endpoint) and whole body production (WBP) and conversion rates of the amino acids. As secondary endpoints, lean soft tissue, and fat mass were assessed by dual-energy X-ray absorptiometry, upper and lower muscle function by handgrip and single leg isokinetic dynamometry, brain (cognitive, wellbeing) health by assessments, daily functional performance by measuring 6-minute walk distance, 4-meter gait speed, and postural balance, and quality of life by questionnaire. Plasma enrichments and concentrations were analyzed by LC-MS/MS, and systemic inflammatory profile and metabolic hormones by Luminex. ResultsHMB + EPA/DHA but not EPA/DHA supplementation increased postabsorptive netPB (p=0.028), and WBPs of glutamine (p=0.024), taurine (p=0.039), and tyrosine (p=0.036). Both EPA/DHA and HMB + EPA/DHA supplementation resulted in increased WBP of phenylalanine (p<0.05). EPA/DHA but not HMB + EPA/DHA was able to increase WBP of arginine (p=0.030), citrulline (p=0.008), valine (p=0.038), and conversion of citrulline to arginine (p=0.009). Whole body and extremity fat mass were reduced after HMB + EPA/DHA supplementation only, whereas lean soft tissue was increased after EPA/DHA (p=0.049) and HMB + EPA/DHA (p=0.073). No other significant findings were observed. Reductions in several proinflammatory cytokines were observed in the HMB + EPA/DHA group including IL-2, IL-17, IL-6, IL-1 receptor antagonist, IL-12P40, and TNF-β (p<0.05). ConclusionsTen weeks of supplementation with 2 g of EPA/DHA daily is sufficient to induce muscle gain in COPD but HMB is needed to induce fat loss. Whether HMB is solely responsible for the fat mass loss or has a synergistic effect with EPA/DHA remains unclear. The increase in net protein breakdown observed with HMB + EPA/DHA supplementation may not indicate harmful muscle catabolism but rather a beneficial enhanced protein turnover cycling associated with increased lean soft tissue. Clinical Trial RegistryClinicalTrials.gov; NCT03796455

Acrylamide detection and reduction in meat products using organic acids, fruit extracts, and probiotics

Grilled foods are an important source of acrylamide, which has neurotoxic, genotoxic, and carcinogenic properties. The current study aims to evaluate the level of acrylamide in beef, chicken, and fish products, especially those requiring high cooking temperatures, using High Performance Liquid Chromatography (HPLC). Reduction of acrylamide by organic acids i.e., (citric acid, malic acid, tartaric acid, and lactic acid) and fruit extracts of lemon, apple, and grape has also been investigated. The results revealed that the highest mean acrylamide concentration was found in chicken products (grilled chicken) which recorded 8.32 μg/100 g, followed by beef products (beef grilled) with a concentration of 7.91 μg/100 g, and fish products (pan-fried fish burgers) which recorded 6.77 μg/100 g). Furthermore, the mixture of organic acid has the highest effect on reducing the level of acrylamide in a chemical model system. Moreover, the fruit extract mixture was more effective in reducing the percentage of acrylamide in the grilled chicken than organic acids mixture. Finally, the addition of fruit extract improved the sensory properties of grilled chickens. In sum, this study offers novel and promising natural strategies to decrease acrylamide in meat products toward further future application in meat industry to deliver safe food to consumers.

Bright yellow fluorescent carbon dots as selective nanoprobe for detection of 2-nitrophenol and 4-nitrophenol in aqueous medium

Different types of phenolic pollutants pose a major risk to the environment and the health of living things. It is therefore crucial for their selective recognition especially nitrophenols. In this work, yellow fluorescent carbon dots (C-dots) were used as selective nanoprobe to efficiently detect 2-nitrophenol (2-NP) and 4-nitrophenol (4-NP). One-pot synthetic method was adopted for making C-dots from o-phenylenediamine and oleic acid mixture. The synthesized C-dots showed an excitation wavelength of 420 nm with Stokes shift of up to 135 nm. These C-dots exhibited instantaneous selective detection of 2-NP and 4-NP in aqueous solution with a detection limit of 6.4 nM and 4.8 nM respectively. Upon incubated with 2-NP and 4-NP, the C-dots’ fluorescence underwent quenching with a maximum extent of respective 80 % and 83 %. By comparing with other analogs of analyte, it was discovered that the emission intensity of the C-dots remained unchanged. Static quenching was proposed behind the changes of fluorescence after the treatment with 2-NP and 4-NP. Such type of C-dots will demonstrate the selective sensing platform in real field application.

Enabling Downstream Processing of Lignin Effluent from Cosolvent Enhanced Lignocellulosic Fractionation (CELF) Process through Controlled Electrocatalytic Oxidation and Reduction

Lignin which is a complex organic polymer is abundant in nature. But due to its recalcitrant nature, it can't be converted to value added products easily. Previous studies have found that 40–60 million tons of lignin wastes are generated from the pulp and paper industry globally [1]. The sustainability of these industries can be ensured by converting these wastes into valuable products through environmentally friendly processes. Currently, there are many prevalent catalytic technologies for converting lignin to valuable fuels and chemicals. But these technologies use large amounts of energy and harsh reaction conditions. As a result, catalyst recovery and decomposition often become difficult under such harsh conditions. Besides, bonds between lignin precursors are cleaved unselectively and the selectivity of aromatic products is reduced. An electrocatalytic approach may allow improved control, and few studies have evaluated the electrocatalytic oxidation and reduction of lignin in organic solvents.Organic solvents like tetrahydrofuran (THF) are of interest for lignin electrocatalysis due to their use in the promising cosolvent enhanced lignocellulosic fractionation (CELF) process. Also, THF is a renewable solvent as it can be produced sustainably from the conversion of lignocellulosic biomass. In CELF process, high purity technical lignin can be produced at milder temperatures (1800C) from a mixture of THF and sulfuric acid. Thus, this process has the capability to overcome biomass recalcitrance by breaking β-O-4 aryl ether interunit linkages. Using electrocatalytic conversion processes, additional β-O-4, interunit linkages can be broken down selectively. As a result, if these two processes are integrated, a high amount of phenolic hydroxyl groups with low-content aryl ether linkages will be produced, making the product suitable for the development of biofuels and other chemicals. This study shows that by using controlled electrocatalytic oxidation and reduction in THF/aqueous acidic electrolytes in the ratio of 2:1, nonpolar β-O-4 linkages can be cleaved [2]. This ratio was chosen to mimic the electrolyte composition environment of the CELF pretreatment. The results from both attenuated total reflection-infrared spectroscopy (ATR-IR) and NMR characterization are consistent and show that β-O-4 interlinkage bonds were broken. Quantitative calculations from NMR show that during controlled oxidative potential holds (constant potential oxidation), the presence of aromatic structural components of the lignin polymer increased by 28.67% and aliphatic structural components decreased by 32.73%. On the other hand, during controlled reductive potential holds (constant potential reduction), the presence of aromatic structural compounds decreased by 33.50% and aliphatic structural compounds decreased by 78.43%. These results indicate that electrooxidation and electroreduction may be used strategically to cleave interunit linkages. Finally, it can be said, if electrochemical degradation of lignin is used as a secondary treatment along with the CELF process, it will substantially increase the possibility of transforming lignin into value-added products.References Collins, M. N., Nechifor, M., Tanasă, F., Zănoagă, M., McLoughlin, A., Stróżyk, M. A., Culebras,M., & Teacă, C. A. (2019). Valorization of lignin in polymer and composite systems for advanced engineering applications–a review. International journal of biological macromolecules, 131, 828-849.Hasan, M., Akbari, A., & Greenlee, L. F. (2023). Combined Electrocatalytic Oxidation and Reduction to Selectively Cleave β-O-4 Linkage of Lignin over Platinum Electrode in Organic Solvent: Secondary Treatment Opportunity for CELF Process. ACS Sustainable Chemistry & Engineering. Figure 1

Kinetic Resolution as a General Approach to Enantioenrichment in Prebiotic Chemistry.

ConspectusThe origin of the single chirality of the chemical building blocks of life remains an intriguing topic of research, even after decades of experimental and theoretical work proposing processes that may break symmetry and induce chiral amplification, a term that may be defined as the enhancement of enantiomeric excess starting from prochiral substrates or from a racemic mixture or a small imbalance between enantiomers. Studies aimed at understanding prebiotically plausible pathways to these molecules have often neglected the issue of chirality, with a focus on the stereochemical direction of these reactions generally being pursued after reaction discovery. Our work has explored how the stereochemical outcome for the synthesis of amino acids and sugars might be guided to rationalize the origin of biological homochirality. The mechanistic interconnection between enantioenrichment in these two groups of molecules provides insights concerning the handedness extant in modern biology. In five separate examples involving the synthesis of life's building blocks, including sugars, RNA precursors, amino acids, and peptides, kinetic resolution emerges as a key protocol for enantioenrichment from racemic molecules directed by chiral source molecules. Several of these examples involve means not only for chiral amplification but also symmetry breaking and chirality transfer across a range of racemic monomer molecules. Several important implications emerge from these studies: one, kinetic resolution of the primordial chiral sugar, glyceraldehyde, plays a key role in a number of different prebiotically plausible reactions; two, the emergence of homochirality in sugars and amino acids is inherently intertwined, with clear synergy between the biological hand of each molecule class; three, the origin story for the homochirality of enzymes and modern metabolism points toward kinetic resolution of racemic amino acids in networks that later evolved to include sophisticated and complete catalytic and co-catalytic cycles; four, a preference for heterochiral ligation forming product molecules that cannot lead to biologically competent polymers can in fact be a driving force for a route to homochiral polymer chains; and five, enantioenrichment in complex mixtures need not be addressed one compound at a time, because kinetic resolution induces symmetry breaking and chirality transfer that may lead to general protocols rather than specific cases tailored to each individual molecule. Such chirality transfer mechanisms perhaps presage strategies utilized in modern biology.Our latest work extends the study of monomer enantioenrichment to the ligation of these molecules into the extended homochiral chains leading to the complex polymers of modern biology. A central theme in all of these reactions is the key role that kinetic resolution of a racemic mixture of amino acids or sugars plays in enabling enantioenrichment under prebiotically plausible conditions. This work has uncovered important trends in symmetry breaking, chirality transfer, and chiral amplification. Kinetic resolution of racemic mixtures emerges as a general solution for chiral amplification in prebiotic chemistry, leading to the single chirality of complex biological molecules and genetic polymers.

Spectroscopic and computational methods in the characterization of deep eutectic solvent, Gallic acid, and Glycerol

Several researchers have shown experimentally that Gallic acid has antioxidant, anti-inflammatory, and anti-aging properties, signifying its value in skin care. Glycerol has properties, such as increasing skin hydration, softening skin, and reducing skin dryness. The present work aims to understand the vibrational and spectroscopic study of the interacting mechanism of Deep Eutectic solvent mixture of Gallic acid and Glycerol. The theoretical analysis is performed using the Density Functional Theory with B3LYP/6-311 + g(d,p) level of theory. The optimized structure and frequency of the monomers and their biomolecular complex are obtained using Gauss view 6.0 and Gaussian16. The vibrational analysis is carried out using Vibrational Energy Distribution Analysis. The Natural Bond Orbital, molecular docking of the Glycerol-Gallic acid complex, and the molecular dynamics simulation of the docked protein-ligand system are carried out to understand the mechanism better. The theoretical and experimental frequencies are found to agree with each other. The Molecular Dynamic simulation analysis predicts that the protein-ligand complexation is relatively stable.

Interfacial Enrichment of Lauric Acid Assisted by Long-Chain Fatty Acids, Acidity and Salinity at Sea Spray Aerosol Surfaces.

Surfactant monolayers at sea spray aerosol (SSA) surfaces regulate various atmospheric processes including gas transfer, cloud interactions, and radiative properties. Most experimental studies of SSA employ a simplified surfactant mixture of long-chain fatty acids (LCFAs) as a proxy for the sea surface microlayer or SSA surface. However, medium-chain fatty acids (MCFAs) make up nearly 30% of the FA fraction in nascent SSA. Given that LCFA monolayers are easily disrupted upon the introduction of chemical heterogeneity (such as mixed chain lengths), simple FA proxies are unlikely to represent realistic SSA interfaces. Integrating experimental and computational techniques, we characterize the impact that partially soluble MCFAs have on the properties of atmospherically relevant LCFA mixtures. We explore the extent to which the MCFA lauric acid (LA) is surface stabilized by varying acidity, salinity, and monolayer composition. We also discuss the impacts of pH on LCFA-assisted LA retention, where the presence of LCFAs may shift the surface-adsorption equilibria of laurate─the conjugate base─toward higher surface activities. Molecular dynamic simulations suggest a mechanism for the enhanced surface retention of laurate. We conclude that increased FA heterogeneity at SSA surfaces promotes surface activity of soluble FA species, altering monolayer phase behavior and impacting climate-relevant atmospheric processes.

An Integrated Module Performs Selective ‘On‐Line’ Epoxidation in the Biosynthesis of the Antibiotic Mupirocin.

The delineation of the complex biosynthesis of the potent antibiotic mupirocin, which consists of a mixture of pseudomonic acids (PAs) isolated from Pseudomonas fluorescens NCIMB 10586, presents significant challenges and the timing and mechanisms of several key transformations remain elusive. Particularly intriguing are the steps that process the linear backbone from the initial polyketide assembly phase to generate the first cyclic intermediate PA‐B. These include epoxidation as well as incorporation of the tetrahydropyran (THP) ring and fatty acid sidechain required for biological activity. Here, we show that the mini‐module MmpE performs a rare online (ACP‐substrate) epoxidation and is integrated (‘in‐cis’) into the polyketide synthase via a docking domain. A linear polyketide fragment with 6 asymmetric centres was synthesised using a convergent approach and used to demonstrate substrate flux via an atypical KS0 and a previously unannotated ACP (MmpE_ACP). MmpE_ACP‐bound synthetic substrates were critical in demonstrating successful epoxidation in vitro by the purified MmpE oxidoreductase domain. Alongside feeding studies, these results confirm the timing as well as chain length dependence of this selective epoxidation. These mechanistic studies pinpoint the location and nature of the polyketide substrate prior to the key formation of the THP ring and esterification that generate PA‐B.

An Integrated Module Performs Selective 'On-Line' Epoxidation in the Biosynthesis of the Antibiotic Mupirocin.

The delineation of the complex biosynthesis of the potent antibiotic mupirocin, which consists of a mixture of pseudomonic acids (PAs) isolated from Pseudomonas fluorescens NCIMB 10586, presents significant challenges and the timing and mechanisms of several key transformations remain elusive.Particularly intriguing are the steps that process the linear backbone from the initial polyketide assembly phase to generate the first cyclic intermediate PA-B. These include epoxidation as well as incorporation of the tetrahydropyran (THP) ring and fatty acid sidechain required for biological activity. Here, we show that the mini-module MmpE performs a rare online (ACP-substrate) epoxidation and is integrated ('in-cis') into the polyketide synthase via a docking domain. A linear polyketide fragment with 6 asymmetric centres was synthesised using a convergent approach and used to demonstrate substrate flux via an atypical KS0and a previously unannotated ACP (MmpE_ACP). MmpE_ACP-bound synthetic substrates were critical in demonstrating successful epoxidation in vitro by the purified MmpE oxidoreductase domain. Alongside feeding studies, these results confirm the timing as well as chain length dependence of this selective epoxidation. These mechanistic studies pinpoint the location and nature of the polyketide substrate prior to the key formation of the THP ring and esterification that generate PA-B.

Electrochemical Synthesis of Isoquinoline Sulfone Compounds and Study of their Inhibition of Acetolactate Synthase Enzyme Activity

AbstractBoth of sulfone compounds and isoqunoline derivatives are important compounds. In this paper, Isoquinoline C1 and C3 Sulfone compounds have been synthesized by electrochemical means using isoquinoline N‐Oxides and some sodium benzenesulfinate as reactants, inexpensive and easily available sodium iodide as electrolytes, and a mixture of acetonitrile, water and acetic acid as reaction solvents. By using the method, a series of isoquinoline sulfone compounds have been synthesized in high yields. The reaction does not need oxidants and catalysts, and the reaction conditions are mild, environmentally friendly, efficient and suitable. In addition, we also carried out ALS enzyme inhibition experiments on the synthesized isoquinoline sulfone compounds, six of the isoquinoline sulfone compounds synthesized herein were found to inhibit ALS enzyme at a high rate, four of them inhibited ALS enzyme at a rate comparable to that of the commercialized herbicides Halosulfuron and Broadstrike, and the other two compounds also inhibited ALS enzyme at a rate higher than that of Halosulfuron and Broadstrike. Therefore, it is possible to find lead compounds with good herbicidal activity potential from these 6 compounds.

Supraperiosteal technique protocol for forehead filling with a mixture of calcium hydroxyapatite and hyaluronic acid: Double-blind, randomized controlled clinical trial.

The current study aims to investigate the safety and efficacy of using calcium hydroxyapatite (CaHA) versus CaHA associated with hyaluronic acid (HA) for forehead volume replacement and contour restoration without forehead irregularities. This interventional study involved 132 participants in a two-arm, parallel, double-blind trial for forehead treatment using the supraperiosteal technique. Group A received CaHA, and Group B received a combination of CaHA and HA as filler materials. Follow-up assessments occurred at 30 and 180 days, incorporating the 5-point Global Aesthetic Improvement Scale (GAIS) and photographic analysis for forehead volume replacement, contour restoration, and without forehead irregularities. Safety assessments included monitoring adverse events, particularly nodules. The study included all 132 enrolled patients who completed the trial. Applying CaHA in combination with HA resulted in a statistically significant improvement in both GAIS scale scores and the reduction of forehead irregularities. The total incidence of nodules was 3.7%. Group A had four times more occurrences of nodules than Group B. Furthermore, Group B exhibited lower rates of forehead irregularities following the treatment compared to Group A. The supraperiosteal application of CaHA and HA for forehead treatment demonstrates superior efficacy in addressing signs of aging compared to the isolated use of CaHA.

The Antioxidant and HDAC-Inhibitor α-Lipoic Acid Is Synergistic with Exemestane in Estrogen Receptor-Positive Breast Cancer Cells.

Anti-estrogenic therapy is established in the management of estrogen receptor (ER)-positive breast cancer. However, to overcome resistance and improve therapeutic outcome, novel strategies are needed such as targeting widely recognized aberrant epigenetics. The study aims to investigate the combination of the aromatase inhibitor exemestane and the histone deacetylase (HDAC) inhibitor and antioxidant α-lipoic acid in ER-positive breast cancer cells. First, the enantiomers and the racemic mixture of α-lipoic acid, and rac-dihydro-lipoic acid were investigated for HDAC inhibition. We found HDAC inhibitory activity in the 1-3-digit micromolar range with a preference for HDAC6. Rac-dihydro-lipoic acid is slightly more potent than rac-α-lipoic acid. The antiproliferative IC50 value of α-lipoic acid is in the 3-digit micromolar range. Notably, the combination of exemestane and α-lipoic acid resulted in synergistic behavior under various incubation times (24 h to 10 d) and readouts (MTT, live-cell fluorescence microscopy, caspase activation) analyzed by the Chou-Talalay method. α-lipoic acid increases mitochondrial fusion and the expression of apoptosis-related proteins p21, APAF-1, BIM, FOXO1, and decreases expression of anti-apoptotic proteins survivin, BCL-2, and c-myc. In conclusion, combining exemestane with α-lipoic acid is a promising novel treatment option for ER-positive breast cancer.

Influence of bulk-phase acidity, organic fraction, and dissolved oxygen on the photosensitized renoxification of nitrate in NaNO3/humic acid mixtures

Nitrate renoxification significantly influences atmospheric nitrogen cycling and global OH budgets. Although numerous nitrite acid (HONO) formation pathways from nitrate photolysis have been widely reported, the influence of various environmental factors and aerosol properties on reactive nitrogen production remains largely unclear. In this work, we employed NaNO3/humic acid (HA) as a model nitrate photosensitization system to investigate the crucial roles of aerosol acidity, organic fraction, and dissolved oxygen in the production of HONO, NO2, and NO2-. The presence of HA at 10 mg/L resulted in a remarkable increase in HONO production rates by approximately 2–3 times and NO2- concentration by 3–6 times across a pH range of 5.2 to 2.0. Meanwhile, the molar fraction of gaseous HONO in total N(III) production increased from 4 % to 69 % as bulk-phase pH decreased from 5.2 to 2.0. The higher organic fraction (i.e., 20 and 50 mg/L HA concentration) instead inhibited HONO and NO2 release. The presence of dissolved oxygen was found to be adverse for reactive nitrogen production. This suggests that the HA photosensitizer promoted the secondary conversion of NO2 to HONO mainly via reduced ketyl radical intermediates, while superoxide radical formation might exert a negative effect. Our findings provide comprehensive insights into reactive nitrogen production from photosensitized nitrate photolysis mediated by various external and internal factors, potentially accounting for discrepancies between field observations and model simulations.

Enhanced lithium host performance of multi-walled carbon nanotubes through acidic functionalization for lithium–sulfur batteries

Carbon nanotubes (CNTs) have been explored as a potential cathode material for lithium-sulfur (Li–S) batteries owing to their unique structure. However, traditional CNTs exhibit poor dispersion properties when preparing electrodes. The non-uniform distribution of the conductive agents hinders the formation of enough sites for sulfur loading, which results in the aggregation of sulfur/Li2S and severe polarization. In this study, we propose the acidic functionalization of CNTs in the cathode structure as a practical solution for mitigating the poor dispersion and polysulfide shuttling in lithium-sulfur batteries. Multiwalled CNTs were functionalized by oxidation through acidic treatment using sulfuric, nitric, and mixed acids. The cathode prepared with a mixture of sulfuric and nitric acids showed a coulombic efficiency of 99 % after 100 cycles, with a discharge capacity of 743 mAh g−1. These findings demonstrate the effectiveness of the acidic functionalization of CNTs as a promising approach for enhancing the electrochemical performance and commercial viability of lithium-sulfur batteries.