The aging behavior of degradable plastic polylactic acid under the interaction of environmental factors.

Microplastics leaching from aging biodegradable plastics pose potential environmental threats. This study used response surface methodology (RSM) to investigate the impact of temperature, light, and humidity on the aging characteristics of polylactic acid (PLA). Key evaluation metrics included the C/O ratio, functional groups, crystallinity, surface topography, and mechanical properties. Humidity was discovered to have the greatest effect on the ageing of PLA, followed by light and temperature. The interactions between temperature and light, as well as humidity and sunlight, significantly impact the aging of PLA. XPS analysis revealed PLA underwent aging due to the cleavage of the ester bond (O-C=O), resulting in the addition of C=O and C-O. The aging process of PLA was characterized by alterations in surface morphology and augmentation in crystallinity, resulting in a decline in both tensile strength and elongation. These findings might offer insights into the aging behavior of degradable plastics under diverse environmental conditions.

Microalgae to biodiesel: A novel green conversion method for high-quality lipids recovery and in-situ transesterification to fatty acid methyl esters.

Greenhouse gases (GHGs) emissions due to increasing energy demand have raised the need to identify effective solutions to produce clean and renewable energy. Biotechnologies are an effective platform to attain green transition objectives, especially when synergically integrated to promote health and environmental protection. In this context, microalgae-based biotechnologies are considered among the most effective tools for treating gaseous effluents and simultaneously capturing carbon sources for further biomass valorisation. The production of biodiesel is regarded as a promising avenue for harnessing value from residual algal biomass. Nonetheless, the existing techniques for extracting lipids still face certain limitations, primarily centred around the cost-effectiveness of the process.This study is dedicated to developing and optimising an innovative and cost-efficient technique for extracting lipids from algal biomass produced during gaseous emissions treatment based on algal-bacterial biotechnology. This integrated treatment technology combines a bio-scrubber for degrading gaseous contaminants and a photobioreactor for capturing the produced CO2 within valuable algal biomass. The cultivated biomass is then processed with the process newly designed to extract lipids simultaneously transesterificated in fatty acid methyl esters (FAME) via In Situ Transesterification (IST) with a Kumagawa-type extractor. The results of this study demonstrated the potential application of the optimised method to overcome the gap to green transition. Energy production was obtained from residuals produced during the necessary treatment of gaseous emissions. Using hexane-methanol (v/v = 19:1) mixture in the presence KOH in Kumagawa extractor lipids were extracted with extraction yield higher than 12% and converted in fatty acid methyl esters. The process showed the enhanced extraction of lipids converted in bio-sourced fuels with circular economy approach, broadening the applicability of biotechnologies as sustainable tools for energy source diversification.

[Chemical constituents from roots of Kadsura heteroclita].

The dichloromethane fraction of Kadsura heteroclita roots was separated and purified by chromatographic techniques(e.g., silica gel, Sephadex LH-20, ODS, MCI column chromatography) and semi-preparative HPLC. Twenty compounds were isolated from K. heteroclita, and their structures were identified by NMR, MS, UV, and X-ray single crystal diffraction techniques. Twenty compounds were isolated from K. heteroclita, which were identified as xuetongdilactone G(1), mallomacrostin C(2), 3,4-seco(24Z)-cychmrt-4(28),24-diene-3,26-dioic acid 3-methyl ester(3), nigranoic acid(4), methyl ester schizanlactone E(5), schisandronic acid(6), heteroclic acid(7), wogonin(8),(2R,3R)-4'-O-methyldihydroquercetin(9), 15,16-bisnor-13-oxo-8(17),11E-labdadien-19-oic acid(10), stigmast-4-ene-6ß-ol-3-one(11), psoralen(12),(1R,2R,4R)-trihydroxy-p-menthane(13), homovanillyl alcohol(14), 2-(4-hydroxyphenyl)-ethanol(15), coniferaldehyde(16),(E)-7-(4-hydroxy-3-methoxyphenyl)-7-methylbut-8-en-9-one(17), acetovanillone(18), vanillic acid(19) and vanillin(20). Compound 1 is a new compound named xuetongdilactone G. Compounds 2-3 and 8-20 are isolated from K. heteroclita for the first time.

Novel glycosidase from Paenibacillus lactis 154 hydrolyzing the 28-O-ß-D-glucopyranosyl ester bond of oleanane-type saponins.

Oleanane-type ginsenosides are a class of compounds with remarkable pharmacological activities. However, the lack of effective preparation methods for specific rare ginsenosides has hindered the exploration of their pharmacological properties. In this study, a novel glycoside hydrolase PlGH3 was cloned from Paenibacillus lactis 154 and heterologous expressed in Escherichia coli. Sequence analysis revealed that PlGH3 consists of 749 amino acids with a molecular weight of 89.5 kDa, exhibiting the characteristic features of the glycoside hydrolase 3 family. The enzymatic characterization results of PlGH3 showed that the optimal reaction pH and temperature was 8 and 50 °C by using p-nitrophenyl-ß-D-glucopyranoside as a substrate, respectively. The Km and kcat values towards ginsenoside Ro were 79.59 ± 3.42 µM and 18.52 s-1, respectively. PlGH3 exhibits a highly specific activity on hydrolyzing the 28-O-ß-D-glucopyranosyl ester bond of oleanane-type saponins. The mechanism of hydrolysis specificity was then presumably elucidated through molecular docking. Eventually, four kinds of rare oleanane-type ginsenosides (calenduloside E, pseudoginsenoside RP1, zingibroside R1, and tarasaponin VI) were successfully prepared by biotransforming total saponins extracted from Panax japonicus. This study contributes to understanding the mechanism of enzymatic hydrolysis of the GH3 family and provides a practical route for the preparation of rare oleanane-type ginsenosides through biotransformation. KEY POINTS: • The glucose at C-28 in oleanane-type saponins can be directionally hydrolyzed. • Mechanisms to interpret PlGH3 substrate specificity by molecular docking. • Case of preparation of low-sugar alternative saponins by directed hydrolysis.

Evaluation of phthalate migration potential in vacuum-packed.

In recent years, the presence and migration of PAEs in packaging materials and consumer products has become a serious concern. Based on this concern, the aim of our study is to determine the possible migration potential and speed of PAEs in benthic fish stored in vacuum packaging, as well as to monitor the storage time and type as well as polyethylene (PE) polymer detection.As a result of the analysis performed by µ-Raman spectroscopy, 1 microplastic (MP) of 6 µm in size was determined on the 30th day of storage in whiting fish muscle and the polymer type was found to be Polyethylene (PE) (low density polyethylene: LDPE). Depending on the storage time of the packaging used in the vacuum packaging process, it has been determined that its chemical composition is affected by temperature and different types of polymers are formed. 10 types of PAEs were identified in the packaging material and stored flesh fish: DIBP, DBP, DPENP, DHEXP, BBP, DEHP, DCHP, DNOP, DINP and DDP. While the most dominant PAEs in the packaging material were determined as DEHP, the most dominant PAEs in fish meat were recorded as BBP and the lowest as DMP. The findings provide a motivating model for monitoring the presence and migration of PAEs in foods, while filling an important gap in maintaining a safe food chain.

Plant-Derived Caffeic Acid and Its Derivatives: An Overview of Their NMR Data and Biosynthetic Pathways.

In recent years, caffeic acid and its derivatives have received increasing attention due to their obvious physiological activities and wide distribution in nature. In this paper, to clarify the status of research on plant-derived caffeic acid and its derivatives, nuclear magnetic resonance spectroscopy data and possible biosynthetic pathways of these compounds were collected from scientific databases (SciFinder, PubMed and China Knowledge). According to different types of substituents, 17 caffeic acid and its derivatives can be divided into the following classes: caffeoyl ester derivatives, caffeyltartaric acid, caffeic acid amide derivatives, caffeoyl shikimic acid, caffeoyl quinic acid, caffeoyl danshens and caffeoyl glycoside. Generalization of their 13C-NMR and 1H-NMR data revealed that acylation with caffeic acid to form esters involves acylation shifts, which increase the chemical shift values of the corresponding carbons and decrease the chemical shift values of the corresponding carbons of caffeoyl. Once the hydroxyl group is ester, the hydrogen signal connected to the same carbon shifts to the low field (1.1~1.6). The biosynthetic pathways were summarized, and it was found that caffeic acid and its derivatives are first synthesized in plants through the shikimic acid pathway, in which phenylalanine is deaminated to cinnamic acid and then transformed into caffeic acid and its derivatives. The purpose of this review is to provide a reference for further research on the rapid structural identification and biofabrication of caffeic acid and its derivatives.

Latest Trends in Lipase-Catalyzed Synthesis of Ester Carbohydrate Surfactants: From Key Parameters to Opportunities and Future Development.

Carbohydrate-based surfactants are amphiphilic compounds containing hydrophilic moieties linked to hydrophobic aglycones. More specifically, carbohydrate esters are biosourced and biocompatible surfactants derived from inexpensive renewable raw materials (sugars and fatty acids). Their unique properties allow them to be used in various areas, such as the cosmetic, food, and medicine industries. These multi-applications have created a worldwide market for biobased surfactants and consequently expectations for their production. Biobased surfactants can be obtained from various processes, such as chemical synthesis or microorganism culture and surfactant purification. In accordance with the need for more sustainable and greener processes, the synthesis of these molecules by enzymatic pathways is an opportunity. This work presents a state-of-the-art lipase action mode, with a focus on the active sites of these proteins, and then on four essential parameters for optimizing the reaction: type of lipase, reaction medium, temperature, and ratio of substrates. Finally, this review discusses the latest trends and recent developments, showing the unlimited potential for optimization of such enzymatic syntheses.

Design, Synthesis and Biological Evaluation of Novel Phenyl-Substituted Naphthoic Acid Ethyl Ester Derivatives as Strigolactone Receptor Inhibitor.

Strigolactones (SLs) are plant hormones that regulate several key agronomic traits, including shoot branching, leaf senescence, and stress tolerance. The artificial regulation of SL biosynthesis and signaling has been considered as a potent strategy in regulating plant architecture and combatting the infection of parasitic weeds to help improve crop yield. DL1b is a previously reported SL receptor inhibitor molecule that significantly promotes shoot branching. Here, we synthesized 18 novel compounds based on the structure of DL1b. We performed rice tillering activity assay and selected a novel small molecule, C6, as a candidate SL receptor inhibitor. In vitro bioassays demonstrated that C6 possesses various regulatory functions as an SL inhibitor, including inhibiting germination of the root parasitic seeds Phelipanche aegyptiaca, delaying leaf senescence and promoting hypocotyl elongation of Arabidopsis. ITC analysis and molecular docking experiments further confirmed that C6 can interact with SL receptor proteins, thereby interfering with the binding of SL to its receptor. Therefore, C6 is considered a novel SL receptor inhibitor with potential applications in plant architecture control and prevention of root parasitic weed infestation.

In Vivo Absorption and Lymphatic Bioavailability of Docosahexaenoic Acid from Microalgal Oil According to Its Physical and Chemical Form of Vectorization.

Docosahexaenoic acid (DHA) is an essential fatty acid (FA) with proven pro-health effects, but improving its bioavailability is becoming a public health issue. The bioavailability of DHA from microalgal (A) oil has been comprehensively assessed, particularly in terms of the molecular structuring capabilities offered by A-oil. Here, we explored the impact of five DHA-rich formulas differing in terms of (i) molecular structure, i.e., ethyl ester (EE), monoglyceride (MG), or triglyceride (TG), and (ii) supramolecular form, i.e., emulsified TG or TG + phospholipids (PL blend) on the lymphatic kinetics of DHA absorption and the lipid characteristics of the resulting lipoproteins. We demonstrated in rats that the conventional A-DHA TG structure afforded more effective DHA absorption than the EE structure (+23%). Furthermore, the A-DHA MG and A-DHA emulsions were the better DHA vectors (AUC: 89% and +42%, respectively) due to improved lipolysis. The A-DHA MG and A-DHA emulsion presented the richest DHA content in TG (+40%) and PL (+50%) of lymphatic chylomicrons, which could affect the metabolic fate of DHA. We concluded that structuring A-DHA in TG or EE form would better serve for tissue and hepatic metabolism whereas A-DHA in MG and emulsion form could better target nerve tissues.

Prenatal organophosphate esters exposure and neurodevelopment trajectory in infancy: Evidence from the Shanghai Maternal-Child Pairs Cohort.

BACKGROUND: Concerns remain about the neurotoxic properties of the ubiquitous organophosphate esters (OPEs), the replacement of the toxicant polybrominated diphenyl ethers. OBJECTIVES: We examined the associations of prenatal exposure to OPEs and their mixtures with early-life neurodevelopment trajectories. METHODS: Totally 1276 mother-child pairs were recruited from the Shanghai Maternal-Child Pairs Cohort. A high-performance liquid chromatography-triple quadrupole mass spectrometer was used to measure the levels of 7 OPEs in cord serum. Ages and Stages Questionnaires was used to examine children's neuropsychological development at 2, 6, 12, and 24 months of age. Group-based trajectory models were applied to derive the neurodevelopmental trajectories. Multiple linear regression and logistic regression model were performed to assess the relationships between OPEs exposure and neurodevelopment and trajectories. Mixtures for widely detected OPEs (n = 4) were investigated using quantile-based g-computation. RESULTS: Tributyl phosphate (TBP), tris (2-butoxy ethyl) phosphate (TBEP), tris(1,3-dichloro-2-propyl) phosphate (TDCPP), and 2-ethylhexyl diphenyl phosphate (EHDPP), had detection rates >50 %. TDCPP had the highest median concentration (1.02 µg/L) in cord serum. EHDPP concentrations were negatively associated with scores in most domains at 12 months of age, with effect values (ß) ranging from -1.89 to -0.57. EHDPP could negatively affect the total ASQ (OR = 1.07, 95 % CI: 1, 1.15) and gross-motor (OR = 1.09, 95 % CI: 1.02, 1.17) trajectory in infancy. Joint exposure to OPEs was associated with decreased scores in the total ASQ, gross-motor, fine-motor and problem-solving domain of 12-month-old infants, with ß ranging from -5.93 to -1.25. In addition, the qgcomp models indicated significant positive associations between the concentrations of OPEs mixtures and risks of the persistently low group of the total ASQ, gross-motor and fine-motor development in early childhood. The impact of OPEs was more pronounced in boys. DISCUSSION: Our findings suggested OPEs, especially EHDPP, had a persistently negative effect on neurodevelopment during the first 2 years.

Differential responses of rumen and fecal fermentation and microbiota of Liaoning cashmere goats after 2-hydroxy-4-(methylthio) butanoic acid isopropyl ester supplementation.

The 2-hydroxy-4-(methylthio) butanoic acid isopropyl ester (HMBi), a rumen protective methionine, has been extensively studied in dairy cows and beef cattle and has been shown to regulate gastrointestinal microbiota and improve production performance. However, knowledge of the application of HMBi on cashmere goats and the simultaneous study of rumen and hindgut microbiota is still limited. In this study, HMBi supplementation increased the concentration of total serum protein, the production of microbial protein in the rumen and feces, as well as butyrate production in the feces. The results of PCoA and PERMANOVA showed no significant difference between the rumen microbiota, but there was a dramatic difference between the fecal microbiota of the two groups of Cashmere goats after the HMBi supplementation. Specifically, in the rumen, HMBi significantly increased the relative abundance of some fiber-degrading bacteria (such as Fibrobacter) compared with the CON group. In the feces, as well as a similar effect as in the rumen (increasing the relative abundance of some fiber-degrading bacteria, such as Lachnospiraceae FCS020 group and ASV32), HMBi diets also increased the proliferation of butyrate-producing bacteria (including Oscillospiraceae UCG-005 and Christensenellaceae R-7 group). Overall, these results demonstrated that HMBi could regulate the rumen and fecal microbial composition of Liaoning cashmere goats and benefit the host.

The application of phenylboronic acid pinacol ester functionalized ROS-responsive multifunctional nanoparticles in the treatment of Periodontitis.

Periodontitis is an inflammatory disease induced by the complex interactions between the host immune system and the microbiota of dental plaque. Oxidative stress and the inflammatory microenvironment resulting from periodontitis are among the primary factors contributing to the progression of the disease. Additionally, the presence of dental plaque microbiota plays a significant role in affecting the condition. Consequently, treatment strategies for periodontitis should be multi-faceted. In this study, a reactive oxygen species (ROS)-responsive drug delivery system was developed by structurally modifying hyaluronic acid (HA) with phenylboronic acid pinacol ester (PBAP). Curcumin (CUR) was encapsulated in this drug delivery system to form curcumin-loaded nanoparticles (HA@CUR NPs). The release results indicate that CUR can be rapidly released in a ROS environment to reach the concentration required for treatment. In terms of uptake, HA can effectively enhance cellular uptake of NPs because it specifically recognizes CD44 expressed by normal cells. Moreover, HA@CUR NPs not only retained the antimicrobial efficacy of CUR, but also exhibited more pronounced anti-inflammatory and anti-oxidative stress functions both in vivo and in vitro. This provides a good potential drug delivery system for the treatment of periodontitis, and could offer valuable insights for dental therapeutics targeting periodontal diseases.

A formal vinylic substitution reaction for the synthesis of α,ß-unsaturated enol esters and their anticancer potential.

Arylsulfonyl group-bearing α,ß-unsaturated enol esters were readily assembled via the Cs2CO3-mediated union of 2-bromoallyl sulfones and cinnamic acids. The overall transformation is equivalent to an sp2 carbon-oxygen coupling reaction, and therefore constitutes a formal vinylic substitution. Several of the products display promising levels of antiproliferative activities higher than that of the anticancer drug carboplatin. Thiophenol reacted with 2-bromoallyl sulfones under identical conditions to afford α-thiophenyl-α'-tosyl acetone via an apparent aerial oxidation.

Phthalate acid esters: A review of aquatic environmental occurrence and their interactions with plants.

The increasing use of phthalate acid esters (PAEs) in various applications has inevitably led to their widespread presence in the aquatic environment. This presents a considerable threat to plants. However, the interactions between PAEs and plants in the aquatic environment have not yet been comprehensively reviewed. In this review, the properties, occurrence, uptake, transformation, and toxic effects of PAEs on plants in the aquatic environment are summarized. PAEs have been prevalently detected in the aquatic environment, including surface water, groundwater, seawater, and sediment, with concentrations ranging from the ng/L or ng/kg to the mg/L or mg/kg range. PAEs in the aquatic environment can be uptake, translocated, and metabolized by plants. Exposure to PAEs induces multiple adverse effects in aquatic plants, including growth perturbation, structural damage, disruption of photosynthesis, oxidative damage, and potential genotoxicity. High-throughput omics techniques further reveal the underlying toxicity molecular mechanisms of how PAEs disrupt plants on the transcription, protein, and metabolism levels. Finally, this review proposes that future studies should evaluate the interactions between plants and PAEs with a focus on long-term exposure to environmental PAE concentrations, the effects of PAE alternatives, and human health risks via the intake of plant-based foods.

Organophosphate esters (OPEs) in corals of the South China Sea: Occurrence, distribution, and bioaccumulation.

Organophosphate esters (OPEs) have garnered significant attention in recent years. In view of the enormous ecosystem services value and severe degradation of coral reefs in the South China Sea, this study investigated the occurrence, distribution, and bioaccumulation of 11 OPEs in five coral regions: Daya Bay (DY), Weizhou Island (WZ), Sanya Luhuitou (LHT), Xisha (XS) Islands, and Nansha (NS) Islands. Although OPEs were detected at a high rate, their concentration in South China Sea seawater (1.56 ± 0.89 ng L-1) remained relatively low compared to global levels. All OPEs were identified in coral tissues, with Luhuitou (575 ± 242 ng g-1 dw) showing the highest pollution levels, attributed to intense human activities. Coral mucus, acting as a defense against environmental stresses, accumulated higher ∑11OPEs (414 ± 461 ng g-1 dw) than coral tissues (412 ± 197 ng g-1 dw) (nonparametric test, p < 0.05), and their compositional characteristics varied greatly. In the case of harsh aquatic environments, corals increase mucus secretion and then accumulate organic pollutants. Tissue-mucus partitioning varied among coral species. Most OPEs were found to be bioaccumulative (BAFs >5000 L kg-1) in a few coral tissue samples besides Triphenyl phosphate (TPHP). Mucus' role in the bioaccumulation of OPEs in coral shouldn't be ignored.

Proposed molecular mechanism of non-competitive inhibition using molecular dynamics simulations between α-glucosidase enzyme and mangostin compound as antidiabetic.

CONTEXT: Further understanding of the molecular mechanisms is necessary since it is important for designing new drugs. This study aimed to understand the molecular mechanisms involved in the design of drugs that are inhibitors of the α-glucosidase enzyme. This research aims to gain further understanding of the molecular mechanisms underlying antidiabetic drug design. The molecular docking process yielded 4 compounds with the best affinity energy, including γ-Mangostin, 1,6-dimethyl-ester-3-isomangostin, 1,3,6-trimethyl-ester-α-mangostin, and 3,6,7-trimethyl-ester-γ-mangostin. Free energy calculation with molecular mechanics with generalized born and surface area solvation indicated that the 3,6,7-trimethyl-γ-mangostin had a better free energy value compared to acarbose and simulated maltose together with 3,6,7-trimethyl-γ-mangostin compound. Based on the analysis of electrostatic, van der Waals, and intermolecular hydrogen interactions, 3,6,7-trimethyl-γ-mangostin adopts a noncompetitive inhibition mechanism, whereas acarbose adopts a competitive inhibition mechanism. Consequently, 3,6,7-trimethyl-ester-γ-mangostin, which is a derivative of γ-mangostin, can provide better activity in silico with molecular docking approaches and molecular dynamics simulations. METHOD: This research commenced with retrieving protein structures from the RCSB database, generating the formation of ligands using the ChemDraw Professional software, conducting molecular docking with the Autodock Vina software, and performing molecular dynamics simulations using the Amber software, along with the evaluation of RMSD values and intermolecular hydrogen bonds. Free energy, electrostatic interactions, and Van der Waals interaction were calculated using MM/GBSA. Acarbose, used as a positive control, and maltose are simulated together with test compound that has the best free energy. The forcefields used for molecular dynamics simulations are ff19SB, gaff2, and tip3p.

Fungal-Bacterial Mutualism: Species and Strain-Dependent Simultaneous Modulation of Branched-Chain Esters and Indole Derivatives in Fermented Sausages through Metabolite Cross-Feeding.

The precise impact of species and strain diversity on fungal-bacterial interactions and the overall community functioning has remained unclear. First, our study revealed how Debaryomyces hansenii influences diverse bacteria to accumulate key metabolites in a simulated fermented food system. For flavor, D. hansenii promoted the accumulation of branched-chain esters in Staphylococcus xylosus by promoting growth and facilitating the precursor branched-chain acids transformations but hindered the accumulation of Staphylococcus equorum. Furthermore, fungal-bacterial interactions displayed diversity among S. equorum strains. For bioactive compounds, species and strain diversity of lactic acid bacteria (LAB) also influences the production of indole derivatives. Then, we investigated specific metabolic exchanges under reciprocal interaction. Amino acids, rather than vitamins, were identified as the primary drivers of the bacterial growth promotion. Moreover, precursor transformations by D. hansenii played a significant role in branched-chain esters production. Finally, a synthetic community capable of producing high concentrations of branched-chain esters and indole derivatives was successfully constructed. These results provide valuable insights into understanding and designing synthetic communities for fermented sausages.

Delay in the fine-tuning of locomotion in infants with meconium positive to biomarkers of alcohol exposure: a pilot study.

INTRODUCTION: Prenatal alcohol exposure causes a variety of impairments to the fetus called Fetal Alcohol Spectrum Disorders (FASD). Since it is very difficult to identify women that consume alcohol during pregnancy, different methods have been studied to evaluate alcohol exposure. Ethyl Glucuronide (EtG) and Fatty Acid Ethyl Esters (FAEEs) are commonly used to measure alcohol consumption in individuals at-risk for alcohol abuse, including pregnant women. MATERIALS AND METHODS: We conducted a study of two cohorts of 1.5 year-old infants (of mothers without a history of alcohol abuse) with or without meconium samples positive to both EtG and FAEEs and we evaluated their cognitive-behavioral development by the Griffiths Mental Developmental Scale (GMDS) method. Our protocol included 8 infants with meconium positive to alcohol metabolites (EtG and FAEEs) and 7 with meconium negative to alcohol metabolites. RESULTS: None of the 8 alcohol metabolites positive meconium infants exhibited distinctive facial features and growth retardation of severe FASD, showing that other factors may contribute to the FASD onset but elevations in EtG and FAEEs in the meconium were significantly associated with disrupted neurodevelopment and adaptive functions within the first year and a half of life. Indeed, we found out that infants with meconium positive for both EtG and FAEEs, although without displaying any FASD morphological features, had a delay in the fine regulation of their own locomotory capabilities. CONCLUSIONS: Further analyses and larger studies are needed to estimate the right link between prenatal alcohol exposure and the different range of disorders connected but this study provides an additional step in the field of FASD in order to suggest early treatments for at-risk newborns and infants.

[Effect of asiaticoside on systolic blood pressure and relaxation of isolated thoracic aorta of rats].

OBJECTIVE: To investigate the effect of asiaticoside on blood pressure and relaxation of thoracic aorta in rats and explore the underlying mechanism. METHODS: SD rats treated with 50 and 100 mg/kg asiaticoside by daily gavage for 2 weeks were monitored for systolic blood pressure changes, and histological changes of the thoracic aorta were evaluated using HE staining. In isolated rat endothelium-intact and endothelium-denuded thoracic aorta rings, the effects of asiaticoside on relaxation of the aortic rings were tested at baseline and following norepinephrine (NE)- and KCl-induced constriction. The vascular relaxation effect of asiaticoside was further observed in NE-stimulated endothelium-intact rat aortic rings pretreated with L-nitroarginine methyl ester, indomethacin, zinc protoporphyrin Ⅸ, tetraethyl ammonium chloride, glibenclamide, barium chloride, Iberiotoxin, 4-aminopyridine, or TASK-1-IN-1. The aortic rings were treated with KCl and NE followed by increasing concentrations of CaCl2 to investigate the effect of asiaticoside on vasoconstriction induced by external calcium influx and internal calcium release. RESULTS: Asiaticoside at 50 and 100 mg/kg significantly lowered systolic blood pressure in rats without affecting the thoracic aorta histomorphology. While not obviously affecting resting aortic rings with intact endothelium, asiaticoside at 100 mg/kg induced significant relaxation of the rings constricted by KCl and NE, but its effects differed between endothelium-intact and endothelium-denuded rings. In endothelium-intact aortic rings pretreated with indomethacin, ZnPP Ⅸ, barium chloride, glyburide, TASK-1-IN-1 and 4-aminopyridine, asiaticoside did not produce significant effect on NE-induced vasoconstriction, and tetraethylammonium, Iberiotoxin and L-nitroarginine methyl ester all inhibited the relaxation effect of asiaticoside. In KCland NE-treated rings, asiaticoside obviously inhibited CaCl2-induced vascular contraction. CONCLUSION: Asiaticoside induces thoracic aorta relaxation by mediating high-conductance calcium-activated potassium channel opening, promoting nitric oxide release from endothelial cells and regulating Ca2+ influx and outflow, thereby reducing systolic blood pressure in rats.

Threading the needle: Achieving simplicity and performance in cellulose alkanoate ω-carboxyalkanoates for amorphous solid dispersion.

Most active pharmaceutical ingredients (APIs) suffer from poor water solubility, often keeping them from reaching patients. To overcome the issues of poor drug solubility and subsequent low bioavailability, amorphous solid dispersions (ASDs) have garnered much attention. Cellulose ester derivatives are of interest for ASD applications as they are benign, sustainable-based, and successful in commercial drug delivery systems, e.g. in osmotic pump systems and as commercial ASD polymers. Synthesis of carboxy-pendant cellulose esters is a challenge, due in part to competing reactions between carboxyls and hydroxyls, forming ester crosslinks. Herein we demonstrate proof-of-concept for a scalable synthetic route to simple, yet highly promising ASD polymers by esterifying cellulose polymers through ring-opening of cyclic succinic or glutaric anhydride. We describe the complexity of such ring-opening reactions, not previously well-described, and report ways to avoid gelation. We report synthesis, characterization, and preliminary in vitro ASD evaluations of fifteen such derivatives. Synthetic routes were designed to accommodate these criteria: no protecting groups, no metal catalysts, mild conditions with standard reagents, simple purification, and one-pot synthesis. Finally, these designed ASD polymers included members that maintained fast-crystallizing felodipine in solution and release it from an ASD at rather high 20 % drug loading (DL).