Associations of Serum Perfluoroalkyl Substances and Placental Human Chorionic Gonadotropin in Early Pregnancy, Measured in the UPSIDE Study in Rochester, New York.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are widely detected in pregnant women and associated with adverse outcomes related to impaired placental function. Human chorionic gonadotropin (hCG) is a dimeric glycoprotein hormone that can indicate placental toxicity. OBJECTIVES: Our aim was to quantify the association of serum PFAS with placental hCG, measured as an intact molecule (hCG), as free alpha-(hCGα) and beta-subunits (hCGß), and as a hyperglycosylated form (h-hCG), and evaluate effect measure modification by social determinants and by fetal sex. METHODS: Data were collected from 326 pregnant women enrolled from 2015 to 2019 in the UPSIDE study in Rochester, New York. hCG forms were normalized for gestational age at the time of blood draw in the first trimester [multiple of the median (MoM)]. Seven PFAS were measured in second-trimester maternal serum. Multivariate imputation by chained equations and inverse probability weighting were used to evaluate robustness of linear associations. PFAS mixture effects were estimated by Bayesian kernel machine regression. RESULTS: Perfluorohexane sulfonic acid (PFHxS) [hCGß: 0.29 log MoM units per log PFHxS; 95% confidence interval (CI): 0.08, 0.51] and perfluorodecanoic acid (PFDA) (hCG: -0.09; 95% CI: -0.16, -0.02) were associated with hCG in the single chemical and mixture analyses. The PFAS mixture was negatively associated with hCGα and positively with hCGß. Subgroup analyses revealed that PFAS associations with hCG differed by maternal race/ethnicity and education. Perfluoropentanoic acid (PFPeA) was associated with hCGß only in Black participants (-0.23; 95% CI: -0.37, -0.09) and in participants with high school education or less (-0.14; 95% CI: -0.26, -0.02); conversely, perfluorononanoic acid (PFNA) was negatively associated with hCGα only in White participants (-0.15; 95% CI: -0.27, -0.03) and with hCGß only in participants with a college education or greater (-0.19; 95% CI: -0.36, -0.01). These findings were robust to testing for selection bias, confounding bias, and left truncation bias where PFAS detection frequency was <100%. Two associations were negative in male (and null in female) pregnancies: Perfluoroundecanoic acid (PFUnDA) with hCGα, and PFNA with h-hCG. CONCLUSIONS: Evidence was strongest for the association between PFHxS and PFDA with hCG in all participants and for PFPeA and PFNA within subgroups defined by social determinants and fetal sex. PFAS mixture associations with hCGα and hCGß differed, suggesting subunit-specific types of toxicity and/or regulation. Future studies will evaluate the biological, clinical and public health significance of these findings. https://doi.org/10.1289/EHP12950.

Environmental sustainability assessment of biodegradable bio-based poly(3-hydroxybutyrate-co-3-hydroxyvalerate) from agro-residues: Production and end-of-life scenarios.

In the context of a circular bio-based economy, more public attention has been paid to the environmental sustainability of biodegradable bio-based plastics, particularly plastics produced using emerging biotechnologies, e.g. poly(3-hydroxybutyrate-co-3-hydroxyvalerate) or PHBV. However, this has not been thoroughly investigated in the literature. Therefore, this study aimed to address three aspects regarding the environmental impact of PHBV-based plastic: (i) the potential environmental benefits of scaling up pellet production from pilot to industrial scale and the environmental hotspots at each scale, (ii) the most favourable end-of-life (EOL) scenario for PHBV, and (iii) the environmental performance of PHBV compared to benchmark materials considering both the pellet production and EOL stages. Life cycle assessment (LCA) was implemented using Cumulative Exergy Extraction from the Natural Environment (CEENE) and Environmental Footprint (EF) methods. The results show that, firstly, when upscaling the PHBV pellet production from pilot to industrial scale, a significant environmental benefit can be achieved by reducing electricity and nutrient usage, together with the implementation of better practices such as recycling effluent for diluting feedstock. Moreover, from the circularity perspective, mechanical recycling might be the most favourable EOL scenario for short-life PHBV-based products, using the carbon neutrality approach, as the material remains recycled and hence environmental credits are achieved by substituting recyclates for virgin raw materials. Lastly, PHBV can be environmentally beneficial equal to or even to some extent greater than common bio- and fossil-based plastics produced with well-established technologies. Besides methodological choices, feedstock source and technology specifications (e.g. pure or mixed microbial cultures) were also identified as significant factors contributing to the variations in LCA of (bio)plastics; therefore, transparency in reporting these factors, along with consistency in implementing the methodologies, is crucial for conducting a meaningful comparative LCA.

Production of polyhydroxyalkanoates by engineered Halomonas bluephagenesis using starch as a carbon source.

A novel α-amylase Amy03713 was screened and cloned from the starch utilization strain Vibrio alginolyticus LHF01. When heterologously expressed in Escherichia coli, Amy03713 exhibited the highest enzyme activity at 45 °C and pH 7, maintained >50 % of the enzyme activity in the range of 25-75 °C and pH 5-9, and sustained >80 % of the enzyme activity in 25 % (w/v) of NaCl solution, thus showing a wide range of adapted temperatures, pH, and salt concentrations. Halomonas bluephagenesis harboring amy03713 gene was able to directly utilize starch. With optimized amylase expression, H. bluephagenesis could produce poly(3-hydroxybutyrate) (PHB), poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), and poly(3-hydroxybutyrate-co-4-hydroxybutyrate) (P34HB). When cultured for PHB production, recombinant H. bluephagenesis was able to grow up to a cell dry weight of 11.26 g/L, achieving a PHB titer of 6.32 g/L, which is the highest titer that has been reported for PHB production from starch in shake flasks. This study suggests that Amy03713 is an ideal amylase for PHA production using starch as the carbon source in H. bluephagenesis.

Electrospun films incorporating humic substances of application interest in sustainable active food packaging.

Sustainable active food packaging is essential to reduce the use of plastics, preserve food quality and minimize the environmental impact. Humic substances (HS) are rich in redox-active compounds, such as quinones, phenols, carboxyl, and hydroxyl moieties, making them functional additives for biopolymeric matrices, such as poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV). Herein, composites made by incorporating different amounts of HS into PHBV were developed using the electrospinning technology and converted into homogeneous and continuous films by a thermal post-treatment to obtain a bioactive and biodegradable layer which could be part of a multilayer food packaging solution. The morphology, thermal, optical, mechanical, antioxidant and barrier properties of the resulting PHBV-based films have been evaluated, as well as the antifungal activity against Aspergillus flavus and Candida albicans and the antimicrobial properties against both Gram (+) and Gram (-) bacterial strains. HS show great potential as natural additives for biopolymer matrices, since they confer antioxidant, antimicrobial, and antifungal properties to the resulting materials. In addition, barrier, optical and mechanical properties highlighted that the obtained films are suitable for sustainable active packaging. Therefore, the electrospinning methodology is a promising and sustainable approach to give biowaste a new life through the development of multifunctional materials suitable in the active bio-packaging.

Therapeutic effect of Sanhua decoction on rats with middle cerebral artery occlusion and the associated changes in gut microbiota and short-chain fatty acids.

Sanhua decoction (SHD), a traditional prescription, has long been used in treating ischemic stroke (IS). However, the therapeutic effect of SHD and the associated changes in gut microbiota and short-chain fatty acids (SCFAs) are uncertain. In this study, a rat model of IS was established by the middle cerebral artery occlusion (MCAO). By evaluating the cerebral infarct area and brain tissue pathology, it was found that SHD ameliorated IS-related symptoms in MCAO rats. Using 16S rRNA gene sequencing, we found that SHD reduced abnormally elevated Lactobacillus and opportunistic pathogens such as Desulfovibrio, but increased some beneficial bacteria that produce SCFAs, including Clostridia, Lachnospiraceae, Ruminococcaceae, and Coprococcus. KEGG analysis revealed that SHD regulates several pathways, including D-arginine and D-ornithine metabolism, polyketide sugar unit biosynthesis, and cyanoamino acid metabolism, which are significantly altered in MCAO rats. By gas chromatography-mass spectrometry detection of SCFAs, we found that fecal acetic acid, valeric acid, and caproic acid were significantly increased in MCAO rats, whereas propionic acid and isobutyric acid were decreased. SHD reversed the changes in acetic acid and propionic acid in the model rats and significantly increased fecal butyric acid. In addition, MCAO rats had significantly higher serum levels of acetic acid, butyric acid, isovaleric acid, and valeric acid, and lower levels of caproic acid. Altered serum levels of butyric acid, isovaleric acid, valeric acid, and caproic acid were restored, and the level of isobutyric acid was reduced after SHD administration. Spearman analysis revealed that cerebral infarct area had a strong correlation with Bifidobacterium, Desulfovibrio, Lachnospiraceae, Lactobacillus, acetic acid, valeric acid, and caproic acid. Overall, this study demonstrates for the first time that the effect of SHD on IS may be related to gut microbiota and SCFAs, providing a potential scientific explanation for the ameliorative effect of SHD on IS.

Valeric acid reduction by chitosan oligosaccharide induces autophagy in a Parkinson's disease mouse model.

Parkinson's disease (PD) is a central nervous system disease with the highest disability and mortality rate worldwide, and it is caused by a variety of factors. The most common medications for PD have side effects with limited therapeutic outcomes. Many studies have reported that chitosan oligosaccharide (COS) crossed blood-brain barrier to achieve a neuroprotective effect in PD. However, the role of COS in PD remains unclear. The present study demonstrated that COS increased dopaminergic neurons in the substantia nigra (SN) and ameliorated dyskinesia in a PD mouse model. Moreover, COS reduced gut microbial diversity and faecal short-chain fatty acids. Valeric acid supplementation enhanced the inflammatory response in the colon and SN, and it reversed COS - suppressed dopamine neurons damage. Autophagy was involved in COS modulating inflammation through valeric acid. These results suggest that COS reduces bacterial metabolites - valeric acid, which diminishes inflammation via activating autophagy, ultimately alleviating PD.

Lactobacillus acidophilus suppresses non-alcoholic fatty liver disease-associated hepatocellular carcinoma through producing valeric acid.

BACKGROUND: Gut probiotic depletion is associated with non-alcoholic fatty liver disease-associated hepatocellular carcinoma (NAFLD-HCC). Here, we investigated the prophylactic potential of Lactobacillus acidophilus against NAFLD-HCC. METHODS: NAFLD-HCC conventional and germ-free mice were established by diethylnitrosamine (DEN) injection with feeding of high-fat high-cholesterol (HFHC) or choline-deficient high-fat (CDHF) diet. Orthotopic NAFLD-HCC allografts were established by intrahepatic injection of murine HCC cells with HFHC feeding. Metabolomic profiling was performed using liquid chromatography-mass spectrometry. Biological functions of L. acidophilus conditional medium (L.a CM) and metabolites were determined in NAFLD-HCC human cells and mouse organoids. FINDINGS: L. acidophilus supplementation suppressed NAFLD-HCC formation in HFHC-fed DEN-treated mice. This was confirmed in orthotopic allografts and germ-free tumourigenesis mice. L.a CM inhibited the growth of NAFLD-HCC human cells and mouse organoids. The protective function of L. acidophilus was attributed to its non-protein small molecules. By metabolomic profiling, valeric acid was the top enriched metabolite in L.a CM and its upregulation was verified in liver and portal vein of L. acidophilus-treated mice. The protective function of valeric acid was demonstrated in NAFLD-HCC human cells and mouse organoids. Valeric acid significantly suppressed NAFLD-HCC formation in HFHC-fed DEN-treated mice, accompanied by improved intestinal barrier integrity. This was confirmed in another NAFLD-HCC mouse model induced by CDHF diet and DEN. Mechanistically, valeric acid bound to hepatocytic surface receptor GPR41/43 to inhibit Rho-GTPase pathway, thereby ablating NAFLD-HCC. INTERPRETATION: L. acidophilus exhibits anti-tumourigenic effect in mice by secreting valeric acid. Probiotic supplementation is a potential prophylactic of NAFLD-HCC. FUNDING: Shown in Acknowledgments.

Revisiting the Role of Valeric Acid in Manipulating Ulcerative Colitis.

BACKGROUND: Ulcerative colitis (UC) is characterized by a complicated interaction between mucosal inflammation, epithelial dysfunction, abnormal activation of innate immune responses, and gut microbiota dysbiosis. Though valeric acid (VA), one type of short-chain fatty acids (SCFAs), has been identified in other inflammatory disorders and cancer development, the pathological role of VA and underlying mechanism of VA in UC remain under further investigation. METHODS: Studies of human clinical specimens and experimental colitis models were conducted to confirm the pathological manifestations of the level of SCFAs from human fecal samples and murine colonic homogenates. Valeric acid-intervened murine colitis and a macrophage adoptive transfer were applied to identify the underlying mechanisms. RESULTS: In line with gut microbiota dysfunction in UC, alteration of SCFAs from gut microbes were identified in human UC patients and dextran sodium sulfate -induced murine colitis models. Notably, VA was consistently negatively related to the disease severity of UC, the population of monocytes, and the level of interluekin-6. Moreover, VA treatment showed direct suppressive effects on lipopolysaccharides (LPS)-activated human peripheral blood mononuclear cells and murine macrophages in the dependent manner of upregulation of GPR41 and GPR43. Therapeutically, replenishment of VA or adoptive transfer with VA-modulated macrophages showed resistance to dextran sodium sulfate-driven murine colitis though modulating the production of inflammatory cytokine interleukin-6. CONCLUSIONS: In summary, the research uncovered the pathological role of VA in modulating the activation of macrophages in UC and suggested that VA might be a potential effective agent for UC patients.

The study collectively indicated that valeric acid (VA) was consistently negatively related to the disease severity of UC, and hypofunction of macrophage driven by VA impeded the progression of UC.

Females smell differently: characteristics and significance of the most common olfactory sensilla of female silkmoths.

In the silkmoth Bombyx mori, the role of male sensilla trichodea in pheromone detection is well established. Here we study the corresponding female sensilla, which contain two olfactory sensory neurons (OSNs) and come in two lengths, each representing a single physiological type. Only OSNs in medium trichoids respond to the scent of mulberry, the silkworm's exclusive host plant, and are more sensitive in mated females, suggesting a role in oviposition. In long trichoids, one OSN is tuned to (+)-linalool and the other to benzaldehyde and isovaleric acid, both odours emitted by silkworm faeces. While the significance of (+)-linalool detection remains unclear, isovaleric acid repels mated females and may therefore play a role in avoiding crowded oviposition sites. When we examined the underlying molecular components of neurons in female trichoids, we found non-canonical co-expression of Ir8a, the co-receptor for acid responses, and ORco, the co-receptor of odorant receptors, in long trichoids, and the unexpected expression of a specific odorant receptor in both trichoid sensillum types. In addition to elucidating the function of female trichoids, our results suggest that some accepted organizational principles of the insect olfactory system may not apply to the predominant sensilla on the antenna of female B. mori.

The Halophilic Bacterium Paracoccus haeundaensis for the Production of Poly(3-Hydroxybutyrate-co-3-Hydroxyvalerate) from Single Carbon Sources.

The study objective was to evaluate the potential production of polyhydroxyalkanoates (PHAs), a biodegradable plastic material, by Paracoccus haeundaensis for which PHA production has never been reported. To identify the most effective nitrogen-limited culture conditions for PHAs production from this bacterium, batch fermentation using glucose concentrations ranging from 4 g l-1 to 20 g l-1 with a fixed ammonium concentration of 0.5 g l-1 was carried out at 30°C and pH 8.0. A glucose supplement of 12 g l-1 produced the highest PHA concentration (1.6 g l-1) and PHA content (0.63 g g-1) thereby identifying the optimal condition for PHA production from this bacterium. Gas chromatography-mass spectrometry analysis suggests that P. haeundaensis mostly produced copolymer types of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) [P(3HB-co-3HV)] from glucose concentrations at 12 g l-1 or higher under the nitrogen-limited conditions. When several other single carbon sources were evaluated for the most efficient PHA production, fructose provided the highest biomass (2.8 g l-1), and PHAs (1.29 g l-1) concentrations. Results indicated that this bacterium mostly produced the copolymers P(3HB-co-3HV) from single carbon sources composing a range of 93-98% of 3-hydroxybutyrate and 2-7% of 3-hydroxyvalerate, whereas mannose-supplemented conditions produced the only homopolymer type of P(3HB). However, when propionic acid as a secondary carbon source were supplemented into the media, P. haeundaensis produced the copolymer P(3HB-co-3HV), composed of a 50% maximum monomeric unit of 3-hydroxyvaleric acid (3HV). However, as the concentration of propionic acid increased, cell biomass and PHAs concentrations substantially decreased due to cell toxicity.

Characterization of simultaneous ammonium and nitrate removal and microbial communities in airlift reactor using 3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV) as carbon source and biofilm carrier.

As a novel trend, solid carbon sources are applied to act as electron donors and biofilm carrier in biological denitrification process. In this study, simultaneous nitrate and ammonium removal process in an airlift sequencing batch reactor using 3-hydroxybutyrate-co-3-hydroxyvalerate (PHBV) as carbon source and biofilm carrier under intermittent aeration conditions was established to treat effluent of synthetic marine recirculating aquaculture system. The results showed that maximum nitrate and ammonia nitrogen removal rates of 0.45 and 0.09 kg m-3 d-1 were achieved. No significant nitrite accumulation was found during 200-day operation, while effluent dissolved organic carbon accumulation and particle size reduction significantly increased. Microbial community analysis and batch tests illuminate that the generated sludge and attached biofilm played important roles in nitrogen removal. This study demonstrates the potential mechanism for the nitrogen removal process mediated by 3-hydroxybutyrate-co-3-hydroxyvalerate and provide a new idea for the alternative solutions of solid carbon sources.

Enrichment of mixed methanotrophic cultures producing polyhydroxyalkanoates (PHAs) from various environmental sources.

Methanotrophic bacteria can use atmospheric methane (CH4) as a sole carbon source for the growth and production of polyhydroxyalkanoates (PHA). The development of CH4 bioconversion processes relies heavily on the selection of an efficient methanotrophic culture. This research assessed the effect of selected growth conditions, such as nitrogen sources on the enrichment of methanotrophic cultures from various environments for PHA accumulation. Nitrate-based medium favoured the culture growth and selection for PHA-producing methanotrophic cultures with Methylocystis sp. as a major genus and accumulation of up to 27 % polyhydroxybutyrate (PHB) in the biomass. Three PHB-producing cultures: enriched from waste activated sludge (AS), peat bog soil (PB) and landfill biocover soil (LB) were then tested for their ability to produce PHA copolymer at different CH4:O2 ratios. All enriched cultures were able to utilise valeric acid as a cosubstrate for the accumulation of PHA with a 3-hydroxyvaleric (3HV) fraction of 21-41 mol% depending on the inoculum source and CH4 concentration. The process performance of selected cultures was evaluated and compared to the culture of reference strain Methylocystis hirsuta DSM 18500. All mixed cultures irrespective of their inoculum source had similar levels of 3HV fraction in the PHA (38 ± 2 mol%). The highest poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) production was observed for AS culture at 10 % CH4 with an accumulation of 27 ± 3 % of dry cell weight (DCW), 3HV fraction of 39 ± 2 mol% and yield of 0.42 ± 0.02 g-PHA/g-substrate.

Halomonas alkaliantarctica as a platform for poly(3-hydroxybutyrate-co-3-hydroxyvalerate) production from biodiesel-derived glycerol.

Polyhydroxyalkanoates (PHAs) are biodegradable polyesters produced by a wide range of microorganisms, including extremophiles. These unique microorganisms have gained interest in PHA production due to their ability to utilise low-cost carbon sources under extreme conditions. In this study, Halomonas alkaliantarctica was examined with regards to its potential to produce PHAs using crude glycerol from biodiesel industry as the only carbon source. We found that cell dry mass concentration was not dependent on the applying substrate concentration. Furthermore, our data confirmed that the analysed halophile was capable of metabolising crude glycerol into poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer within 24 h of the cultivation without addition of any precursors. Moreover, crude glycerol concentration affects the repeat units content in the purified PHAs copolymers and their thermal properties. Nevertheless, a differential scanning calorimetric and thermogravimetric analysis showed that the analysed biopolyesters have properties suitable for various applications. Overall, this study described a promising approach for the valorisation of crude glycerol as a future strategy of industrial waste management to produce high value microbial biopolymers.

Copolymers and Blends Based on 3-Hydroxybutyrate and 3-Hydroxyvalerate Units.

This review presents a comprehensive update of the biopolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), emphasizing its production, properties, and applications. The overall biosynthesis pathway of PHBV is explored in detail, highlighting recent advances in production techniques. The inherent physicochemical properties of PHBV, along with its degradation behavior, are discussed in detail. This review also explores various blends and composites of PHBV, demonstrating their potential for a range of applications. Finally, the versatility of PHBV-based materials in multiple sectors is examined, emphasizing their increasing importance in the field of biodegradable polymers.

Masking effects on iso-valeric acid recognition by sub-threshold odor mixture.

Masking unpleasant odors with pleasant-smelling odorants has a long history and is utilized in various industries, including perfumery and consumer products. However, the effectiveness of odor masking is idiosyncratic and temporary. In this study, we employed Sniff olfactometry (SO) to investigate the psychophysics of masking using brief 70 ms stimulations with mixtures of the mal-odorant iso-valeric acid (IVA) and different masking agents. IVA is a component of human sweat that can overpower its smell and is often associated with unpleasant descriptors such as "gym locker," "smelly feet," "dirty clothes," and so on. Traditionally, high concentrations of pleasant-smelling odorants are used to mitigate the unpleasantness of IVA in situations involving clothing or environments contaminated with IVA. To examine the masking effects of sub-threshold levels of various masking agents (neohivernal, geraniol, florhydral, decanal, iso-longifolanone, methyl iso-eugenol, and s-limonene) on IVA, we conducted experiments using SO to measure the probability of recognizing IVA after 70 ms stimulations with headspaces containing mixtures of super-threshold concentrations of IVA and sub-threshold concentrations of IVA suppressors. The study involved nine subjects, and on average, a single masking agent was found to decrease IVA recognition probability by 14-72%. Moreover, a sub-threshold odor mixture consisting of 6 masking agents demonstrated a substantial decrease in IVA recognition, with a reduction of 96%.

In Vivo and In Silico Analgesic Activity of Ficus populifolia Extract Containing 2-O-ß-D-(3',4',6'-Tri-acetyl)-glucopyranosyl-3-methyl Pentanoic Acid.

Natural product-based structural templates have immensely shaped small molecule drug discovery, and new biogenic natural products have randomly provided the leads and molecular targets in anti-analgesic activity spheres. Pain relief achieved through opiates and non-steroidal anti-inflammatory drugs (NSAIDs) has been under constant scrutiny owing to their tolerance, dependency, and other organs toxicities and tissue damage, including harm to the gastrointestinal tract (GIT) and renal tissues. A new, 3',4',6'-triacetylated-glucoside, 2-O-ß-D-(3',4',6'-tri-acetyl)-glucopyranosyl-3-methyl pentanoic acid was obtained from Ficus populifolia, and characterized through a detailed NMR spectroscopic analysis, i.e., 1H-NMR, 13C-DEPT-135, and the 2D nuclear magnetic resonance (NMR) correlations. The product was in silico investigated for its analgesic prowess, COX-2 binding feasibility and scores, drug likeliness, ADMET (absorption, distribution, metabolism, excretion, and toxicity) properties, possible biosystem's toxicity using the Discovery Studio®, and other molecular studies computational software programs. The glycosidic product showed strong potential as an analgesic agent. However, an in vivo evaluation, though at strong levels of pain-relieving action, was estimated on the compound's extract owing to the quantity and yield issues of the glycosidic product. Nonetheless, the F. populifolia extract showed the analgesic potency in eight-week-old male mice on day seven of the administration of the extract's dose in acetic acid-induced writhing and hot-plate methods. Acetic acid-induced abdominal writhing for all the treated groups decreased significantly (p < 0.0001), as compared to the control group (n = 6) by 62.9%, 67.9%, and 70.9% of a dose of 100 mg/kg (n = 6), 200 mg/kg (n = 6), and 400 mg/kg (n = 6), respectively. Similarly, using the analgesia meter, the reaction time to pain sensation increased significantly (p < 0.0001), as compared to the control (n = 6). The findings indicated peripheral and central-nervous-system-mediated analgesic action of the product obtained from the corresponding extract.

Emricasan for the treatment of liver cirrhosis: a meta-analysis of randomized controlled trials.

Introduction: The efficacy of emricasan for liver cirrhosis remains controversial. We conduct a systematic review and meta-analysis to explore the influence of emricasan versus placebo on the treatment of liver cirrhosis. Methods: We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through August 2021 and included randomized controlled trials (RCTs) assessing the efficacy of emricasan versus placebo for liver cirrhosis. This meta-analysis was performed using the random-effect model. Results: Four RCTs were included in the meta-analysis. Overall, compared with control group for liver cirrhosis, emricasan treatment had no substantial impact on MELD (SMD=-0.19; 95% CI=-0.44 to 0.06; P=0.14), INR (SMD=0.12; 95% CI=-0.13 to 0.37; P=0.36), total bilirubin (SMD=-0.27; 95% CI=-0.56 to 0.01; P=0.06), serum albumin (SMD=0; 95% CI=-0.25 to 0.25; P=1.00) or adverse events (OR=1.35; 95% CI=0.56 to 3.24; P=0.50). Conclusions: Emricasan treatment provided no benefit for the treatment of liver cirrhosis.

Electrospun Poly(3-Hydroxybutyrate-Co-3-Hydroxyvalerate)/Olive Leaf Extract Fiber Mesh as Prospective Bio-Based Scaffold for Wound Healing.

Polyhydroxyalkanoates (PHAs) are a family of biopolyesters synthesized by various microorganisms. Due to their biocompatibility and biodegradation, PHAs have been proposed for biomedical applications, including tissue engineering scaffolds. Olive leaf extract (OLE) can be obtained from agri-food biowaste and is a source of polyphenols with remarkable antioxidant properties. This study aimed at incorporating OLE inside poly(hydroxybutyrate-co-hydroxyvalerate) (PHBHV) fibers via electrospinning to obtain bioactive bio-based blends that are useful in wound healing. PHBHV/OLE electrospun fibers with a size of 1.29 ± 0.34 µm were obtained. Fourier transform infrared chemical analysis showed a uniform surface distribution of hydrophilic -OH groups, confirming the presence of OLE in the electrospun fibers. The main OLE phenols were released from the fibers within 6 days. The biodegradation of the scaffolds in phosphate buffered saline was investigated, demonstrating an adequate stability in the presence of metalloproteinase 9 (MMP-9), an enzyme produced in chronic wounds. The scaffolds were preliminarily tested in vitro with HFFF2 fibroblasts and HaCaT keratinocytes, suggesting adequate cytocompatibility. PHBHV/OLE fiber meshes hold promising features for wound healing, including the treatment of ulcers, due to the long period of durability in an inflamed tissue environment and adequate cytocompatibility.

Alternating Isotactic Polyhydroxyalkanoates via Site- and Stereoselective Polymerization of Unsymmetrical Diolides.

Naturally produced, biodegradable polyhydroxyalkanoates (PHAs) promise more sustainable alternatives to nonrenewable/degradable plastics, but biological PHA's stereomicrostructures are strictly confined to isotactic (R)-polymers or copolymers of random sequences. Chemical synthesis via catalyzed ring-opening polymerization (ROP) of cyclic (di)esters offers expedient access to diverse PHA microstructures, including those with defined comonomer sequences and tacticities. However, the synthesis of alternating isotactic PHAs has not been achieved by the existing methodologies. Here, we report the design of unsymmetrically disubstituted eight-membered diolides (rac-8DLR1-R2) and their site- and stereoselective ROP with discrete chiral catalysts, enabling the synthesis of alternating isotactic PHAs, poly(3-hydroxybutyrate-alt-3-hydroxyvalerate) (alt-P3HBV) and poly(3-hydroxybutyrate-alt-3-hydroxyheptanoate) (alt-P3HBHp), with high to quantitative (>99%) alternation and isotacticity and Mn up to 113 kDa and D = 1.01. Physical properties of such PHAs are substantially determined by the degree of backbone sequence alternation and tacticity, ranging from amorphous to semi-crystalline materials. The alt-P3HBV shows significantly improved mechanical performance relative to the constituent homopolymers. Intriguingly, enantiomeric (R)-alt-P3HBV and (S)-alt-P3HBV, synthesized by kinetically resolved ROP of rac-8DLMe-Et, form a stereocomplex with a significantly enhanced Tm (by 53 °C), while the enantiomeric homopolymers do not form a stereocomplex.