Oleanolic acid (OA) being the ubiquitous compound in the plant kingdom is studied for both the neuroprotective and neurotoxic properties. The mechanism of acetylcholinesterase (AChE) inhibitory potential of OA is investigated using the molecular dynamic simulations (MD) and docking as well as membrane-like and in vitro tests. There are also applied SH-SY5Y human neuroblastoma cells as well as in vivo on the zebrafish tests. The inhibitory potential towards the AChE enzyme is examined using the TLC-bioautography assay (the IC50 value is 9.22 μM). The CH- interactions between the central fragment of the ligand molecule and the aromatic cluster created by the His440, Phe288, Phe290, Phe330, Phe331, Tyr121, Tyr334, Trp84 and Trp279 side chains are observed. The in vitro tests carried out on the SH-SY5Y cells indicates that the viability rate is reduced to 71.5%, 61%, and 43% at the concentrations of 100 µg/mL, 300 µg/mL, and 1000 µg/mL, respectively after 48 hours of incubation whereas cytotoxicity against the tested cell line with the IC50 value is 714.32 ± 32.40 µg/mL. The in vivo tests on the zebrafish prove that there is no difference between the control and experimental groups as regards the mortality rate and morphology (P>0.05).

Among phosphorylated derivatives, phosphinates occupy a prominent place due to their ability to be bioisosteres of phosphates and carboxylates. These properties imply the necessity to develop efficient methodologies leading to phosphinate scaffolds. For the past years our team have explored the nucleophilic potential of silylated phosphonite towards various electrophiles. In this paper, we propose to extend our study over other electrophiles. We describe here the implementation of a cascade reaction between (trimethylsilyl)imidates and hypophosphorous acid mediated by a Lewis acid allowing the synthesis of aminomethylenebisphosphinate derivatives.

Ningxiang pigs exhibit a diverse array of fatty acids, making them an intriguing model for exploring the genetic underpinnings of Fatty acid metabolism. In this study, we conducted a genome-wide association study using a dataset comprising 50,697 SNPs and samples from over 600 Ningxiang pigs. Our investigation yielded novel candidate genes linked to five saturated fatty acids (SFAs), four monounsaturated fatty acids (MUFAs), and five polyunsaturated fatty acids (PUFAs). Re-markably, 37, 21, and 16 SNPs showed significant associations with SFAs, MUFAs, and PUFAs, respectively. Notably, ALGA0047587, H3GA0046208, DRGA0016063, and ALGA0031262 demonstrated substantial phenotypic variance (≥ 30%) in Arachidic acid (C20:0), Elaidic Acid (C18:1n-9(t)), and Arachidonic acid (C20:4n-6), respectively. Several significant SNPs were posi-tioned proximally to previously reported genes. In total, we identified 11, 6, and 5 candidate genes associated with SFAs, MUFAs, and PUFAs, respectively. These findings hold great promise for advancing breeding strategies aimed at optimizing meat quality and enhancing lipid metabolism within the intramuscular fat (IMF) of Ningxiang pigs.

Current low meat production in Omani goats under traditional feeding regimes justifies a study of the effects of Spirulina Platensis (SP) supplementation on goats’ performance. Hence, this study aimed to evaluate the effect of incorporating SP into diets on carcass characteristics, fatty acid profile and meat quality traits of two Omani goat breeds. Thirty-six eleven-month-old bucks from the Jabbali and Sahrawi goat breeds (n= 18/breed) were divided into three groups (control, Treatment 1, and treatment 2). All animals received a conventional concentrate feed ration (con-trol (CON) consisting of pellets creep fed. Animals were fed SP daily with Treatment 1 (T1) fed at 2g/head and Treatment 2 (T2) fed at 4g/head. Sahrawi bucks showed a highly significant response to SP feeding compared to Jabbali bucks. Average daily gain and carcass traits (body length, leg length and the rack weight) of Sahrawi bucks were significantly higher in the T1 group than in the CON group. The weights of omental and kidney fat increased in T1 group of Sahrawi goats, while it increased in T2 group of Jabbali goats compared to CON group. Ultimate pH increased in T1 group and meat color (lightness) increased in T2 group in both LD and SM muscles of Sahrawi goats. Most of PUFA n-6 and n-6/n-3 ratio increased in T1 group, while most of MUFA2 and PUFA n-3 fatty acids increased in T2 group of Sahrawi goats. In addition, a significant decrease in pentadecanoic and margaric acids of Sahrawi goats was observed by adding SP to the diet com-pared to the control group. The study concluded that incorporating SP (2g and 4g/head) into the diet of Omani goats, especially Sahrawi goats, can increase growth performance, improve fatty acid composition and meat quality.

Alginate films (2% w·v-1) were prepared with varying concentrations (5-20% w/w) of citric acid and aqueous grape seed extract (GSE) filtrate (11.66 ± 1.32 g GAE/L) by the solvent-evaporation method. Crosslinking alginate via ester bonds (FTIR analysis) with citric acid up to 10% (w/w) led to a 33% increase in tensile strength, a 34% reduction in water vapor transmission rate (WVTR), and had no impact on elongation at break. Crosslinking alginate with citric acid in presence of GSE increased the tensile strength by 17%, decreased WVTR by 21%, and significantly improved DPPH scavenging activity. Moreover, after incubation for 24 h at 37°C, the film-forming solutions exhibited increased antimicrobial activity, resulting in 0.5 and 2.5-log reductions for Escherichia coli and Staphylococcus aureus, respectively, compared to the values obtained without the addition of GSE. The stronger inhibitory effect observed against Gram-positive bacteria can be attributed to the unique composition and structure of their cell walls, which create a barrier that restricts the penetration of polyphenols into the cells. pH adjustment of the GSE film-forming solution from 2.0 to 10.0 shifted the UV/VIS absorption spectra, resulting in a colour change from yellow to red. The findings of this study have showcased the potential of combining GSE and citric acid to enhance the functionality and bioactivity of alginate films for applications in smart food packaging.

MicroRNAs (miRNAs) regulate plant growth and development and their responses to biotic and abiotic stresses. Although extensive studies show that miR159 family members regulate leaf and flower development in Arabidopsis thaliana, the roles of miRNAs in soybean (Glycine max) are poorly understood. Here, we identified six MIR159 genes in soybean, MIR159aMIR159f, and investigate their expression patterns in plants under low-phosphorus (low-P), NaCl, or abscisic acid (ABA) treatments. In soybean leaves, MIR159e and MIR159f expression was induced by low-P treatment, while in roots, MIR159b, MIR159c, MIR159e, and MIR159f expression was upregulated. In flowers, low-P led to upregulation of MIR159a, MIR159b, MIR159c, and MIR159f, but downregulation of MIR159d and MIR159e. In soybean nodules, MIR159b was upregulated but MIR159a, MIR159c, and MIR159d was downregulated under P deficiency. NaCl treatment induced MIR159a, MIR159b, MIR159c, and MIR159e expression in leaves, and MIR159aMIR159f expression in roots. ABA treatment upregulated MIR159a, MIR159b, and MIR159c but downregulated MIR159d, MIR159e, and MIR159f in leaves. These results suggest that miR159 family members function in plant abiotic stress responses. Moreover, total P content in leaves was significantly lower in plants overexpressing MIR159e than in the wild type, suggesting that miR159e may regulate P absorption and transport in soybean.

Cancer is a catchall term that refers to a collection of more than one chronic disease that can adversely affect the body, including the organs of the body. These diseases can be grouped together under the umbrella term "cancer." Cancer is a catch-all term that is used to refer to a number of different diseases. During the process of looking for new chemical entities, it was found that certain compounds with a basic nucleus of benzoic acid (BA) exhibit a remarkable anticancer potential. This was discovered while the researchers were looking for new chemical entities. In the sixteenth century, the aromatic chemical known as BA, which is also known as an aromatic carboxylic acid, was discovered. BA is also referred to as an aromatic carboxylic acid. When it comes to the chemical synthesis of a wide range of different active molecules, the utilization of a sizeable quantity of BA as a raw material is absolutely necessary. In addition to being present in a variety of other naturally occurring compounds, the BA moiety is the component that is responsible for the activity of the naturally occurring compounds vanillin, gallic acid, and syringic acid. In the synthesis of a wide variety of synthetic bioactive molecules, the BA scaffold is utilized as a building block. The drugs furosemide, bumetanide, benzocaine, tetracaine, and bexarotene are all examples of molecules that fall into this category. The scope of this review article allows for the discussion of a number of noteworthy and recent achievements of BA derivatives in terms of their effectiveness against cancer.

Peptides of hydrolysates of food proteins are an easily digestible source of amino acids necessary for the body to adapt to physical stress. Commercially significant hydrolysates include whey protein, casein, and other animal proteins. Hydrolysates of plant proteins are gaining popularity, but they are less common, then animal ones. Soy protein isolate is promising for obtaining the hydrolysates due to its affordable price and balanced amino acid profile. However, there are no direct studies showing an improvement in the result of physical activity when eating soy protein isolate hydrolysate (SPIH). In this work, for the first time, the study was conducted on the safety and efficacy of SPIH during physical load on model animals (rats). It was shown that the hydrolysate did not lead to pathological changes in the viscera, food intake, and weight of animals did not differ from the control group (animals consumed whey protein). Under physical load rats enteral fed SPIH showed a tendency to adapt more quickly to physical stress than the control group and the group of animals that was fed by free amino acids. The metabolites of animal blood serum were studied by NMR spectroscopy. It was shown that by the 95th minute after feeding in the group of rats receiving SPIH, the difference of proteinogenic amino acids concentrations in blood between individuals was significantly less than in the groups receiving whey protein or a mixture of amino acids. In other words, individual biochemical and physiological characteristics of individuals did not affect the assimilation of amino acids of hydrolysate.

Pozol is a Mexican beverage prepared from fermented nixtamalized maize dough. To contribute to understanding its complex microbial ecology, the effect of inoculating on MRS-starch pure and mixed cultures of amylolytic Sii-25124 and non-amylolytic W. confusa 17, isolated from pozol, were studied on their interactions and fermentation parameters. These were compared with L. plantarum A6, an amylolytic strain isolated from cassava. Microbial growth, kinetic parameters, amylolytic activity, lactic acid production, and hydrolysis products from starch fermentation were measured. The population dynamics were followed by qPCR. L. plantarum A6 showed higher enzymatic activity, lactic acid, biomass production, and kinetic parameters than pozol LAB in pure cultures. Mixed culture of each pozol LAB with L. plantarum A6 showed a significant decrease in amylolytic activity, lactic acid yield, specific growth rate, and specific rate of amylase production. The interaction between Sii-25124 and W. confusa 17 increased the global maximum specific growth rate (µ), the lactic acid yield from starch (Ylac/s), lactic acid yield from biomass (Ylac/x), and specific rate of lactic acid production (qlac) by 15, 30, 30, and 40%, respectively compared with the pure culture of Sii-25124. Interactions between the two strains are essential for this fermentation.

The ubiquity of amino acids in carbonaceous meteorites has suggested that amino acids are widespread in the Universe, serving as a common class of components for the emergence of life. However, parameters for modeling amino acid polymerization at mineral–water interfaces remain limited, although the interfacial conditions inevitably exist on planets with surface liquid water. Here, we present a set of extended triple-layer model parameters for aspartate (Asp) and aspartyl-aspartate (AspAsp) adsorptions on ferrihydrite, anatase, and γ-alumina determined based on the experimental adsorption data. By combining the parameters with the reported thermodynamic constants for amino acid polymerization in water, the impacts of these minerals on Asp dimerization are calculable over a wide range of environmental conditions. It was predicted, for example, that ferrihydrite strongly increases the AspAsp/Asp equilibrium ratio in neutral to acidic pH; the ratio in the adsorbed state reaches 40% even from a low Asp concentration (0.1 mM) at pH 4. This percentage is approximately 5 × 107 times higher than that attainable without mineral (8.5 × 10–6%). Our exemplified approach enables us to screen wide environmental settings for abiotic peptide synthesis from a thermodynamic perspective, thereby narrowing down the geochemical situations to be explored for life’s origin on Earth and Earth-like habitable planets.

Cationised hemp cellulose was prepared by etherification with two quaternary ammonium salts: 3-chloro-2-hydroxypropyl trimethyl ammonium chloride (CHPTAC) and glycidyltrimethylammonium chloride (GTMAC) and examined for (i) the efficiency of Cr(VI) removal under acid mine-drainage (AMD) conditions, and (ii) antibacterial activity. Adsorbents were characterised by electron microscopy, Fourier transform infrared (FTIR), CP-MAS ¹³C nuclear magnetic resonance (NMR) spectroscopy, elemental composition and surface charge. FTIR and solid state ¹³C NMR confirmed the introduction of quaternary ammonium moieties on cellulose. ¹³C NMR also showed that cationisation decreased the degree of crystallisation and lateral dimensions of cellulose fibrils. Nevertheless, 47 % - 72% of Cr(VI) ions were removed from solutions at pH 4, by 0.1 g of CHPTAC and GTMAC-cationised cellulose, respectively. Adsorption kinetics followed the pseudo-second order model and isotherms were best described by the Freundlich and Dubinin-Radushkevich models. When GTMAC-modified cellulose was applied to AMD contaminated water (pH 2.7), however, Cr(VI) uptake removal decreased to 22% likely due to competition from Al and Fe ions. Nevertheless, cationised materials displayed considerable antibacterial effects, reducing the viability of Escherichia coli by up to 45 % after just 3 hours of exposure. Together, these results suggest that cationised cellulose can be applied in the treatment of Cr(VI)-contaminated mine water particularly if pre-treatments to reduce Fe and Al concentrations are applied.

Like other viruses, SARS-COV-2 too mutating and thus creating divergent variants across the world. Protein sequence variation occurs due to non-synonymous single-nucleotide polymorphism (SNP) that alter the amino acid. Amino acid substitutions on homooligomer interfaces may change the structure of the protein and hence alter the regular or known functional activities of a viral protein. Studies reveal that even a single point mutation in virus protein can significantly change their biology, leads to peculiar pathogenic properties. Therefore, an in-depth investigation of the amino acid substitution in the genomic signature of a protein is highly essential for the rapidly evolving virus-like SARS-COV-2. Investigation of world-wide and country-specific substitution features may be crucial and highly essential to decipher pathogenicity. These might be also helpful to precise structure prediction and identification of possible therapeutic targets for effective drug design. We perform extensive analysis towards highlighting and characterizing the amino acid substitution signature occurs in the four structural proteins (Spike-S, Nucleocapsid-N, Membrane-M, Envelope-E) of SARS-COV-2. We use a total of 9587 viral sequences reported from 49 different countries across the globe. In this study, we try to study the amino acid substitution patterns and its impact on change in biochemical properties, thereby possible changes in protein structures. We perform the following analysis: a) isolating and grouping variants we considered, for different protein sequences; b) identifying amino acid substitution type that are frequently and rarely occurring and reporting their location within the sequence; c) change in chemical properties due to amino acid substitution; and f) highlight country-specific divergent variation and substitution signature. In terms of mutational changes, E and M proteins are relatively stable than N and S proteins. A significant quantity of variations is observed in spike (S) proteins. Our study further reveals an interesting fact that the substitution location is random in N protein, whereas the substitution sites in M protein is less varying and almost stable. Substitutions specific to active sub-domains in S and N proteins reveals that sub-domains like Heptapeptide Repeat (HR2), Fusion peptides (FP), and Transmembrane (TM), which are involved in cellular membrane fusion and entry of the virus into the host cells, are significantly mutated. Majority of the substitutions leads to change in biochemical properties (side chain and hydropathy) of amino acid. A good number of exclusive variants are found specific to a particular country. We strongly believe that the current findings will be helpful for protein structure analysis of viral structural proteins and antiviral drug discovery.

Aflatoxin biosynthesis is correlated with oxidative stress and is proposed to function as a secondary defense mechanism to redundant intracellular reactive oxygen species (ROS). We find that the antioxidant gallic acid inhibits aflatoxin formation and growth in A. flavus in a dose-dependent manner. Global expression analysis (RNA-Seq) of gallic acid treated A. flavus showed that 0.8% (w/v) gallic acid revealed two possible routes of aflatoxin inhibition. Gallic acid significantly inhibited the expression of farB, encoding a transcription factor that participates in peroxisomal fatty acid β oxidation, a fundamental contributor to aflatoxin production. Secondly, the carbon repression regulator encoding gene creA was significantly down regulated by gallic acid treatment. CreA is necessary for aflatoxin synthesis and aflatoxin biosynthesis genes were significantly downregulated in DcreA mutants. In addition, the results of antioxidant enzyme activities and the lipid oxidation levels coupled with RNA-Seq data of antioxidant genes indicated that gallic acid may reduce oxidative stress through the glutathione- and thioredoxin-dependent systems in A. flavus.

Fatty acids play a major role in determining membrane biophysical properties. Staphylococcus aureus produces branched-chain fatty acids (BCFAs) and straight-chain fatty acids (SCFAs), and can incorporate exogenous SCFAs and straight-chain unsaturated fatty acids (SCUFAs). Many S. aureus strains produce the triterpenoid pigment staphyloxanthin, and the balance of BCFAs, SCFAs and staphyloxanthin determines membrane fluidity. Here, we investigated the relationship of fatty acid and carotenoid production in S. aureus using a pigmented strain (Pig1), its carotenoid-deficient mutant (Pig1ΔcrtM) and the naturally non-pigmented Staphylococcus argenteus that lacks carotenoid biosynthesis genes and is closely related to S. aureus. Fatty acid compositions in all strains were similar under a given condition indicating that staphyloxanthin does not influence fatty acid composition. Strain Pig1 had decreased membrane fluidity as measured by fluorescence anisotropy than the other strains under all conditions indicating that staphyloxanthin helps maintain membrane rigidity. We could find no evidence for correlation of expression of crtM and fatty acid biosynthesis genes. Supplementation of medium with glucose increased SCFA production and decreased BCFA and staphyloxanthin production, whereas acetate-supplementation also decreased BCFAs but increased staphyloxanthin production. We believe that staphyloxanthin levels are influenced more through metabolic regulation than responding to fatty acids incorporated into the membrane.

Flower bud formation and flowering in chrysanthemum occur under short day conditions (SD), but the molecular basis for the switch to reproductive growth is less well understood than in model plants. Here, a spontaneous mutant able to flower under long days is described. In an attempt to reveal the pathway(s) involved in the formation of flower buds under contrasting daylengths, transcriptome sequencing was carried out in plants grown both under SD and under long day conditions (LD). A number of differentially transcribed genes involved in the various known flowering pathways were identified. Both circadian clock genes and CmFTL3 were up-regulated under SD, thereby inducing floral bud formation and flowering. The gibberellin (GA) signalling pathway-related genes GA20ox and GID1 were up-regulated in the mutant under LD, while the catabolic gene GA2ox and GAI was down-regulated, thereby inducing the transcription of CmFTL1, SOC1 and LFY. The GA content of the leaf was higher in the mutant than in the wild type under LD. When treated with GA, the mutant flowered earlier under both SD and LD, but there was no other detectable phenotype difference between the two lines. The indication was that the photoperiod pathway majorly regulates flower bud formation and flowering time in chrysanthemum under SD. GA signalling pathway only plays a subsidiary role for flowering. However, the GA signalling pathway predominated for flowering under LD.

We evaluated the mono- and combination-therapy effects of valproic acid (VPA) and doxorubicin (DOX) in hepatocellular carcinoma (HCC) and identified a specific and efficient, synergistic anti-proliferative effect of the VPA and DOX combination in HCC cells, especially HepG2 cells; this effect was not apparent in MIHA cells, a normal hepatocyte cell line. The calculation of the coefficient of drug interaction confirmed the significant synergistic effect of the combination treatment. Concurrently, the synergistic apoptotic cell death caused by the VPA and DOX combination treatment was confirmed by Hoechst nuclear staining and western blot analysis of caspase-3 and poly (ADP-ribose) polymerase (PARP) activation. Co-treatment with VPA and DOX enhanced reactive oxygen species (ROS) generation and autophagy, which were clearly attenuated by ROS and autophagy inhibitors, respectively. Furthermore, as an indication of the mechanism underlying the synergistic effect, we observed that DOX internalization, which was induced in the VPA and DOX combination-treated group, occurred via by the caveolae-mediated endocytosis pathway. Taken together, our study uncovered the potential effect of the VPA and DOX combination treatment with regard to cell death, including induction of cellular ROS, autophagy, and the caveolae-mediated endocytosis pathway. Therefore, these results present novel implications in drug delivery research for the treatment of HCC.

Overhydration (OH) is a prevalent medical problem occuring in patients with kidney failure, but a specific marker has still not been found. Currently, clinicians employ techniques such as bioimpedance spectroscopy (BIS), ultrasound (US) markers of fluid overload or markers of heart and kidney function such as NT-pro-BNP, GFR or creatinine levels. New serum markers, including but not limited to Ca-125, Galectin-3 (Gal-3), Adrenomedullin (AMD) and Urocortin-2 (UCN-2), are presently under research, displaying promising results. The necessity to ascertain a more precise marker of overhydration is urgent mainly because physical examination is exceptionally imprecise. Signs and symptoms of fluid overload, like edema or gradual increase of body mass, are not always present, notably in patients with chronic kidney disease. This review paper summarizes actual knowledge of a patient's hydration status estimation, focusing specifically on kidney diseases.

Gastrointestinal cancers are still the leading cause of death worldwide. This is related, among other things, to non-specific symptoms, especially in the initial stages, and also to limited possibilities of treatment. Therefore, research is still being conducted to improve the detection of this type of cancer and increase the effectiveness of therapy. The potential application of natural compounds in cancer management deserves special attention. In the group of such products there are polyphenolic compounds which reveal e.g. anti-oxidative, anti-carcinogenic, anti-inflammatory, anti-diabetic and neuroprotective properties. One of such polyphenols is rosmarinic acid, commonly found in plants such as Boraginaceae and Nepetoideae subfamilies of the Lamiaceae (mint) family, including Origanum vulgare, Rosmarinus officinalis Thymus masticmasti chinaythia koreana, Ocimum sanctum, and Hyptis pectinate. A number of studies considers the positive effects of rosmarinic acid in the treatment of many cancers, including gastrointestinal ones such as oral, stomach, pancreas, colon, and liver. The main aim of this paper was to focus on the summarized mechanisms of the action of rosmarinic acid in gastrointestinal cancers.

The URAT1 protein is crucial in absorbing urate in human kidneys. A recent study showed that that Xenopus tropicalis (tropical clawed frog) appears to lack renal urate transporters. This finding raises questions regarding the origin of the SLC22A12 gene which encodes URAT1. The origin of the SLC22A12 gene is being discussed through two hypotheses. The first hypothesis, termed the URAT1-early hypothesis, posits that SLC22A12 was present in the common ancestor of tetrapods and was subsequently lost in amphibian lineages. The second hypothesis, the URAT1-late hypothesis, suggests that the SLC22A12 gene arose uniquely within the lineage leading to mammals. The purpose of this study is to determine which hypothesis is more reasonable for describing the origin of SLC22A12. This study suggests that the SLC22A12 gene the SLC22A12 gene was generated via a fusion of the SLC22A6 and SLC22A20 genes. Thus, the URAT1-late hypothesis is more likely to explain the origin of the SLC22A12 gene. X. tropicalis lacks the SLC22A12 gene, probably because the emergence of SLC22A12 occurred after the divergence of the ancestors of mammals and amphibians. The evolutionary studies of the SLC22A12 will offer valuable insights on how to choose model organisms for studies of the uric acid transporter URAT1.

Biodiesel, a potent replacement for petroleum diesel, is derived from fatty acids in biomass through transesterification, which is renewable, non-toxic, and biodegradable and is a powerful replacement for petroleum diesel. Lewis acid has been proven effective for esterification and transesterification. The Lewis base enhances the electrophilic and nucleophilic properties of the molecules that bind to it, leading to the remarkable versatility in the Lewis base catalytic reaction. Many studies have shown that Lewis acid/base catalyzed in-situ transesterification is a fast and environmentally friendly method for producing biodiesel. The utilization of Lewis acid-base sites to catalyze transesterification has been shown to enhance their efficiency and utilization of ac-id-base active sites. This review explores biodiesel production by different catalysts using Lewis acid-base sites, the conditions for catalytic transesterification, the effects of different reaction parameters on biodiesel production, and biodiesel production process.

Infections are a common post-operative ailment for patients who have received a dental implant or device and can be attributed to biofilm formation in tissue or on the implant. Many current solutions for oral hygiene have side effects and affect the natural oral microbiome. 2-heptylcyclopropane-1-carboxylic acid (2CP) is a medium-chain fatty acid and synthetic diffusible signaling factor that can prevent and disperse biofilm. The purpose of this work was to evaluate an immersion strategy for coating hydroxyapatite (HAp) with 2CP to prevent biofilm attachment on and around natural teeth and dental implants. The release profile of 2CP-loaded and 2CP+oral rinse-loaded HAp coupons (n=6) was assessed by a 3-day exposure to phosphate buffered saline (PBS). Antimicrobial properties against Porphyromonas gingivalis and cytocompatibility of 2CP-loaded HAp coupons (n=4) were also assessed alone and in combination with 0.12% chlorhexidine gluconate oral rinse. The majority of 2CP is released by 12 hours. 2CP, oral rinse, and 2CP+oral rinse significantly reduced P. gingivalis viability, though direct contact assay demonstrates a significant reduction in Saos-2 viability for oral rinse and 2CP+oral rinse coupons. Immersion or rinsing hydroxyapatite with 2CP could inhibit biofilm-associated dental infections and prevent further complications including caries, gingivitis, and peri-implantitis.

This study investigates the implementation of equipment to obtain pyroligneous acid as an alternative to control aphids in mandarin cultivation on the El Arrayanal farm, Monte Olivo parish, Carchi province, Ecuador. Derived from mandarin pruning biomass using a dry distillation pilot oven, pyroligneous acid is an ecological option compared to synthetic phytosanitary products, with less impact on the environment and human health. Using a DBCA design, different concentrations of pyroligneous acid (250 ml, 500 ml, 750 ml, and 1000 ml) applied to immature shoots affected by aphids were analyzed. The 1000 ml concentration achieved 98% control of the pest. Analysis by Gas Chromatography and Mass Spectrometry (GC-MSD) and Total Polyphenols confirmed the effectiveness of pyroligneous acid. The results of the study, carried out in the research and linkage laboratories of the State University of Bolívar, Guaranda, Ecuador, demonstrated significant differences between the doses applied (p-value <0.005), with greater control in the treatment of 1000 ml of acid pyroleño compared to the 250 ml, 500 ml and 750 ml treatments. This pyroligneous acid has multiple uses in organic agriculture as a bioherbicide, biofungicide, biorepellent and foliar and root biostimulant, representing an alternative to obtain sustainable organic products. Despite operational limitations, local pyrolysis technology can be optimized to increase production, positioning pyroligneous acid as a viable and sustainable alternative in organic agriculture, promoting efficient waste management and reducing the use of chemicals.

This study deals with the preparation of adsorbents from a commercial xerogel by chemically modifying its surface with concentrated mineral acids and alkali metal chlorides, their physicochemical characterization, and their use as adsorbents for gallic acid in aqueous solution. The prepared adsorbents have a high specific surface area (347-563 m2 g-1), better pore development for samples treated with alkali metal chlorides than with mineral acids and are more acidic than the initial xerogel (p.z.c range 2.49-6.87 vs. 7.20). The adsorption properties of the commercial xerogel improved over a wide range of pH and temperature. The experimental results indicate that the adsorption process is thermodynamically favored.

Melittin, a natural antimicrobial peptide, displays a broad-spectrum antimicrobial activity, which has caused increasing attention as a potential antibiotic alternative. However, melittin has not been used widely at present due to its high hemolysis and low proteolytic stability. In this study, N-terminal fatty acid was conjugated to melittin to develop new melittin-derived lipopep-tides (MDLs) for improving the limitation of melittin. Our results showed that, the antimicrobial activity of MDLs was increased by 2 to 16 times compared with native melittin, and the stability of these MDLs against trypsin and pepsin degradation was increased by 50 to 80%. Besides, the hemolytic of the MDLs decreased when the length of the carbon chain of fatty acids exceeded 10. Among them, the newly designed analog Mel-C8 showed optimal antimicrobial activity and protease stability. The antimicrobial mechanism studied revealed that the MDLs showed a rapid bactericidal effect by interacting with LPS or LTA and penetrating the bacterial cell membrane. In conclusion, we designed and synthesized a new class of MDLs with potent antimicrobial activity, high proteolytic stability, and low hemolysis through N-terminal fatty acid conjugation.

Pt-coated Ni layer supported on Ni foam catalyst (denoted PtNi/Nifoam) was investigated for the oxidation of the formic acid (FAO) in acidic media. The prepared PtNi/Ni foam catalyst was studied as a function of the formic acid (FA) concentration at bare Pt and PtNi/Nifoam catalysts. The catalytic activity of the PtNi/Nifoam catalysts, studied on the basis of the ratio of the direct and indirect current peaks (jd)/(jnd) for the FAO reaction, showed values about 10 times higher compared to those on bare Pt, particularly at a low formic acid concentrations, reflecting the superiority of the former catalysts for the oxidation of FA to CO2. Ni foams provide a large surface area for the FOR while synergistic effects between Pt nanoparticles and Ni-oxy species layer on Ni foams contribute significantly to the enhanced oxidation of FA via the direct pathway, making it almost equal to the indirect pathway, particularly at low formic acid concentrations.

This work aimed at producing lactic acid (LA) from sugarcane bagasse after steam explosion at 195 ºC for 7.5 and 15 min. Enzymatic hydrolysis was carried out with Novozymes’ Cellic CTec3 and/or Cellic HTec3, whereas fermentation was performed with Bacillus coagulans DSM2314. Water-washing of pretreated solids before enzymatic hydrolysis improved both hydrolysis and fermentation yields. The presence of xylo-oligosaccharides (XOS) in substrate hydrolysates reduced hydrolysis efficiency, but their effect on fermentation was negligible. The presence of fermentation inhibitors in C5 streams was circumvented by adsorption on activated carbon powder with no detectable sugar losses. High carbohydrates-to-LA conversions (Yp/s) of 0.88 g·g-1 were obtained from enzymatic hydrolysates of water-washed steam-exploded materials that were produced at 195°C, 7.5 min and the use of centrifuged-but-never-washed pretreated solids decreased Yp/s by 16%. However, when the detoxified C5 stream was added at a 10% ratio, Yp/s was raised to 0.93 g·g-1 for an LA productivity of 2.55 g·L-1·h-1. Doubling the pretreatment time caused a decrease in Yp/s to 0.78 g·g-1, but LA productivity was the highest (3.20 g·L-1·h-1). For pretreatment at 195°C for 7.5 min, elimination of water washing seemed feasible, but the use of longer pretreatment times made it mandatory to eliminate fermentation inhibitors.

High-performance electromagnetic interference (EMI) shielding materials with ultralow density and environment friendly properties are greatly demanded to address electromagnetic radiation pollution. Herein, carbon nanotubes/polylactic acid (CNTs/PLA) materials with different CNTs contents, which exhibit characteristics of light weight, environmental protection and good chemical stability, are fabricated by 3D printing technology, where CNTs are evenly distributed and bind well with PLA. The performances of 3D printed CNTs/PLA composite are improved compared to pure 3D printed PLA composite, which include mechanical properties, conductive behaviors and electromagnetic interference (EMI) shielding. The EMI shielding effectiveness (SE) of CNTs/PLA composite could be improved when the contents of CNTs increase. When it reaches 15 wt%, the EMI SE of 3D printed CNTs/PLA composite could get up to 47.1 dB, which shields 99.998% of electromagnetic energy. Meanwhile, the EMI shielding mechanism of 3D printed CNTs/PLA composite is mainly of absorption loss, and it generally accounted for more than 80% of the total shielding loss. These excellent comprehensive performances endow the 3D printed CNTs/PLA composite with great potential for use in industrial and aerospace area.

Aqueous enzymatic method is a green oil extraction technology with limited industrial application owing to the need for demulsification of the oil body intermediate product. Existing demulsification methods have problems including low demulsification rates and high costs, such that new methods are needed. Free fatty acids produced by lipid hydrolysis can affect the stability of peanut oil body (POB) at a certain concentration. After screening even-carbon fatty acids with carbon chain lengths below ten, caproic acid was selected for demulsification of POB using response surface methodology and a Box–Behnken design. Under the optimal conditions (caproic acid concentration, 0.22%; material-to-liquid ratio, 1:4.7 (w/v); time, 61 min; and temperature, 79 C), a demulsification rate of 97.87% was achieved. Caproic acid not only adjusted the reaction system pH to cause aggregation of the POB interfacial proteins, but also decreased the interfacial tension and viscoelasticity of the interfacial film with increasing caproic acid concentration to realize POB demulsification. Compared with pressed oil and soxhlet-extracted oil, the acid value and peroxide value of caproic acid demulsified oil were increased, while the unsaturated fatty acid content and oxidation induction time were decreased. However, the tocopherol and tocotrienol contents were higher than those of the soxhlet-extracted oil. This study provides a new method for the demulsification of POB.

Manganese sludge, an industrial waste in the ferroalloy industry, contains various components and holds significant importance for sustainable development through its valorization. This study focuses on characterizing a manganese sludge and investigating its behavior during sulfuric acid leaching. The influence of process conditions, including temperature, acid concentration, liquid to solid ratio, and leaching duration, was examined. The results revealed that Mn, Zn, and K are the main leachable components, and their leaching rates increase with increasing temperature, liquid to solid ratio, and time. However, acid concentration requires optimization. High leaching rates of 90% for Mn, 90% for Zn, and 100% for K were achieved. Moreover, it was found that Pb in the sludge is converted to sulfate during the leaching which yields a sulfate concentrate rich in PbSO4. The leaching process for Mn and Zn species appears to follow a second or -third order reaction, and the calculation of rate constants indicated that Mn leaching kinetics are two to five times higher than those for Zn. Thermodynamic calculations were employed to evaluate the main chemical reactions occurring during leaching.

Malignancy is a fatal disease with an increasing incidence with each passing year, and the early diagnosis of malignancy can significantly improve the cure rate of patients, which has profound implications for saving patients' lives. The changes of miRNA are closely related to the occurrence of malignant tumors. The expression of miRNA in many malignant tumors is obviously different and unique from that in normal tissues. In this study, a strategy for amplifying microRNA (miRNA) signal was designed using duplex specific nuclease (DSN), which was then combined with Peptide nucleic acid (PNA) probe hybridization technology to prepare a sensitive and efficient paper-based lateral flow biosensor (LFB) for the detection of pancreatic cancer (PC) associated microRNA-10b. The performance evaluation results of the LFB showed that the detection limit of miR-NA-10b is 5 nM/mL, and carries demonstrated well specificity, stability, reproducibility. The biosensor prepared in this paper can provide accurate and rapid detection of miRNA-10b. The detection results play a guiding role in the early diagnosis of PC. Meeting the clinical need for largescale screening of individuals at high risk of PC. Providing new avenues to achieve early mass screening in individuals at high risk of PC.

Thermoplastic molded regenerated silk was proposed as structural material in tissue engineering applications, mainly for application in bone. The protocol allows to obtain a compact non-porous material with a compression modulus in the order of a Giga Pascal starting from silk fibroin by compressing a silk fibroin lyophilized sponge of powder in mold at temperature higher than the glass transition temperature (Tg). The main purpose of the produced resin was the osteofixation and other structural applications in which the lack of porosity was not an issue. In this work, we introduced the use of citric acid in the thermoplastic molding protocol of SF to obtain a porosity inside the structural material. In addition to the previously developed protocols the addition of citric acid allowed us to obtain a structural material. The CA powder during the compression acted as a template for the pore formation. In addition, the CA was able to effectively crosslink the SF chain improving the mechanical strength. This effect was proved both evaluating the compression modulus and by studying the spectra obtained by Fourier infrared spectroscopy (FTIR). This protocol may be applied in the near future to the production of a structural bone scaffold.

Biochar is a carbon allotrope obtained by pyrolysis of biomass, usually agro-waste. Owing to the demand for sustainable development, biochar is continuously raising much hope in the scientific community. However, in order to impart it with new properties, its modification is required, either in situ during pyrolysis, or after the carbonization process. Herein, we propose a new direct approach to obtain bimetallic copper/nickel nanoparticle-loaded on olive stone biochar. The bimetallic-coated biochar and the reference materials bare biochar, copper-loaded and nickel-loaded biochar were prepared at 400 °C under a stream of dinitrogen from olive pit powder particles impregnated first with citric acid (CA), and then with copper and nickel nitrates. We have employed citric acid in the process in order to check its effect on the structural and textural properties of biochar supporting the metallic nanoparticles. Surprisingly, citric acid induced the formation of agglomerated or even raspberry-shaped, bimetallic copper/nickel nanoparticles. Large 450-500 nm-sized agglomerates of ~80 nm bimetallic CuNi NPs were noted for B-CA@CuNi. Interestingly, for biochar material prepared with initial Cu/Ni=10 molar ratio (B-CA@CuNi10/1), the bimetallic NPs formed unusual nano-raspberries (1748 nm in size) which are agglomerates of individual 10-20 nm-sized CuNi10/1 nanoparticles. The B-CA@CuNi and reference materials were characterized by Raman spectroscopy, scanning electron microscopy (SEM)/energy-dispersive X-ray spectroscopy (EDX), X-ray diffraction (XRD) and magnetometry. The B-CA@CuNi and B-CA@Ni materials could be attracted efficiently with a magnet, but not B-CA@CuNi10/1 due to a low nickel loading. B-CA@CuNi was tested as a catalyst for the degradation of methyl orange (MO). Discoloration was noted within 10 min, much faster than a similar material prepared in the absence of CA. B-CA@CuNi could be recycled at least 3 times with exhibit as fast discoloration catalysis performance. This paper stresses the important role of citric acid in shaping the bimetallic nanoparticles loaded in situ on biochar during the slow pyrolysis process and to enable faster catalysed discoloration of organic dye solution.

Poly (Lactic Acid) (PLA) / Ground Tire Rubber (GTR) blends using Dicumyl peroxide (DCP) as a crosslinking agent were prepared as a route to recycle wastes rubber from the automotive industry. The GTR were exposed to grinding and exhibited mechanical damage, traduced at the rubber network scale by chains scission and/or chemical cross-links breakage. Such damage is accompanied by a decrease of 80% of the rubber chains network density of the initial tire buffing but found independent on the type of grinding (cryogenic, dry ambient) or on the GTR size (from <400 µm to <63 µm). Moreover, the finest sieved GTR contain the largest the amount of reinforcing elements (carbon black, clay) that can be advantageously used in PLA/GTR blends. The melt-blending of these finest GTR particles obtained by cryo-grinding at an amount of 15 wt.% and in presence of the crosslinking agent (DCP), resulted in an optimum improvement of the ductility, energy at break and impact strength of the PLA/GTR blends as compared to neat PLA, while maintaining its stiffness. The results were attributed to (i) the good dispersion of the fine GTR particles into the PLA matrix, (ii) the partial re-crosslinking of the GTR particles and co-crosslinking at PLA/GTR interface and (iii) the presence of reinforcing carbon black into the GTR particles and clay particles dispersed into the PLA matrix.

On the primitive Earth, both L- and D-amino acids would have been present. However, only L-amino acids are essential blocks to construct proteins in modern life. To study the relative stability of D-amino acid substituted peptides, a variety of computational methods were applied. Ten prebiotic amino acids (Gly, Ala, Asp, Glu, Ile, Leu, Pro, Ser, Thr, and Val) were previously determined by multiple meteorite, spark discharge, and hydrothermal vent studies. Some previously reported early Earth polypeptide analogs were focused on in this study. Tripeptides composed of only Asp, Ser, and Val exemplified that different positions (i.e., N-terminus, C-terminus, and middle) made a difference in the minimal folding energy of peptides, while the chemical classification of amino acid (hydrophobic, acidic, or hydroxylic) did not show a significant difference. Hierarchical cluster analysis for dipeptides with all possible combinations of the proposed ten prebiotic amino acids and their D-amino acid substituted derivatives generated five clusters. Primordial simple polypeptides were modeled to test the significance of molecular fluctuations, secondary structure occupancies, and folding energy differences based on these clusters. We found peptides with α-helices, long β-sheets, and long loops are usually less sensitive to D-amino acid replacements in comparison to short β-sheets. Intriguingly, amongst 129 D-amino acid residues, mutation sensitivity profiles presented that the ratio of more to less stable residues was about 1. In conclusion, some combinations of a mixture of L- and D-amino acids can potentially act as essential building blocks of life.

Ustilago maydis, member of the Ustilaginaceae family, is a promising host for the production of several metabolites including itaconic acid. This dicarboxylate has great potential as a bio-based building block in the polymer industry, and is of special interest for pharmaceutical applications. Several itaconate overproducing Ustilago strains have been generated by metabolic and morphology engineering. This yielded stabilized unicellular morphology through fuz7 deletion, reduction of by-product formation through deletion of genes responsible for itaconate oxidation and (glyco)lipid production, and the overexpression of the regulator of the itaconate cluster ria1 and the mitochondrial tricarboxylate transporter encoded by mttA from Aspergillus terreus. In this study, itaconate production was further optimized by consolidating these different optimizations into one strain. The combined modifications resulted in itaconic acid production at theoretical maximal yield, which was achieved under biotechnologically relevant fed-batch fermentations with continuous feed.

Current study aims to evaluate the possibilities to increase part strength by optimizing the FFF process parameters. Five different CAD models of parts with same coupling dimensions but different shape inherited from a recent study were converted into test samples with Ultimaker 2 3D printer. The main measure of success was the sample strength, defined as the load at which the first crack in the stressed area of the part appeared. Three different modifications to the FFF process with verified positive effect on interlayer bonding were applied. First modification included raising the extrusion temperature and disabling printed part cooling. Second modification consisted in reduction of the layer thickness. Third modification combined the effects of the first and the second ones. For four out of five shapes tested applied process modifications resulted in significant strengthening of the part. The shape that exhibited the best results was subject to further research by creating special printing mode. The mode included fine-tuning of three technological parameters on different stages of the part fabrication. As result it was possible to increase the part strength by 108% only by tuning printing parameters of the best shape designed with increasing its weight by 8%.

Lipid-based drugs are emerging as an interesting class of novel anticancer drugs with the potential to target specific cancer cell metabolic pathway linked to their proliferation and invasiveness. In particular, ω−3 polyunsaturated fatty acids (PUFA) derivatives such as epoxides and their bioisosteres have demonstrated the potential to suppress growth and promote apoptosis in triple-negative human breast cancer cells MDA-MB-231. In this study 16-(4’-chloro-3’-trifluorophenyl)carbamoylamino]hexadecanoic acid (ClFPh-CHA), an anticancer lipid derived from ω−3,17,18-epoxyeicosanoic acid, was formulated as a stable nanoemulsion with size around 150 nm and narrow droplet size distribution (PDI<0.200) through phase-inversion emulsification process followed by high pressure homogenization in view of an oral administration. The ClFPh-CHA-loaded nanoemulsions were able to significantly decrease the relative tumor volume in mice bearing an intramammary tumor xenograft at all doses tested (2.5, 10 and 40 mg/kg) after 32 days of daily oral administration. Furthermore, absolute tumor weight was decreased to 50% of untreated control at 10 and 40 mg/kg, while intraperitoneal administration could achieve a significant reduction only at the highest dose of 40 mg/kg. Results suggest that oral administration of ClFPh-CHA formulated as a nanoemulsion has a sufficient bioavailability to provide an anticancer effect in mice and that the activity is at least equal if not superior to that obtained by a conventional parenteral administration of equivalent doses of the same drug.

The aim of this study (first analytical approach) was to obtain data on the fatty acid composition of gluten-free foods (bakery products) for celiac people. The study included 35 different products (snacks, biscuits, bakery products, pasta, flours, etc.) from several manufacturers. After extraction and esterification, the fatty acid content was determined by GC-MS. The monounsaturated fatty acids (MUFAs) are the major constitutes (57%) of the fatty acids pool followed by saturated fatty acids (SFAs) (30%) and polyunsaturated fatty acid (13%). Only fifteen, of the thirty-five gluten free samples analyzed, provide adequate energy intake, while in eleven samples, saturated fatty acids take more energy than that recommended by EFSA. It has emerged that local producers generally use the finest raw materials (olive oil, etc.) compared to the industries which, as has been pointed out, in many cases use palm and palm kernel oils although gluten free commercial products are high added value foods, expensive and intended for a particularly sensitive public.

Abstract: Measures to counteract AMD generation need to start at the mineral surface, inhibiting mineral-oxidizing, acidophilic microbes. Laboratory and long-term field tests with pyrite-containing mining wastes, where Carbonaceous Phosphate Mining Waste (CPMW) was added, resulted in low acidity, and near neutral drainage. The effect was reproducible, nd confirmed by several independent research groups. This was shown to involve an organic coating, likely a biofilm. The biofilm formation was confirmed when CPMW was added to lignite coal waste with an initial pH of 1. Forty five days after the addition, the coal waste was dominated by heterotrophic microorganisms in biofilms. A review of the scientific literature supports that CPMW has physical and chemical characteristics which are capable of inducing a strong inhibitory effect on sulphide oxidation by forming an organic coating over the mineral surface. CPMW characteristics appear to provide the cornerstone of a new technology for the reduction of sulphide oxidation in mine wastes. An hypothesis for testing this technology is presented which could result in an economical and sustainable approach to mine waste and water management.

Abnormal Tau phosphorylation and aggregation into neuronal paired helical filaments and neurofibrillary tangles cause tauopathies, a class of neurodegenerative diseases, that include Alzheimer’s disease, frontotemporal dementia and parkinsonism linked to chromosome 17, progressive supranuclear palsy, Pick's disease, and corticobasal degeneration. Glycogen synthase kinase-3β (GSK-3β) is the most critical kinase to phosphorylate Tau. We have developed the linoleic acid derivative 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA), with cyclopropane rings instead of cis-double bonds, as an anti-dementia drug. DCP-LA serves as a selective activator of PKCε and a potent inhibitor of protein tyrosine phosphatase 1B (PTP1B). DCP-LA prevents Tau phosphorylation due to PKCε-mediated direct inactivation of GSK-3β, to PKCε/Akt-mediated inactivation of GSK-3β, and to receptor tyrosine kinase-mediated inactivation of GSK-3β in association with PTP1B inhibition. DCP-LA targeting GSK-3β, thus, could become a valid drug for treatment of tauopathies.

Pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0) have been described as dietary biomarkers of dairy-fat consumption with varying degrees of reliability between studies. It remains unclear how the total amount of dietary fat; one of the main confounding factors in these biomarker investigations, affects C15:0 and C17:0 circulating compositions independently to their relative intake. Additionally, it is unknown how changes in the dietary total-fat affects other fatty acids in circulation. Through two dietary studies with different total-fat levels but maintaining individual fatty acid compositions we were able to see how the dietary total-fat affects the fatty acids in circulation. We saw that there was a significant, proportionate, and robust decrease in the endogenous C15:0 levels with an increase in dietary total-fat. However, there was an increase in the circulating C17:0 compositions as the total-fat increased. To conclude, the dietary total-fat content and fat-type have a very complex influence on the relative compositions of circulating fatty acids, which are independent to the actual dietary fatty acid composition. Knowing how to manipulate circulating C15:0 and C17:0 composition is far-reaching in nutritional/pathological research as they highlight a dietary route to attenuate the development of metabolic disease (both by reducing risk and improving prognosis).

Ozone is considered a promising food preservation technique and has gained great interest because of its strong oxidizing properties and significant antimicrobial efficacy, and because its decomposition leaves no residue in food. In the present study the combined effect of ozone and citric acid treatment on quality and shelf life of freshly cut lettuce packaged under a passive modified atmosphere during cold storage was investigated. Lettuce were washed, cut and treated with ozone at 0.5, 1.0 or 1.5 ppm for 45 minutes. Another batch was treated with citric acid and 3 additional batches were treated with ozone at the above concentrations plus citric acid. Headspace analysis, color parameters, pH, microbiological and sensory analysis were monitored during cold storage. Carbon dioxide production rates increased significantly (p

Celiac disease is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten, affecting approximately 1% of the global population and two million Americans. An increasing number of studies have identified a link between celiac disease and adverse maternal and fetal outcomes during pregnancy and after birth. Additionally, both celiac disease and pregnancy are associated with an increased risk for nutrient deficiencies, specifically vitamin B12 and folate. Deficiencies in these key nutrients are linked with several negative maternal and fetal health outcomes including preeclampsia, gestational diabetes, spontaneous abortion/miscarriage, preterm birth, NTDs, Intrauterine Growth Restriction, and low gestational age and birthweight. This review examines the current literature related to the folate trap and vitamin B12 deficiency in patients with celiac disease and pregnant women independently, and to provide rationale for future research to explore the correlation between the folate to B12 ratio in pregnant woman with celiac disease.

Diabetes mellitus, a chronic and non-transmissible disease, triggers a wide range of micro- and macrovascular complications. The differentiation of pancreatic β-like cells (PβLCs) from induced pluripotent stem cells (iPSCs) offers a promising avenue for regenerative medicine aimed at treating diabetes. Current differentiation protocols strive to emulate pancreatic embryonic development by utilizing cytokines and small molecules at specific doses to activate and inhibit distinct molecular signaling pathways, directing the differentiation of iPSCs into pancreatic β cells. Despite significant progress and improved protocols, the full spectrum of molecular signaling pathways governing pancreatic development and the physiological characteristics of the differentiated cells are not yet fully understood. Here, we report a specific combination of cofactors and small molecules that successfully differentiate iPSCs into PβLCs. Our protocol has shown to be effective, with the resulting cells exhibiting key functional properties of pancreatic β cells, including the expression of crucial molecular markers (pdx1, nkx6.1, ngn3) and the capability to secrete insulin in response to glucose. Furthermore, the addition of vitamin C and retinoic acid in the final stages of differentiation led to the overexpression of specific β cell genes.

Chenodeoxycholic acid (CA) is a naturally occurring bile acid that is produced in the liver from cholesterol. Three CA complexes using Zn(II), Mg(II), and Ca(II) ions were synthesized to examine the chelation tendencies of CA towards these metal ions. The complexation reaction of CA with the metal ions under investigation was conducted with a 1:1 molar ratio (CA to metal) at 60-70°C in natural media (pH 7-8), which consisted of a binary solvent of MeOH and H2O (1:1). The resulting CA complexes were characterized using analytical data (metal, H, C, and Cl, analysis) and spectral data (UV-visible, FT-IR, and 1H NMR) to elucidate the complexes’ structures. The results suggested that CA in anion form utilized oxygen atoms of the carboxylate group (-COO−) to capture Zn(II), Mg(II), and Ca(II) ions. This produced complexes with the general compositions of [Zn(CA)(H2O)Cl], [Mg(CA)(H2O)Cl]H2O, and [Ca(CA)(H2O)Cl]2H2O, respectively. The Kirby-Bauer disc diffusion assay was then used to explore the bioactivity of the CA complexes toward three fungal species, three Gram-positive bacteria, and two Gram-negative bacteria. The Ca(II) and Mg(II) complexes exhibited marked inhibitory effects on the cell growth of the fungal species Aspergillus niger with potency equal to 127% and 116% of the activity of the positive control, respectively. The Zn(II) and Ca(II) complexes strongly inhibited the growth of Penicillium sp., while the Zn(II) and Mg(II) complexes showed strong growth inhibition towards the Gram-negative species Pseudomonas aeruginosa.

Structure based biological and chemical properties of 4-(carboxyamino)-benzoic acid has been studied by quantum chemical methods. The revamped geometric structure and its quantum chemical parameters were obtained by DFT-B3LYP/6-311G method. Normal mode analysis is performed to assign the fundamental vibrational frequencies as per the potential energy distribution (PED) by using the VEDA program. Simulation of IR and Raman spectral patterns are observed by refinement of scale factors. TD-DFT approach is used to explore the excited states of molecule and prediction of electronic absorption spectra. NMR chemical shifts of the molecule are determined by the gauge independent atomic orbital method. The molecular docking is performed to recognize the binding energy of the ligand with the dynamic site of protein. In our docking analysis, the protein 5DT6 shows the best results than other three proteins which could be used for further analysis. Further inter and intra molecular interactions, electrophilic, nucleophilic and chemical reactivity sites are found by molecular electrostatic potential, HOMO-LUMO and Global chemical reactivity descriptors. Thermodynamic property of the title compound is also reported. The determined quantum chemical parameters show high reactivity and the dipole moment was sufficiently high enough to induce nonlinear characteristics which are required for applications in optoelectronic devices.

Almond (Prunus dulcis (Mill.) D.A.Webb) is one of the largest nut crops in the world. Recently, phenolic compounds, mostly stored in almond skin, have been associated with much of the health-promoting behavior associated with their intake. The almond skin enriched fraction obtained from cold-pressed oil residues of the endemic Moroccan Beldi ecotypes is particularly rich in chlorogenic acid. In this study, both almond skin extract (AE) and chlorogenic acid (CHL) supplements, similar to traditional positive control resveratrol, significantly increased the replicative life-span of yeast compared to the untreated group. Our results showed that AE and CHL significantly reduced the production of reactive oxygen and nitrogen species (ROS/RNS), most likely due to their ability to maintain mitochondrial function during aging, as indicated by the maintenance of normal mitochondrial membrane potential in treated groups. This may be associated with the observed activation of the anti-oxidative stress response in treated yeast, which results in activation at both gene expression and enzymatic activity levels for SOD2 and SIR2, the latter being an upstream inducer of SOD2 expression. Interestingly, the differential gene expression induction of mitochondrial SOD2 gene at the expense of the cytosolic SOD1 gene confirms the key role of mitochondrial function in this regulation. Furthermore, AE and CHL have contributed to the survival of yeast under UV-C-induced oxidative stress, by reducing the development of ROS / RNS, resulting in a significant reduction in cellular oxidative damage as evidenced by decreased membrane lipid peroxidation, protein carbonyl content and 8-oxo-guanine formation in DNA. Together, these results demonstrate the interest of AE and CHL as new regulators in the replicative life-span and control of the oxidative stress response of yeast.

We performed a systematic review and meta-analysis to evaluate the role of gastric acid suppressant use on outcomes of tyrosine kinase inhibitors (TKIs) and oral chemotherapy. We identified all researches evaluating the effect of GAS use on patients receiving oral chemotherapy or TKIs for solid tumors. The pooled hazard ratios (HRs) and 95% confidence interval (95% CI) for overall survival (OS) and progression-free survival (PFS) were calculated with fixed-effects or random-effects model. The study population included n=16 retrospective studies and 372,418 patients. Series concerned gastrointestinal tract tumors (n=5 studies), renal cell carcinomas (RCC, n=3 studies), non-small cell lung cancers (NSCLC, n=5 studies), and soft tissue sarcomas or mixed histologies solid tumors in n=3 studies. The pooled HRs for OS and PFS were 1.31 (95% CI: 1.20–1.43; P<01) and 1.3 (95%CI 1.07-1.57; P<0.01) for GAS and no GAS users, respectively. Only studies of EGFR mutated NSCLC patients receiving TKIs and those with colorectal cancer receiving oral chemotherapy showed a significant correlation between GAS and poor survival. Our study supports the evidence of a possible negative impact of concomitant GAS therapy on survival outcomes of patients receiving oral anti-cancer drugs.

Marula seed cake (MSC) is a nutritionally-rich natural feed resource that can enhance the healthiness of animal-derived foods (ADFs) for human consumption. This study compared the health-related fatty acid (FA) profiles of MSC products from South Africa and Eswatini. Composite samples monthly collected from both countries were analysed for FAs. MSC products from both countries were found to be dominated by oleic acid (>70%), followed by palmitic, linoleic and stearic acids. Consequently, both products had their FA totals dominated by ƩMUFA followed by ƩSFA, ƩPUFA, Ʃn-6 PUFA and Ʃn-3 PUFA. Both oleic and stearic acids were higher (P < 0.01) whilst linoleic (P < 0.001), α-linolenic (P < 0.05), margaric (P < 0.05), palmitoleic (P < 0.05) and eicosatrienoic (P < 0.05) acids were lower in South African in comparison to Eswatini MSC. Consequently, South African MSC had higher ƩMUFA (P < 0.01) but lower ƩPUFA (P < 0.001), Ʃn-6 PUFA (P < 0.001) and Ʃn-3 PUFA (P < 0.05). Also, Eswatini MSC had higher n-6 : n-3 PUFA, PUFA : SFA (P = 0.001) and PUFA : MUFA (P < 0.05) ratios. Further, MSC products from both countries had similarly (P > 0.05) low atherogenicity and high desaturase indices. In conclusion, both country products are rich particularly in oleic acid and their incorporation into farm animal diets would increase content of the MUFA in ADFs and, consequently, improve health benefits to human consumers.

The present paper addresses dynamic risks in the automotive industry factories, specifically the car lead-acid batteries manufacturing area. The main analyzed risk is represented by the fire risk. Battery manufacturing process is described and analyzed from the fire risk perspective and the hazard areas are identified. The investigation methodology uses case studies for different lead-acid battery formation processes, combined with 3D simulations using PyroSym platform, and it is based on the author's experience in the battery manufacturing field for about ten years. The results of the case studies are compared using the same inputs, but different specific process conditions, and conclusions are formulated. To avoid the fires and mitigate the risk, a series of actions are proposed in the last sections. As a general conclusion, the actual research demonstrates that the complex and dynamic risks from the automotive industry, associated with Industry 5.0 must be analyzed using combined methods, classical and modern, including 3D simulations, to get great results.

This study presents polyaniline (PANI) synthesis and characterization using a novel acid-assisted polymerization technique. Two PANI suspensions with different ammonium peroxydisulfate (APS) concentrations were synthesized at room temperature, i.e. the ratio of aniline to APS was 10:1 for PANI1 and 5:1 for PANI2. SEM measurements revealed distinct structures: a porous nanofibrillar structure for PANI1 and a densely packed structure for PANI2. The electrochemical performance of the fabricated PANI/glassy carbon (GC) electrodes was evaluated using a three-electrode cell configuration in the scan rates of 10 mV/s and 30 mV/s. The PANI1/GC heterostructure exhibited a specific capacitance of 160 F/g, while this value increased to 407 for the PANI2/GC. This research contributes not only to the understanding of PANI synthesis at room temperature but also to its potential applications in electrochemical energy storage devices.

The ever-increasing demand for seafood-containing diets, especially fish, primarily due to their superior nutritional value, has impacted the availability of wild stocks, necessitating the focus on other underutilised aquaculture species. In this study, the proximate and fatty acid (FA) composition of the indigenous black South African mussel (Choromytilus meridionalis) was investigated. The effects of the hot-smoking as preservation method on the proximate composition for mussels were assessed using the standard AOAC protocols; while gas chromatography-flame ionised detection (GC-FID) was used to determine the FA content. The moisture level in hot-smoked mussels significantly (P

The reaction between 5-acetylbarbituric acid and 4-dimethylthiosemicarbazide or 4-hexamethyleneiminyl thiosemicarbazide produces 5-acetylbarbituric-4-dimethylthiosemicarbazone (H2AcbDM) and 5-acetylbarbituric-4N-hexamethyleneiminyl thiosemicarbazone (H2Acbhexim). Eight new complexes with different cooper (II) salts have been prepared and characterized using elemental analysis, molar conductance, UV–vis, ESI-HRMS, FT-IR, magnetic moment, EPR and cyclic voltammetry. In addition, three-dimensional molecular structures of [Cu(HAcbDM)(H2O)2](NO3)·H2O (3a), [Cu(HAcbDM)(H2O)2]ClO4 (4), and [Cu(HAcbHexim)Cl] (6) were determined by single crystal X-ray crystallography, and was carried out an analysis of their supramolecular structure. The H-bonded assemblies were further studied energetically using DFT calculations, MEP surface and QTAIM analyses. In these complexes, the thiosemicarbazone coordinates to the metal ion in an ONS-tridentate manner, in the O-enolate/S-thione form. The electrochemical behavior of the thiosemicarbazones and their copper(II) complexes has been investigated at room temperature using the cyclic voltammetry technique in DMFA. The Cu(II)/Cu(I) redox system was found to be consistent with the quasi-reversible diffusion-controlled process.

Alcohol abuse can lead to alcoholic liver disease, becoming a major global burden. Hovenia dulcis fruit peduncle polysaccharides (HDPs) has the potential to alleviate alcoholic liver injury may play essential roles in treating for alcohol-exposed liver disease, however, the hepatoprotective effects and mechanisms remain unclear. In this study, the hepatoprotective effects of HDPs and its potential mechanisms were investigated in alcohol-exposed mice by liver metabolomics and gut microbiome. The results found that HDPs reduced medium-dose alcohol-caused dyslipidemia (significantly elevated T-CHO, TG, LDL-C), elevated liver glycogen levels and inhibited intestinal-hepatic inflammation (significantly decreased IL-4, IFN-γ and TNF-α), consequently reversing hepatic pathological changes. By applying gut microbiome analysis, HDPs showed significant decreases in Proteobacteria while significant increases in Firmicutes at the phylum level, and increased Lactobacillus abundance while decreased Enterobacteria abundance, maintaining the composition of gut microbiota. Further hepatic metabolomics analysis revealed that HDPs had a regulatory effect on hepatic fatty acid metabolism, by increasing the major metabolic pathways including arachidonic acid metabolism and glycerophospholipid metabolism and identified two important metabolites C00157 and C04230 involved in the above metabolism. Overall, HDPs reduced intestinal dysbiosis and hepatic fatty acid metabolism disorders in alcohol-exposed mice, suggesting that HDPs has a beneficial effect on alleviating alcohol-induced hepatic metabolic disorders.

APC mutation is the main driver mechanism of CRC development and leads to constitutively activated WNT signaling, overpopulation of ALDH+ stem cells (SCs), and incomplete differentiation. We previously reported that retinoic acid (RA) receptors are selectively expressed in ALDH+ SCs, which provides a way to target cancer SCs with retinoids to induce differentiation. Hypotheses: A functional link exists between WNT and RA pathways, and APC mutation generates a WNT:RA imbalance that decreases retinoid-induced differentiation and increases ALDH+ SCs. Accordingly, to restore parity in WNT:RA signaling, we induced wt-APC expression in APC-mutant CRC cells and assessed the ability of all-trans-retinoic acid (ATRA) to induce differentiation. Notably, ATRA substantially increased expression of the WNT-target gene, CYP26A1, and inducing wt-APC reduced this expression by 50%. Thus, RA and WNT pathways crosstalk to modulate CYP26A1 metabolism of retinoids. We found that inducing wt-APC augments ATRA-induced cell differentiation by: i) decreasing cell proliferation; ii) suppressing ALDH1A1 expression; iii) decreasing ALDH+ SCs; iv) increasing neuroendocrine cell differentiation. Furthermore, NanoString profiling/bioinformatics identified a novel CYP26A1-based network that links WNT and RA signaling. Moreover, CYP26A1 inhibitors sensitized CRC cells to the anti-proliferative effect of drugs that downregulate WNT signaling. Notably. in wt-APC-CRCs, decreased CYP26A1 improves patient survival. These findings have strong potential for clinical translation.

The critical enzyme Dihydrofolate Reductase-Thymidylate Synthase in Leishmania major (LmDHFR-TS) serves a dual-purpose role and is essential for DNA synthesis, a cornerstone of the parasite's reproductive processes. Consequently, the development of inhibitors against LmDHFR-TS is crucial for the creation of novel anti-Leishmania chemotherapies. In this study, we employed an in-house database containing 314 secondary metabolites derived from cinnamic acid that occurred in the Asteraceae family. We conducted a combined ligand/structure-based virtual screening to identify potential inhibitors against LmDHFR-TS. By consensus analysis of both approaches, we identified three compounds, i.e., lithospermic acid (237), diarctigenin (306), and isolappaol A (308), that exhibited a high probability of being inhibitors according to both approaches and were consequently classified as promising hits. Subsequently, we expanded the binding mode examination of these compounds within the active site of the test enzyme through molecular dynamics simulations, revealing a high degree of structural stability and minimal fluctuations in its tertiary structure. The in-silico predictions were then validated through in-vitro assays to examine the inhibitory capacity of the top-ranked naturally-occurring compounds against LmDHFR-TS recombinant protein. The test compounds effectively inhibited the enzyme with IC50 values ranging from 6.1 to 10.1 μM. In contrast, other common cinnamic acid derivatives (i.e., flavonoid glycosides) from the Asteraceae family, such as hesperidin, isovitexin 4′-O-glucoside, and rutin, exhibited low activity against this target. The selective index (SI) for all tested compounds was determined using HsDHFR, with moderate inhibitory effect. Among these hits, lignans 306 and 308 demonstrated the highest selectivity, displaying superior SI values compared to methotrexate, the reference inhibitor of DHFR-TS. Therefore, continued research into the anti-leishmanial potential of these C6C3-hybrid butyrolactone lignans may offer a brighter outlook for combating this neglected tropical disease.

Research conducted on individuals with depression reveals that major depressive disorders (MDDs) coincide with diminished levels of the inhibitory neurotransmitter γ-aminobutyric acid (GABA) in the brain, as well as modifications in the subunit composition of the primary receptors (GABAA receptors) responsible for mediating GABAergic inhibition. Furthermore, there is substantial evidence supporting the significant role of GABA in regulating stress within the brain, which is a pivotal vulnerability factor in mood disorders. Although there is substantial evidence indicating that GABA may be affecting GABA receptors in peripheral tissues, there is comparatively less evidence supporting its direct action within the brain. Emerging evidence highlights that GABA may exert beneficial effects on the brain and psyche through the gut-brain axis. GABA is readily available and approved as a food supplement in many countries. While GABA enjoys wide consumer acceptance in Eastern Asian markets, with many consumers reporting favorable effects on stress regulation, mood, and sleep, rigorous independent research is still largely lacking. Basic research, coupled with initial clinical findings, makes GABA an intriguing neuro-nutritional compound deserving of clinical studies in individuals with depression and other psychological problems.

Zinc, being a part of many proteins and enzymes, plays an important role in the vital processes of the body. Racemic α-lipoic acid (LA) has a wide range of biological activities: antioxidant, antidiabetic, anticancer, and it is also used in diseases such as Parkinson's and Alzheimer's. Nowadays, the synthesis and structural studies of new zinc complexes with biologically active compounds are of great importance for drug discovery. This work shows the studies carried out on the synthesis, structure, identification, also biological activity using in silico methods of a complex compound based on LA and zinc. A complex compound of zinc with LA (ZnLA) was synthesized in the presence of LA and zinc acetate in ethanol. The identification of ZnLA by (FT-IR, XRD and TGA-DTA), also DFT calculations at the B3LYP/def2-TZVPP level of theory was performed. The molecular docking investigation involved docking ZnLA with two different protein receptors such us Glycogen phosphorylase (2GPA) and Kv potassium channel beta subunit (1ZSX) using CB-Dock 2 server and Auto-Dock Vina program to determine the mechanism of action and biological activity. This study reveals potential ligand-protein interactions at the atomic level and suggests that the treatment of diabetes (non-insulin dependent) with ZnLA.

Age-related macular degeneration, a leading cause of visual loss and dysfunction in the devel-oped world, is a disease initiated by genetic polymorphisms that impairs negative regulation of complement. Proteomic investigation points to altered glycosylation and loss of SIGLEC medi-ated glyco-immune checkpoint parainflammatory homeostasis as a main determinant for the vi-sion impairing complications of macular degeneration. The effect of altered glycosylation on microglial maintained retinal para-inflammatory homeostasis and eventual recruitment and polarization of peripheral blood monocyte derived macrophages (PBMDM) into the retina can explain the phenotypic variability seen in this clinically heterogenous disease. Restoring gly-co-immune checkpoint control with a sialic acid mimetic nanoparticle targeting microgli-al/macrophage SIGLECs to regain retinal para inflammatory homeostasis is a promising thera-peutic that could halt the progression of and improve visual function in all stages of macular de-generation.

The amino acids (AAs) and vitamins imbalances are observed in celiac disease (CD). This study evaluated the plasma profile of vitamin A and AAs and the expression level of IL-2, IL-4, IL-10, IL-12 and TGFβ in CD patients. A total of 60 children and adults with CD and 40 healthy controls (HCs) were included. Plasma profile of Vitamin A and AAs and the mRNA expression levels of target genes were assessed. Active adult patients exhibited a decrease in Vitamin A levels (p=0.04) and an increase in IL-2 (p=0.008) and IL-12 (p=0.007) mRNA expression compared to HCs. Treated adult patients showed elevated Serine (p=0.003) and Glycin (p=0.04) levels, as well as increased IL-12 (P&lt;0.0001) mRNA expression, and a decrease in Tryptophan (p=0.04) levels relative to the controls. Additionally, treated adult patients had higher plasma levels of Threonine compared to both active (p=0.04) and control (p=0.02) subjects, and increased mRNA expression of IL-4 (p=0.01) in comparison to active patients. In active children with CD, IL-2 mRNA level was found to be higher than in controls (P&lt;0.0001) and in treated children (p=0.005). Treated children with CD exhibited decreased plasma levels of Tryptophan (p=0.01) and Isoleucine (p=0.01) relative to the controls, and increased mRNA expression of TGFβ (p=0.04) relative to active patients. Managing Retinoic acid levels is crucial to alleviate intestinal inflammation of CD patients. Threonine, tryptophan, and Isoleucine are potential therapeutic options for treating CD, and targeting serine, histidine, tyrosine, and aspartate may hold promise as therapeutic targets for CD patients.

Tdp1 and Tdp2 are DNA repair enzymes that repair DNA damages caused by various agents, including anticancer drugs. Thus, these enzymes resist anticancer therapy and could be the reasons of resistance to such widely used drugs as topotecan and etoposide. In the present work, we found compounds capable of inhibiting both enzymes among derivatives of (-)-usnic acid. Both (+)- and (-)-enantiomers of compounds act equally effectively against Tdp1, and only (-)-enantiomers inhibited Tdp2. Surprisingly, the compounds protect HEK293FT wild type cells from the cytotoxic effect of etoposide but potentiate it against Tdp2 knockout cells. We assume that the sensitizing effect of the compounds in the absence of Tdp2 is associated with effective inhibition of Tdp1, which could take over the functions of Tdp2.

Saussurea neoserrata Nakai offers a reliable and efficient source of antioxidants that can help alleviate adverse skin reactions triggered by air pollutants. Air pollutants, such as particulate matter (PM), have the ability to infiltrate the skin and contribute to the higher occurrence of cardiovascular, cerebrovascular, and respiratory ailments. Individuals with compromised skin barriers are particularly susceptible to the impact of PM since it can be absorbed more readily through the skin. This study investigated the impact of protocatechuic acid and syringin, obtained from the n-BuOH extract of S. neoserrata Nakai, on the release of PGE₂ and PGD₂ induced by PM₁₀. Additionally, it examined the gene expression of enzymes involved in the synthesis of PGE₂ and PGD₂ in human keratinocytes. The findings of this research highlight the potential of utilizing safe and efficient plant-derived antioxidants in dermatological and cosmetic applications to mitigate the negative skin reactions caused by exposure to air pollution.

: Exploiting the relationship between the stacking modes of molecules and room-temperature phosphorescence (RTP) performance is of great important to design afterglow materials. A series of coordination polymers base on carbazole–isophtalic acid are synthesized. These compounds exhibit stacking-dependent RTP. It reveals that the phosphorescence efficiency is not proportional to the overlap of p–p stacking, the triplet excited states of discrete dimer mode rather than H-aggregation can dominate the generation of room-temperature phosphorescence. Besides, compounds 1 and 2 exhibit obvious time-dependent RTP with the afterglow color from orange to green, and show white-light emission owing to fluorescence and phosphorescence dual emission. These results indicate that coordination induction is an efficient approach to regulate the aggregation of chromophores, further modulate the room-temperature phosphorescence.

Due to its high specific surface area and rich porous structure, acacia-derived porous activated carbon is the most potentially effective material for wastewater treatment. This research study aimed to prepare activated carbon using Acacia erioloba seedpods as carbonaceous materials and phosphoric acid as an activating agent. The specific surface area of the prepared activated carbon sample was characterised by Brunauer–Emmett–Teller instrument. The specific surface area value was 387 m²/g. The activated carbon prepared was then sieved into three different particle sizes of 50, 100 and 200 micrometres and characterised using various analytical procedures, including proximate analysis to study moisture content, ash content, volatile matter content and fixed carbon content. The bulk density, SEM, power of hydrogen, iodine number and methylene blue number index were also investigated to determine the adsorption properties of the prepared activated carbon. Batch adsorption dynamics for the removal of organic compounds such as methylene blue and unsaturated character of fatty acid from aqueous solution were also carried out at room temperature to evaluate the prepared activated carbon's applicability in water treatment. The iodine number was 528, 638, and 554 mg/g for the 50, 100, and 200 μm activated carbon particles, respectively. From the results, the adsorption of methylene blue favoured the Freundlich adsorption model, showing higher correlation (R²) values than the Langmuir model. The results indicate that methylene blue particles were adsorbed on heterogeneous surfaces.

One of the most interesting groups of fatty acid derivates is the group of conjugated fatty acids, from which the most researched are conjugated linoleic acid (CLA) and conjugated linolenic acid (CLNA), which are associated with countless health benefits. Sex pheromone mixture of some insect species, including tobacco horn-worm (Manduca sexta), are typical for the production of uncommon C16 long conjugated fatty acids with two and three conjugated double bonds, as opposed to C18 long CLA and CLNA. In this study, M. sexta desaturases MsexD2 and MsexD3 were expressed in multiple strains of Y. lipolytica with different genotypes. Experiments with supplementation of fatty acid methyl esters into the medium resulted in production of novel fatty acids. Using GCxGC-MS 20 new fatty acids with two or three double bonds were identified. Fatty acids with conjugated or isolated double bonds or combination of both were produced in trace amounts. Results of this study prove that Y. lipolytica is capable of synthesizing C16 conjugated fatty acids. Further genetic optimization of the Y. lipolytica genome and optimization of the fermentation process could lead to increased production of novel fatty acid derivatives with biotechnologically interesting properties.

Arjunolic acid (AA) is a triterpenoid saponin majorly found in the Terminalia arjuna and is claimed to exert the cardiovascular protective effects as a phytomedicine. However, it is unclear how AA exerts the effects at the molecular level. Hence, this study used an in vitro model using lipopolysaccharide (LPS)-stimulated H9C2 and C2C12 myotubes to investigate the cardioprotective effects of arjunolic acid (AA) via MyD88-dependant TLR4 downstream signaling markers expression. The myotubes were developed by differentiating rat H9C2 and mouse C2C12 myoblast cells. The MTT viability assay was used to assess the cytotoxicity of AA. LPS induced in vitro cardiovascular disease model was developed in H9C2 and C2C12 myotubes. The treatment groups were designed such as control (untreated), LPS control, positive control (LPS+ pyrrolidine dithiocarbamate (PDTC)-25 µM), and treatment groups were co-treated with LPS and three doses of AA (50, 75, and 100 µM). The changes in the expression of TLR4 downstream signaling markers were evaluated through High Content Screening (HCS) and Western Blot (WB) analysis. The outcomes demonstrated that the expression of MyD88, MAPK, JNK, and NFκB markers were significantly upregulated in the LPS-treated groups compared to the untreated control. Evidently, the HCS analysis revealed that MyD88, NF-κB, p38, and JNK were significantly downregulated in the H9C2 myotube in the AA treated groups (50, 75, and 100 µM). For, the C2C12 myotube, the expression of NFκB was downregulated. TLR4 marker expression in H9C2 and C2C12 myotubes was subsequently decreased by AA treatment, suggesting possible cardioprotective effects of AA.

Modern technologies for recycling electronic waste (e-waste) impose high economic efficiency and environmental safety requirements. Among existing technologies, hydrometallurgy is considered the most promising technology for e-waste recycling. Increasing attention to the chlorination method is associated with the complex recycling of low-grade ores containing noble metals and secondary polymetallic raw materials. In this paper, we propose a new scheme for leaching metals from computer printed circuits (PCBs) pre-crushed in a disintegrator: the processes of chlorine production and hydrochlorination are implemented in one reactor under the action of alternating current (AC) of industrial frequency (50 Hz). It was found that complete leaching of gold is achieved from fine fractions of raw materials containing 0.03% and 0.01% of the gold at an experiment duration of 2 hours, a current density of 0.66 A·cm-2, and a solid/liquid ratio of 8.6 g·L-1. Under the same conditions of the electrochemical leaching process from the fraction of raw material with a gold content of 0.08%, the degree of metal leaching is 80.5%. At the same time, with an increase in the copper content in the raw material from 1.40% to 6.13%, an increase in the degree of its leaching from 84.6% to 95.2%, respectively, is observed. These results will serve as a foundation for developing a complex technology for recovering valuable metals from PCBs.

This study focused on the characterization of lactic acid bacteria (LAB) in a renowned traditional Italian cheese, Pecorino di Farindola, to select an autochthonous culture and investigate its po-tential for the improvement of safety and functional properties. Two hundred and six LAB isolated throughout production and maturation from nine cheese lots of three farms were identified by 16S rRNA gene sequencing and tested for the presence of genes encoding virulence factors, vancomycin resistance (for enterococci), biogenic amines (BAs) and bacteriocin production, for antimicrobial activity, and for the capacity to survive in the gastro-intestinal tract (GIT) based on tolerance to low pH and bile salts and adhesion to CaCo-2 cells. A Lacticaseibacillus paracasei isolate was used in cheese making and determined a decline of spiked Listeria monocytogenes and Escherichia coli O157 faster than in control cheese. The autochthonous bacterial groups were numerically unaffected, apart from lactobacilli that were recovered in higher numbers in the cheese with added L. paracasei. Based on Repetitive Extragenic Palyndrome (Rep) PCR profiles, the added strain possibly dominated until day 88 in cheese. Results encourage further trials with autochthonous cultures to efficiently inhibit hazardous bacteria and enrich a functional microbiota in Pecorino di Farindola and similar cheeses.

The experiments were designed to know the function of ascorbic acid against salinity on germination, different biochemical and micronutrients concentrations of Solanum melongena. Ascorbic acid was applied as foliar spray on leaves and given in roots through irrigation at 100 and 200 ppm to the plants growed in non saline, 60mM and 100mM salt stress conditions. Different biochemical parameters i.e. chlorophyll, carotenoids, carbohydratrates, protein and micro nutrients concentrations of Solanum melongena were observed under different salt stress concentrations from control (non-saline), 60mM NaCl and 100mM NaCl solutions. The rates of different biochemical parameters and micro nutrients concentrations exhibited decrease in saline media in comparison with their respective control while ascorbic acid used as a foliar spray and through irrigation in roots at the concentration of 100 ppm and 200 ppm resulted promotion in non saline control as compared with salt concentrations media. It was determined that chlorophyll concentration was decreased considerably under salt stress. Amongst micro nutrients ionic composition of Na, K and Na/K ratio resulted that plants treated with different NaCl concentrations at 60mM NaCl and 100mM salt concentrations showed increase in Na and K ions and ascorbic acid were used as a foliar spray and in roots showed decrease in Na and K ions. Overall from the outcomes of the study it was observed that salinity stress significantly decrease vegetative and reproductive parameters that could be improved with the using of ascorbic acid. Best concentration found were 200 ppm ascorbic acid contributed towards an increase in growth irrespective of non-saline and saline conditions. Based on these findings, ascorbic acid treatment helps in alleviating the negative effects of salinity.

The aim of this study was to investigate the effect of condensed tannin (CTs) with differing molecular weight on their capacity to modify the fatty acid profile in milk. Twenty multiparous crossbred lactating dairy goats were assigned in a randomized complete block design (RCBD), and were subjected to receive the dietary treatments as followings; T1: control (with no CTs supplementation), T2: supplemented with mangosteen peel in a concentrate as a source of low molecular weight CTs at level of 3.0 %DM of CTs equivalent, T3: supplemented with the same diet with T2 but added with polyethylene glycol (PEG, as tannin inactivator) as the control of T2, and T4: supplemented with quebracho CT extract (UNITAN ATO, Buenos Aires, Argentina; 75-77 % tannins) in a concentrate as a source of high molecular weight CTs at level of 3.0 %DM of CTs equivalent, and T5) supplemented with the same diet with T4 but added with PEG as the control of T4. No significant change was detected for feed intake and nutrient digestibility indicate that CTs at level of 3.0 %DM of diet did not showed the detrimental effect to feed intake and nutrient digestibility, however, ruminal fermentation parameters and milk yield and milk compositions did not affected by different source of CT inclusion.

Spike protein is the surface glycoprotein of the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) necessary for the entry of the virus via the transmembrane receptors of the human endothelial cells of the respiratoty system for the virus to be engulfed causing COVID-19 disease after priming by type II transmembrane protease TMPRSS2 and then binding with the angiotensin-converting enzyme 2 (ACE2). Therefore, mutations and amino acid variants analysis are essential in understanding the mechanism of binding of spike protein with its receptor to have an insights on possibilities to design a peptide or nucleotide-based vaccine for COVID-19. Here, we employed Iterative Threading Assembly Refinement (I-TASSER) and Multiple Alignment using Fast Fourier Transform (MAFFT) to predict the three-dimensional monomer structure of spike protein of SARS-CoV-2 and to analyze the amino acid variants for protein sequences from GISAID database for samples collected from Jordan in a try to find an explanation for the low confirmed number of COVID-19 in Jordan. Our Protein Homology/analogY Recognition Engine V 2.0 (Phyre2) findings showed four single amino acid variants (SAV) found in 20 samples of SARS-CoV-2. What is equal to 5% of samples showed tyrosine deletion at Y144 located in the SARS-CoV-like_Spike_S1_NTD (N terminal domain), 62% showed aspartate substitution to glycine at D614G located in the SARS-CoV-2_Spike_S1_RBD (spike recognition binding site), 5% showed aspartate substitution to tyrosine at D1139Y and 5% showed glycine substitution to serine at G1167S both located in the Corona_S2 domain. The findings have shown lower mutational sensitivity in all variants that might not affect the function of spike glycoprotein except for D614G, which has the highest mutational sensitivity score (5 out of 9) indicating a higher likelihood to affect the function of the spike protein. This might suggest, in general, a reduced transmitability of SARS-CoV-2 in Jordan.

This study was aimed at investigating the protective effects of glass ionomer cement (GIC) and surface pre-reacted glass ionomer (S-PRG) fillers used as dental restorative materials on demineralization of bovine enamel. GlasIonomer FX ULTRA (FXU), Fuji IX GP Extra (FIXE), CAREDYNE RESTORE (CDR) were used as GICs. PRG Barrier Coat (BC) was used as the S-PRG filler. They were incubated in a lactic acid solution (pH = 4.0) for 6 d at a temperature of 37 °C. The mineral was etched from the enamel surface, and a large number of Ca and P ions were detected in solution. The Al, F, Na, Sr, and Sr ions were released in GICs and S-RPG fillers. The Zn ion was released only in CDR and the B ion was released only in BC. The presence of apparent enamel prism peripheries was observed after 6 d of treatment for the group containing only enamel blocks. pH values for the FXU, FIXE, CDR, BC, and enamel block groups after 6 d were 6.5, 6.6, 6.7, 5.9, and 5.1, respectively. Therefore, the observed pH neutralization effect suppressed progression of caries due to the release of several ions from the restoratives.

Background and objectives: This study were designed to determine uric acid concentration and renal histopathology of M. calabura L. stem bark extract in diabetic rats and to compare the natural product of M. calabura L. stem bark extract with allopurinol. Materials and Methods: A completely randomized design was used for the experiment which consisted of 6 treatment groups, each consisting of 4 rats, as follows: 1) NR, normal rat; 2) KN, diabetic rat (negative control); 3) KP, diabetic rats given allopurinol 10 mg/kg body weight; 4) EM150, diabetic rats given the test extract 150 mg/kg body weight/day; 5) EM300, diabetic rats given the test extract 300 mg/kg body weight/day; and 6) EM450, diabetic rats given the test extract 450 mg/kg body weight/ day. Results: The results showed that M. calabura L. stem bark extract decrease (p<0.05) uric acid levels in diabetic rats and no specific damage to renal proximal tubular cells was seen. Conclusions: It was concluded that M. calabura L. stem bark extract has a potential as an antihyperuricemic in diabetic rats. The recommended does was 300 mg/kg body weight to provide a significant effect on reducing the uric acid level in diabetic rats. Our findings support the use of this plant as a treatment for gout and other inflammatory diseases.

Our study aims to implement a strategy to reduce the carbon steel corrosion rate in sulfuric acid solution, using an expired drug with adsorption affinity on the metal surface. To investigate the corrosion protection efficiency of an environmental friendly inhibitor, namely neomycin sulfate (NMS), the electrochemical measurements were applied on carbon steel immersed in 1.0 M H₂SO₄ solution with and without NMS. The protective layer formed on the steel surface was studied by atomic force microscopy (AFM). The potentiodynamic polarization and electrochemical impedance spectroscopy (EIS) showed that the presence of the neomycin sulfate in acid solution leads to the decrease in corrosion current density (i_corr) and the increase of polarization resistance (R_p). The mixed mechanism between physical and chemical adsorption of NMS molecules on the steel surface was proposed according to the Langmuir adsorption isotherm. The Atomic Force Microscopy (AFM) indicated that the NMS molecules contributed to a protective layer formation by their adsorption on the steel surface. The AFM parameters such as: root-mean-square roughness (R_q); average roughness (R_a) and maximum peak to valley height (R_p-v) revealed that in the presence of NMS a smoother surface of carbon steel was obtained, compared to the steel surface corroded in sulfuric acid blank solution.

Background: Previously, our laboratory has provided evidence that pre-administration of the antioxidant, lipoic acid covalently bonded to various naturally occurring antioxidants, enhanced neuroprotective capacity compared to the administration of lipoic acid on its own. The naturally occurring compound scopoletin, a coumarin derivative, has been shown in various in vitro studies to have both antioxidant and anti-inflammatory mechanism of actions. To date, the effect of scopoletin on neuronal cell death in an in vivo model of ischemia or ischemia-reperfusion has not been investigated. Therefore, the present investigation was designed to determine if scopoletin on its own, or a co-drug consisting of lipoic acid and scopoletin covalent bond, named UPEI-400, would be capable of demonstrating a similar neuroprotective efficacy. Methods: Using a rodent model of stroke in male rats (anesthetized with Inactin®; 100 mg/kg, iv), the middle cerebral artery was permanently occluded for 6 hours (pMCAO), or in separate animals, occluded for 30 min followed by 5.5 hrs of reperfusion (ischemia/reperfusion; I/R). Results: Pre-administration of either scopoletin or UPEI-400 significantly decreased infarct volume in the I/R model (p<0.05), but not in the pMCAO model of stroke. However, UPEI-400 was ~1000 times more potent as compared to scopoletin on its own. The optimal dose of UPEI-400 was then injected during the occlusion and at several time points during reperfusion and significant neuroprotection was observed for up to 150 mins following the start of reperfusion (p<0.05). Conclusion: The data suggest that synthetic combination of scopoletin with lipoic acid (UPEI-400) is a more effective neuroprotectant that either compound on their own. Also, since UPEI-400 was only effective in a model of I/R, it is possible that it may act to enhance neuronal antioxidant capacity and/or upregulate anti-inflammatory pathways to prevent the neuronal cell death.

Foliage-feeding fall armyworm (Spodoptera frugiperda) and root-feeding western corn rootworm (Diabrotica virgifera virgifera) are maize (Zea mays L.) pests that cause significant yield losses. Jasmonic acid (JA) play pivotal defense role against insects. 12-oxo-phytodienoic acid (12-OPDA) is converted into JA by peroxisome-localized OPDA reductases (OPR). However, little is known about the physiological functions of cytoplasmic OPRs. Here, we show that disruption of ZmOPR2 reduced wound-induced JA production and defense against FAW while accumulating more JA catabolites. Overexpression of ZmOPR2 in Arabidopsis enhanced JA production and defense against beet armyworm (Spodoptera exigua). In addition, lox10opr2 double mutants were more susceptible than either single mutant, suggesting that ZmOPR2 and ZmLOX10 uniquely and additively contributed to defense. In contrast to the defensive role of ZmOPR2 and ZmLOX10 in leaves, single mutants did not display any alteration in root herbivory defense against WCR. Feeding on lox10opr2 double mutants resulted in increased WCR mortality associated with greater herbivory-induced production of insecticidal death acids and ketols. Thus, ZmOPR2 and ZmLOX10 cooperatively inhibit synthesis of these metabolites during herbivory by WCR. We conclude that ZmOPR2 and ZmLOX10 regulate JA-mediated resistance in leaves against FAW while suppressing insecticidal oxylipin synthesis in roots during WCR infestation.

Acid stress poses a common challenge for bacteria in diverse environments by the presence of inorganic (e.g., mammals’ stomach) or organic acids (e.g., feed additives; acid-based disinfectants). Limited knowledge exists regarding acid-tolerant strains of specific serotypes, clonal lineages, or sources in human/animal pathogens, namely non-typhoidal Salmonella enterica (NTS) and Enterococcus faecium (Efm). This study evaluated acidic pH and peracetic acid (PAA) susceptibility of Efm (n=72) and NTS (n=60) from diverse epidemiological/genetic backgrounds, and with multiple antibiotic resistance profiles. Efm minimum growth/survival-pH was 4,5-5/3-4 and for NTS 4,0-4,5/3,5-4,0. Among Efm, only those of clade-non-A1 (non-hospital associated) or food chain demonstrated greater tolerance to acidic pH compared to clade-A1 (hospital-associated clones) or clinical isolates (P<0.05). MDR (multidrug-resistant) NTS survived better to acidic pH (P<0.05). The MICPAA/MBCPAA was 70-120/80-150mg/L for Efm and 50-70/60-100mg/L for NTS. Efm-clade-A1 or MDR strains exhibited higher PAA tolerance than clade-non-A1 or non-MDR ones (P<0.05). Higher tolerance was found in non-MDR and clinical NTS than in food chain isolates (P<0.05), but not between different serogroups. This unique study identifies specific NTS or Efm populations more tolerant to acidic pH or PAA, emphasizing the need for further research to tailor control measures of public health and food safety within a One Health framework.

Kummerowia striata is a traditional medicine used for the therapy of inflammation-related diseases. Herein, we investigated the anti-melanogenic and antioxidant activities of an ethanolic extract of K. striata (EKS) using a number of in vitro and cell culture model systems. The anti-melanogenic effect was assessed in B16F10 melanoma cells based on melanin synthesis and in vitro tyrosinase inhibitory activity and the anti-oxidant activity assays were performed using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2ʹ-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS); EKS exhibited strong anti-oxidant activities in both the assays. The expression of tyrosinase, tyrosinase-related protein 1, tyrosinase-related protein 2, and microphthalmia-associated transcription factor was decreased in a dose-dependent manner at mRNA and protein levels upon treatment with EKS. Notably, EKS did not affect the cell viability at all the EKS concentrations used in this study, indicating that EKS-mediated inhibition of melanin synthesis is not accompanied with cytotoxicity. Collectively, our findings demonstrate, for the first time, that EKS possesses anti-melanogenic and anti-oxidant activities, and suggest that further evaluation and development of EKS as a functional supplement or cosmetic might be useful for skin whitening and for reduction wrinkles.

To investigate the composition of caproic acid-producing bacterial communities in sub-high-temperature Daqu, we analyzed four different Daqu samples from Sichuan. After enriching the samples with a specialized medium, we performed high-throughput sequencing of 16S rRNA gene amplicons on the metagenomic DNA from both the Daqu samples and the enrichment cultures. Our analysis focused on identifying and characterizing the caproic acid-producing bacterial communities present in Daqu. The results revealed that enrichment increased both the diversity and abundance of potential caproic acid-producing bacteria in Daqu. The predominant caproic acid-producing bacteria, with a relative abundance greater than 1%, included Clostridium sensu stricto 18 (2.19% to 69.00%), Clostridium sensu stricto 15 (1.76% to 7.65%), as well as smaller amounts of Clostridium sensu stricto 12, Clostridium sensu stricto 1, Clostridium sensu stricto 10, Clostridium sensu stricto 7, and Caproiciproducens. Specifically, Q1 Daqu was characterized by the presence of Clostridium sensu stricto 18 and Clostridium sensu stricto 15. Q2 Daqu featured Clostridium sensu stricto 1, Caproiciproducens, and Clostridium sensu stricto 18. Q3 Daqu included Clostridium sensu stricto 18 and Caproiciproducens. Q4 Daqu contained Clostridium sensu stricto 18 and Clostridium sensu stricto 1. These findings indicate that there are variations in the composition of caproic acid-producing bacterial communities among different sub-high-temperature Daqu samples from Sichuan. This preliminary analysis provides a theoretical basis for further studies on caproic acid bacteria in Daqu and offers insights into the development of high-quality Daqu, which may enhance the quality of Nongxiangxing liquor.

Isothermal Nucleic Acid Amplification based-Lateral Flow Testing (INAA-LFT) has emerged as a robust technique for on-site pathogen detection, providing a visible indication of pathogen nucleic acid amplification that rivals or even surpasses the sensitivity of real-time quantitative PCR. The isothermal nature of INAA-LFT ensures consistent conditions for nucleic acid amplification, establishing it as a crucial technology for rapid on-site pathogen detection. However, despite its considerable promise, the widespread application of isothermal INAA amplification-based lateral flow testing faces several challenges. This review provides an overview of the INAA-LFT procedure, highlighting its advancements in detecting plant viruses. Moreover, the review underscores the imperative to address existing limitations and emphasizes ongoing research efforts dedicated to enhancing the applicability and performance of this technology in the realm of rapid on-site testing.

In recent decades, given the important role of gamma-aminobutyric acid (GABA) in human health, scientists have paid great attention to the enrichment of this chemical compound in food using various methods, including microbial fermentation. Moreover, GABA or GABA-rich products have been successfully commercialized as food additives or functional dietary supplements. Several microorganisms can produce GABA, including bacteria, fungi, and yeasts. Among GABA-producing bacteria, lactic acid bacteria (LAB) are commonly used in the production of many fermented foods. Lactiplantibacillus plantarum (previously Lactobacillus plantarum) has a long history of natural occurrence and safe use in a variety of food products. This LAB species provides functional properties to various fermented foods by producing a variety of bioactive compounds, including GABA. The present review aims, after a preliminary excursus on the function and biosynthesis of GABA, to provide an overview on the current uses of microorganisms and in particular of L. plantarum in the production of GABA, with a detailed focus on fermented foods.

The accumulation of loss of function mutations in the uricase gene well explains the high urate levels in hominoids (apes and humans) compared to other mammals. The loss of human uricase activity may have allowed humans to survive environmental stressors, evolution bottlenecks, and life-threatening pathogens. While high urate levels may contribute to developing cardiometabolic disorders such as hypertension and insulin resistance, low urate levels may increase the risk for neurodegenerative diseases. The double-edged sword effect of uric acid has resurrected a growing interest in the antioxidant role of urate and the role of the uricase gene in modulating the risk of obesity. Characterizing both the effect of uric acid levels and the uricase gene in different animal models may provide new insights into the potential therapeutic benefits of uric acid and novel uricase-based therapy.

In the last decades, studies on the inflammatory signaling pathways in multiple pathological contexts revealed new targets for novel therapies. Among the family of G-protein-coupled Proteases Activated Receptors, PAR2 was identified as a driver of the inflammatory cascade in many pathologies, ranging from autoimmune disease to cancer metastasis. For this reason, many efforts have been focused on the development of potential antagonists of PAR2 activity. This work focuses on a small molecule, 1-Piperidine Propionic Acid (1-PPA), previously described to be active against inflammatory processes, but whose target is still unknown. Stabilization effects observed by cellular thermal shift assay coupled to in-silico investigations, including molecular docking and Molecular Dynamics simulations, suggested that 1-PPA binds PAR2 in an allosteric pocket of the receptor inactive conformation. In addition, this compound was found able to inhibit platelet aggregation, a process mediated by PAR family members, including PAR2. Since the allosteric pocket binding 1-PPA is highly conserved in all the members of the PAR family, the evidence reported here suggests that 1-PPA could represent a promising new small molecule targeting PARs with antagonistic activity.

Polyphenol ellagic acid (EA) possesses anti-oxidant, anti-inflammatory, anti-carcinogenic, anti-diabetic and cardio protection activities, remarking it an interesting multi-targeting profile. EA also controls the central nervous system (CNS) since it was proven to reduce the immobility time of mice in both the forced swimming and the tail-suspension tests, with an efficiency comparable to that of classic antidepressants. Interestingly, the anti-depressant-like effect was almost nulled by the concomitant administration of selective antagonists of the noradrenergic receptors, suggesting the involvement of these cellular targets in the central effects elicited by EA and its derivatives. By in silico and in vitro studies, we discuss how EA engages with human α2A-ARs and α2C-AR catalytic pockets, comparing EA behaviour with those ones of known agonist and antagonist. Structurally, the hydrophobic residues surrounding α2A-AR pocket confer specificity on the intermolecular interactions and hence lead to favourable binding of EA in the α2A-AR, with respect to α2C-AR. Moreover, EA seems to better accommodate within α2A-ARs into TM5 area, closely to S200 and S204 which play a crucial role for activation of aminergic GPCRs such as the α2-AR, highlighting its promising role as a partial agonist. Consistently, EA mimics clonidine in inhibiting noradrenaline exocytosis from hippocampal nerve endings in an yohimbine-sensitive fashion that confirms the engagement of naïve α2-ARs in the EA-mediated effect.

Folic acid, one of the 13 essential vitamins, plays an important role in cardiovascular development. Mutations in folic acid synthesis gene 5,10-methylenetetrahydrofolate reductase (MTHFR) is significantly associated with the occurrence of congenital heart disease. However, the mechanisms underlying the regulation of cardiac development by mthfr gene are poorly understood. Here, we exposed zebrafish embryos to excessive folate or folate metabolism inhibitors. And we established a knock-out mutant of mthfr gene in zebrafish by using CRISPR/Cas9. The zebrafish embryos of insufficient or excessive folic acid, and mthfr-/- mutant all gave rise to early pericardial edema and cardiac defect at 3 days after fertilization(dpf). Furthermore, the folic acid treated embryos showed abnormal movement at 5dpf. The expression levels of cardiac marker genes hand2, gata4 and nppa changed in the abnormality of folate metabolism embryos and mthfr-/- mutant, and there is evidence that they are related to the change of methylation level caused by the change of folate metabolism. In conclusion, our study provides a novel model for the in-depth study of MTHFR gene and folate metabolism. And our results reveal that folic acid has a dose-dependent biphasic effect on early cardiac development.

This work focuses on the support effect on the performances of Co-based catalysts for the acetic acid steam reforming. SBA-15, a well ordered hexagonal mesoporous silica structure, and CeO2 have been selected as the supports, with the impact of chromium addition also being investigated. Better acetic acid steam reforming performances have been recorded for CeO2 compared to SBA-15 supported catalysts and, in particular, the 7Co/CeO2 catalyst showed the highest values of acetic acid conversions with enhanced H2 yields below 480°C, in comparison to the other investigated catalytic formulations. In addition, more pronounced coke depositions and acetone concentrations have been obtained with CeO2 supported catalysts, due to the tendency of ceria to catalyse the ketonization reaction. Chromium addition to Co/SBA-15 catalysts led to an enhancement in the activity towards acetic acid steam reforming, while on CeO2 supported catalysts no improvement in the catalysts activity was observed; however, on both SBA-15 and CeO2 supported catalysts, Cr addition reduced the amount of coke deposited on the catalysts surface.

We evaluated the change in water dispersibility of lactic acid bacteria (LAB, Enterococcus faecalis KH2) upon powderization and its influence on their efficacy. When cultured LAB are washed, heat-killed, and powdered, adhesion between LAB occurs and they form aggregation (non-treated LAB, n-LAB). However, a dispersed LAB (d-LAB) powder with less aggregates can be prepared by treating them with a high-pressure homogenizer and adding an excipient during powdering. n-LAB or d-LAB was administered to mice and the Peyer's patches in the small intestine were observed. n-LAB administration showed a high amount of aggregated LAB drifting in the intestinal mucosa, whereas d-LAB reached the Peyer's patches and was taken up into the Peyer's patches. Evaluation in a mouse influenza virus infection model showed that d-LAB was more effective than n-LAB in influenza yield of bronchoalveolar lavage fluids (BALFs) on day 3 post-infection, neutralizing antibody titers of sera and influenza virus-specific IgA in the feces on day 14 post-infection. Thus, the physical properties of LAB affect their efficacy; controlling their water dispersibility can improve their effectiveness.

The search for economical and sustainable sources of PUFAs within the framework of the circular economy is encouraged by their proven beneficial effects on health. The extraction of monkfish liver oil (MLO) for the synthesis of omega-3 ethyl esters was performed evaluating two blending systems and four green solvents. Moreover, the potential solubility of the MLO in green solvents was studied using the predictive simulation software COSMO-RS. The production of the ethyl esters was performed by one or two step reactions. Novozym 435, two resting cells (Aspergillus flavus and Rhizopus oryzae) obtained in our laboratory and mix of them were used as biocatalysts in a solvent-free system. The yields for Novozym 435, R. oryzae and A. flavus in the one-step esterification were 63%, 61% and 46%, respectively. The hydrolysis step in the two-step reaction led to 83%, 88% and 93% of free fatty acids (FFA) for Novozym 435, R. oryzae and A. flavus respectively. However, Novozym 435 showed the highest yield in the esterification step (85%) followed by R. oryzae (65%) and A. flavus (41%). Moreover, selectivity in front of polyunsaturated fatty acids of R. oryzae lipase was evidenced, since it did slightly esterified docosahexaenoic acid (DHA) in all the esterification reactions tested.

Perfluorooctanoic acid (PFOA), C7F15COOH, has been widely employed over the past fifty years, causing an environmental problem due to its dispersion and low biodegradability. Furthermore, the high stability of this molecule, conferred by the high strength of the C-F bond makes it very difficult to remove. In this work, electrochemical techniques are applied for PFOA degradation in view to study the influence of the cathode on defluorination. For this purpose, boron doped diamond (BDD), Pt, Zr and stainless steel have been tested as cathodes working with BDD anode at low electrolyte concentration (3.5 mM) to degrade PFOA at 100 mg/L. Among these cathodic materials, Pt improves the defluorination reaction. The electro-degradation of a PFOA molecule starts by a direct exchange of one electron at the anode and then follows a complex mechanism involving reaction with hydroxyl radicals and adsorbed hydrogen on the cathode. It is assumed that Pt acts as an electrocatalyst, enhancing PFOA defluorination by the reduction reaction of perfluorinated carbonyl intermediates on the cathode. The defluorinated intermediates are then more easily oxidized by HO• radicals. Hence, high mineralization (xTOC: 76.1%) and defluorination degrees (xF-: 58.6%) were reached with Pt working at current density j = 7.9 mA/cm2. This BDD-Pt system reaches a higher efficiency in terms of defluorination for a given electrical charge than previous works reported in literature. Influence of the electrolyte composition and initial pH are also explored.

Introduction: Increased oxidative stress, including elevated homocysteine (Hcy) plasma levels, and lowered levels of antioxidants participate in the pathophysiology and progression of chronic kidney disease (CKD). Paraoxonase (PON)1 activity and folic acid are antioxidants which play a role in Hcy metabolism. However, there are no data whether, in CKD, treatment with folic acid improves glomerular filtration rate (GFR) through effects on PON1 activity and Hcy concentrations. Methods: In the current study, we determined PON1 genotypes and activity, Hcy and estimated GFR (eGFR) both before and after treatment with folic acid (5 mg/d) versus no treatment during three consecutive months in 113 outpatients with CKD classified into stages 4, 3b and 3a. Results: PON1 CMPAase and AREase activities were significantly lower in patients allocated to CKD stage 4 as compared with stages 3b and 3a. Treatment with folic acid significantly improved eGFR and increased levels of CMPAase and AREase in patients allocated to classes 4 and 3b, but not 3a. The improvement of eGFR was associated with increased CMPAase and AREase activities, while the latter were associated with increased levels of folic acid. Treatment with folic acid significantly reduced plasma Hcy levels and the Hcy/PON1 activity ratio. The effects of folic acid increasing PON1 activities were not mediated by changes in Hcy. Discussion: Treatment of CKD patients in early/intermediate stages of CKD patients improves oxidative stress by rebalancing the prooxidant (Hcy) / antioxidant (PON1 activities) ratio. Treatment with folic acid significantly improves eGFR and these effects are mediated via increased PON1 activities. Treatment with folic acid in phase G3b and G4 may reduce renal disease progression by enhancing antioxidant defenses.

Tough and antimicrobial dual-crosslinked poly((trimethylamino)ethyl methacrylate chloride)-phytic acid hydrogel (pTMAEMA-PA) has been synthesized by adding chemical crosslinker and docking physical crosslinker of multivalent phytic acid into a cationic polyelectrolyte network. By increasing the loading concentration of PA, the tough hydrogel exhibits compressive stress of >1 MPa, along with high elasticity and fatigue-resistant properties. The enhanced mechanical properties of pTMAEMA-PA were stem from multivalent ion effect of PA via the formation of ion bridges within polyelectrolytes. In addition, a comparative study for a series of pTMAEMA-counterion complexes was conducted to elaborate the relationship between swelling ratio and mechanical strength. The study also revealed secondary factors, such as ion valency, ion specificity and hydrogen bond formation, holding crucial roles in tuning mechanical properties of the polyelectrolyte hydrogel. Furthermore, in bacteria attachment and disk diffusion tests, pTMAEMA-PA exhibits superior fouling resistance and antibacterial capability. The results reflect the fact that PA enables chelating strongly with divalent metal ions, hence, disrupting the outer membrane of bacteria, as well as dysfunction of organelles, DNA and protein. Overall, the work demonstrated a novel strategy for preparation of tough polyelectrolyte with antibacterial capability via docking PA to open up the potential use of PA in medical application.

For the effective utilization of rice husk, organosolv fractionation was investigated to separate three main components (glucan, xylose, and lignin) with low acid concentration. Reaction temperatures of 170–190 °C, ethanol concentrations of 50–70% (v/v), and sulfuric acid concentrations of 0–0.7% (w/v) were investigated, with the reaction time and liquid-to-solid ratio kept constant at 60 min and 10, respectively. The fractionation conditions for the efficient separation into the three components of rice husk were determined to be 180 °C, 60% (v/v) of ethanol, and 0.25% (w/v) of sulfuric acid. Under these fractionation conditions, 86.8% of the xylan and 77.5% of the lignin were removed from the rice husk, and xylose and lignin were obtained from the liquid in 67.6% and 49.8% yields, respectively. The glucan digestibility of the fractionated rice husk was 85.2% with an enzyme loading of 15 FPU (filter paper unit) of cellulase per g-glucan.

An exploratory Life Cycle Assessment was carried out to provide insight into the environmental impacts of using the green seaweed Ulva spp. as a feedstock for production of bioplastic. The study focused on the production of lactic acid as a precursor of polylactic acid. The studied production process consists of (1) the cultivation of Ulva spp. in Integrated Multitrophic Aquaculture, (2) the processing of the biomass for solubilisation of sugars, (3) the fermentation of the sugars to lactic acid and (4) isolation of lactic acid from the fermentation broth. The study identifies environmental hotspots and compares the experimental seaweed production chain with conventional feedstock. The main hotspot identified is electricity consumption during seaweed cultivation. This impact of electricity consumption can be lowered by reducing energy use and sourcing renewable energy, and by improving the material efficiency in the product chain. To improve understanding of the environmental impacts of the production process, future studies can broaden the system boundaries and broaden the scope of sustainability issues included in the environmental assessment.

Electrospinning is the versatile technique to generate large quantities of micro- or nano-fibers from a wide variety of shapes and sizes of polymer. Natural bone is a hierarchically composites with the dispersion of inorganic ceramic along organic polymer. The aim of this study, the electrospun poly (lactic acid) (PLA) mats coated with chitosan (CH) and calcium silicate (CS) powder were fabricated. The morphology, chemical composition, and surface properties of CS/CH-PLA composites were characterized by scanning electron microscopy, X-ray diffraction, and Fourier transform infrared spectroscopy. In vitro, the CS/CH-coated PLA mats increased the formation of apatite on the surface when soaking in cell cultured medium. During culture, the adhesion and proliferation of the human mesenchymal stem cells (hMSCs) cultured on CS/CH-PLA were significantly promoted relative to those on PLA. Collagen I and fibronectin levels and promoted cell adhesion were observed upon an increase in CS content. Further, compared to PLA mats without CS/CH, CS10 and CS15 mats markedly enhanced the proliferation of hMSCs as well as their osteogenesis properties, which was characterized by bone-related gene expression. Our results demonstrated that the biodegradable and electroactive CS/CH-PLA mats had potential application as an ideal candidate for bone tissue engineering. Together, findings from this study clearly demonstrated that PLLA-C2S composite scaffold may function as an ideal candidate for bone tissue engineering.

Fragile X Syndrome (FX) is the most common form of inherited cognitive impairment and falls under the broader category of Autism Spectrum Disorders (ASD). FX is caused by a CGG trinucleotide repeat expansion in the non-coding region of the X-linked Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene, leading to its hypermethylation and epigenetic silencing. Animal models of FX rely on the deletion of the Fmr1 gene which fail to replicate the epigenetic silencing mechanism of the FMR1 gene seen in human patients. Human stem cells carrying FX repeat expansions have provided a better understanding of the basis of the epigenetic silencing of FMR1. Previous studies have found that 5-Azacytidine (5Azac) can reverse this methylation; however, 5Azac can be toxic and may limit its therapeutic potential. Here, we show that the dietary factor Ascorbic Acid (AsA) can reduce DNA methylation in the FMR1 locus and lead to an increase in FMR1 gene expression in FX iPSCs and cerebral organoids. In addition, AsA treatment rescued neuronal gene expression and the morphological defects observed in FX iPSC-derived cerebral organoids. Hence, we demonstrate that the dietary co-factor AsA can partially revert molecular and morphological defects seen in human FX models in vitro. Our findings have implications for the development of novel therapies for FX in the future.

Drug–targeted integrated nanofiber development is a current research trend. Potential materials for the development of such systems include Poly (vinyl alcohol) (PVA) and chitosan (CS) nanofibers, which are traditionally fabricated by electrospinning aqueous solutions of these polymers with acetic acid. To improve drug integration, the binary-solvent system was converted into a multi–solvent system by the adding of ethanol. This caused noticeable shifts in the solvent system's solubility parameter, the interaction of the various component forces, and optical and rheological properties of PVA-CS solution. The results show that solution containing 4% PVA, 3% CS, 15% ethanol and 45% acetic acid is optimal for the increasing of manufacturing productivity, improving the morphology and diameter of PVA–CS nanofibers, without changing in chemical bonding composition. The XRD spectrum revealed that the alterations in the crystal lattice and diameter of the PVA–CS nanofibers leaded to the variation in their thermal and tensile properties.

Stem cells can be used to treat diabetic mellitus and complications. ω3-docosahexaenoic acid (DHA) derived lipid mediators are inflammation-resolving and protective. This study found novel DHA-derived 7S,14R-dihydroxy-4Z,8E,10Z,12E,16Z,19Z-docosahexaenoic acid (7S,14R-diHDHA), a maresin-1 stereoisomer biosynthesized by leukocytes and related enzymes. Moreover, 7S,14R-diHDHA can enhance mesenchymal stem cell (MSC) functions in the amelioration of diabetic mellitus and retinal pericyte loss in diabetic db/db mice. MSCs treated with 7S,14R-diHDHA were delivered into db/db mice i.v. every 5 days for 35 days. Blood glucose levels in diabetic mice were lowered by 7S,14R-diHDHA-treated MSCs compared to control and untreated MSC groups, accompanied by improved glucose tolerance and higher blood insulin levels. 7S,14R-diHDHA-treated MSCs increased insulin+ β-cell ratio and decreased glucogan+ α-cell ratio in islets, as well as reduced macrophages in pancreas. 7S,14R-diHDHA induced MSC functions in promoting MIN6 β-cell viability and insulin secretion. 7S,14R-diHDHA induced MSC paracrine functions by increasing the generation of hepatocyte growth factor and vascular endothelial growth factor. Furthermore, 7S,14R-diHDHA enhanced MSC functions to ameliorate diabetes-caused pericyte loss in diabetic retinopathy by increasing their density in retina in db/db mice. Our findings provide a novel strategy for improving therapy for diabetes and diabetic retinopathy using 7S,14R-diHDHA-primed MSCs.

Use of antibiotics and other chemicals to combat disease outbreaks have been a bottleneck for the sustainable growth of shrimp industry. Among various replacement proposed, organic acid (OA) and their salts (OS) are commonly used by farmers and feed millers. However, in free forms, their requirement is very high (2-3 kg/MT) as they tend to disassociate before reaching the hindgut. The dosage can be reduced by microencapsulation of the ingredients. In this study, a 63-day trial was conducted to assess the effects of OA and OS (COMP) microencapsulated (ENCAP) with fat (HF), fat + alginate (HA), wax esters – (WE), and HA and WE (HAWE) on performance, digestive enzyme, immune, and resistance to Vibrio parahaemolyticus. A positive control (PC, 200 g/kg fishmeal - FM) and a negative control (NC, 130 g/kg FM) diet were formulated. Eight other diets were formulated supplementing NC diet with microencapsulated OA (OAHF, OAHA, OAWE, OAHAWE) and OS (OSHF, OSHA, OSWE, OSHAWE). Among the ENCAPs, significant difference was observed in serum malondialdehyde (P = 0.026) where HF showed the lowest level (6.4 ±0.3 mmol/L). Significant interactions between COMP and ENCAP were observed in lipid deposition (P = 0.047), serum alkaline phosphatase and acid phosphatase (P < 0.0001), and hepatopancreatic and serum phenol oxidase (P < 0.0001). Despite no differences, 96-h mortality during pathogenic Vibrio parahaemolyticus challenge in all treatment diets (45% - 56%) was lower compared to the NC diets (63%). In conclusion, use of HF microencapsulated OA diets could provide improved performance and disease resistance that could contribute to the reduction of antibiotic use by the shrimp industry.

The phenylpropanoid pathway is a major secondary metabolite pathway that helps plants overcome biotic and abiotic stress and produces various by-products that promote human health. Its byproduct, chloroquinic acid (CQA), is a soluble phenolic compound present in many angiosperms. Hy-droxycinnamate-CoA shikimate/quinate transferase(BAHDs superfamily enzyme) is a significant en-zyme that plays a role in accumulating CQA biosynthesis. This study analyzed transcriptome-wide identification of the phenylpropanoid to chloroquinic acid biosynthesis candidate genes in A. spathulifolius flowers and leaves. Transcriptomic analyses of the flowers and leaves showed a differential expression of the PPP and CQA biosynthesis regulated unigenes. An analysis of PPP captive unigenes revealed the following: the major duplication of the key enzyme, PAL, 120 unigenes in leaves and 76 in flowers; the gene encoding C3’H, 169 unigenes in leaves and 140 unigenes in flowers; duplicated unigenes of 4CL, 41 in leaves and 27 in flowers. In addition, C4H unigenes had 12 unigenes in the leaves of A. spathulifolius and four in the flowers. The characterization of the BAHDs superfamily members identified 82 in leaves and 72 in flowers. Among them, phylogenetic analysis showed that five unigenes encoded HQT and three en-coded HCT in A. spathulifolius. The three HQT are common to both leaves and flowers, whereas the two HQT were specialized for leaves. The pattern of HQT synthesis was upregulated in flowers, whereas HCT was expressed strongly in the leaves of A. spathulifolius. Overall, 4CL, C4H, and HQT are expressed strongly in flowers, and caffeic acid and HCT show more expression in leaves. Therefore, CQA biosynthesis occurs in the flowers of A. spathulifolius rather than leaves.

Pyracantha angustifolia has been used in traditional medicine to treat a range of diseases of the stomach and improve digestion, blood circulation, diarrhea, dysentery, and hemostasis. This study evaluated bioactivity-guided fractionation as a means to identify therapeutic phytochemicals from P. angustifolia that can attenuate melanogenesis and oxidation. Seven compounds with inhibitory effects on melanin production and tyrosinase (TYR) activity, as well as ABTS and DPPH radical scavenging activities, and have not been reported as whitening materials, were isolated from the n-butanol fraction from P. angustifolia leaves (PAL). Among the seven compounds, p-hydroxybenzoic acid beta-d-glucosylester (HG), and cimidahurinine (CD) had strong inhibitory effects of melanin production, TYR activity, and ABTS and DPPH radical scavenging activities. Western blot analysis showed that HG and CD suppressed tyrosinase-related protein (TYRP)-1 and TYRP-2 expression. These results suggest that P. angustifolia containing active compounds, such as HG and CH, is a potent therapeutic candidate for the development of hypopigmenting agents.