This study aimed to evaluate the fatty acid (FAs) profile in milk from commercial farms with varying pasture levels in the diet during spring and fall, and to investigate the physical and chemical properties of butter to assess the impact of FAs on technological and nutritional properties. Milk sampling was conducted biweekly from six farms, categorized into high (HP) and low (LP) pasture treatments based on pasture intake: >60% and <35%, respectively. Butter was made from a pasture-based system (GRZ) and a confined system (C). No differences were observed in milk fat percentage between HP and LP in either season. High pasture had 85-66% more conjugated linoleic acid (CLA, p=0.01), 74-48% more trans-vaccenic acid (TVA, p=0.01), and 21-15% more branched- chain FAs (BCFA, p=0.006) than LP in spring and fall, respectively. In fall, butter from C had lower saturated FAs (SFA, p=0.005), higher unsaturated FAs (UFA, p=0.008), and a lower spreadability index (SI, p=0.005) than GRZ, resulting in softer butter. In conclusion, HP in both seasons had higher contents of FAs considered healthy for consumers compared to LP. Contrary to expectations, in fall, C showed higher UFATVA and lower SFA in butter, leading to better technological characteristics than GRZ.

The effect of land use on sandy soils of southern Botswana was carried out by comparing the composition and properties of soil organic matter. Virgin and disturbed soils were sampled from savanna ecosystems (Central District and Kweneng District). The biodegradability of organic matter was evaluated by incubation in the laboratory. Humic fractions were quantified and humic acids were analyzed by visible and infrared spectroscopy. The results indicate that continued disturbance, whether due to grazing or subsistence farming, has resulted in small significant changes in the concentration of available nutrients and organic matter in the soil. Nevertheless, substantial changes could be established in soil C/N ratio, humic acid/fulvic acid ratio and in the biodegradability of soil organic matter and the structural characteristics of humic acids. The increased aromaticity of humic acid (visible and IR spectroscopies) following disturbance, suggests increased biogeochemical activity and/or the impact of abiotic processes (such as periodic fires) selectively removing aliphatic constituents. The overall results indicate a low potential soil fertility, the sustainable preservation of which depending more on features related to quality than to the total amount of the soil organic matter, which shows considerable aromatization parallel to its degree of association with the mineral fraction.

PURPOSE: To investigate the oxylipin profiles in aqueous humor of primary open angle glaucoma (POAG) patients. METHODS: Aqueous humor samples were collected from 17 POAG patients and 15 cataract subjects and subjected to the liquid chromatography-mass spectrometry (LC-MS) analysis to detect the oxylipins. The prediction potential of the differential abundant oxylipins was assessed by the receiver operating characteristic (ROC) curves. Pathway and correlation analyses on the oxylipins and clinical and biochemical parameters were also conducted. RESULTS: The LC-MS analysis detected a total of 76 oxylipins, of which 29 oxylipins reached the detection limit. The multivariate analysis identified 5 differential abundant oxylipins, 15-keto-prostaglandin F2 alpha (15-kPGF2α), Leukotriene B4 (LTB4), 12,13-Epoxyoctadecenoic acid (12,13-Epome), 15-Hydroxyeicosatetraenoic acid (15-HETE) and 11-Hydroxyeicosatetraenoic acid (11-HETE). The 5 oxylipins are enriched in the arachidonic acid metabolism and linoleic acid metabolism pathways. Pearson correlation analysis showed that 11-HETE was positively correlated with intraocular pressure and central corneal thickness and negatively with cup/disk ratio in the POAG patients. In addition, 15-kPGF2α was positively correlated with visual field defect, and LTB4 was negatively correlated with macular thickness.  CONCLUSIONS: This study revealed the oxylipin profile in the aqueous humor of POAG patients. Oxylipins involved in arachidonic acid metabolism pathway could play a role in POAG and anti-inflammatory therapies could be potential treatment strategies for POAG.

The primary objective of this systematic review study was to investigate the effectiveness, durability, and adverse events of PLLA treatment for aesthetic indications. The search strategy was performed in MEDLINE (Ovid). The electronic literature search of five databases was performed, from the inception of the databases until 12th of February 2024. This was to identify randomized clinical trials that assessed PLLA treatment in adult individuals exhibiting facial aging and/or facial lipoatrophy. Risk of bias was assessed using the Cochrane Risk-of-Bias Tool for Randomized Trials (RoB 2). Eleven RCTs out of 1467 identified citations were included. Four studies showed increased dermal thickness, significant improvement in facial lipoatrophy severity and aesthetic clinical scores, after PLLA treatment with its effects sustained for at least 25 months. Two studies demonstrated the superiority of PLLA over injectable human collagen. Also, three studies showed positive results favoring PLLA when compared with PH gel in lipoatrophy severity, trans epidermal water loss, skin quality, elasticity, and patient satisfaction. All adverse events were mild-to-moderate in intensity, and the main ones worth noting were bruising, hematoma, tenderness, nodules, and edema. Five out of 11 studies were considered as high risk of bias. The evidence on the effectiveness and safety of PLLA for facial rejuvenation is of low quality; thus, the reported high effectiveness, safety, and long-lasting effects for this purpose, should be further investigated.

To clarify effects of weathered coal humic acid on water-stable aggregates and pore characteristics of reclaimed cambisol, this research analyzed the evolution characteristics of soil aggregates and pores. Effects of different humic acid dosages (0, 1%, 3%, and 5% by weight) and application period (1 year, 2 years, and 3 years) on soil aggregates and organic carbon components in soil water-stable aggregates were investigated. The results showed that water-stable macroaggregates (>0.25 mm) had the highest content in the first year; but in the third year, water-stable microaggregates (0.053–0.25 mm) had the highest content, and silt and clay (<0.053 mm) were at a maximum. In the third year of 5% treatment, mean weight and geometric mean diameters were the largest, soil structure was the most stable, and TOC and water-stable microaggregates (0.053–0.25 mm) in soil had the highest proportions. For 5% treatment, the majority of irregular pores were independent in the first year, and number of pores decreased in the second year, but average pore volume increased, forming robust connected pores. In the third year, the number of elongated and irregular pores increased. In the third year of 5% treatment, most pores were irregular and of size >100 μm, and soil structure was the most stable.

Background and Objectives To compare navigator-gated three-dimensional T1-weighted gradient-echo sequences (NG-3D T1W-GRE) with standard breath-hold T1W-GRE (BH T1W-GRE) for the detection of HCC nodules in patients with chronic viral hepatitis which undergo at magnetic resonance imaging (MRI) using gadoxetic acid. Methods and materials We evaluated 58 patients with hepatic nodules at least 1 cm in diameter detected by ultrasound who underwent liver MRI including NG-3D T1W-GRE sequences and breath hold T1-weighted gradient-echo sequences with different flip angles(FA) at 10-25-40° after contrast administration of gadoxetic acid at magnetic scanner operating at1.5 Tesla. Image quality and relative hepatic and nodular enhancement were evaluated by three blinded reviewers. Results In these patients, image quality of NG-3D T1W-GRE was assessed significantly better than quality of BHT1W- GRE (P < 0.005) and relative enhancement was significantly higher than that of BH- T1W-GRE ( P

The reaction between cadmium nitrate tetrahydrate and N,N'-bis(pyridin-3-ylmethyl)oxalamide (L) in 1:3 molar ratio in water/acetonitrile (1:6 v/v) mixture afforded single crystals of compound 1 suitable for X-ray diffraction analysis. Compound 1 consists of the coordination polymer (CP) [[Cd(L)2(H2O)2](NO3)2·4H2O]∞, in which CdII ions are bridged by the neutral L antiperiplanar N-ligands in a wavy ribbon fashion developing along the c-axis. Two trans-disposed water molecules complete the pseudo-octahedral coordination geometry of the metal ion. The crystal packing of 1 revealed the interplay between π-π stacking interactions and an intricate hydrogen-bonded network involving oxalamides, nitrates and water molecules. The donor properties of L and the intermolecular interactions in compound 1 are interpreted based on hybrid-DFT calculations.

(1) Background: Gamma-aminobutyric acid (GABA) is one of the inhibitory neurotransmitters with beneficial effects including sedative property. However, despite various clinical trials, scientific evidence regarding the impact of orally ingested GABA, whether natural or synthesized through biological pathways, on sleep is not clear.; (2) Methods: The present study work evaluated GABA-A biding affinity of GABALAGEN(GBL), a low-molecular-weight collagen infused with GABA, through receptor binding assays. The sedative effects of GBL were investigated through electroencephalography (EEG) analysis in the electro foot shock (EFS) stress-induced sleep animal model and then we examined the expression orexin, GABAA receptor in the brain region using immunohistochemistry.; (3) Results: We found that on the binding assay, GBL displayed high affinity to GABAA receptor (IC50 value, 31.5µg/mL)). Also, after treatment of GBL, percent of total time of REM and NREM were significantly and dose-dependently increased compared to the Con group. Consistent with behavioral results, the GBL-treated groups showed that the expression of GABAA receptor immune-positive cells in the VLPO were markedly and dose-dependently increased compared to the Con group. Also, the GBL-treated groups showed that the expression of orexin immune-reactive cells in the LH were significantly decreased compared to the Con group.; (4) Conclusions: In conclusion, GBL showed efficacy and potential to be used as an anti-stress therapy to treat sleep deprivation through antagonism of GABA receptors and consequent inhibition of orexin activity.

Polyalcohol liquefaction can be done by acid or basic catalysis producing polyols with different properties. This study compared the mechanical properties of foams produced using polyols from liquefied Cytisus scoparius obtained by acid and basic catalysis and using two different foam catalysts. The differences were monitored using FTIR analysis. Acid-catalyzed liquefaction yielded 95.1 %, with the resultant polyol having an OH index of 1081 mg KOH/g while basic catalysis yielded 82.5 %, with a similar OH index of 1070 mg KOH/g. Generally, compressive strength with dibutyltin dilaurate (DBTDL) ranged from 16 - 31 kPa (acid-liquefied polyol) and 12 -21 kPa (base-liquefied polyol), while with stannous octoate (TIN), it ranged from 17 - 42 kPa (acid) and 29 - 68 kPa (base). Increasing water content generally decreased the compressive modulus and strength of foams. Higher water content led to a higher absorption at 1670 cm-1 in the FTIR spectrum due to the formation of urea. Higher isocyanate indices generally improved compressive strength, but high amounts led to unreacted isocyanate that could be seen by a higher absorption at 2265 cm-1 and 3290 cm-1. DBTL was shown to be the best foam catalyst due to higher trimer conversion seen in the spectra by a higher absorption at 1410 cm-1. Acid and base-derived polyols lead to different polyurethane foams with different FTIR spectra, particularly with a higher absorption at 1670 cm-1 for foams from acid-derived liquefaction.

This paper investigates the potential of different fermentation feedstocks towards succinic acid production. Three alternative flowsheets were constructed and modelled in SuperPro Designer™, utilizing different fermentation substrates: crude glycerol (a by-product of the biodiesel industry), a commercial 95% glucose syrup and pure glycerol. Techno-economic analysis of the modelled plants showed that all three potential investments can be economically profitable, with the crude glycerol case as the most promising one. The succinic acid production cost for the crude glycerol scenario is estimated at 3.59 $/kg, while a thorough study of the capacity effect to the economics showed that it could drop as low as $2.6 $/kg. Parametric analysis and optimization performed on a flowsheet level, indicated opportunities for lowering the production cost down to 3 $/kg, a value that could pave the framework for a further potential decrease in the selling price of the product.

The recyclable paper based on photochromic materials not only reduces the pollution in the paper manufacture process, but also reduces the pollution caused by the use of ink, which receives wide attention. In this paper, a serial of PMoA-PWA/ZnO/PVP hybrid films which had different ratio of PMoA/PWA was prepared by the ultrasonic composite method. The results indicated that the hybrid film prepared when the ratio of PMoA to PWA was 3 had the best photochromic performance. In this system, ZnO was the photosensitizer while PMoA/PWA was the chromophore. The photochromic mechanism of PMoA-PWA/ZnO/PVP hybrid film was based on the photogenerated electron transfer mechanism. ZnO generated photoelectron under the excitation of visible light, then PMoA and PWA obtained the photoelectron and produced photoreduction reaction to generate heteropolyblue. The visible light photochromic paper was prepared by loaded PMoA-PWA/ZnO/PVP hybrid film (A3) on A4 paper. Application test showed that the prepared paper had extremely stable, excellent and reversible visible light photochromic properties, whether it was printing patterns or words and could replace the ordinary paper to realize the reuse of paper.

Fungal infections caused by Candida spp. are responsible for high hospital morbidity and mortality rates. Therefore, there is a continuous search for new antifungal medicines, particularly ones with anti-Candida activity. This review analyzed articles published between 2002 and 2023 considering the anti-Candida activity of chemical compounds identified or isolated in plants of the Anacardiaceae family. In addition, the in-silico prediction of the isolated compounds described was performed. The analysis of 35 studies showed that extracts, essential oils, and compounds from the anti-Candida activity were frequently determined in vitro using the minimum inhibitory concentration (MIC). The most commonly tested species were Candida albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, and C. guilliermondii, respectively. Essential oils were the most used form (37% of the studies). The isolated compounds with antifungal effects include cardanol, estragole, trans-anethole, β-caryophyllene, myrcene, catechin-3-o-rhamnoside, β-sitosterol-3-O-glucoside, 24Z-isomasticadienolic acid, oleanolic acid, and oleanolic aldehyde. The in-silico evaluation of those isolated compounds revealed the compounds' drug-likeness and possible antifungal activity. However, some of them showed high toxicity. In conclusion, compounds from the Anacardiaceae family show promise for developing new therapeutic antifungal drugs, especially in combination with conventional antifungals.

Glioblastoma is a highly malignant brain tumor consisting of heterogeneous cellular population. The transformed metabolism of glioblastoma cells supports their growth and division on the background of their milieu. One might hypothesize that the transformed metabolism of a primary glioblastoma could be well adapted to limitations in the variety and number of substrates imported into the brain parenchyma and present it their microenvironment. Additionally, the phenotypic heterogeneity of cancer cells could promote the variations among their metabolic capabilities regarding the utilization of available substrates and release of metabolic intermediates. With the aim to identify the putative metabolic footprint of different types of glioblastoma cells, we exploited the possibility for separation of polar and ionic molecules present in culture media or cell lysates by hydrophilic interaction liquid chromatography (HILIC). The mass spectrometry (MS) was then used to identify and quantify the eluted compounds. The introduced method allows the detection and quantification of more than 150 polar and ionic metabolites in single run, those may be present either in culture media or cell lysates and provide data for polaromic studies within metabolomics. The method was applied to analyze the culture media and cell lysates derived from two types of glioblastoma cells, T98G and U118. The analysis revealed that even the both types of glioblastoma cells share several common metabolic aspects, they also exhibit differences in their metabolic capability. This finding agrees with the hypothesis about metabolic heterogeneity of glioblastoma cells. Furthermore, the combination of both analytical methods, HILIC-MS, provides a valuable tool for metabolomic studies based on the simultaneous identification and quantification of a wide range of polar and ionic metabolites - polaromics.

The etiology of Autism Spectrum Disorder (ASD) has been linked to both genetic and epigenetic factors. Among the epigenetic factors, exposure to valproic acid (VPA), an antiepileptic and mood-modulating drug, has been shown to induce characteristic traits of ASD when exposed during embryogenesis. Conversely, in animal models, Enriched Environment (EE) has demonstrated positive behavioral and neural effects, suggesting its potential as a complementary treatment to pharmacological approaches in central nervous system disorders. In this study, we utilized zebrafish to model ASD characteristics induced by VPA and hypothesized that sensory stimulation through EE could ameliorate the behavioral and neuroanatomical features associated with ASD. To test this hypothesis, we assessed social behavior, cerebellar volume, and Purkinje cell populations via histology and immunohistochemistry after exposing the fish to EE. The results revealed that zebrafish exposed to VPA exhibited social deficits, reduced cerebellar cortex volume, and a decrease in c-Fos-positive cells in the Purkinje layer. In contrast, VPA-exposed fish treated with EE showed increased socialization, augmented cerebellar cortex volume, and an elevation in c-Fos-positive Purkinje cells. These findings suggest that alterations induced by VPA may be ameliorated through EE treatment, highlighting the potential therapeutic impact of sensory stimulation in conditions related to ASD.

Cisplatin is a widely used anticancer drug for treating solid tumors, but it is associated with severe side effects, including nephrotoxicity. Various studies have suggested that the nephrotoxicity of cisplatin could be overcome; nonetheless, an effective adjuvant drug has not yet been established. Oleanolic acid acetate (OAA), a triterpenoid isolated from Vigna angularis, is commonly used to treat inflammatory and allergic diseases. This study aimed to investigate the protective effects of OAA against cisplatin-induced apoptosis and necroptosis using TCMK-1 cells and a mouse model. In cisplatin-treated TCMK-1 cells, OAA treatment significantly reduced Bax and cleaved-caspase3 expression, whereas increased Bcl-2 expression. Moreover, in cisplatin-induced kidney injury mouse model, OAA treatment alleviated weight loss in the body and major organs and also relieved cisplatin-induced nephrotoxicity symptoms. RNA sequencing analysis of kidney tissues identified lipocalin-2 as the most upregulated gene by cisplatin. Additionally, necroptosis-related genes such as receptor interacting protein kinase (RIPK) and mixed lineage kinase domain like (MLKL) were identified. In vitro study, the phosphorylation of RIPKs and MLKL was reduced by OAA pretreatment in both cisplatin-treated cells and cells boosted by co-treatment with z-VAD-FMK. In conclusion, OAA could protect the kidney from cisplatin-induced nephrotoxicity and may serve as an anticancer adjuvant.

Alveolar Rhabdomyosarcoma (ARMS), an invasive subtype of Rhabdomyosarcoma (RMS), is associated with chromosomal translocation events resulting in one of two oncogenic fusion genes PAX3-FOXO1 or PAX7-FOXO1. ARMS patients exhibit an overexpression of the pleiotropic cytokine Transforming growth factor beta (TGF-β). This overexpression of TGF-β1 causes an increased expression of a downstream transcription factor called SNAIL, which promotes Epithelial to Mesenchymal Transition (EMT). Overexpression of TGF-β also inhibits myogenic differentiation, making ARMS patients highly resistant to chemotherapy. In this review, we first describe different types of RMS and then focus on ARMS and the impact of TGF-β in this tumor type. We next highlight current chemotherapy strategies including a combination of FDA approved drugs vincristine, actinomycin D, and cyclophosphamide (VAC), Cabozantinib, Bortezomib, Vinorelbine, AZD 1775 and cisplatin. Lastly, we discuss chemotherapy agents that target the differentiation of tumor cells in ARMS which include all trans retinoic acid (ATRA) and 5-Azacytidine. Improving our understanding of the role of signaling pathways, such as TGF-β1, in the development of ARMS tumor cells differentiation will help inform more tailored drug administration in the future.

DNA-binding transcription factors are broadly characterized as proteins that bind to specific sequences within genomic DNA and modulate the expression of downstream genes. This study focused on KojR—a transcription factor involved in the metabolism of kojic acid, which is an organic acid synthesized in Aspergillus oryzae and is known for its tyrosinase-inhibitory properties. However, the regulatory mechanism underlying KojR-mediated kojic acid synthesis in remains unclear. Hence, we aimed to obtain a comprehensive identification of KojR-associated genes using genomic Systematic Evolution of Ligands by Exponential enrichment (gSELEX-Seq) and RNA-Seq. During the genome-wide exploration of KojR-binding sites via gSELEX-Seq and identification of KojR-dependent differentially expressed genes (DEGs) using RNA-Seq, we confirmed that KojR directly regulates kojT, as was previously reported. We also observed that kojA expression, which may be controlled by KojR, was significantly reduced in a ΔkojR strain. Notably, no binding of KojR to the kojA promoter region was detected. Furthermore, certain KojR-dependent DEGs identified in the present study were associated with enzymes implicated in the carbon metabolic pathway of A. oryzae. This strongly indicates that KojR plays a central role in carbon metabolism in A. oryzae.

This review provides insight into the role that obesity, but especially mediators of the adipose tissue, have in both renal disease and transplantation. In particular, we focus on the functions of leptin and adiponectin, inflammatory mediators with widely known clinical implications, as well as on the role of arachidonic acid-derived eicosanoid metabolites. These latter compounds, epoxyeicosatrienoic (EETs) and hydroxyeicosatetraenoic (HETEs) acids, which modulate the liberation of cytokines in the adipose tissue, are generated in the epoxygenase pathway of arachidonic biotransformation via CYP450 enzymes. There is accumulating evidence suggesting that EETs and HETEs may have a critical role in the onset and outcome of chronic kidney disease and renal transplantation. Finally, we also discuss the reported effect that the presence of genetic variants in leptin, adiponectin, EETs and HETEs-related genes may cause in renal patients and recipients. The levels of cytokines of the adipose tissue and related compounds play a remarkable role in both renal disease and transplant. Accordingly, novel therapeutic strategies are being developed based on the modulation of their concentrations in patients with various diseases.

Synthesis of natural products with complicated architecture often requires segments having the functional groups that can be structurally transformed with the desired stereogenic centers. Bicyclic ?-lactones have a great potential for a suitable segment for natural product synthesis. However, the stereoselective construction of such functionalized bicyclic ?-lactones is not as straightforward as one might expect. On the other hand, the Lewis acid template-mediated Diels-Alder reaction is one of the most powerful and versatile methods for providing bicyclic ?-lactones with high regioselectivity and stereoselectivity. In this reaction, the Lewis acid template activates the dienophile as well as linking the diene and dienophile by a temporary tether. Therefore, Diels-Alder reaction smoothly proceeds in a stereocontrolled manner, allowing a simple access to bicyclic ?-lactone as a valuable building block for the synthesis of complicated natural products. In this review, some highlights of the Lewis acid-mediated Diels-Alder reaction, along with its application to the synthesis of biologically active compounds are discussed.

Background: Multiple drug delivery systems obtained by loading nanoparticles (NPs) with different drugs with different physicochemical properties present a promising strategy to achieve synergistic effects between drugs or overcome undesired effects. This study aims to develop a new NP by loading Quercetin (Que) and valproic acid (VPA) onto chitosan. In this context, our study investigated the antioxidant activities of chitosan NPs loaded with single and dual drugs containing Que against oxidative stress. Method: The synthesis of single (Que or VPA) and dual-drug (Que and VPA) loaded chitosan NPs, characterization of the NPs, conducting in vitro antioxidant activity studies, and analysis of the cytotoxicity and antioxidant activity of the NPs in SH-SY5Y cell lines were performed. Result: The NP applications that protected cell viability to the greatest extent against H2O2-induced cell damage were, respectively, 96 µg/ml of Que-loaded chitosan NP (77.30%, 48 h), 2 µg/ml of VPA-loaded chitosan NP (70.06%, 24 h), 96 µg/ml of blank chitosan NP (68.31%, 48 h), and 2 µg/ml of Que and VPA-loaded chitosan NP (66.03%, 24 h). Conclusion: Our study establishes a successful paradigm in developing drug-loaded NPs, with uniform and homogeneous distribution of drugs onto NPs. Chitosan NPs loaded with both single and dual drugs possessing antioxidant activity were successfully developed.

Background: Estrogen homeostasis is crucial for bladder function, and estrogen deprivation resulting from ovarian removal or ovarian dysfunction may lead to various bladder dysfunctions. However, the specific mechanisms are not fully understood. Methods: We simulated estrogen deprivation using a rat ovariectomy model and supplemented estrogen through subcutaneous injections. The metabolic characteristics of bladder tissue were analyzed using non-targeted metabolomics, followed by bioinformatics analysis to preliminarily reveal the association between estrogen deprivation and bladder function. Results: We successfully established a rat model with estrogen deprivation and, through multivariate analysis and validation, identified several promising biomarkers represented by 3, 5-tetradecadiencarnitine, lysoPC (15:0), and cortisol. Furthermore, we explored estrogen deprivation-related metabolic changes in the bladder primarily characterized by amino acid metabolism imbalance. Conclusions: This study, for the first time, depicted the metabolic profile of bladder resulting from estrogen deprivation, providing an important experimental basis for future research on bladder dysfunctions caused by estrogen deprivation.

The historical and cultural use of food as a remedy for diseases is evident in societies, such as using Hibiscus sabdariffa to address conditions like hypertension and high blood glucose. The natural biocompounds in this plant, including Delphinidin-3-Sambubioside (DS3), Quercetin (QRC), and Hibiscus Acid (HA), have been linked to various health benefits. Despite individual attention, molecular targets for these compounds remain unclear. In this study, in-silico analysis employed bioinformatic tools; including Swiss Target Prediction, ShinnyGo 0.77, KEGG, and Stringdb, to identify molecular targets, pathways, and hub genes. A PubMed literature search complemented the results. DS3 demonstrated potential modifications in genes related to nitrogen and glucose metabolism, inflammation, angiogenesis, and cell proliferation, particularly affecting the PI3K-AKT pathway. QRC displayed interconnected targets across multiple pathways, with overlap with DS3 and a focus on cancer-related pathways. HA showed distinct targets, particularly associated with nervous system-related pathways. These findings highlight the need for targeted research on the molecular effects of DS3, QRC, and HA, providing valuable insights into potential therapeutic pathways.

The present review revisits representative studies addressed to develop efficient carbon-based heterogeneous catalysts for two important reactions, namely, the production of hydrogen from formic acid and the hydrogenation of carbon dioxide to formic acid. The HCOOH-CO2 system is considered a promising couple for a hydrogen storage system that would be involved in an ideal carbon-neutral cycle. Significant advancements have been achieved in those catalysts designed to catalyze the dehydrogenation of formic acid under mild reaction conditions, while much effort is still needed to catalyze the challenging CO2 hydrogenation reaction. The design of carbon-based heterogeneous catalysts for these reactions encompasses both the modulation of the properties of the active phase (particle size, composition, and electronic properties), as well as the modification of the supports by means of incorporation of nitrogen functional groups. These approaches are herein summarized to provide a compilation of the strategies followed in recent studies to set the basis for a hydrogen storage system attained by the HCOOH-CO2 couple.

Acid mine drainage (AMD) contamination is the primary environmental issue in industrial areas and where geological mining occurs. The oxidative dissolution of sulphide minerals causes AMD, natural ecosystems depend on microbial diversity and functioning at their best. This review presents the long-term effects of AMD water such as pollution from heavy metals (HM) on humans and plants, and the solution to the problem of heavy metal pollution by microbes metal interactions.

Background: Deoxycholic acid (DCA) is a secondary bile acid produced by gut bacteria. Its serum concentration increases in cardiovascular disease (CVD). We hypothesized that DCA may affect hemodynamic parameters in rats. Methods: The concentration of DCA in systemic blood was measured with liquid chromatography coupled with mass spectrometry. Arterial blood pressure (BP), heart rate (HR) and echocardiographic parameters were evaluated in anesthetized, male, 3-4-month-old Sprague-Dawley rats administered intravenously (IV) or intracerebroventricularly (ICV) with investigated compounds. Mesenteric artery (MA) reactivity was tested ex vivo. Results: The baseline plasma concentration of DCA was 0.24 ± 0.03 mg/l. The oral antibiotic treatment produced a large decrease in the concentration. Administered IV, the compound increased BP and HR in a dose-dependent manner. DCA also increased heart contractility and cardiac output. None of the tested compounds: prazosin (an alpha-blocker), propranolol (beta-adrenolytic), atropine (muscarinic receptor antagonist), glibenclamide (K-ATP inhibitor) or DY 268 (FXR antagonist), glycyrrhetinic acid (11HSD2 inhibitor) significantly diminished the DCA-induced pressor effect. ICV infusion did not exert significant HR or BP changes. DCA relaxed MAs. Systemic vascular resistance did not change significantly. Conclusions: DCA increases BP by increasing cardiac output. As a bioactive gut bacteria-derived metabolite, DCA may co the interaction between gut microbiota and the host’s circulatory system.

Nanofibers are one of the most attractive materials that can modify functionalities for developing new kinds of specific applications, mainly used as a biomedical material. Herein, we designed and prepared the antibacterial nonwoven fiber mats of PLA and PLA composited with Ag nanoparticles by electrospinning. The effects of varying filler contents on their chemical, surface morphology, thermal, water absorbency, and antibacterial properties were investigated using FTIR, SEM/EDS, DSC, swelling ratio, and qualitative and quantitative antibacterial tests. FTIR and EDS spectra indicated that Ag nanoparticles were incorporated in the PLA without chemical bonding. SEM revealed that the average diameter of the PLA nanofibers containing the Ag nanoparticles was more significant than those without those particles. Besides, fiber diameters are proportionally the amount of Ag nanoparticle contents. DSC indicated that the Ag nanoparticles can be incorporated within the PLA-matrix without strongly affecting their thermal properties. Moreover, the crystallinity of the composite nonwoven fiber mats was higher than those of fiber mats in the neat PLA. Accordingly, the antibacterial activities revealed that all the composite nanofiber mats exhibited excellent against S. aureus and E. coli bacterial strains. In addition, in the cell toxicity study, all produced hybrids nonwoven fiber mats induced a reduction in cell viability for the L929 fibroblast cells. Our results suggest that the designed and prepared nonwoven fiber mats may have good potential for use in the biomedical field, particularly in wound dressing applications

Electrochemical Impedance Spectroscopy techniques were applied in this work to 9 lead-acid battery prototypes fabricated industrially, divided on three type/technology packages. Frequency dependent impedance changes were interpreted during successive charge/discharge cycles on two distinct stages: 1) immediately after fabrication; and 2) after a controlled aging procedure to 50% Depth of Discharge, following industrial standards. By investigating their State of Health behaviour vs electrical response, three methods were employed, namely the (Q-Q0) total charge analysis, the decay values of Constant Phase Element in the equivalent Randles circuits, and the resonance frequency of the circuit. A direct correlation has been found for prediction of the best performant batteries in each package, thus allowing a qualitative analysis capable to provide the decay of the battery State of Health. We emphasized which parameters are directly connected with their lifetime performance in both stages, and by consequence, which type/technology battery prototype emphasize the best performance. Based on this methodology, the industrial producers can further establish the quality of the novel batteries in terms of performance vs lifespan, allowing them to validate the novel technological innovations implemented in the current prototypes.

Nemaline myopathy (NM) is one of the most common forms of congenital myopathy and it is identified by the presence of "nemaline bodies" (rods) in muscle fibers by histopathological exam-ination. The most common forms of NM are caused by mutations in the ACTA1 (Actin Alpha 1) and NEB (Nebulin) genes. Clinical features include hypotonia and muscle weakness. Unfortunate-ly, there is no curative treatment and the pathogenetic mechanisms remains unclear. In this man-uscript, we examined the pathophysiological alterations in NM using dermal fibroblasts derived from patients with mutations in ACTA1 and NEB genes. Patients’ fibroblasts were stained with rhodamine phalloidin to analyze the polymerization of actin filaments by fluorescence microsco-py. We found that patients' fibroblasts showed incorrect actin filament polymerization compared to control fibroblasts. Actin filament polymerization defects was associated with mitochondrial dysfunction. Furthermore, we identified two mitochondrial boosting compounds, linoleic acid (LA) and L-carnitine (LCAR), that improved the formation of actin filaments in mutant fibro-blasts and corrected mitochondrial bioenergetics. Our results indicate that cellular models can be useful to study the pathophysiological mechanisms involved in NM and to find new potential therapies. Furthermore, targeting mitochondrial dysfunction with LA and LCAR can revert the pathological alterations in NM cellular models.

Alheira is a naturally fermented meat sausage traditionally made in the Portuguese region of Trás-os-Montes. Lactic Acid Bacteria (LAB) have been found to be the dominant microorganisms in alheira. This study aimed: 1) to characterize technological features and in vitro antimicrobial activity of LAB isolates; and 2) to reveal associations between such phenotypic characteristics and the isolates genotypically identified to species level through amplification and sequencing of the 16S ribosomal gene. Sixty-two LAB isolates were identified and Enterococcus faecium was the most prevalent (32.3%), followed by Leuconostoc mesenteroides (19.4%) and Latilactobacillus sakei (17.7%), aligning with previous research on traditional Portuguese fermented meat sausages. The phenotypic analysis of LAB isolates indicated diverse acidification capacities, proteolytic activities, and inhibitory effects against foodborne pathogens. Comprising the technological attributes, L. paracasei and L. mesenteroides had higher proteolytic activity (3.46 and 3.43 mm), whereas E. faecium and L. paracasei stood out for their acidifying capacity, with mean pH after 6 h of 5.78 and 6.03, respectively. Overall, lactobacilli presented higher inhibition diameter against the pathogens Staphylococcus aureus, Listeria monocytogenes and Salmonella Typhimurium. Although the mechanisms for inhibition of pathogen growth needs to be further elucidated, these findings enhance our understanding of LAB diversity and functionality in alheira sausages, contributing to product safety and quality assessment.

The practice of voluntary depigmentation is still prevalent in Africa, with a wide range of lightening cosmetics used. Our objective was to research and quantify three regulated and/or prohibited depigmenting ingredients present in lightening cosmetics sold in Ouagadougou. Twenty-nine lightening cosmetic samples were collected from vendors and HPLC analysis was subsequently conducted to identify and measure the concentrations of hydroquinone, clobetasol propionate, and kojic acid. The presence of hydroquinone was indicated on the label of 13.79% of the products, while 51.72% contained it after analysis. Furthermore, none of the products mentioned a concentration of hydroquinone exceeding 2.00%, even though 27.58% of them contained high concentrations. For clobetasol propionate, its presence was stated on the labels of 13.79% of the products, while 31.03% contained it. One sample had a clobetasol content exceeding 0.05%, although none mentioned a concentration higher than this value. Finally, while 24.13% of the samples claimed to contain kojic acid, only 17.24% did. We also observed that 41.38% of the samples contained combinations of two depigmenting ingredients investigated, with a predominance of the hydroquinone + clobetasol propionate (27.38%). These results demonstrate that manufacturers' declarations regarding the compositions of active ingredients in lightening cosmetics can sometimes be deceptive.

Acid promoted amination of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine with anilines have been studied using hydrochloric acid. Four alcoholic solvents and water were evaluated as reaction medium, and the highest rate was observed in water. Although the initial rate increased by using higher concentration of acid, this leads to more solvolysis of the pyrrolopyrimidine, reducing the potential yield. The substrate scope of the amination of 4-chloro-7H-pyrrolo[2,3-d]pyrimidine in water using 0.1 equivalent of hydrochloric acid was evaluated using 20 aniline derivatives with variance in basicity and steric bulk. Preparative useful reactions were seen for 14 of the 20 derivatives. Unsuited anilines are ortho substituted anilines with a pKa below 1. Aliphatic and benzylic amines react poorly under these conditions, but such aminations can proceed well in water without acid. Pyrrolopyrimidines with a low water solubility, also reacted slowly in water, however they could easily be aminated in 2-propanol.

The interactions of metal ions with fulvic acids resulted in changes in the particle size and charge. Particle size distribution was trimodal for fulvic acids, bimodal for fulvic complexes with calcium and magnesium, and copper-fulvic complexes had only one size fraction. The compensation of negative charge of carboxylic and phenolic functional groups by positive charged metal ions resulted in the increase in zeta potential which was getting closer to zero in the case of copper-fulvic complexes. However, all metal humic complexes behaved as colloidally unstable which resulted in visually observable sedimentation. Calorimetric measurements provided positive values of changes in enthalpy which indicated endothermic processes. In contrast quantum chemical calculations as well as experiments with model compounds provided negative values indicated exothermic processes. Changes in Gibbs energy were determined as negative and changes in entropy as positive which meant spontaneous processes.

Abstract: A multitude of biotic and abiotic stress factors do harm to plants by bringing about diseases and inhibiting normal growth and development. As an omnipotent signaling molecule, salicylic acid (SA) plays crucial roles in plants' tolerance responses to both biotic and abiotic stresses, thereby maintaining plants’ normal growth and improving yields under stresses. In view of this, this paper mainly discusses the role of SA in both biotic stresses, and abiotic stresses of plants. SA regulates the expression of genes involved in defense signaling pathways, thus enhancing plants’ immunity. In addition, SA mitigates the negative effects of abiotic stresses, and acts as a signaling molecule to induce the expression of stress-responsive genes and the synthesis of stress-related proteins. In addition, SA also improves certain yield-related photosynthetic indexes, thereby enhancing crop yield under stresses. On the other hand, SA acts with other signaling molecules in regulating plants’ growth and improving tolerances under stresses. This paper reviews recent advances in SA’s roles in plant stress tolerances, so as to provide theoretical references for further studies concerning the decryption of molecular mechanisms for SA’s roles and the improvement of crop management under stresses.

Background: Vitamin B12 is a water-soluble vitamin with important cellular functions and is an essential vitamin. The aim of this study is to determine the B12 levels of children in the period from the 6th month when they start taking additional foods to the age of 7 and the risk factors affecting them. Methods: One hundred pediatric patients aged 6-72 months who were diagnosed with vitamin B12 deficiency and their parents who agreed to participate in Istanbul Atlas University, Medical Faculty, “Medicine Hospital” Pediatric Clinic between September 2022 and June 2023 were prospectively included in this study. Results: B12 deficiency was significantly higher in the 6-11 (25%) month group than those in the 12-23 (5.8%) and 24-47 (2.8%) month groups. Homocysteine levels were highest in those with insufficient B12 levels compared to the other groups. There was no statistically significant difference in weekly dairy and meat consumption levels between age groups. B12 levels were lower in the 6-11-month group than in the other groups. Homocysteine levels were highest in those with insufficient B12 levels [<200 pg/mL (148 pmol/L)]. Folic acid levels were lower in the 24-47 month and 48-72 month groups than in the 6-11 month and 12-23 month groups. Conclusions: The results obtained in this study showed that low vitamin B12 and increased homocysteine levels seem to be important risk factors in children, especially from the 6th month when they start taking additional foods. The diagnosis of B12 deficiency can be confirmed by elevated serum total homocysteine levels, which are evidence of functional cobalamin deficiency.

This work studied sorption regularities and assessed thermal stability and resistance to microbial degradation of humic acid as a result of 3 sorption cycles on bentonite clay, kaolinite, and muscovite using TGA/DSC, XRD, hydrophobic chromatography, light and electron microscopy, etc. The experiment revealed that kaolinite sorbed more humic acids (HAs) in terms of unit surface area (1.03 × 10-3 C, g/m2) compared to bentonite (0.35 × 10-3 C, g/m 10-3 g/m2). Sorption at pH 4.5 was accompanied by HA fractionation in amphiphilicity and chemical composition. HA was sorbed mainly due to hydrophobic components on the surface of all sorbents. HA was not intercalated into the interlayer spaces of montmorillonite during sorption. Sorption due to hydrophilic interactions was mostly performed on muscovite and bentonite than on kaolinite. Sorption was followed by a change in the chemical composition of HA and decreased C/N compared to free HA, indicating selective sorption of nitrogen-containing compounds which is most characteristic of muscovite. Only a relatively thermolabile HA fraction was adsorbed on all minerals while its thermal stability increased compared to that before the experiment. Thermal stability and ratio of the Exo2/Exo1 peak areas on the DSC curves of sorbed HA increased with each subsequent sorption cycle. Thermal stability and resistance to microbial oxidation of sorbed HA showed the following relationship: the higher the thermal stability, the less available is sorbed HA for utilization by microorganisms.

The present study aimed to evaluate the effect of the citric acid on the properties of solid pine wood, which were submitted to thermomechanical treatment. A preliminary test was performed in a previous study to evaluate the influence of different temperatures of pressing and concentrations of citric acid over the physical properties of wood. After choosing the best treatments (170°C and 5% and 10% of citric acid) it was evaluated the effect of these on the chemical properties (SEM, FTIR and pH), on the density profile using an X-ray microtomography, and on the resistance to ageing through abrasion test. The result of the chemical analysis allowed to observe an increase of the presence of ester functional groups, as well as a better coverage and higher acidity of the surface. The density profile technique allowed to observe the formation of peaks of density on the surface where the acid was applied. Lastly, it was also possible to verify an increase in the resistance to abrasion because of the application of the citric acid.

The adaptation of plants to biotic and abiotic stress depends on their abilities to sense their surroundings and to generate and transmit corresponding signals to different parts of their body that can evoke changes necessary for optimizing growth and defense. Light has been shown to be one of the key environmental factors that modulate the physiology of both plants and animals via the diverse photoreceptors found in them. Both plants and animals contain a large repertoire of intra- and intercellular signals molecules that include organic and inorganic. One such molecule is a neurotransmitter, γ-aminobutyric acid (GABA), a non-protein amino acid, that rapidly accumulates in plant tissues in response to biotic and abiotic stress and regulates plant growth. Lots of research has been done on GABA in plants for slightly more than half a century now: Its discovery in plant tissues was immediately followed by physiological and biochemical studies. Thereafter molecular-genetics era of cloning the genes encoding the GABA shunt enzymes and transporters, and recombinant expression and purification of the enzymes in vitro to elucidate their regulatory properties and substrate specificity was established. Recently the discovery of the first bona fide GABA target proteins in plants, the ALMTs suggest that GABA indeed could be one of the signaling molecules in plants. All this research did not address in detail the relationship between light and GABA. To better understand the role of GABA in relation to light we set up six light conditions to investigate the changes in the hypocotyl and root growth in Arabidopsis thaliana under different light conditions, including total light, total dark, light blocker, gradient light, shoot dark, shoot dark with blocker. We treated the seedlings with 3-MPA, a GABA inhibitor, using different concentrations grown under different light conditions between 24 to 96 h. Our results show that both the root and hypocotyl are modulated by GABA when grown under different light conditions. These results clearly suggest a link in the signaling pathway of GABA with photoreceptor signaling pathways.

Purpose: The study aimed to investigate the efficacy of TXA supplemented with local infiltration analgesia (LIA) in reducing blood loss in patients undergoing total knee replacement. Materials: A retrospective study on 530 individuals with a mean age of 71,44 years after posterior stabilized total knee arthroplasty was evaluated. Patients were divided into three groups, corresponding to the method of bleeding control: I - patients without additional bleeding protocol (control group); II - patients with iV TXA administration (TXA group); III - patients with exact TXA protocol combined with intraoperative local infiltration analgesia (TXA + LIA group). Blood loss was measured as a substitute for blood loss by maximal Hb drop compared to preoperative Hb level. Results: The mean hospitalization for patients from the control group was 7.02 (SD 1.34) days, 6.08 (SD 1.06) days for the TXA group, and 5.56 (SD 0.79) for the TXA + LIA group. The most significant hemoglobin drop was found in the control group, which amounted to an average of 30.08% output value. In the TXA group, the decrease in hemoglobin was, on average, 25.17% (p<0.001), and in the TXA + LIA group, it was 23.67% (p<0.001). A decrease in the rate of allogeneic blood transfusions was observed, which was 24.4% in the control group, 9.9% in the TXA group, and 8% in TXA + LIA group (p<0.01). Conclusions: Compared to the separate administration of tranexamic acid, the combination of perioperative administration with local infiltration analgesia statistically significantly reduces blood loss in patients after total knee replacement.

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.

Idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung disease characterized by progressive parenchymal fibrosis and respiratory failure. In a model of bleomycin-induced pulmonary fibrosis, the antifibrotic and anti-inflammatory activity of Longidaza (bovhyaluronidase azoxymer), which contains a conjugate of the hyaluronidase enzyme with a high molecular weight synthetic carrier azoxymer bromide, was investigated. Experiments were conducted in male C57BL/6 mice. Longidaza was administered at different doses by intranasal and intramuscular routes. Histology, hematology and enzyme-linked immunosorbent assay were used in the study. The use of Longidaza reduced pulmonary fibrosis as evidenced by an improvement in histopathologic damage to the lungs, a decrease in the area of connective tissue and the levels of profibrotic factors (TGF-β1, hydroxyproline, collagen I) in lung tissue. In addition, Longidaza inhibited the inflammatory response in pulmonary fibrosis, decreased the levels of IL-6, TNF-α, hyaluronic acid in lung tissue and the recruitment of inflammatory cells into lung tissue. The highest therapeutic efficacy was observed with the use of Longidaza at doses of 120 and 1200 U/kg intramuscularly, which was superior to that of the reference drug pirfenidone axunio. The data presented in this study suggest that Longidaza is a new and promising drug for the treatment of IPF that warrants further investigation in patients with fibrotic interstitial lung disease.

Lewis acid zeolites play an important role in industrially important green reactions closely related to fine chemicals and biomass conversion. Titanium-doped TS-1 zeolite is a milestone Lewis acid zeolite, which widely uses in industrially significant green oxidation processes with hydrogen peroxide as an oxidant under mild conditions. TS-1 Zeolites are normally synthesized in basic condition under hydrothermal treatment. Up to now, it is still not successful to synthesize active TS-1 Lewis acid zeolite by using inorganic alkali, e.g. NaOH or KOH as base, which are cheaper and more stable compared with quaternary ammonium hydroxide or organic amines used in the traditional synthesis. Here, inorganic base of NaOH was firstly employed in synthesizing active TS-1 zeolites. The crucial factor was the control of adverse effects of sodium cations on the incorporation of active titanium cations. A higher catalytic activity could be achieved by further reducing the size of the TS-1 crystal by seed-added strategy, which could approach the catalytic activity of commercial catalyst while the production cost was much lower than the commercial TS-1 catalysts, indicating great commercial potential and the possibility of preparing other cheap Lewis acid catalysts by using inorganic alkali.

Abstract: To compare the use of variable mechanical ventilation with conventional mechanical ventilation in porcine model of ARDS. Methods: Animals were divided into two groups (n = 6), conventional ventilation and variable ventilation with bi-oscillatory PEEP. For induction of ARDS, intravenous oleic acid was used until a P/F ratio of 200 to 300 mmHg. The animals were ventilated with pressure control, FiO2 1.0, inspiration-expiration ratio = 1:2, tidal volume 6 ml/kg with the initial respiratory rate adjusted to maintain an end tidal CO2 tension of 35 to 45 mmHg. Variable ventilation was characterized by the oscillation of PEEP from 5 to 10 cmH2O every 4 respiratory cycles, in convencional ventilation group PEEP was set from 5 cmH2O. Ventilatory, hemodynamic parameters, oxidative stress, antioxidant enzymes, Interleukin 8 (IL8) and 17-a (IL17a) and histological analyzes were evaluated; Results: The use of BiPEEP demonstrated improvement in lung compliance and PaO2 in relation to control. The levels of oxidative stress and antioxidant enzymes showed no significant difference. There was no difference in IL17a between groups. In IL8 there was a significant increase in the lung base of control in relation to BiPEEP, and a reduction in the apex of BiPEEP in relation to control. The control group showed changes in lung morphology characterized by cellular infiltrates, a thickening of the alveolar septae and atelectasis, which were attenuated in BiPEEP group; (4) Conclusions: The use of variable ventilation with bi-oscillatory level of PEEP demonstrates a potential ventilatory strategy in an experimental model of ARDS.

Development of bioresponsive extrudable hydrogels for 3D bioprinting is imperative to address the growing demand for scaffold design and efficient and reliable methods of tissue engineering and regenerative medicine. This study proposed genipin-crosslinked gelatin-hyaluronic acid hydrogel bioink with different amounts of gelatin tailored for 3D bioprinting, focusing on high cell density loading and less artificial extra-cellular matrix (ECM) effect, as well as exploring their potential applications in tissue engineering. The bioresponsiveness of these hydrogel scaffolds was successfully evaluated in different physiological conditions. 3D and four-axis printing of complex structures such as shapes of hollow tube, star, pyramid, and four-axis tubular scaffolds prove the hydrogel’s high extrusion ability and post-printing shape fidelity. Cytocompatibility and high cell density 3D bioprinting using this moderately stable hydrogel exhibit high potential for precise cell-delivery modes in tissue engineering as well as regenerative medicine.

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.

Nowadays, there is evidence that bacteria can contribute to cancer formation and interfere with therapy by mediating its carcinogenesis and related infection. Moreover, it is acknowledged that microbial infections and antibiotic resistance represent severe economic and health risks to society. These facts have led to the developing of several new techniques for impeding crucial biological processes in microbial cells. One of these techniques centers on using metal-chelating agents, which can disrupt the microorganism's vital metal metabolism by obstructing metal uptake and bioavailability for critical reactions. Additionally, nanotechnology has made a wide range of nanomaterials available for possible uses in the antibacterial industry. This complex field is shaped by antimicrobial nanoparticles, also investigated as therapeutic and drug-delivery tools. Halloysite nanotubes (HNTs) are naturally occurring tubular clay nanomaterials consisting of aluminosilicate kaolin sheets rolled up several times. The aluminon and siloxane groups on the surface of HNTs facilitate the formation of hydrogen bonds with biomaterials on their surface. These properties make HNTs crucial in a wide range of applications, such as in environmental sciences, wastewater treatment, dye removal, nanoelectronics and nanocomposite fabrication, catalytic studies, coatings for glass or anti-corrosive coatings, cosmetics, flame retardants, stimulus-response, and in forensic sciences. This work aimed to produce an antibacterial material by combining the properties of halloysite nanotubes with the ability of kojic acid to chelate iron. Starting from kojic acid, a simple nucleophilic substitution involving the hydroxyl groups on the surface of the nanotubes was performed. The obtained material was characterized by IR and SEM, and its ability to chelate iron was evaluated. Finally, the capacity to load drugs such as resveratrol and curcumin was also evaluated by UV analysis. In this way, a new bio-based material that can be used as a drug carrier and antimicrobial was produced.

Nanomaterials such as pH-responsive polymers are promising for targeted drug delivery systems, due to the difference in pH between tumor and healthy regions. However, there is a significant concern about the application of these materials in this field due to their low mechanical resistance, which can be mitigated by combining these polymers with mechanically resistant inorganic materials such as mesoporous silica nanoparticles (MSN) and hydroxyapatite (HA). Mesoporous silica has interesting properties such as high surface area and hydroxyapatite has been widely studied to aid in bone regeneration, providing special properties adding multifunctionality to the system. Furthermore, fields of medicine involving luminescent elements such as rare earth are an interesting option in cancer treatment. The present work aims to obtain a pH-sensitive hybrid system based on silica and hydroxyapatite with photoluminescent and magnetic properties. The nanocomposites were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), nitrogen adsorption methods, CHN elemental analysis, Zeta Potential, scanning electron microscopy (SEM), and transmission electron microscopy (TEM), vibrational sample magnetometry (VSM), and photoluminescence analysis. Incorporation and release studies of the antitumor drug doxorubicin were performed to evaluate the potential use of these systems in targeted drug delivery. The results showed the luminescent and magnetic properties of the materials and showed suitable characteristics for application in the release of pH-sensitive drugs.

Recently, the popularity of fermented foods has increased significantly. Lactofermented vegetable juice products are particularly important for our diet. The combination of the richness of the ingredients derived from vegetable juices and the products formed during lactic fermentation is a valuable source of nutrients. This study aimed to analyse the selected properties of fermented beetroot, carrot, and beetroot-carrot juices. The juices obtained from beetroot and carrot were fermented with bacterial strains Lactiplantibacillus plantarum or Levilactobacillus brevis. Density, extract, dry matter content, pH, total acidity, pigments (betalain or carotenoids), color, and LAB count were measured in the samples. The results obtained in this study showed that the used LAB strains were capable of fermenting the analyzed juices. It was proven that Lactiplantibacillus plantarum was a better strain for fermentation ion of vegetable juice. This might have been influenced by the fermentation temperature and the duration of the fermentation. However, this strain had a lower effect on carotenoids, which are water-insoluble pigments, than Lactiplantibacillus plantarum. The opposite observation was made for betalain, a water-soluble pigment with nitrogen in its structure.

Traditional grain vinegar is fermented using multiple acetic acid bacteria (AAB) at various temperatures. A single AAB showed high acid–producing ability at 30 °C with a 5% alcohol concentration and an initial pH adjusted to 4.0. Multiple AAB were similar to single AAB, but the optimal initial pH was 3.0. Acid production ability according to the type of AAB was higher in multiple AAB than that for single AAB. That is, using multiple AAB helped to increase the titratable acidity of traditional grain vinegar. In addition, increasing the titratable acidity and content of volatile flavor compounds was advantageous when two, rather than four, AAB types were mixed and used. Titratable acidity was high at medium temperatures (30 °C), but volatile flavor compounds increased at low temperatures (20 °C) under multiple AAB. A 16S rDNA–based microbiome taxonomic profiling analysis identified differences in beta diversity due to multiple AAB and fermentation temperatures. In particular, beta diversity analysis revealed a specific pattern when a mixture of Acetobacter ascedens GV–8 and Acetobacter pasteurianus GV–22 were fermented at low temperature (20 °C). Therefore, we propose the application of multiple AAB with acidic and flavor–producing properties in traditional grain vinegar.

Green microalgae including those from the genus Lobosphaera are exploited in biotechnology to obtain valuable fatty acids e.g., arachidonic acid (C20:4, ARA) for the production of infant formulae, food and feed additives. In nature, microalgae frequently exist in naturally immobilized state (as biofilms) with limited cell division rate and increased stress resilience. In biotechnology, immobilization of microalgae on artificial cell carriers simplifies biomass harvesting, increases culture robustness and productivity. The choice of suitable cell carrier is central to biotechnology of immobilized culture. Cell carriers based on the natural amine-containing polymer chitosan and synthetic polyethylenimine (PEI) are promising candidates for immobilization of phototrophic microorganisms. This is the first report on the effects of immobilization on PEI and chitosan on the accumulation and composition of polyunsaturated fatty acids, including ARA, in Lobosphaera sp. IPPAS C-2047. The immobilization on PEI increased ARA percentage in the total tatty acids and ARA accumulation by 72% and 81%, compared with the suspended cells cultured respectively in complete or nitrogen-deprived medium 14 days. Immobilization of Lobosphaera sp. on the chitosan-based carrier declined ARA but increased oleic and α-linoleic acid percentages. Mechanisms of the effects of immobilization on fatty acid profiles of the microalgae are discussed.

Mandatory fortification of food with the synthetic folic acid (FA) was instituted in 1998 to reduce the incidence of neural tube defects. Adequate folate status is correlated with numerous health benefits. However, elevated consumption of FA is controversially associated with deleterious effects on health. We previously reported that excess FA mimicked folate depletion in a lymphoblastoid cell line. To explore the impact of FA intake from fortified food, we conducted an observational human study on 33 healthy participants aged 18-40 not taking any supplements. Food intake, anthropomorphic measurements, and blood samples were collected and analyzed. Our results show that individuals belonging to the highest tertile of folic acid intake, as well as ones with the highest folic acid to total folate intake ratio (FAR), display a significantly greater incidence of lymphocyte genomic damage. A decrease in global DNA methylation is observed in the highest tertile of FAR compared to the lowest (P=0.055). A downward trend in the overall gene expression of select DNA repair and one carbon cycle genes (MGMT, MLH1, UNG, MTHFR, MTR) is noted with increased folate status and FA intake. These results provide supporting evidence that high consumption of FA from fortified foods can precipitate genomic instability in peripheral lymphocyte in-vivo.

Degradation of intracellular components through autophagy is a fundamental process to maintain cellular integrity and homeostasis. Recently a glycogen-selective autophagy pathway has been described, termed ‘glycophagy’. Glycogen is a primary storage depot and regulator of glucose availability, and glycophagy is emerging as a critical physiological process involved in energy metabolism. Glycophagy-mediated degradation of glycogen appears to operate in parallel with the well-described canonical pathway of glycogenolysis involving glycogen phosphorylase. Evidence suggests that starch-binding domain protein-1 (Stbd1) is a key glycogen-binding protein involved in tagging glycogen for glycophagy, and that Gabarapl1 is primarily involved as the Atg8 family protein recruiting the Stbd1-glycogen complex into the forming glycophagosome. The nuances of glycophagy protein machinery, regulation and lysosomal glucose release are yet to be fully elucidated. In this mini-review, we critically analyze the current evidence base for glycophagy as a selective-autophagy process of physiological importance and highlight areas where further investigation is warranted.

Background: Primary central nervous system lymphomas (PCNSLs) are sensitive to chemotherapy. Standard treatment is high-dose methotrexate (MTX)-based chemotherapy. There are no reports of successful treatment of acute uric acid nephropathy with rasburicase after MTX administration in PCNSL. Case presentation: A 54-year-old man with a history of gout presented with character change and memory loss. MRI showed a large, enhancing mass spanning the bilateral frontal lobes and right temporal lobe. After endoscopic biopsy, MTX, procarbazine and vincristine (MPV) regimen was initiated for treatment of PCNSL. After initiation of chemotherapy, the patient suffered from a gout attack and blood examination revealed acute renal failure (ARF) and hyperuricemia. The considered causes of ARF included MTX toxicity and acute urid acid nephropathy. Since a good response to chemotherapy was observed, the latter was assumed. After improvement of renal function, MTX was resumed, initiating rasburicase for control of hyperuricemia. A complete response was obtained after induction chemotherapy. Hyperuricemia was controlled with rasburicase and renal function was preserved. Conclusions: Acute uric acid nephropathy should be considered when ARF occurs after initiation of MTX in PCNSL. For newly diagnosed PCNSL patients with large tumors or hyperuricemia, upfront usage of rasburicase should be considered to prevent it.

Ring necked-pheasant (Phasianus colchicus) is bird of order Galliformes. Ring necked-pheasant is also known as gallinaceous bird and game bird. It looks like chicken bird. It is national bird of South Dakota. It is mostly found in wild areas but in Pakistan it exists as Domestic bird. It has high proteins and low fat in its meat. The present study was conducted to check the effect of ascorbic acid on sperm Motility, sperm cytoplasmic membrane integrity, sperm livability and acrosome integrity of Ring-necked pheasant at different concentrations of ascorbic acid (0mM, 1mM, 2mM, 3mM and 4mM) were used. Semen was collected by abdominal massage technique. Motility of sperm was greater than 70%.Then it was processed further. The cryopreservation of semen was checked at various stages like Post Dilution, Post Cooling, Post Equilibration and Post Thawing. Semen was cooled from post-dilution stage (37⁰ C) to post-cooling (20⁰C).Then it further cooled gradually to get post-equilibration stage (4⁰ C) within 24 hours. After that 10% glycerol was added to the sample. Then it was transferred to liquid nitrogen (LN₂) cylinder for 24 hours. After thawing stage sample was removed from LN₂ cylinders and placed in water bath for 4 hours to achieve post-thawing. Then performed sperm quality assays at each stage of cryopreservation. Sperm motility was assessed by Neubauer Chamber Hemocytometer. Plasma Membrane Integrity was checked by using Hypo Osmotic Swelling Test with the help to 2% Eosin. Sperm livability was assessed by Lake’s glutamate solution and sperm Acrosome Integrity was checked by dual staining technique by using Formal citrate solution and Giemsa stain. The better results were seen at 3mM treatment of ascorbic acid. Sperm motility percentage was significantly different (P < 0.05) on 3mM treatment on all the stages of cryopreservation rather than other treatments. Plasma membrane integrity assay also showed good results at same concentration (P < 0.05) on all the stages of cryopreservation rather than other treatments. At the sperm livability stage 3mM treatment showed significantly difference (P < 0.05) on all the stages of cryopreservation rather than other treatments. The sperm acrosome integrity showed highest percentage on 3mM treatment (P < 0.05) on all stages of cryopreservation rather than other treatments. Effect of ascorbic acid on all the quality parameters (sperm motility, plasma membrane integrity, livability and acrosome integrity) was showed significant difference (P < 0.05) at 3mM treatment of ascorbic acid as compare to control as well as remaining treatments. It was seen that by increasing the concentration of ascorbic acid from 3mM concentration to onward it shows negative results on its cryopreservation. Now this cryopreserved semen can be transfer from one place to another place to obtain good varieties as well as better genetic characteristics of this species.

Cells have metabolic flexibility that allows them to adapt to changes in substrate availability. Two highly relevant metabolites are glucose and fatty acids (FA), and hence, glycolysis and fatty acid oxidation (FAO) are key metabolic pathways leading to energy production. Both pathways affect each other, and in the absence of one substrate, metabolic flexibility allows cells to maintain sufficient energy production. Here we show that glucose starvation or sustained pyruvate dehy-drogenase (PDH) activation by dichloroacetate (DCA) induce a large genetic remodeling to pro-pel FAO. The extracellular signal-regulated kinase 5 (ERK5) is a key effector of this multistep metabolic remodeling. First, there is an increase in the lipid transport by expression of low-density lipoprotein receptor-related proteins (LRP), e.g. CD36, LRP1 and others. Second, an increase of the expression of members of the acyl-CoA synthetase long-chain (ACSL) family acti-vates FA. Finally, the expression of the enzymes that catalyze the initial step in each cycle of FAO, i.e. the acyl-CoA dehydrogenases (ACADs), is induced. All of these pathways lead to enhanced cellular FAO. In summary, we show here that different families of enzymes, which are essential to perform FAO, are regulated by the signaling pathway, i.e. MEK5/ERK5, which transduces changes from the environment to genetic adaptations.

The objective of this study was to identify key transcription factors involved in lipid metabolism and immune response related to the differentially expressed genes (DEG) from the liver samples of 35 pig model for metabolic diseases fed diets containing either 1.5 or 3.0% soybean oil (SOY1.5 or SOY3.0). A total of 281 DEG between SOY1.5 and SOY3.0 diets (log2fold-change ≥ 1 or ≤ −1; FDR-corrected p-value &lt; 0.1) were identified, in which 129 were down-regulated and 152 were up-regulated in SOY1.5 group. The functional annotation analysis detected transcription factors linked to lipid homeostasis and immune response, such as RXRA, EGFR, and SREBP2 precursor. These findings demonstrated that key transcription factors related to lipid metabolism could be modulated by dietary inclusion of soybean oil. It could contribute to nutrigenomics research field that aims to elucidate dietary interventions in animal and human health, as well as to drive the food technology and science.

Brinjal is a beautiful vegetable crop with strong nutritional properties specifically folate concentration and total chlorogenic acid content. These vitamins and minerals are very much effective in building up the immune system, whilst chlorogenic acid content protects the human body against heart illnesses, liver issues and diabetes. The quantity of these chemicals changes from cultivar to cultivar largely based upon the location of growth and changing environmental circumstances. Many plant breeding strategies are used to alleviate the losses but have proved to be less successful. Whereas the use of molecular markers and other biotechnology technologies have created a road for creating climate smart brinjal with maximum yields and nutritious contents.

Water is essential for all living things however its pain has become serious. Many industrial activities cause its pollution by the release of polluting byproduct. Waste water treatment is hence necessary. In this context, the waste water of the textile industry containing Red Acid 52 was treated by the solid waste of the washed natural phosphate byproduct. Natural phosphate was also studied. The solid materials were first characterized by chemical analysis, Fourier Transform Infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The phosphate materials were after that, tested in the adsorption of the Red Acid 52. The experimental data indicated that the phosphate waste rock allowed the removal of Red Acid 52. Its maximum retention capacity attained 18.4 mg.g-1. Calcinations of materials inhibits the removal capacity found reduced by 60 to 70%. The adsorption kinetics of the Red Acid 52 on the material is well described by the pseudo second order model while the adsorption isotherms are identified by the Langmuir model. Hereafter, the thermodynamic study revealed that the adsorption process is spontaneous and exothermic. Keywords: Waste water, Phosphate co-product, Adsorption, Red Acid 52.

Dental pulp tissue engineering (TE) quests to regenerate dentin/pulp complex by combining a suitable supporting matrix, stem cells, and biochemical stimuli. Such procedures foresee a matrix that can be easily introduced into the root canal system (RCS) and tightly adhere to dentin walls to assure the dentin surface's proper colonization with progenitor cells capable of restoring the dentin/pulp complex. Herein was investigated an injectable self-setting hyaluronic acid-based (HA) hydrogel system, formed by aldehyde-modified (a-HA) with hydrazide-modified (ADH), enriched with platelet lysate (PL), for endodontic regeneration. The hydrogels' working (wT) and setting (sT) times, the adhesion to the dentine walls, the hydrogel's microstructure, and the delivery of human Dental Pulp Cells (DPCs) were studied in vitro. Hydrogels incorporating PL showed a suitable wT and sT and a porous microstructure. The tensile tests showed that the breaking point occurs after 4.13 mm deformation. While in the indentation test after 1.3 mm deformation. Both breaking points occur in the hydrogel extension. The HA/PL hydrogels exhibited supportive properties and promoted cell migration toward dentin surfaces in vitro. Overall, these results support using PL-laden HA injectable hydrogels (HA/PL) as a biomaterial for DPCs encapsulation, thereby displaying great clinical potential towards endodontic regenerative therapies.

The absence of interdental papillae leads to the appearance of black triangle. For most patients, the appearance of these triangles is an important reason for concern and affects their social relationships. Multiple reconstruction techniques have been developed with different degrees of success and predictability. The main aim of this study was to evaluate the efficiency of hyaluronic acid (HA) injected into interproximal papillae six months after injection and to perform a systematic review and meta-analysis. After a systematic review, five articles were selected: a clinical randomised controlled trial and four clinical trials. In total, eighty-five patients with a deficiency in upper papillae in the front of the maxilla and jaw were included in the study. The height variable was evaluated (mm) six months after HA injection. In total, one hundred and four interproximal papillae were studied. Three articles showed an important difference in favour of intervention. The total result regarding in the injection of AH was favourable with an approximate average filling of 0.7 mm in the height of the interdental papilla. The injection of HA for the reconstruction of deficient papillae in the region of the upper and lower maxilla was a possible option treatment strategy.

Ferulic acid (FA) is known for its excellent antioxidant properties that can provide a lot of health benefits. One of its drawbacks is being unstable under UVA light that limits its potency. In this study, new peptides LW2 (QNKRFYFRKNQ) and CW2 (a cyclic form of LW2) have been designed based on bovine serum albumin site ⅡA conformation. UVA irradiation experiment was performed to investigate the protective ability of these peptides towards FA against UVA damage. The percentage of FA remaining under UV irradiation by the protection of CW2 and LW2 was 83%, 76% respectively. The results showed the importance of the cationic residues and hydrophobic residues included in the peptide sequences. Moreover, the cyclic rigid structure showed more protecting ability over that of the linear counterpart.

With the extension of the post-catch circulation time, a series of changes had taken place in the soft tissue of the live clams, resulting in the decline of its quality. This study investigated the quality changes of clams (Ruditapes philippinarum) in cold chain and was mainly focused on the rehydration process, which included gradient heating rehydration (GR) and sudden heating rehydration (SR). It was found that the GR had a better effect on the quality of clams than the SR. The GR stage clams showed a higher survival rate, glycogen content and adenylate energy charge (A.E.C) value than the SR stage clams. Conversely, the GR stage clams showed lower lactic acid content and K-value than the SR stage clams. The results indicated that the gradient heating rehydration was beneficial to the quality of clams. The transportation and rehydration strategies benefited both producers and shellfish merchants to save total cost.

Histone deacetylase (HDAC) inhibitors are class of drugs used in the cancer treatment. Here, we developed a library of 19 analogues of Vorinostat, an HDAC inhibitor used in lymphomas treatment. In Vorinostat, we replaced the hydrophobic phenyl group with various tricyclic ‘caps’ possessing a central, eight-membered, heterocyclic ring, and investigated the HDAC activity and cytotoxic effect on the cancer and normal cell lines. We found that three out of the 19 compounds, based on dibenzo[b,f]azocin-6(5H)-one, 11,12-dihydrodibenzo[b,f]azocin-6(5H)-one and benzo[b]naphtho[2,3-f][1,5]diazocine-6,14(5H,13H)-dione scaffolds, showed better HDACs inhibition than the referenced Vorinostat. In leukemic cell line MV4-11 and in lymphoma cell line – Daudi three compounds showed lower IC50 values than Vorinostat. These compounds had higher activity and selectivity against MV4-11 and Daudi cell lines than reference Vorinostat. We also observed a strong correlation between HDACs inhibition and the cytotoxic effect. Cell lines derived from solid tumors: A549 (lung carcinoma) and MCF-7 (breast adenocarcinoma) as well as reference Balb/3T3 (normal murine fibroblasts) were less susceptible to compounds tested. Developed derivatives show superior properties than Vorinostat, thus they are applicable as selective agents for leukemia and lymphoma treatment.

A series of chiral complexes of the form Ir(NHC)2(aa)(H)(X) (NHC = N-heterocyclic carbene, aa = chelated amino acid, X = halide) was synthesized by oxidative addition of -amino acids to iridium(I) bis-NHC compounds and screened for asymmetric transfer hydrogenation of ketones. Following optimization of the reaction conditions, NHC, and amino acid ligands, high enantioselectivity was achieved when employing the Ir(IMe)2(l-Pro)(H)(I) catalyst (IMe = 1,3-dimethylimidazol-2-ylidene), which asymmetrically reduces a range of acetophenone derivatives in up to 95% enantiomeric excess.

Accelerated degradation of collagen membranes (CMs) in diabetic rats is associated with increased infiltration of macrophages and blood vessels. Since pre-implantation immersion of CMs in cross-linked high molecular weight hyaluronic acid (CLHA) delays membrane degradation, we evaluated its effect on the number of macrophages and endothelial cells (ECs) within the CM. Diabetes was induced with streptozotocin in 16 rats, while 16 healthy rats served as control. CM discs were labeled with biotin, soaked in CLHA or PBS and implanted under the scalp. Fourteen days later, CMs were embedded in paraffin and the number of macrophages and ECs within the CMs was determined using antibodies against CD68 and Transglutaminase II, respectively. Diabetes increased the number of macrophages and ECs within the CMs (∼2.5-fold and 4-fold, respectively). Immersion of CMs in CLHA statistically significantly reduced the number of macrophages (p<0.0001) in diabetic rats, but not that of ECs. In the healthy group, CLHA had no significant effect on the number of either cells. Higher residual collagen area and membrane thickness in CLHA-treated CMs in diabetic animals were significantly correlated with reduced number of macrophages but not ECs. Immersion of CM in CLHA inhibits macrophage infiltration and reduces CM degradation in diabetic animals.

Fermented milk product "Laban" in Libya is one of the most a traditional fermented milk product consumed a refreshing drink, particularly in the warm season The average values of the physicochemical including titratable acidity, pH, total solids, and fat were 0.73%, 4.16, 8.12%, and 1.54% respectively. Coliform, yeast and mold counts were 21×10⁴, 39×10⁴, and 41 ×10³ cfu/ ml., respectively. Most strains of coliform bacteria were Serratia odorifera, Escherichia coli 1, E. coli 2. and Klebsiella oxytoca. The average Lactococcus, Streptococcus, Mesophilic Lactobacillus / Leuconostoc and Thermophilic Lactobacillus counts were 99 ×10⁷, 96 ×10⁷, 93 ×10⁷ and 15 ×10⁷ cfu / ml. respectively. A total of 142 lactic acid bacteria (LAB) isolates were identified to the genus level as Lactobacillus (48.59%), Lactococcus (43.66%), Streptococcus (4.93%) and Leuconostoc (2.82%). Sugar fermentation tests revealed the most frequent Lactobacillus species found to be Lactobacillus delbrueckii ssp. lactis (62.32%), followed by Lactobacillus plantarum (31.88%). Furthermore, other selected LAB isolates were identified by API 50 CH test as Lactococcus lactis ssp. lactics, Lactobacillus pentosus, Lactobacillus brevis, and Leuconostoc mesenteroides ssp. cremoris. Thus, our research documented the lactic acid bacteria strains and will provides fundamental basic and useful information for further studies of strain selection starter culture, with regard to the industrial production of fermented dairy milk products.

Quantum leaps advances in the single-molecule investigative science have been made possible over the past decades through the implication of nanopores, as versatile components on dedicated biosensors. Here, we employed the nanopore-tweezing technique to capture amino acid-functionalized, peptide-nucleic acids (PNA) with -hemolysin-based nanopores, and correlate the ensuing stochastic fluctuations of the ionic current through the nanopore with the composition and order of bases in the PNAs primary structure. We demonstrate that while the system enables detection of distinct bases on homopolymeric PNA or triplet bases on heteropolymeric strands, it also reveals rich insights into the conformational dynamics of the entrapped PNA within the nanopore, relevant for perfecting the recognition capability single-molecule sequencing.

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.

Chitosan is a chitin-derived fiber, extracted from the shellfish shells, a by-product of fish industry, or from fungi grown in bioreactors. In oenology, it is used for the control of Brettanomyces spp., for the prevention of ferric, copper and protein casse and for clarification. The International Organisation of Vine and Wine established the exclusive utilization of fungal chitosan to avoid the eventuality of allergic reactions. This work focuses on the differences between two chitosan categories, fungal and animal chitosan, characterizing several samples in terms of chitin content and degree of deacety-lation. In addition, different acids were used to dissolve chitosans, and their effect on viscosity and on the efficacy in wine clarification were observed. Results demonstrated that, even if fungal and animal chitosans shared similar chemical properties (deacetylation degree and chitin content), they showed different viscosity depending on the acid used to dissolve them. A significant difference was discovered on their fining properties, as animal chitosans showed a faster and greater sedimentation compared to the fungal, independently from the acid used for their dissolution. This suggests that physic-chemical differences in the molecular structure occur between the two chitosan categories and that this affect significantly their technologic (oenological) properties.

The Hippo pathway regulates a complex signalling network which mediates several biological functions including cell proliferation, organ size and apoptosis. Several scaffold proteins regulate the crosstalk of the members of the pathway with other signalling pathways and play an important role in the diverse output controlled by this pathway. In this study we have identified the scaffold protein IQGAP1 as a novel interactor of the core kinases of the Hippo pathway, MST2 and LATS1. Our results indicate that IQGAP1 scaffolds MST2 and LATS1, supresses their kinase activity, and YAP1-dependent transcription. Additionally, we show that IQGAP1 is a negative regulator of the non-canonical pro-apoptotic pathway and may enable the crosstalk between this pathway and the ERK and AKT signalling modules. Our data also show that bile acids regulate the IQGAP1-MST2-LATS1 signalling module in hepatocellular carcinoma cells which could be necessary for the inhibition of MST2-dependent apoptosis and hepatocyte transformation.

The study aimed to elucidate the optimum level of elemental sulfur, fresh cassava root (FCR), and urea and their effect on gas production, ruminal fermentation, thiocyanate concentration, and in vitro degradability. A 3×2×4 in a completely randomized design were conducted. Factor A was level of sulfur at 0%, 1%, and 2% of concentrate dry matter (DM), factor B was level of urea at 2% and 4% of concentrate DM, and factor C was level of the FCR at 0, 200, 300, and 400 mg of the total substrate. The study found that elemental sulfur, urea, and FCR had no interaction effect on the kinetics of gas, ruminal fermentation, hydrogen cyanide (HCN), and in vitro degradability. Elemental sulfur supplementation (P<0.05) significantly increased the gas produced from an insoluble fraction (b), in vitro DM degradability and either neutral detergent fiber or acid detergent fiber degradability, and propionate (C3) concentration while decreased the ruminal HCN concentration. Urea levels showed a (P<0.05) significant increase of the potential extent of gas production, ruminal NH3-N, and total volatile fatty acid (VFA). FCR supplementation (P<0.05) significantly increased the gas produced from an immediate soluble fraction (a), gas produced from insoluble fraction, gas production rate constant, total VFA, C3 concentration, and HCN while decreased ruminal pH, acetate, and butyrate concentration. It could be concluded that 2% elemental sulfur, 4% urea, and 300 mg FCR showed a greater effect on gas production, ruminal fermentation, and HCN reduction.

We investigated effects of molecular hydrogen (H2) supplementation on acid-base status, pulmonary gas exchange responses, and local muscle oxygenation during incremental exercise. Eighteen healthy, trained subjects in a randomized, double-blind, crossover design received H2-rich calcium powder (HCP) (1500 mg/day, containing 2.544 µg/day of H2) or H2-depleted placebo (1500 mg/day) for 3 consecutive days. They performed cycling incremental exercise starting at 20-watts work rate, increasing by 20 watts/2 min until exhaustion. Breath-by-breath pulmonary ventilation (VE) and CO2 output (VCO2) were measured and muscle deoxygenation (deoxy[Hb + Mb]) was determined via time-resolved-NIRS in the vastus lateralis (VL) and rectus femoris (RF). Blood gases' pH, lactate, and HCO3− concentrations were measured at rest and 120-, 200-, and 240-watt work rates. At rest, the HCP group had significantly lower VE, VCO2, and higher HCO3−, PCO2 versus placebo. During exercise, a significant pH decrease and greater HCO3− continued until 240-watts work rate in HCP. The VE was significantly lower in HCP versus placebo, but HCP did not affect the gas exchange status of VCO2 or oxygen uptake (VO2). HCP increased absolute values of deoxy[Hb + Mb] at the RF but not VL. Thus, HCP-induced hypoventilation would lead to lower pH and secondarily impaired balance between O2 delivery and utilization in the local RF during exercise, suggesting that HCP supplementation, which increases the at-rest antioxidant potential, affects the lower ventilation and pH status during incremental exercise. HPC induced a significantly lower O2 delivery/utilization ratio in the RF but not the VL, which may be because these regions possess inherently different vascular/metabolic control properties, perhaps related to fiber-type composition.

Hyperuricemia is a risk factor for gout. It has been well observed that a large proportion of hyperuricemia individuals have never had a gout attack(s), while some patients with gout can have a normuricemia. This raises a puzzle of the real role of serum uric acid (SUA) in the occurrence of gout attacks. As the molecule of uric acid has its dual effects in vivo with antioxidant property as well as being an inflammatory promoter, it has been placed in a delicate position in balancing metabolisms. Gout seems to be a multifactorial metabolic disease and its pathogenesis should not rely solely on hyperuricemia or MSU crystal. This critical review aims to unfold the mechanisms of the SUA role participating in gout development. It also discusses some key elements which are prerequisite for the formation of gout in association with the current therapeutic regime. The compilation should be helpful in precisely fighting for a cure of gout clinically and pharmaceutically.

Coffee is rich in caffeine (CF), chlorogenic acid (CGA) and phenolics. Differing types of coffee beverages and brewing procedures may result in differences in total phenolic contents (TPC) and biological activities. Inflammation and increases of platelet activation and aggregation can lead to thrombosis. We focused on determining the chemical composition, antioxidant activity and inhibitory effects on agonist-induced platelet aggregation and cyclooxygenase (COX) of coffee beverages in relation to their preparation method. We prepared instant coffee and brewed coffee beverages using drip, espresso and boiling techniques. Coffee extracts were assayed for their CF and CGA contents using HPLC, TPC using colourimetry, platelet aggregation with an aggregometer and COX activity using ELISA. The findings have shown all coffee extracts, except the decaffeinated types, contained nearly equal amounts of CF, CGA and TPC. Inhibitory effects of coffee extracts on platelet aggregation differed depending on the activation pathways induced by different agonists. All espresso, drip and boiled coffee extracts caused dose dependent inhibition of platelet aggregation induced by ADP, collagen, epinephrine, and arachidonic acid (ARA). The most marked inhibition was seen at low doses of collagen or ARA. Espresso and drip extracts inhibited collagen-induced platelet aggregation more than purified caffeine or CGA. Espresso, boiled and drip coffee extracts were also a more potent inhibitors of COX-1 and COX-2 than purified caffeine or CGA. We conclude that inhibition of platelet aggregation and COX-1 and COX-2 may contribute to anti-platelet and anti-inflammatory effects of espresso and drip coffee extracts.

Poly lactic acid (PLA) has made inroads for commercial market segment with lot many unique characteristics such as tenacity, low flame rate, moisture regain percentage, loss of ignition percentage, heat of combustion, UV resistance, Elastic recovery and higher melting point allowed it to be the fastest moving material in today's commercial market. An attempt has been made to test the feasibility and biocompatibility aspect of PLA with cement mix. The basic strength and physical test results were carried out and published in an article, to the continuation of the work, micro-structural study was conducted to evaluate the elemental characteristics. Thermo gravimetric analysis revealed that PLA either in granular form or filament will hold good for the inclusion into construction applications, provided degradation aspects are to be looked out for improvisation. From DSC it was found that PLA in filament form is the best inclusion material for construction application, however the tenacity of fibers has to checked, as currently available filaments in market does not have high tenacity value. From EDX reports, 30% inclusion of PLA as replacement for fine aggregate has constituent members as Calcium carbonate(CaCO3), Silica(SiO2) and Wollastonite (CaK) resulted in best composition among the rest. FESEM images revealed that, proper gradation in size, rough surface of PLA granular form or filament form will definitely enhance the mechanical/physical or even chemical behavior of PLA.

As symbionts of fungi and algae, lichens produce a variety of secondary products which pharmacological activities. This study aimed to investigate the anti-inflammatory activities of Heterodermia hypoleuca and its main compound, atraric acid. The results confirmed that atraric acid could regulating induced pro-inflammatory cytokine, nitric oxide, induced nitric oxide synthase and cyclooxygenase-2 expression by lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Means while, atraric acid down-regulated expression of phosphorylated IκB, ERK and nuclear factor kappa B (NFκB) signaling pathway to exhibit anti-inflammatory effects in LPS-stimulated RAW264.7 cells. Based on these results, the anti-inflammatory effect of atraric acid during LPS-induced endotoxin shock in a mouse model was confirmed. In the atraric acid treated-group, cytokine production was decreased in the peritoneum and serum, and each organ damaged by LPS-stimulation was recovered. These results show that atraric acid has an anti-inflammatory effect and its molecular mechanism may be involved in the inactivation of the ERK/NFκB signaling pathway, demonstrating its value as a potential therapeutic for inflammatory diseases.

Gambogic acid, a common traditional Chinese medicine and widely distributed throughout South China, Vietnam, Cambodia, and Thailand. It is prenylated xanthone which is the significant bioactive compound of gamboge. Gambogic acid is known as a strong apoptotic inducer in cancer cells. It has been found as strong anticancer agent against various types of cancer cells lines such as breast cancer, pancreatic, and cervical cancer. It induces apoptosis, down regulates the anti-apoptotic proteins (survivin and BCL2,) and down regulates the activities of P-glycoprotein in drug sensitive human breast MCF-7 and drug-resistant MCF-7/ADR cells. Similarly, it also exerts alteration in P13K, AKT, p21, MMP-2 &-9, and phosphorylated-AKT expressions. The current review highlights the anticancer and chemo-preventive perspectives of gambogic acid and its mechanistic role against human and animal cancers.

Background and objectives: The hepatoprotective activity of vitamin E and C is evident due to their ability of modulating the antioxidant pathway. In this study, we have evaluated the effects of α-tocopherol and ascorbic acid on paracetamol induced liver damage with offsetting various levels of drug treatment following an in vivo experimental protocol on Wistar albino male rats. Materials and Methods: The level of lipid peroxidation as well as histological examination of liver tissues were observed among 50 Wistar albino male rats to evaluate hepatoprotective effect of α-tocopherol and ascorbic acid on hepatocytes. The experiment was divided into 5 groups (10 rats in each group)- Basal control group (Group-I, with propylene glycol), Paracetamol treated control group (Group –II), α-tocopherol pretreated & paracetamol treated group (Group –III), Ascorbic acid pretreated & paracetamol treated group (Group –IV) and Ascorbic acid pretreated & paracetamol treated group (Group –IV). Results: The mean (± SD) Malondialdehyde (MDA) concentration were significantly reduced in α-tocopherol pretreated and paracetamol treated group (P<0.001), Ascorbic acid pretreated and paracetamol treated group (P≤0.05) and combined α-tocopherol with ascorbic acid pretreated & paracetamol treated group (P<0.001). Statistically significant differences in histological findings of rat liver were observed in paracetamol treated control group (P<0.001), ascorbic acid pretreated and paracetamol treated group (P<0.001). The serum alanine aminotransferase (ALT) level was also significantly higher in paracetamol treated group (P<0.001), α-tocopherol pretreated plus paracetamol treated group (P≤0.05) and in ascorbic acid pretreated plus paracetamol treated group (P<0.001). Conclusion: The combined pretreatment of α-tocopherol & ascorbic acid have better hepatoprotective effects than α-tocopherol or ascorbic acid alone against paracetamol induced liver damage. The decrement of free radicals produced by vitamin E could be a better hepatoprotective antioxidant than vitamin C in paracetamol induced toxicity.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel evolutionarily divergent RNA virus etiological agent of COVID-19, is responsible for present devastating pandemic respiratory illness. To explore the genomic signatures, we comprehensively analyzed 2,492 complete and/or near-complete genome sequences of SARS-CoV-2 strains reported from across the globe to the GISAID database up to 30 March 2020. Genome-wide annotations revealed 1,407 nucleotide-level mutations at different positions throughout the entire genome of SARS-CoV-2. Moreover, nucleotide deletion analysis found nine deletions throughout the genome, including in polyprotein (n=6), ORF10 (n=1) and 3´-UTR (n=2). Evidence from the systematic gene-level mutational and protein profile analyses revealed a large number of amino acid (aa) substitutions (n=722), making the viral proteins heterogeneous. Notably, residues of receptor-binding domain (RBD) having crucial interactions with angiotensin-converting enzyme 2 (ACE2), and cross-reacting neutralizing antibody were found to be conserved among the analyzed SARS-CoV-2 strains, except for replacement of Lysine with Arginine at 378 position of the cryptic epitope of a Shanghai isolate, hCoV-19/Shanghai/SH0007/2020 (EPI_ISL_416320). Our method of genome annotation is a promising tool for monitoring and tracking the epidemic, the associated genetic variants, and their implications for the development of effective control and prophylaxis strategy.

Ellagic acid, a polyphenolic compound present in fruits and berries, has recently been object of extensive research for its antioxidant activity, which might be useful for the prevention and treatment of cancer, cardiovascular pathologies, and neurodegenerative disorders. Its protective role justifies numerous attempts to include it in functional food preparations and in dietary supplements not only to limit the unpleasant collateral effects of chemotherapy. However, ellagic acid use as chemopreventive agent has been debated because of its poor bioavailability associated to low solubility, limited permeability, first pass effect, and interindividual variability in gut microbial transformations. To overcome these drawbacks, various strategies for oral administration including solid dispersions, micro-nanoparticles, inclusion complexes, self-emulsifying systems, polymorphs have been proposed. Here, we have listed an updated description of pursued micro/nanotechnological approaches focusing on the fabrication processes and the features of the obtained products, as well as on the positive results yielded by in vitro and in vivo studies in comparison to the raw material. The micro/nano-sized formulations here described might be exploited for pharmaceutical delivery of this active, as well as for the production of nutritional supplements or for the enrichment of novel foods.

A variety of myricetin derivatives bearing ferulic acid amide scaffolds were designed and synthesized. The structures of all title compounds were determined by 1 H NMR, 13 C NMR, 19 F NMR and HRMS. Preliminary bioassays suggested that some of the target compounds exhibited remarkable antiviral activities. In particular, compound 4l possessed significant protection activity against tobacco mosaic virus (TMV), with an half maximal effective concentration (EC50) value of 196.11 μg/mL, which was better than commercial agent ningnamycin (447.92 μg/mL). Meanwhile, microscale thermophoresis (MST) indicated that compound 4l have strong binding capability to tobacco mosaic virus coat protein (TMV-CP) with dissociation constant (Kd) values of 0.34 μmol/L, which was better than ningnamycin (0.52 μmol/L). These results suggest that novel myricetin derivatives bearing ferulic acid amide scaffolds may be considered as an activator for antiviral agents.

Increasing pesticide resistance in plant pathogens is major concern in agriculture production. Research on ecofriendly alternatives of chemical pesticides are more in demand in pesticide industry. In the current study, an ethyl acetate extract from the endophytic fungus Trichoderma sp. EFI 671, isolated from the stem parts of the medicinal plant Laurus sp., was screened for bioactivity against plant pathogens (Fusarium graminearum, Rhizoctonia solani, Sclerotinia sclerotiorum and Botrytis cinerea), insect pests (Spodoptera littoralis, Myzus persicae, Rhopalosiphum padi) and plant parasites (Meloidogyne javanica). The bioactive components have been characterized following a bioassay-guided isolation against M. persicae. The chemical study of this bioactive extract resulted in the isolation of 1-oleoyl-2-linoleoyl-3-palmitoylglycerol (1), eburicol (2), (24R)-stigmast-4-ene-3-one or β-sitostenone (3), ergosterol (4) and ergosterol peroxide (5). The free fatty acids present in compound 1 (oleic, linoleic and palmitic) showed strong dose-dependent aphid antifeedant effects against M. persicae. Liquid (PDB, and SDB) and solid (corn, sorghum, pearl millet and rice) growth media were tested in order to optimize the yield and bioactivity of the fungal extracts. Pearl millet and corn gave the highest extract yields. All the extracts from these solid media had strong effects against M. persicae with sorghum being the most active. Corn increased the content in linolenic, pearl millet the oleic and stearic and sorghum oleic and linolenic acids compared to rice. Their antifeedant effects correlated with linoleic /oleic acids. The phytotoxic effects of these extracts against Lolium perenne and Lactuca sativa varied with culture media, with sorghum being the least toxic.

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.

Adsorption is an effective strategy for the removal of pollutants from the wastewater. Herein, a 2-hydroxyterephthalic acid (HTC) modified hypercrosslinked polymer (HTC-HCP) is successfully synthesized via Friedel-Crafts reactions, and used as an adsorbent for the different types of pollutants including organic contaminants and heavy metal ions from wastewater. Excellent adsorption capacities are observed for amines (aniline, p-methylaniline (p-MA), p-chloroaniline (p-CA), and p-aminobenzoic acid (p-ABA)), phenols (phenol, p-chlorophenol (4-CP) Bisphenol A (BPA), 1-Naphthol (1-NP)), dyes (rhodamine B (RhB) and methyl orange (MO)), and metal ions (Pb2+, Hg2+, and Cd2+). The resulting polymers exhibited excellent adsorption performance towards these pollutants. Especially, the removal rate of aniline is above 95% in the concentration of 2.5 mg/L in 40 min at 25 °C. The interaction mechanism has been investigated, and confirmed by FTIR and the theoretical calculation results. It is due to surface complexation and chemisorption between adsorbent and adsorbate. The polymer exhibits good performance such as high adsorption capacity, high separation efficiency, biodegradable properties, and easy regeneration, suggesting that its potential technological applications for the removal of organic compounds and heavy metal ions from actual industrial effluent.

Bauxite residue is the voluminous by-product of alumina production after Bayer process. Its high alkalinity causes disposal problems and harmful environmental impacts. However, the residue contains significant amounts of valuable elements such as rare earth elements including scandium. Greek bauxite residue contains a high amount of scandium close to its main resources. Taking into account scandium limited availability coupled with its high demand in modern technology, bauxite residue could be considered as a potential resource for scandium recovery. In this study, the optimization of scandium extraction from bauxite residue with sulfuric acid is investigated using Taguchi methodology. Based on previous studies acid molarity, leaching time, solid/liquid ratio and reaction temperature were selected as control parameters for the selective Sc recovery. Method optimization targeted the highest concentration of scandium combined with the lowest concentration of iron without taking into account applications constraints. The predicted values resulted by Taguchi methodology were affirmed by a confirmation experiment conducted at optimal conditions. Regression analysis provided the respective equations to be applied on several conditions depending on different applications.

Background: Diets based on meat products are not recommended in the case of ulcerative colitis (UC). However, some foods, as those containing high oleic acid and a low omega-6/omega-3 ratio show anti-inflammatory properties. The objective here is to test if some traditional cured meat products, as acorn-fed ham (high levels of oleic acid), may be useful for controlling inflammatory diseases as UC in animal models. Methods: 3 rat cohorts have been used: vegetable rat feed, control ham and acorn-fed ham (a traditional ham where high oleic acid concentration from acorns is storage in the muscle fat). UC was induced with DSS in drinking water ad libitum for one week. Short-chain fatty acids (SCFAs) and 16S rRNA from bacterial populations were analyzed in cecum samples. Colon samples were analyzed for histological parameters (inflammatory cell density, mucosa damages, myeloperoxidase). Results: In the acorn-fed ham cohort, a protective effect was observed with respect to UC disease activity index, inflammatory cells density, colon mucosa alterations, myeloperoxidase levels, blood total antioxidant capacity and lower levels of pro-inflammatory cytokines, in comparison with feed cohort. Both ham diets caused a reduction in Firmicutes and an increase in Actinobacteria, Bacteroidetes and Proteobacteria in comparison with rat feed diet. Also, acorn-fed ham diet induced changes in gut microbiota composition, with pronounced enrichments in anti-inflammatory bacterial genera such as Alistipes, Bacteroides, Blautia, Butyricimonas and Parabacteroides. Conclusions: In the acorn-fed ham cohort, as a result of the dietary intake of oleic acid and low intake of omega-6 fatty acids, a strong preventive effect against UC symptoms was observed, indicating a valuable effect of this traditional Mediterranean cured meat product.

The reaction mechanism of the carboxylation of K-2-naphthoxide was investigated by density functional theory calculations and spectroscopic studies. The reaction intermediates and products were confirmed by CO₂ adsorbed-FTIR and ¹H-NMR measurements. Four steps of the reaction pathway were identified: CO₂ activation, electrophilic substitution, CO₂-K complex rearrangement, and H-shift, producing 2-hydroxy-1-naphthoic acid (2,1-HNA), 2-hydroxy-3-naphthoic acid (2,3-HNA), and 2-hydroxy-6-naphthoic acid (2,6-HNA). The occurrence of CO₂-K complex rearrangement was also confirmed. These energy profiles of reaction pathways for the reaction intermediates were well consistent the experimental results on the carboxylation of K-2-naphthoxide.

Sepsis is a devastating disease that carries an enormous toll in terms of human suffering and lives lost. Over 100 novel pharmacologic agents which targeted specific molecules or pathways have failed to improve the outcome of sepsis. Preliminary data suggests that the combination of Hydrocortisone, Ascorbic Acid and Thiamine (HAT therapy) may reduce organ failure and mortality in patients with sepsis and septic shock. HAT therapy is based on the concept that a combination of readily available, safe and cheap agents which target multiple components of the host’s response to an infectious agent will synergistically restore the dysregulated immune response and thereby prevent organ failure and death. This paper reviews the rationale for HAT therapy with a focus on vitamin C.

The energy sensor AMP-activated protein kinase (AMPK) is a key player in the control of energy metabolism. AMPK regulates hepatic lipid metabolism through the phosphorylation of its well-recognized downstream target acetyl CoA carboxylase (ACC). Although AMPK activation is proposed to lower hepatic triglyceride (TG) content via the inhibition of ACC to cause inhibition of de novo lipogenesis and stimulation of fatty acid oxidation (FAO), its contribution to the inhibition of FAO in vivo has been recently questioned. We generated a mouse model of AMPK activation specifically in the liver achieved by expression of a constitutively active AMPK using adenoviral delivery. Indirect calorimetry studies revealed that liver-specific AMPK activation is sufficient to induce a reduction in the respiratory exchange ratio and an increase in FAO rates in vivo. This led to a more rapid metabolic switch from carbohydrate to lipid oxidation during the transition from fed to fasting. Finally, mice with chronic AMPK activation in the liver display high fat oxidation capacity evidenced by increased [C14]-palmitate oxidation and ketone body production leading to reduced hepatic TG content and body adiposity. Our findings suggest a role for hepatic AMPK in the remodeling of lipid metabolism between the liver and adipose tissue.

In the human organism various carotenoids are present of which, some are retinoid precursors. The bioactive derivatives of these retinoids are the retinoic acids, which can potently activate nuclear hormone receptors like the retinoic acid receptor and the retinoid X receptor. In our study using an HPLC analytical approach we aimed to assess how plasma carotenoid and retinoid concentrations along with the ratio of their isomers are altered in atopic dermatitis (AD) patients (n=20) compared to healthy volunteers (HV, n=20). We found that plasma levels of the carotenoids lutein (HV 198 ± 68 ng/ml, AD 158 ± 57 ng/ml), zeaxanthin (HV 350 ± 142 ng/ml, AD 236 ± 85) as well as the retinoids retinol (HV 216 ± 89 ng/ml, AD 167 ± 76 ng/ml) and all-trans-retinoic acid (HV 1.1 ± 0.6 ng/ml, AD 0.7 ± 0.5 ng/ml) were significantly lower in AD-patients, while lycopene, α-carotene and β-carotene levels were comparable. In addition the ratios of 13-cis vs. all-trans lycopene as well as 13-cis vs. all-trans retinoic acid were increased in the plasma of AD-patients indicating an AD-specific 13C-isomerisation. A positive correlation with SCORRAD was calculated with 13-cis vs. all-trans lycopene ratio, while a negative correlation was observed with zeaxanthin plasma levels. Based on our results we conclude that in the plasma of AD-patients various carotenoids and retinoids are at lower levels, while the ratio of lycopene isomers was also altered. The higher rate of lycopene and retinoic acid isomerisation products might be a consequence of AD or might result in an altered activation of nuclear hormone receptor signaling pathways and thus maybe partly be responsible for the AD-phenotype and additionally may represent a good plasma marker for AD.

Saturated fatty acids are implicated in the development of metabolic diseases, including obesity and type 2 diabetes. There is evidence, however, that polyunsaturated fatty acids can counteract the pathogenic effects of saturated fatty acids. To gain insight into the early molecular mechanisms by which fatty acids influence hypothalamic inflammation and insulin resistance, we performed time-course experiments in a hypothalamic cell line, using different durations of treatment with the saturated fatty acid palmitate, and the omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA). Western blot analysis revealed that palmitate elevated the protein levels of phospho(p)AKT in a time-dependent manner. This effect seems involved in the pathogenicity of palmitate, as temporary inhibition of the PI3K/AKT pathway by selective PI3K inhibitors prevented palmitate-induced insulin resistance. Similarly to palmitate, DHA also increased levels of pAKT, but to a weaker extent. Co-administration of DHA with palmitate decreased pAKT close to the basal level after 8 h, and prevented palmitate-induced insulin resistance after 12 h. Measurement of the inflammatory markers pJNK and pNFκB-p65 revealed tonic elevation of both markers in the presence of palmitate alone. DHA alone transiently induced elevation of pJNK, returning to basal levels by 12 h treatment. Co-administration of DHA with palmitate prevented palmitate-induced inflammation after 12 h, but not at earlier time points.

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.

Carbonic Anhydrases (CAs) are a superfamily of metalloenzymes widespread in all life kingdoms, classified into seven genetically different families (α-θ). These enzymes catalyse the reversible hydration of carbonic anhydride (CO2), generating bicarbonate (HCO3-) and protons (H+). Fifteen isoforms of human CA (hCA I-XV) have been isolated, their presence being fundamental for the regulation of many physiological processes. In addition, overexpression of some isoforms has been associated with the outbreak or the progression of several diseases. For this reason, for a long time CA inhibitors (CAIs) are used in the control of glaucoma and as diuretics. Furthermore, the search for new potential CAIs for other pharmacological applications is a very active field. Amino acids constitute the smallest fundamental monomers of protein and, due to their useful bivalent chemical properties, are widely used in organic chemistry. Both proteinogenic and non-proteinogenic amino acids have been extensively used to synthesize CAIs. This article provides an overview of the different strategies that have been used to design new CAIs containing amino acids, and how these bivalent molecules influence the properties of the inhibitors.

Macrophages are cells involved in the primary response to debris derived from wear of implanted CoCr alloys. The biocompatibility of wear particles from a high carbon CoCr alloy produced under polarization in physiological hyaluronic acid (HA) solution was evaluated in J774A.1 mouse macrophages cultures. Polarization was applied to mimic the electrical interactions observed in living tissues. Wear tests were performed in a pin-on-disk tribometer integrating an electrochemical cell in phosphate buffer solution (PBS) and in PBS supplemented with 0.3% HA, physiological synovial fluid concentration, used as lubricant solution. Wear particles produced in 0.3% HA solution showed a higher biocompatibility in J774A.1 macrophages in comparison to those elicited by PBS. A considerable improvement in macrophages biocompatibility in the presence of 0.3 % of HA was further observed by the application of polarization at potentials having current densities typical of injured tissues suggesting that polarization produces an effect on the surface of the metallic material that leads to the production of wear particles that are macrophages biocompatible and less cytotoxic. The results showed the convenience to consider electric interactions together with other particles parameters, as are size and composition, to get a better understanding of the biological effects of the wear products.

Marine water pH is becoming progressively reduced in response to atmospheric CO2 elevation. Considering that marine environments support a vast global biodiversity and provide a variety of ecosystem functions and services, monitoring of the coastal and intertidal water pH assumes obvious significance. Because current monitoring approaches using meters and loggers are typically limited in application in heterogeneous environments and are financially prohibitive, we sought to evaluate an approach to acidification biomonitoring using living gastropod shells. We investigated snail populations exposed naturally to corrosive water in Brunei (Borneo, South East Asia). We show that surface erosion features of shells are generally more sensitive to acidic water exposure than other attributes (shell mass) in a study of rocky-shore snail populations (Nerita chamaeleon) exposed to greater or lesser coastal geochemical acidification (acid sulphate soil seepage, ASS), by virtue of their spatial separation. We develop a novel digital approach to measuring the surface area of shell erosion. Surficial shell erosion of a muddy-sediment estuarine snail, Umbonium vestiarium, is shown to capture variation in acidic water exposure for the timeframe of a decade. Shell dissolution in Neripteron violaceum from an extremely acidic estuarine habitat, directly influenced by ASS inflows, was high variable among individuals. In conclusion, gastropod shell dissolution potentially provides a powerful and cost-effective tool for rapidly assessing marine pH change across a range of spatial and temporal frameworks and coastal intertidal environments. We discuss caveats when interpreting gastropod shell dissolution patterns.

Using the techniques of computer-aided drug design, the docking of Survivin and known active small molecules was simulated and then the key amino acid residue fragment of the target protein was analyzed. It led to the discovery of active groups capable of binding to the critical sites. Through the use of the natural product, Oleanolic Acid, as a lead compound, the introduction of the active groups onto the A-ring, and the modification of the carboxyl group at the C-28 position using esterification or amidation, twenty new Oleanolic acid derivatives had been designed and synthesized.A549 and SGC-7901 cells were used to screen the antitumor activity in vitro through the standard MTT method. The compounds, II₃, III₅ and Ⅳ_4, exhibited more potent cytotoxicity than positive drugs.

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.

Diseases in articular cartilages have affected millions of people globally. Although the biochemical and cellular composition of articular cartilages is relatively simple, there is the limitation in self-repair ability of cartilage. Therefore, developing the strategies for cartilage repair is very important. Here, we reported a new manufacturing process of water-based polyurethane based photosensitive materials with hyaluronic acid and applied the materials for 3D printed customized cartilage scaffolds. The scaffold has high cytocompatibility and is one that closely mimics the mechanical properties of articular cartilages. It is suitable for culturing human Wharton's jelly mesenchymal stem cells (hWJMSCs) and the cells showed an excellent chondrogenic differentiation capacity. We consider that the 3D printing hybrid scaffolds may have potential in customized tissue engineering and facilitate the development of cartilage tissue engineering.

Consumption of refined foods and beverages high in sugar make the teeth susceptible to the formation of biofilm, and lead to dental caries and diseases of the oral cavity such as periodontitis and periodontal disease. The aim of the present study was to determine the ability of selected probiotics to inhibit growth and biofilm formation by the cariogenic bacterium Streptococcus mutans in vitro. We screened strains of latic acid bacteria (LAB) (n=120) from the Bioresources Collection and Research Center (BCRC), saliva of healthy adults and infant stool. The antimicrobial activity of LAB in vitro was evaluated by agar spot culture and co-culture of the S. mutans strains. We determined the effect of heating and dilution factors (2- and 4-fold) on the antagonistic activity of LAB. Antagonistic substances in the spent culture suspensions (SCS) of LAB were precipitated by extraction with ammonium sulphate and chloroform to characterise the protein and lipophilic fractions. Results of co-culturing show that the SCS of the three LAB strains (Lactobacillus pentosus 13-1, 13-4 and Lactobacillus crispatus BCRC 14618) subjected to heat treatment showed significantly high antimicrobial activity. We found that substances produced by L. pentosus 13-4 which have the potential to exhibit antimicrobial properties might be lipophilic proteins. Additionally, we infer that the mechanism of reducing biofilm formation by Lactobacillus strains is associated with sucrose-dependent cell–cell adhesion and the gtfC level of glucosyltransferases (Gtfs) in the biofilm. Native LAB strains screened in our study may be used in chewing gums and other processed foods for preventing tooth decay.

Human milk fat is a concentrated source of energy and provides essential and long chain polyunsaturated fatty acids. According to previous experiments, human milk fat is partially lost during continuous enteral nutrition. However, these experiments were done over relatively short infusion times, and a complete profile of the lost fatty acids was never measured. Whether this lost happens considering longer infusion times or if some fatty acids are lost more than others remain unknown. Pooled breast milk was infused through a feeding tube by a peristaltic pump over a period of 30 minutes and 4, 12 and 24 hours at 2 ml/hour. Adsorbed fat was extracted from the tubes, and the fatty acid composition was analyzed by Gas chromatography-mass spectrometry. Total fat loss (average fatty acid loss) after 24 hours was 0.6 ± 0.1%. Short-medium chain (0.7%, p=0.15), long chain (0.6%, p=0.56) saturated (0.7%, p=0.4), monounsaturated (0.5%, p=0.15), polyunsaturated fatty (0.7%, p=0.15), linoleic (0.7%, p=0.25), and docosahexaenoic acids (0.6%, p=0.56) were not selectively adsorbed to the tube. However, very long chain fatty (0.9%, p=0.04), alpha-linolenic (1.6%, p=0.02) and arachidonic acids (1%, p=0.02) were selectively adsorbed and therefore lost in a greater proportion than other fatty acids. In all cases, the magnitude of the loss was clinically low.

Chatbots have gained widespread popularity for their task automation capabilities and consistent availability in various domains, including education. However, their ability to adapt to the continuously evolving and dynamic nature of knowledge is limited. This research investigates the implementation of an internet wizard to enhance the knowledge base of an open-domain question-answering chatbot. The proposed approach leverages search engines, particularly Google, and its features, including feature snippets, knowledge graph, and organic search, in conjunction with data science and natural language models. This mechanism empowers the chatbot to dynamically access the extensive and up-to-date knowledge available on the web, enabling the provision of real-time and pertinent answers to user queries sourced from web documents. A pilot study in a higher education context evaluated the chatbot's mechanism and features, confirming its proficiency in generating responses across a broad range of educational and non-educational topics. Positive feedback and high user satisfaction validate these findings. Notably, the chatbot's dynamic feature of retrieving related or follow-up questions from search engines significantly enhances student engagement and facilitates exploration of supplementary information beyond the curriculum.