The effects of the ferrocenyl moiety to enhance the nucleophilicity of the carbonyl group, situated at its adjacent position, have been explored in a series of α-ferrocenyl ketocarboxylic acids. In the presence of trifluoroacetic anhydride, 3-ferrocenoylpropionic acid and 4-ferrocenoylbutyric acid gave 5-ferrocenyl-4-trifluoroacetyl-2(3H)-furanone and 6-ferrocenyl-5-trifluoroacetyl-3,4-dihydropyran-2-one, respectively. Under similar reaction conditions, 2-ferrocenylcarbonylbenzoic acid, a keto carboxylic acid without a β-hydrogen, gave a dimerized lactone, 3,3’-diferrocenyl-3,3’-diphthalide possibly due to radical coupling. The nucleophilic attack of carbonyl oxygen, activated by the ferrocenyl moiety, to the carboxylic carbon, is assumed to be the crucial mechanistic step in forming these lactones. When the carbonyl group was reduced to an alcohol to break its conjugation with the ferrocenyl moiety, saturated lactones were isolated after the acidic workup. These results indicate that the α-ferrocenyl carbinols readily undergo solvolysis under acidic conditions, giving ferrocenylcarbenium ions, which are attacked by the carboxy oxygen to give lactones.

Finishing coatings in the wood-based composites industry not only influence the final appearance of the product but also serve to protect against fungi, and molds, and reduce the release of harmful substances, particularly formaldehyde and volatile organic compounds (VOCs). Carbon-rich materials, such as those derived from birch bark extraction, specifically suberin acids, can fulfil this role. Previous research has demonstrated that adding suberin acid residues (SAR) at 20% and 50% by weight significantly enhances the gas barrier properties of surface finishing materials based on poly(lactide) (PLA) and polycaprolactone (PCL), particularly in terms of Total VOC (TVOC) and formaldehyde emissions. This study aims to explore whether these properties can be further improved through the incorporation of nano-zinc oxide (nano-ZnO). Previous research has shown that these nanoparticles possess strong resistance to biological factors and can positively affect the characteristics of nanofilms applied as surface protection. The study employed PLA and PCL finishing layers blended with SAR powder at 10% w/w and included 2% and 4% nano-zinc oxide nanoparticles. The resulting blends were milled to create a powder, which was subsequently pressed into 1 mm thick films. These films were then applied to raw particleboard surfaces. TVOC and formaldehyde emission tests were conducted. Additionally, the fungal resistance of the coated surfaces was assessed. The results showed that PLA/SAR and PCL/SAR composites with the addition of nano-zinc oxide nanoparticles exhibited significantly improved barrier properties, offering a promising avenue for developing biodegradable, formaldehyde-free coatings in the furniture industry with enhanced features. Furthermore, by utilizing SAR as a post-extraction residue, this project aligns perfectly with the concept of upcycling.

Quite a number of cottonseed varieties are existed. The seeds of each variety produce a different amount of gossypol as a natural toxic compound. The increased interest in this natural product and its toxic effects were enhanced the demand for establishing simple silica-gel-based methods for its isolation, purification, and characterization. Historically, silica gel plays a significant role in isolation and purification of many different natural products. Silica gel is variants and can intro-duce a lab, simple tool for tracking a compound in certain plants during its purification process. In this study, gossypol was isolated and purified in the form of yellow crystals as gossypol acetic ac-id. Several methods and tools were used for its characterization including TLC, preparative TLC, silica gel column, UV/IR spectrophotometer and HPLC (Robust spherical silica gel). A compara-tive study between its amounts in both Egyptian and Chinese varieties were performed. Under the experimental condition, the Egyptian cottonseeds contain 8.705 gm/kg, while the Chinese contains 5.395 gm/kg. Thin Layer Chromatography (TLC) had been flourished the science of the phytochemistry and still popular till nowadays and is recommended for fast, accurate, and inex-pensive evaluation and quantification of gossypol. It is recommended to isolate and purify gossy-pol as gossypol acetic acid using optimized combined methods used in this study. Using Silica gel different protocols will assist and facilitate the parallel comparison and save the compact column from any unexpected contaminants during the purification steps. During each step the silica gel itself could be simply removed by paper filtration.

The emergence of drug-resistant strains of M. tuberculosis (Mtb) and the phenomenon of phe-notypic tolerance to drugs challenge the goal of tuberculosis (TB) elimination worldwide. By using the ex vivo cultures of alveolar macrophages obtained from lung tissues of TB patients after intensive antimicrobial chemotherapy before surgery, different subpopulations of multi-drug-tolerant Mtb with a spectrum of phenotypic and growth features were identified in the same TB lesions. Our results indicative of not only passive mechanisms generating nonheritable resistance of Mtb to antibiotics, which are associated mainly with a lack of Mtb growth, but also some active mechanisms of Mtb persistence, such as cell wall and metabolic pathway remod-eling. In one of the subpopulations, non-acid-fast Mtb have undergone significant repro-gramming with the restoration of acid-fastness, lipoarabinomannan expression and replication in host cells of some patients after withdrawal of anti-TB drugs. Our data indicate the universal stress protein Rv2623 as a clinically relevant biomarker of Mtb that have lost acid-fastness in human lungs. The studies of Mtb persistence, dormancy, and resumption and the identification of biomarkers characterizing these phenomena are very important to develop vaccines and drug regimens with the individualized management of patients for overcoming the re-sistance/tolerance crisis in anti-TB therapy.

Iron oxide nanozymes are a form of nanomaterial with both superparamagnetic and enzyme-mimicking properties. Given the multifunctional nature of iron oxide nanozymes, it is attractive for creating iron oxide hybrid nanozymes through biomolecular modifications to imbue with auxillary properties. Such iron oxide hybrid nanozymes can be useful for rapid and cost-effective analysis of circulating tumor nucleic acids (ctNAs) in patient liquid biopsies during minimal residual disease (MRD) monitoring of cancer recurrence. Herein, the use of streptavidin-modified iron oxide hybrid nanozymes is reported for magnetic enrichment and bioelectrocatalytic sensing of three prostate cancer (PCa) ctRNA biomarkers with high detection specificity and sensitivity (10 copies) over an ultrabroad dynamic range (five orders of magnitude). Furthermore, the feasibility of ctRNA analysis for pre- and post-cancer treatment MRD monitoring is demonstrated using PCa urinary liquid biopsy samples.

The Apetala2/ethylene response factor superfamily refers to a group of transcription factors that share a conserved AP2 DNA binding domain. These factors have been found to have different roles in plant responses to both biotic and abiotic stresses. Samples of hexaploid wheat, tetraploid pasta (or durum wheat), and diploid wheat progenitors were selected. The 29 dehydration-responsive element binding transcription factors in these samples were downloaded from NCBI GenBank for six different countries: Iran, China, Italy, France, Afghanistan, and Azerbaijan. The AP2 domain sequences were identified from the dehydration-responsive element binding transcription factors using PROSITE, ProDom, and SMART software. Next, all sequences were aligned using Multalin and Jalview software. The aligned sequences were then analyzed to identify amino acid locations, types, and frequencies. The multiple alignments showed that approximately 76% of the amino acid residues in the AP2 domains are conserved. According to the amino acid analysis, alanine, serine, and glutamic acid are the most abundant amino acids found in three motifs. The performed phylogenetic analysis illustrates the role of geographical effects on the transcription factor sequences of bread wheat in the Middle East. Significant differences were found between Iranian and Chinese transcription factor sequences. Moreover, genetic variation was observed in the transcription factors of Italian sequences found in pasta and wheat progenitors. Motif structures play a critical role in the domain organization of wheat proteins to enhance the characteristics of assorted metabolic pathways. The structure of the AP2 domain was analyzed by several programs, I-TASSER for instance, to identify the α-helix, β-sheets, and the regions of some significant amino acids in the 3-D model.

Industries are required to utilize treatment technologies to reduce contaminants in wastewater prior discharge and valorize by-products to increase sustainability and competitiveness. Most acid leaching gypsum purification studies have obviated the treatment of the highly acidic wastewater produced. In this work, acidic wastewater from acid leaching purification of post-consumer gypsum was treated to recover a valuable solid product and reusable water. The main aims of this work were to determine the impact of recirculating acidic and treated wastewaters on the efficiency of the acid leaching purification process and to valorize the impurities in the wastewater. Samples were characterized through X-ray fluorescence and X-ray diffraction. SimaPro 9.5 and ReCiPe 2016 midpoint method were used for the life cycle assessment of three wastewater management approaches. The reuse of the acidic wastewater did not improve the chemical purity of gypsum. Soluble impurities were precipitated at pH 10.5 as a magnesium-rich gypsum that could be commercialized as fertilizer or soil ameliorant. The alkaline treated water was reused for 6 acid leaching purification cycles without impacting the efficiency of the purification process. An acid leaching-neutralization-filtration-precipitation approach demonstrated superior overall environmental performance. Barriers and enabling measures for the implementation of an in-house wastewater treatment were identified.

1) Background: Recently, illegal abuse of γ-hydroxybutyric acid (GHB) has increased in drug-facilitated crimes, but determination of GHB exposure and intoxication is difficult due to rapid metabolism of GHB. Its biochemical mechanism has not been completely investigated. And metabolomic study by polyamine profile and pattern analyses was not performed in rat urinefollowing intraperitoneal injection with GHB. 2) Methods: Polyamine profiling analysis by gas chromatography-mass spectrometry combined with star pattern recognition analysis was performed in this study. Multivariate statistical analysis was used to evaluate discrimination between control and GHB administration groups. 3) Results: Six polyamines were determined in control, single and multiple GHB administration groups. Star pattern showed distorted hexagonal shapes with characteristic and readily distinguishable patterns for each group. N¹-Acetylspermine (p < 0.001), putrescine (p <0.006), N¹-acetylspermidine (p <0.009), and spermine (p < 0.027) were significantly increased in single administration group but were significantly lower in the multiple administration group than in the control group. N¹-Acetylspermine was the main polyamine for discrimination between control, single and multiple administration groups. Spermine showed similar levels in single and multiple administration groups. 4) Conclusions: The polyamine metabolic pattern was monitored in GHB administration groups. N¹-Acetylspermine and spermine were evaluated as potential biomarkers of GHB exposure and addiction.

Background: Patients with mild cognitive impairment end up progressing to Alzheimer’s disease (AD) leading to straining burden on public health. R. officinalis long been known as the herb of remembrance and can be a potential cognition enhancer for AD. The aims of the review were to summarize the qualitative and quantitative aspects of R.O and its active constituents in enhancing the cognition. MATERIALS AND METHOD Google scholar and PubMed structured search to find relevant studies that assessed the effect of R.O extract or any of its active constituents on cognitive performance in animals. Data extraction: Following information from each included study was extracted: (1) article information (2) characteristics of study animals (3) type of intervention; type, dose, duration, and frequency of administration of R.O (4) type of outcome measure. Data synthesis: Data were analyzed using Review Manager (RevMan 5.3, 2014] and meta-analysis was performed for the outcome measures on all relevant tasks within the included papers by computing the standardized mean difference ps. RESULTS. 23 studies for qualitative and fifteen for meta-analysis were selected. From fifteen included papers, 22 studies with 35 comparisons were meta-analyzed. Effect sizes for intact animals and impaired animals respectively was (mean g and 95% CI 1.19 [0.74, 1.64; 0.57 [0.19,0.96]. The R. officinalis had positive effect on both groups of animals. The subgroup analyses exhibited substantial unexplained heterogeneity between studies. Mechanisms of R.O was anticholinesterase, procholinergic, antioxidant, anti-amyloid, neuroprotective and anti-inflammatory agent CONCLUSIONS: R.O improves cognitive function. Limitations: Considerable heterogeneity between studies.

Over the years influenza B virus (IBV) contribute annual disease and can lead to serious respiratory disease among humans. More attention should be paid to the mammalian adaptive processes of B viruses and development of vaccines against current influenza. Because of preclinical trials of anti-influenza drugs are conducted mainly on mice, we developed adequate animal model using antigenically-relevant IBV strain for testing anti-influenza drugs and protective efficacy of flu vaccines. We serially passaged Victoria lineage (clade 1A) IBV 17 times in BALB/c mice. The adaptive amino acid substitutions were found in HA (T214I) and NA (D432N). By the electron microscopic examination, we showed spherical and elliptical shapes of IBV. Light microscopy showed that mouse-adapted B virus caused influenza pneumonia on day 6 post inoculation. We evaluated the illness pathogenicity, viral load and histopathological features of mouse-adapted IBV and estimated anti-influenza drugs and vaccine efficiency in vitro and in vivo. Assessment of investigational anti-influenza drug oseltamivir ethoxisuccinate and flu vaccine Ultrix® revealed effectivity against our mouse-adapted influenza B virus.

The single set of electron transporters of the cardiac mitochondrial respiratory chain is organized into three separate supercomplexes. Two of them contain complex I, a dimer of complex III, and two dimers of complex IV. The third supercomplex contains a dimer of complex III and two dimers of complex IV. We also considered two important discoveries. First, the enzymes of β-oxidation of fatty acids are physically associated with respirasome. Second, β-oxidation of fatty acids creates the highest level of QH2 and reverses the flow of electrons from QH2 through complex II, reducing fumarate to succinate. We argue that the respirasome is uniquely adapted for the β-oxidation of fatty acids. The acyl-CoA dehydrogenase complex reduces the membrane’s pool of ubiquinone to QH2, which is instantly oxidized by the 2complex III-4complex IV supercomplex, generating high energization of mitochondria and reversing the electrons flow through the complex II, which reverses the electrons flow through the complex I increasing the NADH/NAD+ ratio in the matrix. The mitochondrial nicotinamide nucleotide transhydrogenase catalyzes a hydride (H-, a proton plus two electrons) transfer across the inner mitochondrial membrane, reducing the cytosolic pool of NADP(H), thus providing the heart with ATP for muscle contraction and energy and reducing equivalents for the housekeeping processes.

During the last decades, zebrafish (Danio rerio) has become one of the most important model organisms to study different physiological and biological phenomena. Research field of carbonic anhydrases (CAs) and carbonic anhydrase related proteins (CARPs) is not an exception in this. The best-known known function of CAs is the regulation of acid-base balance. However, studies performed with zebrafish, among others, have revealed important roles for these proteins in many other physiological processes, some of which have been unpredicted in the light of the previous studies and suggestions. Examples are roles in zebrafish pigmentation as well as motor coordination. Disruption of the function of these proteins may generate even lethal outcomes. In this review, we summarize the current knowledge of CA-related studies performed in zebrafish.

Probiotics make up a large and growing segment of the commercial market of dietary supplements and are touted as offering a variety of human health benefits. Some of the purported positive impacts of probiotics include, but are not limited to, stabilization of the gut microbiota, prevention of gastrointestinal disorders and modulation of the host immune system. Current research suggests that the immunomodulatory effects of probiotics are strain specific and vary in mode of action. Here, we examined the immunomodulatory properties of Bacillus subtilis strain DE111 in a healthy human population. In a randomized, double blind, placebo-controlled four-week intervention, we examined peripheral blood mononuclear cells (PBMCs) at basal levels pre- and post-treatment as well as in response to stimulation with bacterial lipopolysaccharide (LPS). We observed an anti-inflammatory effect of B. subtilis, manifested as a decrease in immune cell populations within the basal state along with an increase in anti-inflammatory immune cells in response to LPS stimulation. Overall gastrointestinal health, microbiota, and circulating and fecal markers of inflammation and gut barrier function were largely unaffected by DE111 treatment. These data suggest that the novel probiotic B. subtilis DE111 may have clinical applications in modulating immune homeostasis via anti-inflammatory mechanisms.

The bioactivities of collagen-hydrolysates, sulfated glucosamine and a special fatty acid enriched dog-food were tested in a dog patient study as potential therapeutic treatment options in early osteoarthritis. Biophysical, biochemical, cell biological and molecular modeling methods support that these well-defined substances may act as effective nutraceuticals. Importantly, the applied collagen-hydrolysates as well as sulfated glucosamine residues from marine organisms were strongly supported by both an animal model and molecular modeling of intermolecular interactions. Molecular modeling of predicted interaction dynamics were evaluated for the receptor proteins MMP-3 and ADAMTS-5. These proteins play a prominent role in the maintenance of cartilage health as well as innate and adapted immunity. Nutraceuticals data were generated in a veterinary clinical study focusing on mobility and agility. Specifically, key clinical parameters were obtained from blood probes of German shepherd dogs with early osteoarthritis symptoms fed with collagen-hydrolysates or sulfated glucosamines. Collagen-hydrolysate, a chondroprotective food supplement was examined by high resolution NMR experiments. Molecular modeling simulations were used to further characterize the interaction potency of collagen-fragments and glucosamines with protein receptor structures. Potential beneficial effects of collagen-hydrolysates, sulfated glycans (i.e. sulfated glucosamine from crabs and mussels) and lipids, especially, eicosapentaenoic acid (extracted from fish oil) on biochemical and physiological processes are discussed here in the context of human and veterinary medicine.

The objective of this study was to evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis compared to standard pathological ultrastaging in patients with early-stage endometrial cancer (EC). A total of 526 SLNs from 191 patients with EC were included in the study. 379 SLNs (147 patients) were evaluated by both methods, OSNA and standard pathological ultrastaging. The central 1-mm portion of each lymph node was subjected to semi-serial sectioning at 200-μm intervals and examined by hematoxylin-eosin and immunohistochemistry with CK19; the remaining tissue was analysed by OSNA for CK19 mRNA. The OSNA assay detected metastases in 19.7% of patients (14.9% micrometastasis and 4.8% macrometastasis), whereas pathological ultrastaging detected metastasis in 8.8% of patients (3.4% micrometastasis and 5.4% macrometastasis). Using the established cut-off value for detecting SLN metastasis by OSNA in EC (250 copies/μl), the sensitivity of the OSNA assay was 92%; specificity was 82%; diagnostic accuracy was 83%, and the negative predictive value was 99%. Discordant results between both methods were recorded in 20 patients (13.6%). OSNA resulted in an upstaging in 12 patients (8.2%). OSNA could aid in the identification of patients requiring adjuvant treatment at the time of diagnosis.

In the literature, the chemical composition of Rhododendron tomentosum is mainly represented by the study of isoprenoid compounds of essential oil. In contrast, the study of the content of flavonoids will contribute to the expansion of the pharmacological action and the use of the medicinal plant for medical purposes. The paper deals with the technology of extracts from Rhododendron tomentosum shoots using ethanol of various concentrations and purified water as an extractant. Extracts from Rhododendron tomentosum were obtained by a modified method that combined the effects of ultrasound and temperature to maximize the extraction of biologically active substances from the raw material. By the method of high-performance thin-layer chromatography in the system of solvents ethyl acetate: formic acid: water (15:1:1) the following substances have been separated and identified: rutin, hyperoside, quercetin, and chlorogenic acid in all the extracts obtained. To quantify the total flavonoids content, a method of spectrophotometric determination based on the reaction of complexation with aluminum chloride has been developed. It has been proved that the course of the complexation reaction and, accordingly, the quantification of the flavonoid structure substances by the spectrophotometric method is influenced by some factors, including the environment, pH, the structure of the complexes, etc. Regardless of the chosen method, for the further production of Rhododendron tomentosum extracts with a higher content of flavonoid structure substance, it is advisable to use 60%, 70%, and 80% ethyl alcohol as extractant.

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

Hyperuricemia (HU), characterized by elevated uric acid (UA) levels in the blood, represents a global health concern associated with various conditions, including cardiovascular diseases, gout, hypertension, metabolic syndrome, renal dysfunction, and neurodegenerative diseases. This review offers a contemporary analysis of HU, encompassing its causes, associated health risks, diagnosis, treatment, and future outlook. Recent studies have underscored the multifaceted origin of HU, implicating genetic predisposition, dietary patterns, lifestyle choices, and environmental influences. Genetic variations affecting enzymes and transporters involved in purine metabolism and UA excretion have been identified, laying the groundwork for personalized treatment strategies. Advances in diagnostic imaging and omics technologies provide enhanced precision in the detection and evaluation of risks. While pharmacological interventions remain central to managing HU, persistent challenges such as treatment resistance prompt exploration of novel drug targets and lifestyle modifications. Chinese herbal medicines offer a potentially alternative approach with fewer side effects. Emerging research on the impact of gut microbiota on UA metabolism opens new therapeutic avenues. Despite progress, challenges such as optimizing treatment duration and understanding long-term effects persist. Collaborative efforts are crucial to address these challenges and advance our comprehension of HU. The integration of precision medicine and holistic patient care approaches holds promise for improving outcomes and enhancing quality of life for individuals with HU.

Heat-stressed lactating dairy cattle exhibit unique metabolic symptoms; many of which are undoubtedly involved in heat-induced subfertility. Because of its known systemic effects, we hypothesized that γ-aminobutyric acid (GABA) participates in the regulation of insulin and progesterone during heat stress. Multiparous lactating Holstein cows (n=6) were studied during four experimental periods: 1) thermoneutral (TN; d 1-5), 2) TN + hyperinsulinemic-hypoglycemic clamp (d 6-10), 3) heat stress (HS; d 16-20), and 4) HS + euglycemic clamp (d 21-25). Blood samples were collected once daily via coccygeal venipuncture into heparinized evacuated tubes. Analysis of GABA concentrations from all four treatment periods yielded no differences. In direct comparison to TN concentrations, plasma GABA tended to be decreased during HS (16.57±2.64 vs 13.87±2.28 ng/ml, respectively, P = 0.06). Both milk production and plasma insulin were moderately correlated with plasma GABA (r=0.35, P<0.01; r = -0.32, P<0.01). Plasma progesterone was correlated with plasma GABA concentrations during TN but not HS. These results are the first to indicate that peripheral GABA could be involved in regulating aspects of production and reproduction during heat stress. More research is needed to determine its precise role(s).

Layered double hydroxides (LDHs) have emerged as promising catalysts for various acid-base catalytic reactions. Due to their unique structure and regulatable dual acid-base properties, they offer more environmentally friendly and sustainable alternatives to traditional liquid acid and base catalysts. This study introduces the structural composition, preparation methods, and acid-base catalytic properties of LDHs-based catalysts. Recent application progress of LDHs and rehydrated LDHs, LDHs-based metal nanocatalysts, and LDHs-based mixed metal oxide catalysts used as solid acid-base catalysts in acid-base green catalytic conversion is reviewed. The challenges and prospects of LDHs-based catalysts as green and sustainable catalysts are summarized and proposed.

The phenomenon of decreased serum uric acid (UA) levels in patients with Parkinson’s disease (PD) and its relationship with purine metabolic pathways remain unclear. We compared inosine, hy-poxanthine, xanthine, and UA levels in serum and cerebrospinal fluid (CSF) of PD patients with those of controls, and investigated the effect of changes in the purine metabolic system on UA levels in PD. Overall, 134 samples (serum, 45 PD patients and 30 controls; CSF, 39 PD patients and 20 controls), were analyzed using liquid chromatography-tandem mass spectrometry. A general linear model (GLM) was used to investigate relationships among purine metabolites. Compared to controls, PD patients had significantly lower UA levels in the serum and CSF, and serum and CSF UA levels were significantly correlated. Additionally, in PD, decreased serum hypoxanthine levels were observed with decreased CSF inosine and hypoxanthine levels, suggesting the involvement of the purine recycling system. GLM analysis indicated that the reduced UA levels in PD were mainly due to sources other than the purine metabolic system, such as exercise, nutritional indices, muscle volume, or adipose tissue. Our results highlight the impairment of purine recycling pathways in PD, as evidenced by the decreased serum hypoxanthine and CSF inosine.

This paper presents the use of Graph Neural Networks (GNNs) to predict the tensile strength of Fused Deposition Modeling (FDM) specimens. In the present work, there are four main input parameters i.e. Infill percentage, Layer height, Print speed and Extrusion temperature while the Tensile Strength is an output parameter were considered. This study includes use of central composite design based response surface methodology to finalize the experimental layout. 3D printed specimen were manufactured as per the ASTM E8 standard on FDM printer using Polylactic Acid (PLA) as filament. Micro-tensile test were performed on the printed specimen as per ASTM E8 standard. The GNN algorithm was trained on a dataset of FDM specimens, achieving a mean squared error (MSE) of 2.47, mean absolute error (MAE) of 1.14, and R-squared value of 0.78. An adjacency matrix, which shows the connections between nodes in a graph. The obtained plot for nodes and weights in a GNN provide valuable information about the model and its performance. The results show the potential of using GNNs in predicting the mechanical properties of additively manufactured specimens and provide a promising direction for further research in this field.

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

N'-(5-bromofuran-2-carbonyl)isonicotinohydrazide (1) was obtained as a white solid in 83% yield by 2-methyl-6-nitrobenzoic anhydride (MNBA)/4-dimethylaminopyridine (DMAP)-catalyzed reaction of 5-bromofuran-2-carboxylic acid and isoniazid in dichloromethane at room temperature. The structure of N'-(5-bromofuran-2-carbonyl)isonicotinohydrazide (1) was elucidated by 1H NMR, 13C NMR, FTIR, and the high resolution mass spectrometers. Molecular docking screening of the title compound (1) on the cyclooxygenase-2 (COX-2) protein (PDB ID: 5IKR) exhibited that compound (1) has a good binding affinity, suggesting that it is very interesting for further structure optimization and in-depth research as a potential COX-2 inhibitor.

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

Platelet and fibrin-rich orthobiologic products, such as autologous platelet concentrates, have been extensively studied and appreciated for their beneficial effects in multiple conditions. PRP and its derivatives, including PRF, have demonstrated encouraging outcomes in clinical and laboratory settings, particularly in the treatment of musculoskeletal disorders such as OA. Although PRP and PRF have distinct characteristics, they share similar properties. The relative abundance of platelets, peripheral blood cells and molecular components in these orthobiologic products stimulate numerous biological pathways. These include inflammatory modulation, augmented neovascularization, and delivery of pro-anabolic stimuli that regulate cell recruitment, proliferation, and differentiation. Furthermore, the fibrinolytic system, which is sometimes overlooked, plays a crucial role in musculoskeletal regenerative medicine by regulating proteolytic activity and promoting the recruitment of inflammatory cells and MSCs in areas of tissue regeneration, such as bone, cartilage, and muscle. PRP acts as a potent signaling agent; however, it diffuses easily, while the fibrin from PRF offers a durable scaffolding effect that promotes cell activity. The combination of fibrin with hyaluronic acid, another well-studied orthobiologic product, has been shown to improve its scaffolding properties, leading to more robust fibrin polymerization. This supports cell survival, attachment, migration, and proliferation. Therefore, the administration of the "power mix" containing HA and autologous PRP + PRF may prove to be a safe and cost-effective approach in regenerative medicine.

The fall armyworm (FAW), Spodoptera frugiperda, has become one of the most important pests on corn in China since it invaded in 2019. Although FAW has not been reported to cause widespread damage to rice plants in China, it has been sporadically found feeding in the field. If FAW infests rice in China, the fitness of other insect pests on rice may be influenced. However, how FAW and other insect pests on rice interact remains unknown. In this study, we found that the infestation of FAW larvae on rice plants prolonged the developmental duration of the brown planthopper (BPH, Nilaparvata lugens (Stål)) eggs, and plants damaged by gravid BPH females did not induce defenses that influenced the growth of FAW larvae. Moreover, co-infestation by FAW larvae on rice plants did not influence the attractiveness of volatiles emitted from BPH-infested plants to Anagrus nilaparvatae, an egg parasitoid of rice planthoppers. FAW larvae were able to prey on BPH eggs laid on rice plants and grew faster compared to those larvae that lacked available eggs. Studies revealed that the delay in development of BPH eggs on FAW-infested plants was probably related to the increase in levels of jasmonoyl-isoleucine, abscisic acid and the defensive compounds in the rice leaf sheaths on which BPH eggs were laid. These findings indicate that if FAW invades rice plants in China, the population density of BPH may be decreased by intraguild predation and induced plant defenses, whereas the population density of FAW may be increased.

Human metapneumovirus is one of major causes of common cold among children, especially infants. Its key enzyme is RNA-dependent RNA-polymerase, which performs both replication and transcription, including capping and cap methylation. The goal of the work is to find possible inhibitors of RNA-dependent RNA-polymerase across the active compounds of Rosaceae plants. The candidates were selected by molecular docking to cap-transferring domain of RNA-polymerase (PDB ID: 4UCZ) in Autodock VINA. Among all the substances tested by docking, ellagic acid derivatives showed the most promising results (affinity values below -10 kcal/mol). Hence, they could be treated as possible candidate drugs against metapneumoviral infection after experimental examination. The main advantage of using these substances should be their low toxicity, which is quite uncommon for selective RNA polymerase inhibitors used in clinical practice. Occurrence of ellagic acid derivatives among the plants from Rosaceae family like raspberry could explain their effect during common cold.

Recurrent hypoglycaemia, a common side-effect of insulin therapy in the treatment of type 1 diabetes, induces impaired glucose-sensing. Better understanding of how astrocytes, important non-neuronal cells in the brain, function in low glucose environments may improve our understanding of recurrent hypoglycaemia-induced defective counterregulation. Astrocytes contribute to glutamatergic signalling, which is required for hypoglycaemia counterregulation and is impaired by recurrent insulin-induced hypoglcyaemia. This study examined the glutamate response of astrocytes when challenged with acute and recurrent low glucose (RLG) exposure. The metabolic responses of cortical (CRTAS) and hypothalamic (HTAS) primary rat astrocytes were measured in acute and recurrent low glucose using extracellular flux analyses. RLG caused mitochondrial adaptations in both HTAS and CRTAS, many of which were attenuated by glutamate exposure during low glucose treatments. We observed an increase in capacity of HTAS to metabolise glutamine after RLG exposure. Demonstrating astrocytic heterogeneity in the response to LG, CRTAS increased cellular acidification, a marker of glycolysis in LG, whereas this decreased in HTAS. The directional change in intracellular Ca2+ levels of each cell type, correlated with the change in extracellular acidification rate (ECAR) during LG. Further examination of glutamate-induced Ca2+ responses in low glucose treated CRTAS and HTAS identified sub-populations of glucose-excited- and glucose-inhibited-like cells with differing responses to glutamate. Lastly, release of the gliotransmitter ATP by HTAS was elevated by RLG, both with and without concurrent glutamate exposure. Therefore, hypothalamic astrocytes adapt to RLG by increasing glutamate uptake and oxidation in a manner that attenuates RLG-induced mitochondrial adaptations.

Malaria rapid diagnosis test (RDT) is crucial for managing the disease, and the effectiveness of detection depends on parameters such as sensitivity and specificity of the RDT. Several factors can affect the performance of RDT. In this study, we focus on pfhrp2 sequence variation and its impact on RDTs targeted by antigens encoded by pfhrp2. Field samples collected during cross-sectional surveys in Tanzania were sequenced to investigate pfhrp2 sequence diversity and evaluate the impact on HRP2-based RDT performance. We observed significant mean differences in amino acid repeats between current and previous studies. Several new amino acid repeats were found to occur at different frequencies, including types AAY, AHHAHHAAN and AHHAA. Based on the abundance of types 2 and 7 amino acid repeats, the binary predictive model was able to predict RDT insensitivity by about 69 % in the study area. About 85% of the major epitopes targeted by Monoclonal antibodies (MAbs) in RDT were identified. Our study suggests that the extensive sequence variation in the pfhrp2 could contribute to reduced RDT sensitivity. The correlation between the different combinations of amino acid repeats and the performance of RDT in different malaria transmission settings should be investigated further.

The interrelationship between periodontal disease, obesity-related hyperlipidemia and mechanical forces as well as their modulating effects on the epigenetic profile of periodontal ligament (PdL) cells are assumed to be remarkably complex. The PdL serves as connective tissue between teeth and alveolar bone for pathogen defense and inflammatory response to mechanical stimuli occurring during tooth movement. Altered inflammatory signaling could promote root resorption and tooth loss. Hyperinflammatory COX2/PGE2 signaling was reported for human PdL fibroblasts (HPdLF) concomitantly stressed with P. gingivalis lipopolysaccharides and compressive force after exposure to palmitic acid (PA). The aim of this study was to investigate to what extent this is modulated by global and gene-specific changes in histone modifications. Quantitative expression of epigenetic key players and global H3Kac as well as H3K27me3 levels were evaluated in dual stressed HPdLF exposed to PA revealing a decreased force-related reduction in repressive H3K27me3. UNC1999-induced H3K27me3 inhibition reversed the hyperinflammatory response of dual-stressed PA-cultures characterized by COX2 expression, PGE2 secretion and THP1 adhesion. Reduced expression of the anti-inflammatory cytokine IL10 and increased association of H3K27me3 at its promoter-associated sites were reversed by inhibitor treatment. Thus, the data highlight an important epigenetic interplay between different stimuli to which the PdL is exposed.

Fatty acids (FFAs) are important biological molecules that serve as a major energy source and are key components of biological membranes. Besides, FFAs play important roles in metabolic regulation and contribute to the development and progression of metabolic disorders like diabetes. Recent studies have shown that FFAs can act as important ligands of G-protein coupled receptors (GPCRs) on the surface of cells and impact key physiological processes. Free fatty acid activated receptors include FFAR1 (GPR40), FFAR2 (GPR43), FFAR3 (GPR41) and FFAR4 (GPR120). FFAR2 and FFAR3are activated by short chain fatty acids like acetate, propionate and butyrate whereas FFAR1 and FFAR4 are activated by medium and long chain fatty acids like palmitate, oleate, linoleate and others. FFARs have generated considerable attention over the last few years and have become attractive pharmacological targets in the treatment of type 2 diabetes and metabolic syndrome. Several lines of evidence point to their importance in the regulation of whole-body metabolic homeostasis including adipose metabolism. Here we summarize our current understanding of the physiological functions of FFAR isoforms in adipose biology and explore the prospect of FFAR based therapies to treat patients with obesity and Type 2 Diabetes.

High-level quantum-chemical computations (G4MP2) are carried out in the study of complexes featuring tetrel bonding between the carbon atom in the carbenoid CB11H11 - obtained by hydride removal in the C-H bond of the known closo-monocarbadodecaborate anion CB11H12() and acting as Lewis acid (LA) - and Lewis bases (LB) of different type; the electron donor groups in the tetrel bond feature carbon, nitrogen, oxygen, fluorine, silicon, phosphorus, sulphur and chlorine atomic centers in neutral molecules as well as anions H(-), OH(-) and F(-). The empty radial 2pr vacant orbital on the carbon center in CB11H11 , which corresponds to the LUMO, acts as a Lewis acid or electron attractor, as shown by the molecular electrostatic potential (MEP) and electron localization funcion (ELF). The thermochemistry and topological analysis of the complexes {CB11H11:LB} are comprehensively analyzed, and classified according to sharing or closed-shell interactions. ELF analysis shows that the tetrel C···X bond ranges from very polarised bonds, as in H11B11C:F() to very weak interactions as in H11B11C···FH and H11B11C···O=C=O.

Introduction: Valproic acid (VPA) is an antiepileptic drug extensively used for treating partial and generalised seizures, acute mania and as prophylaxis for bipolar disorder. Drug-induced liver injury (DILI) persists as a significant issue related to fatal outcomes by VPA. The aim of this study was to increase our knowledge about this condition and to better identify patients affected. Methods: We conducted an observational retrospective case-control study that identified cases of DILI by VPA from the Pharmacovigilance Programme from our Laboratory Signals at La Paz University Hospital from January 2007 to December 2019. From the Therapeutic VPA Monitoring Programme, two control groups were assigned, VPA-tolerant patients and the other with patients who developed mild VPA-related hepatitis but who did not meet the DILI criteria, matched for date, age and sex. Results: A total of 60 patients were included in the study: 15 cases of DILI, 30 VPA-tolerant controls and 15 controls with mild hepatitis. Mean age for the cases was 45.7 years, 4(26.7%) were women and 5(33.34%) were children under 18 years, of them 3(20%) were fatal. Polytherapy with other antiepileptic drugs (p=0.047) and alcohol consumption (p<0.001) were associated with a greater risk of developing DILI by VPA. A diagnosis of epileptic seizure was more frequently related to DILI when compared with the VPA-tolerant controls (p<0.001). The cases developed hepatocellular hepatitis (p<0.001), while the mild hepatitis controls had a higher rate of cholestatic hepatitis (p<0.001). The laboratory lactate dehydrogenase values were statistically higher (even at baseline) in patients with DILI than in both control groups (p= 0.033 and p=0.039). Conclusions: VPA hepatotoxicity remains a considerable problem. This study offers interesting findings for characterising VPA-induced liver injury and at-risk patients.

Objectives To determine the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA) from animal and plant sources on glucolipid metabolism and lipoprotein subfractions in type 2 diabetic patients with dyslipidemia. Methods Participants were recruited from the diabetes clinic at the Guanlin Hospital, Yixing City in Jiangsu province, China, from March 2017 through June 2017. Ninety participants were randomly assigned to take 3g/day fish oil (FO, containing EPA and DHA), 3g/day perilla oil (PO, containing ALA), or 3g/day blend oil containing fish oil and linseed oil (BO, containing EPA, DHA and ALA) for 3 months. The levels of serum glucose, glycated hemoglobin (HbA1c), C-peptide, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-HDL, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), lipoprotein a (Lp(a)), and free fatty acids were determined at baseline and after the 3 months. In addition, four fatty acids in serum and red blood cells membranes (RBCm) were analyzed using gas chromatography-mass spectrometry. The Lipoprint System was used to determine the lipoprotein subfractions. Results All 90 participants completed the final 3-month follow-up at the end of the study. After three months of intervention, blood glucose and HbA1c levels in the PO group were significantly lower than those at the baseline (p < 0.05). On the other hand, in the BO group, the HbA1c, non-HDL, Apo A1 and Lp(a) levels were significantly lower, while the C-peptide levels were significantly higher after intervention compared to the baseline (p < 0.05). In the FO group, the HbA1c and TG levels were significantly lower after the intervention compared to the baseline (p < 0.05). In addition, at the end of the study, there was significant increase in the levels of DPA and DHA in serum and RBCm of the FO group (p < 0.05), while in the BO group, there was significant increase in the levels of EPA, DPA and DHA in RBCm (p < 0.05). Finally, the FO group had the highest levels of large HDL subfractions compared to the BO and PO groups, but had the lowest levels of small HDL subfractions among the three groups. Conclusion For patients with diabetes, plant-derived ω-3 PUFAs are more effective at controlling blood glucose than animal-derived ω-3 PUFAs. However, animal-derived ω-3 PUFAs play a critical role in controlling blood lipids. Particularly, fish oil can effectively increase the beneficial large HDL subfractions and reduce the nonbeneficial small HDL subfractions. Both the animal- and plant-derived ω - 3 PUFAs have practical value in improving glucose and lipids metabolism in T2DM patients with dyslipidemia.

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

The aim of this research was to test recent developments in the use of Remotely Piloted Aircraft Systems or Unmanned Aerial Vehicles (UAV) to map pasture biomass yield and nutrient status, across a selected range of field sites throughout the rangelands of Queensland. Improved pasture management begins with an understanding of the state of the resource base, UAV based methods can potentially achieve this at improved spatial and temporal scales. This study developed predictive models of both pasture yield and pasture nutrient status. An automated pasture height surface modelling technique was developed, tested and used along with field site measurements of pasture yields, to predict further estimates across each field site. Both prior knowledge and automated predictive modelling techniques were employed to predict pasture yield and nutrition. Pasture height surface modelling was assessed against field measurements using a rising plate meter, results reported correlation coefficients (R2) ranging from 0.2 to 0.4 for both woodland and grassland field sites. Accuracy of the predictive modelling was determined from further field measurements of pasture yield and on average indicated an error of 0.8 t ha-1 in grasslands and 1.3 t ha-1 in mixed woodlands across both modelling approaches. Correlation analyses between measures of pasture quality, acid detergent fibre and crude protein (ADF, CP), and spectral reflectance data indicated the visible red (651 nm) and red-edge (759 nm) regions were highly correlated (ADF R2 = 0.9 and CP R2 = 0.5 mean values). These findings agreed with previous studies linking specific absorption features with grass chemical composition. These results conclude that the practical application of such techniques, to efficiently and accurately map pasture yield and quality, is possible at the field site scale, however further research is needed, in particular further field sampling of both yield and nutrient elements across such a diverse landscape, with the potential to scale up to a satellite platform for broader scale monitoring.

SARS-CoV2 RNA depended RNA polymerase is an essential enzyme for the survival of the virus in hosts as it helps in the replication of viral RNA. There are no human polymerases that share either sequence or structural homology with viral RNA depended RNA polymerase. These make it a good target for inhibitor discovery, as a specific inhibitor cannot cross-react with the human polymerases. We have used virtual screening, docking, binding energy calculation and simulation to show that valproic acid Co-A, a metabolite from prodrug valproic acid, forms stable interaction with nsP12 of CoV. Our results suggest valproic acid Co-A could be a potential inhibitor of nsP12 of SARS-CoV2.

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

Metal, primarily Fe and Zn, deficiencies affect over half of the world's population. Human diets with prevalent cereal products cause micronutrient malnutrition. Biofortification is one of the most effective approaches to alleviate malnutrition. Spring wheat genetically stable (M7) mutant lines developed with 100 and 200 Gy gamma treatments to broaden genetic variation and search for new resources were analyzed for nutritionally important minerals (Ca, Mg, K, Fe, and Zn), their bioavailability, and grain protein content (GPC). The variation was 172.3–883.0 mg/kg for Ca, 472.9–1088 mg/kg for Mg, 3128.6–5487.5 mg/kg for K, 40.9–89.0 mg/kg for Fe, and 22.2–89.6 mg/kg for Zn. In mutant lines, among the investigated minerals, the highest increases in concentrations were observed in Fe, Zn, and Ca when compared to the parent. Some mutant lines, mostly in the 100 Gy-derived germplasm, had two to three times higher Fe, Zn, and Ca concentrations, lower phytic acid concentration (1.4–2.1 times), and 6.5–7% higher GPC compare to the parent. Variation was detected for the Ca:Phy, Mg :Phy, Phy:K, Phy:Fe, and Phy:Zn molar ratios, (1.27–10.41, 5.05–18.68, 1.66–4.87, 1.40–5.32 and 1.78–11.78, respectively). The results showed how the genetic variation could be generated through radiation and be useful to develop biofortification by micronutrient varieties with their appropriate bioavailability to overcome malnutrition.

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

The lactic acid bacteria (LAB) have great potential to produce homoexopolysaccharides (HoPS), have been the subject of extensive research efforts, given their health benefits and physicochemical properties. The HoPS functional properties are determined by structural characteristics of varied molecular weights, types of glycosidic linkages, degrees of branching and chemical composition. The dextransucrases (DSases) are responsible of the synthesis of a kind of HoPS (dextran polymers), which are among the first biopolymers produced at industrial scale with applications in medicine and biotechnology. The concept of glycodiversification opens additional applications for DSases. In that sense the design and characterization of new DSases is of prime importance. Previously, we described the isolation and characterization of a novel extracellular dextransucrase (DSR-F) encoding gene. In this study, from DSR-F, we design a novel chimeric dextransucrase DSR-F-∆SP-∆GBD-CBM2a, where DSR-F-∆SP-∆GBD is fused to the carbohydrate-binding module (CBM2a) of the β-1-4 exoglucanase/xylanase Cex (Xyn10A) of Cellulomonas fimi ATCC 484. This dextransucrase variant is active and without alteration in its specificity. The DSR-F-∆SP-∆GBD-CBM2a is purified by cellulose affinity chromatography for the very first time. Our results indicate that new hybrids and chimeric DSases with novel binding capacity to cellulose can be designed to obtain glyco-biocatalysts from renewable lignocellulosic materials.

The recent outbreak of coronavirus disease 2019 caused by the new coronavirus, SARS-CoV-2, has become an international emergency. Since there is no effective therapy for the treatment of this disease, drugs or vaccine that can prevent or cure the SARS-CoV-2 infection are urgently needed. The viral 3-chymotrypsin-like cysteine protease (3CLpro), which plays a key role in the replication of coronavirus, is a potential drug target for the development of anti-SARS-CoV-2 drugs. With the crystal structure of 3CLpro, we performed virtual screening from a small chemical library of a Traditional Chinese Medicine recipe- FuFang Zhenzhu Tiaozhi (FTZ). Five compounds with the best scores were screened and could be considered as potential hit compounds to be investigated further with bioassays for their anti-virus effects.

Ferulic acid esters have been suggested as a group of natural chemicals with sunscreen function. The study aimed to utilize an environment-friendly enzymatic method to produce octyl ferulate by esterification of ferulic acid with octanol. The Box-Behnken design with response surface methodology (RSM) was adopted to evaluate the effects of synthesis variables, including reaction temperature (70–90 °C), enzyme amount (1000–2000 PLU) and stir speed (50–150 rpm), on the molar conversion of octyl ferulate. According to the joint test, both the reaction temperature and enzyme amount had great impacts on the molar conversion. RSM-developed second-order polynomial equation further showed great ability on data-fitting. Based on ridge max analysis, the optimum parameters for the biocatalyzed reaction were: 72 h reaction time, 92.2 °C reaction temperature, 1831 PLU enzyme amount and 92.4 rpm stir speed, respectively. Finally, the molar conversion of octyl ferulate under optimum condition was verified to be 93.2 ± 1.5%. In conclusion, high yield of octyl ferulate synthesized by commercial immobilized lipase under elevated temperature conditions has been suggested, which our findings could broaden the utilization of the lipase and provide a biocatalytic approach, instead of the chemical method, for ferulic acid ester synthesis.

The thermal surface properties of graphenes and carbon materials are of crucial importance in chemistry of materials, chemical engineering, and many industrial processes. (1) Background: The determination of these surface properties is carried out using inverse gas chromatography at infinite dilution which leads to the retention volume of organic solvents adsorbed on solid surfaces. This experimental and fundamental parameter actually reflects the surface thermodynamic interactions between injected probes and solid substrates. (2) Methods: The London dispersion equation and the Hamieh thermal model were used to quantify the London dispersive and polar surface energy of graphenes and carbon fibers as well their Lewis acid-base constants by introducing the coupling amphoteric constant of materials. (3) Results: The London dispersive and polar acid-base surface energies, the free energy of adsorption, the polar enthalpy and entropy, and the Lewis acid-base constants of graphenes and carbon materials were determined. (4) Conclusions: it was showed that graphene exhibited the highest values of London dispersive surface energy, polar surface energy, and Lewis’s acid-base constants. These highest characteristics of graphene justify its great potentiality and uses in many industrial applications.

The rapid spread of African swine fever virus (ASFV), causing severe and often lethal disease in domestic pigs and Eurasian wild boar, continues to be a threat for pig populations and dependent industries. Despite scientific achievements that deepen our understanding of ASFV pathogenesis, alternative transmission routes for ASFV remain to be elucidated. We previously demonstrated the efficient transmission of ASFV from infected boars to naïve recipient gilts via artificial insemination, thereby highlighting the importance of surveillance in boar semen prior to shipment. Since accurate and reliable detection of even low amounts of ASFV in boar semen is key for disease prevention and control, we established a suitable diagnostic pipeline to efficiently detect ASFV genome in boar semen. Here, we assessed sensitivity, specificity and overall performance of various routine nucleic acid extraction kits as well as qPCR protocols in detecting ASFV genome in blood and semen of boars. Feasibility of respective kits and methods for future use in boar studs was also considered. Variability in sensitivity mostly concerned samples with low to very low amounts of ASFV genome. Ultimately, we defined a well-suited pipeline to precisely detect ASFV genome in boar semen, as early as 2 days post ASFV infection.

Background: Feline infectious peritonitis (FIP) is a fatal feline disease classified as either effusive (‘wet’), non-effusive (‘dry’), or a mixture of both forms (‘mixed’). The anti-FIP therapeutic effect of Mutian and molnupiravir, two drugs whose active ingredient is a nucleic acid analog, has been confirmed recently. Methods: Of the cats with FIP, we observed a total of 122 and 56 cases achieved remission after administration of Mutian and molnupiravir as routine treatments, respectively. Changes in clinical indicators suggested to be correlated with FIP remission (weight, hematocrit, and albumin to globulin ratio) before and after the administration of each drug and during follow-up observation were statistically compared for each FIP type. Results: In all three FIP types, administration of either Mutian or molnupiravir resulted in statistically significant increases in these indicators. Furthermore, the effect of Mutian on improving the albumin to globulin ratio was not observed at all in wet FIP, as compared with that of molnupiravir, but statistically significant in mixed and dry (P<0.02 and P<0.003, respectively). These clinical features were all due to differences in fluctuations of circulating globulin levels. Conclusions: These results indicate slight inflammatory responses might be elicited continuously by residual feline coronavirus non-disappeared through molnupiravir treatments.

Dendrobium okinawense is an endangered epiphytic orchid, and there has been no scientific report so far on its propagation. Protocorm is mass of cell, and protocorm-like bodies (PLBs) look alike protocorm produced by vegetative explants in vitro. Regeneration of PLBs is the most efficient technique for the orchids micro-propagation. We used different light emitting diodes (LEDs) for the efficient PLB organogenesis of D. okinawense. PLBs regenartion under green and red LED surpassed respectively 81.1% and 71.6% in numbers, and respectively 80.8% and 57.8% in fresh weight over white fluorescent light. We manipulated the culture media by different concentrations of PCIB and HMI. PLBs organogenesis promoted by low concentration, it increased respectively 35.9% and 19.3% over control by 0.01 mg/L PCIB and 0.01 ml/L HMI in numbers. Green LED and PCIB independently produced mostly similar numbers of new PLBs. Interestingly, culture media with 0.01 mg/L of PCIB further increased 8.5% of the numbers of PLBs under green LED, whereas the culture media with 0.01 mg/L HMI reduced the number of PLBs under green LED. PLBs culture under green LED with very low concentrations of PCIB manipulated culture media can significantly increase their organogenesis of D. okinawense.

This study presents the chemical synthesis, purification, and characterization of a novel non-natural synthetic amino acid. The compound was synthesized in solution, purified, and characterized using NMR spectroscopy, polarimetry, and melting point determination. Dynamic Light 22 Scattering (DLS) analysis demonstrated its ability to form aggregates with an average size of 391 nm, extending to low micrometric sizes. Furthermore, cellular biological assays revealed its ability to enhance fibroblast cell growth, highlighting its potential for tissue regenerative applications. Circular dichroism (CD) spectroscopy showed the ability of the synthetic amino acid to bind serum albumins (using bovine serum albumin (BSA) as a model), and CD deconvolution provided insights into the changes in secondary structures of BSA upon interaction with the amino acid ligand. Additionally, molecular docking using HDOCK software elucidated the most likely binding mode of the ligand inside the BSA structure. We also performed in silico oligomerization of the synthetic compound in order to obtain a model of aggregate to investigate computationally. More in detail, in the dimer formation achieved by molecular self-docking, two distinct poses were observed, corresponding to the lowest and comparable energies, with one pose exhibiting a quasi-coplanar arrangement characterized by a close alignment of two aromatic rings from the synthetic amino acids within the dimer, suggesting the presence of π-π stacking interactions. In contrast, the second pose displayed a non-coplanar configuration, with the aromatic rings oriented in a staggered arrangement, indicating distinct modes of interaction. Both poses were further utilized in the self-docking procedure. Notably, iterative molecular docking of amino acid structures resulted in the formation of higher-order aggregates, with a model of a 512-mer aggregate obtained through self-docking procedures. This model of aggregate presented a cavity capable of hosting therapeutic cargoes and biomolecules, rendering it a potential scaffold for cell adhesion and growth in tissue regenerative applications. Overall, our findings highlight the potential of this synthetic amino acid for tissue regenerative therapeutics and provide valuable insights into its molecular interactions and aggregation behavior.

This study aimed to identify new drug molecules against Leishmania parasites, leishmaniasis's causal agent, using Pistacia atlantica leaves as source. The evaluation of the anti-leishmania potential against the promastigote form of Leishmania. infantum and Leishmania. major was performed. A new in silico study was accomplished using molecular docking, with Autodock vina program, to find the binding affinity of two important phytochemical compounds from this plant (Masticadienonic acid, 3-Methoxycarpachromene) towards the trypanothione reductase as target drugs, responsible for defence mechanism against oxidative stress and virulence of this parasites. Results: Several concentrations showed a significant decrease in cell viability (P<0.0001), with IC50 values of 0.3 mg/ mL for L. infantum and 0.12 mg/ mL L. major; The molecular docking confirms the significant relationship between Leishmania survival and the inhibition of this crucial enzyme. There were promising and new positive results on binding modes of selected ligands and the trypanothione reductase for the first time. Through this work, we propose 3-Methoxycarpachromene and Masticadienonic acid as anti Trypanosomatidae species drug.

Over the last decade, a significant literature has emerged that advocates the potential of different Additive manufacturing (AM) technologies and printable polymeric materials. Nevertheless, large scale printing and complex geometric shapes, with curvatures and non-planar layer deposition, are a challenging process for the traditional gantry-based machine. The 3 degrees of freedom cartesian configuration restricted their capability to planar layered printing and restricted part dimensions. To date, many researchers have used industrial robots to overcomes this limitation. This review gives the reader a good overview of the FDM technique due to its scalability, cost efficiency and a wide range of material printability. A strong emphasis is laid on the PLA and PLA-based composites as promising materials for the FDM process applications. The second part of this paper links the successful use of these materials in the traditional printing process to large scale printing using the robot-based FDM process. This survey presents representative setups for robot-based AM and works that have been used these setups for non-planar material deposition. Finally, we conclude this paper by identifying opportunities for realizing new functional capabilities by exploiting robot-based AM, and we also present the future trends in this area.

Potato is among one of the most important food crops, yet maintaining plant productivity in this drought-sensitive crop has become a challenge. Competition for scarce water resources and the continued effects of global warming exacerbate current constraints on crop production. While plants’ response to drought in above-ground tissues has been well documented, the regulatory cascades in developing tubers have been largely unexplored. Using the commercial Canadian cultivar ‘Vigor’, plants were subjected to a drought treatment under high-tunnels causing a 4 ℃ increase in canopy temperature when compared to the well-watered control. Tubers were sampled for RNAseq and metabolite analysis. Approximately 2600 genes and 3898 transcripts were differentially expressed by at least four-fold in drought-stressed potato tubers, with 75 % and 69 % being down-regulated respectively. A further 229 small RNAs were implicated in gene regulation during drought. The comparison of protein homologues between Solanum tuberosum L. and Arabidopsis thaliana L. indicates that downregulated genes are associated with phenylpropanoid, carotenoid, and patatin biosynthesis. This suggests that there may be nutritive implications to drought stress occurring during the potato tuber bulking phase in sensitive cultivars.

The annual construction and demolition waste (CDW) generated from EU construction sector was 850 million tons, which represented 31% of the total waste generation and about 28% of CDW was ceramics (bricks and tiles). In this study, the feasibility of using CDW brick powder as the precursor of alkali activated mortar (AAM) and extruded polystyrene (XPS) as the lightweight aggregates to form lightweight brick powder AAM (LW-BP-AAM) for non-structural applications was investigated. The thermal conductivity of LP-BPAAM was 0.112 W/m·K with density of about 1,135 kg/m³ which was lower than the counterparts with similar density in literature. The acid resistance of LW-BP-AAM is comparable to conventional fly ash based AAM and superior than ordinary Portland cement. From the scanning electron microscopy with energy dispersive X-ray spectroscopy, there was no severe damage on the surface of LW-BP-AAM but aluminate was removed from the matrix which was further verified in Fourier transform infrared spectroscopy. The mass and strength loss of LP-BP-AAM was 1.5% and 33%, respectively. Although the compressive strength of the LP-BP-AAM was low (about 1.8 MPa), it can be improved by optimising the particle size of the XPS aggregates.

The study delved into the impact of two extrusion processing parameters—screw speed (SS at 400, 600, 800 RPM) and material moisture content in the extruder barrel (M at 12, 15, 18%) at constant feed rate (50 kg/h)—on reducing the content of alternariol (AOH), alternariol monomethyl ether (AME), tenuazonic acid (TeA), and tentoxin (TEN) in whole-grain red sorghum flour. Ultra-performance liquid chromatography coupled with a triple-quadrupole mass spectrometer (UPLC-MS/MS) was used for determination of Alternaria toxin levels. The extruder die temperature ranged between 136 and 177 °C, the pressure at the die was from 0.16 to 6.23 MPa, the specific mechanical energy ranged from 83.5 to 152.3 kWh/t, the torque ranged between 88 to 162.8 Nm, while the mean retention time of material in the barrel was between 5.6 and 13 s. Optimal parameters for reducing the concentration of all Alternaria toxins with the satisfactory quality of sorghum snacks were: SS=400 RPM, M= 12%, with a reduction of 61.4, 76.4, 12.1 and 50.8% for AOH, AME, TeA and TEN, respectively.

There are numerous approaches to model an influence of manufacturing parameters on the dissolution and disintegration of solid dosage forms. A modern approach for modelling and simulating complex and heterogeneous systems such as pharmaceutical tablets focuses on computationally-intensive finite-element or discreet element methods. Industrial challenges such as Process Analytical Technology (PAT) and Quality by Design are stimulating computer-based technologies to design, control and improve the quality of pharmaceutical compacts and their performance. In this study the disintegration and dissolution model based on the numerical solutions of the Noyes-Whitney equation and cellular automata supported disintegration model are proposed and evaluated. The results from in vitro release studies of the mefenamic acid formulations were compared to the calculated release patterns from the tablet structures obtained from microtomography experiments and the purely algorithmically created virtual tablets.

Inhibition of quorum sensing (QS)-dependent biofilm formation and virulence is extensively investigated as a novel approach to combat bacterial pathogens by impeding their ability to cause antibiotic-tolerant diseases. Such strategies are considered a promising alternative to conventional antibacterial therapy since interrupting the central cell-to-cell communication system imposes less selective pressure on the target pathogen. In this study, novel hybrid compounds composed of anthranilic acids substituted with halogens at different positions of the phenyl ring, and 4-(2-aminoethyl/4-aminobuthyl)amino-7-chloroquinoline linked via 1,3,4-oxadiazole were synthesized using standard procedures. Their anti-QS activities were evaluated using Chromobacterium violaceum ATCC31532 (anti-biofilm and bactericidal activities) and Pseudomonas aeruginosa PAO1 (anti-biofilm/-virulence activities). The results showed that compounds 15–19 and 23 inhibited the production of violacein, the QS-inducible pigment, in C. violaceum to a similar extent as the model QS inhibitor - quercetin (83.5–90%). Compound 15 exhibited the strongest effect on P. aeruginosa in the anti-biofilm screening, reducing its ability to form biofilm by almost 50%, while compounds 16 and 19 were able to reduce the biofilm formation by approximately 30%. However, compound 23 did not demonstrate significant anti-biofilm activity and only inhibited pyocyanin production in P. aeruginosa. In conclusion, this study suggests that 1,3,4-oxadiazoles 15, 16, and 19 are the most promising compounds for future research as novel QS inhibitors against Gram-negative bacteria equipped with different QS signaling pathways.

Equipped with an early social predisposition immediately post-birth, humans typically form associations with mothers and other family members through exposure learning, canalized by a spontaneous predisposition to biological motion, face configuration, and other cues of animacy. If impaired, reduced social preferences can lead to social interaction impairments such as autism spectrum disorder (ASD) via misguided canalization. Despite being taxonomically distant, domestic chicks also follow a homologous developmental trajectory toward adaptive socialization through imprinting, which is guided via predisposed preferences that are homologous to those of humans, thereby suggesting that chicks are valid animal models of ASD. In addition to the convergent similarities in predisposition with human newborns, accumulating evidence suggests the construct validity of the chick model. Considering the recent progress in the evolutionary neurobiology of vertebrates, we reviewed the advantages and limitations of the chick model of developmental mental diseases in humans.

Recently, polyacetylene (PA) is receiving a renewed scientific attention due to its electrical properties potentially useful for energy applications (e.g., fabrication of electrodes for batteries and supercapacitors) and unique functional characteristics (e.g., flame retardant, oxygen scavenger, EMI-shielding, etc.). This chemical compound can be obtained in form of a polyacetylene-PVOH copolymers simply by chemical dehydration of poly(vinyl alcohol) (PVOH), which is a very common type of polymer, widely used in packaging and other technological areas. This very inexpensive chemical reaction for the large-scale synthesis of PA/polyvinylenes has been investigated by reacting PVOH with fuming sulfuric acid at room temperature. In this process, PVOH, shaped in form of film, is dipped in fuming sulfuric acid (i.e., H₂SO₄ at 95-97%) and, after complete chemical-dehydration, it has been mechanically removed from the liquid phase by using a nylon sieve. The reduction process leads to a substantial PVOH film conversion to PA as it has been proved by infrared spectroscopy (ATR-mode). Indeed, the ATR spectrum of the reaction product included all characteristic absorption bands of PA. The reaction product has been also characterized by UV-Vis spectroscopy in order to evidence the presence in the structure of conjugated carbon-carbon double bonds of various lengths. Differential scanning calorimetry (DSC) and thermogravimetric analysis have been used respectively to investigate the PA solid-state cis-trans isomerization and thermal stability in air and nitrogen, respectively.

Cinnamomum tamala leaf (CTL), also known as tejpat and Indian bay leaf, is used all over the world for seasoning, flavouring, and medicinal purposes. Numerous researchers are interested in exploring the nutritional and medicinal benefits of CTL due to their potential as nutraceuticals. These characteristics could be explained by the presence of several essential bioactive substances and lipid derivatives. There are no reports available on this species about its metabolites profile. In this work, rapid screen and identify chemical compounds in supercritical (SC)-CO2 extracts of CTL by use of UPLC-Q-TOF-MSE with multivariate statistical analysis approach was established in both negative and positive mode. As a results, a total of 166 compounds, including 66 monocarboxylic fatty acids, 52 dicarboxylic fatty acids, 27 fatty acid amides, and 21 others were tentatively identified based on accurate mass, and the mass spectrometric fragmentation pattern, out of which 142 compounds are common and found in all five CTL extracts. They displayed robust [M+H]+ and/or [M-H]- ions in both low- and high-energy collision-induced dissociations (CIDs). Based on chemical profiling and chemometric analysis, CTL4 (300bar/55°C) extract was found significantly more potent in other CTL’s extracts. A new mono- and di-carboxylic fatty acids, fatty acid amides and other essential bioactive compounds were separated within 20 min runtime and identified in CTL for the first time. The combination of UPLC-Q-TOF-MSE and chemometric analysis is a powerful method to rapidly screen the metabolites profile for the quality control of C. tamala leaf.

Neisseria meningitidis (N. meningitidis) serogroup B (MenB) is the leading cause of invasive meningococcal disease worldwide. The pathogen has a wide range of virulence factors, which are potential vaccine components. Studying the genetic variability of antigens within a population, especially their long-term persistence, is necessary to develop new vaccines and predict the effectiveness of existing ones. The multicomponent 4CMenB vaccine (Bexsero), used since 2014, contains three major genome-derived recombinant proteins: factor H-binding protein (fHbp), Neisserial Heparin-Binding Antigen (NHBA) and Neisserial adhesin A (NadA). Here, we assessed the prevalence and sequence variations of these vaccine antigens in a panel of 5667 meningococcal isolates collected worldwide over the past 10 years and deposited in the PubMLST database. Using multiple amino acid sequence alignments and machine learning methods, we estimated the potential strain coverage by fHbp and NHBA vaccine variants (51 and about 30%, respectively); the NadA antigen sequence was found in only 17.8% of MenB genomes analyzed, but cross-reactive variants were present in less than 1% of isolates. Based on our findings, we proposed various strategies to improve the 4CMenB vaccine and broaden coverage of N. meningitidis strains.

Beef meat production in Uruguay is based on pasture or concentrate feeding systems, leading to differences in meat quality. The objective of this study was to compare the oxidative and color stability during refrigerated retail display of beef meat from these two systems. For this, ten Aberdeen Angus steers were reared and fed on pasture and other ten were finished on a concentrate diet. After slaughter, the Semimembranosus muscle was cut into slices and put in a refrigerated showcase for 3, 6, and 9 days simulating commercial conditions. The β-carotene, α-tocopherol, and fatty acid content were determined before the display, and the lipid and protein oxidation, color parameters, and heme iron content were determined before and during the display. Meat from steers fed pasture had a lower content of intramuscular fat, monounsaturated fatty acids, n-6/n-3 ratio, lipid and protein oxidation, L* and a* values, and a higher content of linolenic acid, DHA, total n-3, β-carotene, and α-tocopherol. In conclusion, meat from pasture-fed steers was more stable during the retail display, which can probably be explained by a higher content of antioxidant compounds, such as β-carotene and α-tocopherol, and presented a healthier fatty acid profile.

Nuclear receptors (NRs) constitute a superfamily of ligand-activated transcription factors with a paramount role in ubiquitous physiological functions such as metabolism, growth, and reproduction. Owing to their physiological role and druggability, NRs are deemed attractive and valid targets for medicinal chemists. Pentacyclic triterpenes (PTs) represent one of the most important phytochemical classes present in higher plants, where oleanolic acid (OA) is the most studied PTs representative owing to its multitude of biological activities against cancer, inflammation, diabetes, and liver injury. PTs possess a lipophilic skeleton that imitates the NRs endogenous ligands. Herein, we report a literature overview on the modulation of metabolic NRs by OA and its semi-synthetic derivatives, highlighting their health benefits and potential therapeutic applications. Indeed, OA exhibited varying pharmacological effects on FXR, PPAR, LXR, RXR, PXR, and ROR in a tissue-specific manner. Owing to those NRs modulation, OA exhibited prominent hepatoprotective properties comparable to ursodeoxycholic acid (UDCA) in a bile duct ligation mice model and antiatherosclerosis effect as simvastatin in a model of New Zealand white (NZW) rabbits. It also demonstrated a great promise in alleviating non-alcoholic steatohepatitis (NASH) and liver fibrosis, attenuated alpha-naphthol isothiocyanate (ANIT)-induced cholestatic liver injury, and controlled blood glucose levels, making it a key player in the therapy of metabolic diseases. We also compiled OA semi-synthetic derivatives and explored their synthetic pathways and pharmacological effects on NRs, showcasing their structure-activity relationship (SAR). To the best of our knowledge, this is the first review article to highlight OA activity in terms of NRs modulation.

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

Transitions from seed to seedling represent a critical developmental step in the life cycle of higher plants, dramatically affecting plant ontogenesis and stress tolerance. The release from dormancy to acquiring the germination ability is defined by a balance of phytohormones, with a substantial contribution of abscisic acid (ABA), which inhibits germination. We studied the embryonic axes of Pisum sativum L. before and after radicle protrusion. Our previous work compared RNA sequencing-based transcriptomics in the embryonic axes isolated before and after radicle protrusion. The current study aims to analyze ABA-dependent gene regulation during the transition of embryonic axes from germination to post-germination stage. First, we determined the levels of abscisates (ABA, phaseic acid, dihydrophaseic acid, and neo-phaseic acid) using the ultra-high-performance liquid chromatography-tandem mass spectrometry. Second, we made a detailed annotation of ABA-associated genes using RNA sequencing-based transcriptome profiling. Finally, we analyzed the DNA methylation pattern in the promoters of the PsABI3, PsABI4, and PsABI5 genes. We showed that changes in the abscisate profile are characterized by the accumulation of ABA catabolites, and the ABA-related gene profile is accompanied by the upregulation of genes controlling the seedling development and the downregulation of genes controlling the water deprivation. The expression of ABI3, ABI4 and ABI5, which encode the crucial transcription factors during late maturation, was downregulated by more than 20-fold, and their promoters exhibited a high level of methylation already at the late germination stage. Thus, although ABA remains important, other regulators seems to be involved in the transition from seed to seedling.

Recent research has identified the gut-brain axis as a key mechanistic pathway and potential therapeutic target in depression. In this paper, the potential role of gut hormones as potential treatments or predictors of response in depression is examined, with specific reference to the peptide hormone motilin. This possibility is explored through two methods: (a) a conceptual review of the possible links between motilin and depression, including evidence from animal and human research as well as clinical trials, and (b) an analysis of the relationship between a functional polymorphism (rs2281820) of the motilin (MLN) gene and cross-national variations in the prevalence of depression. It was observed that (a) there are several plausible mechanisms, including interactions with diet, monoamine, and neuroendocrine pathways, to suggest that motilin may be relevant to the pathophysiology and treatment of depression, and (b) there was a significant correlation between rs2281820 allele frequencies and the prevalence of depression after correcting for multiple confounding factors. These results suggest that further evaluation of the utility of motilin and related gut peptides as markers of antidepressant response is required, and that these molecular pathways represent potential future mechanisms for antidepressant drug development.

Red mud (RM) is composed of a waste alkaline solution (pH = 13.3) obtained from the production of alumina. It contains high concentrations of soluble hematite (Fe2O3), goetite (FeOOH), gibisite [Al(OH)3], a boemite (AlOOH), anatase (Tetragonal - TiO2), rutile (Ditetragonal dipyramidal - TiO2), hydrogarnets [Ca3Al2(SiO4)3−x(OH)4x], and perovskite (CaTiO3). It was shown to be an excellent catalytic mixture for biodiesel production. To demonstrate the value of RM, an environmentally friendly process of transesterification in aqueous medium using waste cooking oil (WCO), MeOH and waste alkaline solution (WAS) obtained from aluminum production was proposed. Triglycerides of WCO reacted with MeOH at 60 oC to yield mixtures of fatty acid methyl esters (FAMEs) in the presence of 0.019% (w/w) WAS/WCO using the WAS (0.204 mol L-1, predetermined by potentiometric titration) from aluminum production by the Bayer process. The use of the new catalyst (WAS) resulted in a high yield of the products (greater than 99% yield).

The abnormal assembly of α-synuclein (α-Syn) is an initial step in the formation of Lewy bodies in the brain, which finally causes the neuronal death, being considered as a pathological hallmark in Parkinson’s disease (PD). Certain food bioactives or their metabolites at very low concentrations can trespass the blood brain barrier (BBB) that might, thereafter, act simultaneously. The aim of this work was to evaluate the inhibitory and destabilising capacities on α-Syn kinetics and the neuroprotective effects of three well-known bioactive compounds able to cross the BBB and present in foods; melatonin (MEL), protocatechuic acid (PCA) and hydroxytyrosol (HT), and their combinations. For this purpose, different in vitro techniques (Thioflavin T (ThT), Transmission Electronic Microscopy (TEM), electrophoresis and MTT assay) were used. All tested compounds and their combinations were able to abolish the toxicity induced by α-Syn. In addition, the combination of PCA (100 µM) +HT (100 µM) showed the highest inhibitory effect against α-Syn fibril formation and destabilises α-Syn fibrils (88 and 62%, respectively). This is the first time that MEL, PCA and HT prove a joint effect against α-Syn aggregation and toxicity when they are tested together.

Powder mixture with given molar ratio Ca/P = 1.67 consisting of brushite (calcium hydrophosphate dihydrate) CaHPO4·2H2O, calcium oxalate monohydrate CaC2O4·H2O in form of whewellite and weddellite and some quantity of quasi-amorphous phase was obtained as a result of the interaction of hydroxyapatite powder Ca10(PO4)6(OH)2 with an aqueous solution of oxalic acid H2C2O4 at a molar ratio of Ca10(PO4)6(OH)2/H2C2O4 = 1:4 under mechanical activation conditions. This powder mixture was used to produce microporous monophase ceramics based on hydroxyapatite Ca10(PO4)6(OH)2 with aperient density of 1.25 g/cm3 after firing at 1200 oC. Microporosity of sintered ceramics was formed due to presence of particles with plate-like morphology, restraining shrinkage during sintering. Microporous ceramics based on hydroxyapatite Ca10(PO4)6(OH)2 with roughness of the surface as a consequence of the created microporosity can be recommended as a biocompatible material for the bone defects treatment and as a substrate for bone cell cultivation.

As novel materials for carbon capture, phase change solvents can separate into two immiscible phases during the CO2 capturing procedure under a certain temperature. The solvent systems can significantly decrease the energy consumption since the solvents can be regenerated by only heating the rich-CO2 phase. In this work, amino acid ionic liquids (AAILs) were synthesized using quaternary ammonium salts and amino acids as raw materials, and the aqueous solutions were prepared as novel liquid-solid phase change solvents. The results showed that the solvents had excellent CO2 absorption capacity, and the AAILs functionalized by glycine and tryptophan exhibited significant phase change properties. The mechanism of phase-change of the solvent were mainly due to the lower solubility of the product after reaction between AAILs and CO2. The solvent with tryptophan as anion could be regenerated by only heating the CO2-riched solid phase, which might significantly decrease energy consumption of regeneration. And the absorbent could be reused with the regenerated absorption ratio up to 79%. The solvent system has great potential in industrial application due to the easy operation process and efficient recycling ability.

The aim of this work was the study and evaluation of winery by-products in the framework of circular bioeconomy. Grape seeds and grape skins from Greek traditional Ionian Islands varieties were analyzed in an attempt to provide the appropriate basis for model development of their sustainable exploitation at a local or regional level. The wastes collected directly from the wineries immediately after the vinification process and analyzed by chromatographic and spectroscopic techniques. Also, annual production and yields were estimated. Grape seed oil quality was evaluated based on fatty acid methyl esters (FAMEs) composition. Grape skins phenolic fraction was extracted by an eco-friendly, non-toxic water-glycerol solvent system and were detected qualitatively. Also, total phenolic content (TPC) and antioxidant activity were measured. Based on estimated yields, our results demonstrate that winery by-products have the potential to promote the cyclical bioeconomy in a modern economic growth model that will reduce waste, and environmental costs as they can be reused as whole material in foods, dietary supplements, cosmetic ingredients, food colorants and preservatives.

Plants are exposed to a variety of abiotic and biotic stresses leading to increased formation of reactive oxygen species (ROS) in plant cells. ROS are capable of oxidizing proteins, pigments, lipids, nucleic acids, and other cell molecules, disrupting their functional activity. During the process of evolution, numerous antioxidant systems were formed in plants, including antioxidant enzymes and low-molecular-weight non-enzymatic antioxidants. Antioxidant systems perform neutralization of ROS and therefore prevent oxidative damage of cell components. In the present review, we focus on the biosynthesis of non-enzymatic antioxidants in higher plant cells such as ascorbic acid (vitamin C), glutathione, flavonoids, isoprenoids, including carotenoids, tocopherol (vitamin E), ubiquinone and plastoquinone. Their functioning and their reactivity with respect to individual ROS are described. The review is also devoted to the modern genetic engineering methods, which are widely used to change the quantitative and qualitative content of the non-enzymatic antioxidants in cultivated plants. These methods allow to obtain various plant lines with given properties in a rather short time. The most successful approaches for plant transgenesis and plant genome editing for the enhancement of the biosynthesis and the content of these antioxidants are discussed.

Background and Objectives: Mucilaginous substances from plant extracts are known to be able to support the lubricating effect of hyaluronic acid (HA) in dry eye disease (DED). In this pilot study, the combined lubricating effect of HA and mallow extract (Malva sylvestris L.) in patients with DED was assessed. Materials and Methods: 20 patients at 5 ophthalmological practices in Italy were treated with eye drops, containing HA and mallow extract on the one hand, and with eye drops containing HA only, on the other hand, in a two-period crossover design. As primary endpoints, the tear film breakup time (TBUT), the reduction of lissamine green staining of the ocular surface (Oxford Scheme, OS), and the safety and efficacy assessment by the ophthalmologists were evaluated. As secondary variables, the patient symptom score, the ocular surface index (OSDI), and the satisfaction, preference and efficacy judgement by the patients were evaluated. All data were analysed descriptively in addition to an exploratory analysis of the target variables. Results: Both products were well tolerated. There were no statistically significant differences, with regard to the TBUT, OS and OSDI, between both treatments. Anyway, the efficacy and safety assessments by the ophthalmologists and the patients showed results in favour of the combined product. Conclusion: The addition of mallow extract to HA containing eye drops enhances the treatment of DED at least with respect to subjective measurements. Further assessments will have to be done to prove and explain this observation in terms of measurable parameters, e.g. markers for inflammatory cytokines.

Vitamin D and ω-3 fatty acids (ω-3) co-supplementation potentially improve type 1 diabetes (T1D) by attenuating autoimmunity and counteracting inflammation.This cohort study preliminary to a randomized control trial (RCT) is aimed to evaluate, in a series of T1D children assuming Mediterranean diet and taking cholecalciferol 1000U/day fromT1D onset, if ω-3 co-supplementation preserves the residual endogen insulin secretion (REIS).Therefore, 22 new onsets of 2017 received ω-3 [eicosapentenoic acid (EPA) plus docosahexaenoic acid (DHA), 60mg/kg/day], and were compared retrospectively vs. 37 previous onsets without ω-3 supplementation. HbA1c%, daily insulin demand (IU/Kg/day) and IDAA1c, a composite index (calculated as IU/Kg/dayx4 + HbA1c%) as surrogate of REIS, were evaluated at recruitment (T0) and 12 months later (T12). In the ω-3 supplemented group, dietary intakes were evaluated at T0 and T12. As outcome, decreased insulin demand (p<0.01), particularly pre-meal boluses (p<0.01), and IDAA1c (p<0.05), were found in the ω-3 group while HbA1c% were not different in the two groups. Diet analysis, at T12 vs. T0, showed that the intake of arachidonic acid (AA) was decreased (p<0.01) in the ω-3 supplemented group while other nutrients were unchanged; at T0, the AA intake was inversely correlated with HbA1c% (p<0.05; r;.0.411). In conclusion, the results suggest that vitamin D plus ω-3 co-supplementation and AA reduction in Mediterranean diet display benefits for T1D children and deserve further investigation.

Basic features of seed dormancy are illustrated. The seed overall regulatory network governs seed metabolism and development, and it is coordinated by plant hormones. A functional model focused on abscisic acid (ABA), the foremost plant hormone in dormancy, is used as a framework to critically discuss the literature. Gibberellins (GAs) have a main role in germination, and the ABA – GAs balance is a typical feature of the seed state: ABA dominates during dormancy and GAs prevail through germination. Thus, the literature converges toward envisaging the development switch between dormancy and germination as represented by the ABA/GAs ratio. The ABA – GAs antagonism is based on mutual inhibition, a feature of the regulatory network architecture that characterizes development trajectories based on a regulatory circuit with a bistable switch. Properties of such kind of regulatory architecture are introduced step by step, and it is shown that seed development – towards either dormancy or germination – is more properly represented by a tristable regulatory circuit, whose intermediate metastable states ultimately take one or the other development trajectory. Although the ABA/GAs ratio can conveniently represent the state of the seed overall regulatory network along the seed development trajectory, specific (unknown) dormancy factors are required to determine the development trajectory. The development landscape is shown to provide a well-suited representation of seed states travelling along developmental trajectories, particularly when the states are envisioned as regulatory circuits. Looking at seed dormancy in terms of regulatory circuits and development landscapes offers a valuable perspective to improve our understanding of this biological phenomenon.

Attempts to find and quantify the supposed low entropy of organisms and its preservation are revised. Absolute entropy of the mixed components of non-living biomass (around -1.6 x 103 J K-1 L-1) is the reference to which other entropy decreases would be ascribed to life. Compartmentation of metabolites and departure from the equilibrium of metabolic reactions account for 1 and 40-50 J K-1 L-1, respectively, decreases of entropy and, though small, are distinctive features of living tissues. DNA and proteins do not supply significant decreases of thermodynamic entropy, but their low informational entropy is relevant for life and its evolution. No other living feature contributes significantly to the low entropy associated to life. The photosynthetic conversion of radiant energy to biomass energy accounts for the most of entropy (2.8 x 105 J K-1 carbon kg-1) produced by living beings. The comparative very low entropy produced in other processes (around 4.8 x102 J K-1 L-1 day-1 in human body) must be rapidly exported outside as heat to preserve the low entropy decreases due to compartmentation and non-equilibrium metabolism. Enzymes and genes are described whose control minimize the rate of production of entropy and could explain selective pressures in biological evolution and the rapid proliferation of cancer cells.

Compounds with tyrosinase inhibitory efficacy could be effective as depigmenting agents. Although a large number of natural and synthetic tyrosinase inhibitors have been reported, few of them are used as skin-whitening agents due to poor activity and safety concerns. 3-(2,4-Dihydroxyphenyl)propionic acid (DPPA), a naturally occurring compound isolated from Ficus carica, was previously discovered as a moderate tyrosinase inhibitor. In this study, the structure-activity relationship study of DPPA was conducted. Compound 3g, with the 2,4-resorcinol subunit and terminal hydrophobic di-butylamino group, was identified with low nanomolar enzymatic IC₅₀ value. Additionally, compound 3g could effectively reduce melanin levels in B16-F10 melanoma cells treated with α-melanocyte-stimulating hormone (α-MSH) without affecting cell viability and proliferation. All these results indicated that compound 3g could be considered as a promising candidate for the treatment of diseases associated with hyperpigmentation.

Maslinic acid (MA) is a natural triterpene from Olea europaea whose pharmacological functions have been showed. The objective of this study was to examine MA effect on cell viability (by MTT assay), reactive oxygen species (ROS levels, by flow cytometry) and key anti-oxidant enzyme activities (by spectrophotometry) in murine skin melanoma (B16F10) cells compared to healthy cells (A10). MA induced cytotoxic effects in cancer cells (IC50 42 µM) whereas no effect was found in A10 cells treated with MA (up to 210 µM). In order to produce a stress situation in cells, 0.15 mM of H2O2 were added. Under stressful conditions, MA protected both cell lines against oxidative damage, decreasing intracellular ROS, being higher in B16F10 than in A10 cells. The treatment with H2O2 and without MA produced different responses in anti-oxidant enzymes activities depending on cell line. In A10 cells, all enzymes were up-regulated, but in B16F10 cells only superoxide dismutase, glutathione S-transferase and glutathione peroxidase increased their activities. MA restored the enzyme activities to similar levels than control group in both cell lines, highlighting that in A10 cells the highest MA doses induced values lower than control. Overall, these findings demonstrate the great anti-oxidant capacity of MA.

The plant graft healing process is an intricate development influenced by numerous endogenous and environmental factors. This process involves the histological changes, physiological and biochemical reactions, signal transduction, and hormone exchanges in the grafting junction. Studies have shown that applying exogenous plant growth regulators can effectively promote the graft healing process and improve the quality of grafted plantlets. However, the physiological and molecular mechanism of graft healing formation remains unclear. In our present study, transcriptome changes in the melon and cucurbita genomes were analyzed between control and NAA treatment, and we provided the first view of complex networks to regulate graft healing under exogenous NAA application. The results showed that the exogenous NAA application could accelerate the graft healing process of oriental melon scion grafted onto squash rootstock through histological observation, increase the SOD, POD, PAL, and PPO activities during graft union development and enhance the contents of IAA, GA3, and ZR except for the IL stage. The DEGs were identified in the plant hormone signal-transduction, phenylpropanoid biosynthesis, and phenylalanine metabolism through transcriptome analysis of CK vs. NAA at the IL, CA, and VB stage by KEGG pathway enrichment analysis. Moreover, the exogenous NAA application significantly promoted the expression of genes involved in the hormone signal-transduction pathway, ROS scavenging system, and vascular bundle formation.

The blue sepal color of hydrangea is due to a metal complex anthocyanin composed of 3-O-glucosyldelphinidin (1) and an aluminum ion with the co-pigments 5-O-caffeoylquinic acid (2) and/or 5-O-p-coumaroylquinic acid (3). The three components, namely, anthocyanin, Al³⁺ and 5-O-acylquinic acids, are essential for blue color development, but the complex is unstable and only exists in aqueous solution. Furthermore, the complex did not give analyzable NMR spectra or crystals. Therefore, many trials to determine the detailed chemical structure of the hydrangea-blue complex have failed to date. Instead, via experiments mixing 1, Al³⁺ and 2 or 3 in a buffered solution at pH 4.0, we obtained the same blue solution derived from the sepals. However, the ratio was not stoichiometric but fluctuated. To determine the composition of the complex, we tried direct observation of the molecular ion of the complex using electrospray-ionization mass spectrometry. In a very low-concentration buffer solution (2.0 mM) at pH 4.0, we reproduced the hydrangea-blue color by mixing 1, 2 and Al³⁺ in ratios of 1:1:1, 1:2:1 and 1:3:1. All solution gave the same molecular ion peak at m/z = 843, indicating that the blue solution has a ratio of 1:1:1 for the complex. By using 3, the observed mass number was m/z = 827 and the ratio of 1, 3 and Al³⁺ was also 1:1:1. A mixture of 1, 3-O-caffeoylquinic acid (4) and Al³⁺ did not give any blue color but instead was purple, and the intensity of the molecular ion peak at m/z = 843 was very low. These results strongly indicate that the hydrangea blue-complex is composed of a ratio of 1:1:1 for 1, Al³⁺ and 2 or 3.

An original approach has been proposed for designing a nanofibrous (NFs) layer using UV-cured polyvinylpyrrolidone (PVP) as a matrix, incorporating mesoporous graphene carbon (MGC) nanopowder both inside and outside the fibres, creating a sandwich-like structure. This architecture is intended to selectively adsorb and detect acetic acid vapours, which are known to cause health issues in exposed workers. The nanocomposite MGC-PVP-NFs layer was fabricated through electrospinning deposition onto interdigitated microelectrodes (IDEs) and stabilised under UV-light irradiation. To enhance the adhesion of MGC onto the surface of the nanocomposite polymeric fibres, the layer was dipped in a suspension of polyethylenimine (PEI) and MGC. The resulting structure demonstrated promising electrical and sensing properties, including rapid responses, high sensitivity, good linearity, reversibility, repeatability, and selectivity towards acetic acid vapours. Initial testing was conducted in a laboratory using a bench electrometer, followed by validation in a portable sensing device based on consumer electronic components (by ARDUINO®). This portable system was designed to provide a compact, cost-effective solution with high sensing capabilities. Under room temperature and ambient air conditions, both laboratory and portable tests exhibited favourable linear responses, with detection limits of 0.16 and 1 ppm, respectively.

This study provides a comprehensive investigation of lactic acid bacteria (LAB) isolated from Argentinean Capsicum annum L. The research covers important aspects, including genotypic characterization, bacterial stress tolerance, adhesion ability, safety evaluation, and functional and technological properties. The predominant isolates were identified as Lactilactobacillus curvatus and Lactiplantibacillus plantarum. Rep-PCR analysis grouped the isolates into 11 clonal groups. Lp. plantarum LVP 40 and LV 46; Levilactobacillus brevis LVP 41, Pediococcus pentosaseus LV P43, and Lt. curvatus LVP44, displayed both safety and resilience against adverse conditions such a slow pH, bile, and simulated gastric and intestinal juices. Moreover, the LAB strains exhibited high hydrophobicity and auto-aggregation percentages, NaCl tolerance, and substantial acidifying capacity. LAB supernatants demonstrated promising surfactant and emulsifying properties. Likewise, they differentially inhibited Staphylococcus aureus and Pseudomonas aeruginosa biofilms, showcasing their potential as antipathogenic agents. Noteworthy some strains displayed considerable co-aggregation with these pathogens, and several isolates showed an effective antimutagenic and detoxifying power, further emphasizing their multifaceted capabilities. Five pepper bacterial strains showcased probiotic properties, suggesting their potential for gut health enhancement. In summary, these LAB strains hold promise as vegetable fermentation starters, contributing to food safety and versatile applications in food science.

Four groups (sugar, lipid, protein and waste based) of bait materials combined with boric acid were evaluated in laboratory and field conditions. When compared to all the sugar-based bait materials, a mixture of honey with boric acid registered to be the most effective in attracting the maximum number (83.00) of red ants followed by a mixture of molasses with boric acid (55.00). Likewise, among the oils tested, the highest number (47.33) of red ants registered was in the mixture of rice bran oil with boric acid followed by mustard oil with boric acid mixture (37.00). Similarly, from the protein-based bait materials, the maximum number of red ants (35.00) attraction was found in the mixture of gram flour with boric acid which was followed by dog biscuits with boric acid mixture (27.67). When all the waste-based bait materials were tested, sugarcane trash with boric acid mixture attracted most of the red ants (96.67) followed by banana peel with boric acid mixture (36.67). Based on the laboratory performance, the two best bait materials in each group were assessed against red ant, Dorylus orientalis in potato crops. Of the 8 bait materials tested, the use of rice bran oil with boric acid was found to be more attractive against red ants (1564.66, 1972.33 and 2636.33 during tuber formation, tuber maturity and harvesting stages, respectively) in potato crop when compared to other bait materials. Additionally, the attraction of D. orientalis was tested separately against rice bran oil, boric acid and rice bran oil in combination with boric acid using Y-tube olfactometer under laboratory conditions. Results indicated that rice bran oil in combination with boric acid had the highest attractiveness ratio of 86.66 per cent followed by boric acid and rice bran at 76.66 and 73.33 per cent, respectively. The outcome of the current investigation can be explored for the management of red ant menace in potato and other field crops, particularly grown under organic cultivation approach.

The product of ozonolysis, Glycero-(9,10-trioxolane)-trioleate (ozonide of oleic acid triglyceride, [OTOA]), was incorporated into polylactic acid/polycaprolactone (PLA/PCL) blend films in the amount of 1, 5, 10, 20, 30, and 40% w/w. The morphological, mechanical, thermal and antibacterial properties of the biodegradable blend after the OTOA addition were studied. According to DSC and XRD data, the crystallinity degree of PLA/PCL+OTOA films tended to decrease with increase in OTOA content that could be explained by its plasticizing effect. Morphological analysis showed that the structure of the films with the OTOA concentration above 20% drastically changed. Specifically, the interface between the PLA/PCL matrix and OTOA was formed, thereby forming a capsule with the embedded antibacterial agent. The moisture permeability of the resulting PLA/PCL+OTOA films decreased due to the formation of uniformly distributed hydrophobic amorphous zones that prevents water penetration. This architecture affects the tensile characteristics of the films: strength decreases to 5.6 MPa, elastic modulus E by 40%. The behavior of film elasticity is associated with the redistribution of amorphous regions in the matrix. Additionally, PLA/PCL+OTOA films with 20, 30 and 40% of OTOA showed good antibacterial properties on Pseudomonas aeruginosa, Raoultella terrigena (Klebsiella terrigena) and Agrobacterium tumefaciens. Developed PLA/PCL+OTOA films could be used as packaging materials and wound dressings. By variation of the OTOA content, it is possible to tailor the physical-chemical and antibacterial properties of the developed films for various applications.

Accurate pathogenic detection in wastewater is critical for safeguarding public health and the environment. However, the presence of free nucleic acids in wastewater samples poses significant challenges to molecular detection accuracy. This comprehensive review explores the current status and future potential of pretreatment methods to remove free nucleic acids from wastewater samples. The study contributes a comprehensive analysis of the mechanisms, strengths, and limitations of various pretreatment approaches, including physical, chemical, and enzymatic processes. The effect of various factors on the removal efficiency of these pretreatment methods is also discussed. This review enhances our comprehension of pretreatment techniques and their vital role in achieving precise pathogenic detection in complex wastewater matrices. Furthermore, it outlines future perspectives and developments for improving the speed and effectiveness of pathogenic detection, contributing significantly to disease surveillance, early warning systems, and environmental protection.

Adenylosuccinic acid (ASA) is a small molecule dicarboxylate that could be a strong clinical development candidate for inherited myopathies involving dysregulated purine nucleotide metabo-lism. Currently, there are no published pharmacokinetic/dynamic or toxicology data available, albeit 10-year clinical trial data in Duchenne muscular dystrophy patients suggests a chronically safe drug. In this study, we tested the toxicity of ASA to cultured myoblasts in vitro and acute systemic toxicity in mice. ASA is a non-toxic small molecule with an LD50> 5000mg/kg. Some background necrotic foci in the liver, kidney and gastrointestinal tract were shown that are likely incidental but warrant follow-up sub-/chronic oral exposure studies.

Three carbon-chain extension genes associated with fatty acid synthesis in cotton, namely GhKAR, GhHAD, and GhENR, play important roles in oil accumulation in cotton seeds. In the present study, these three genes were cloned and characterized. The expression patterns of GhKAR, GhHAD and GhENR in the high seed oil content cultivars 10H1007, 10H1014, and 10H1041 differed somewhat compared with those of 2074B with low seed oil content at different stages of seed development. GhKAR showed all three cultivars showed higher transcript levels than that of 2074B at 10, 40 and 45 DPA. The expression pattern of GhHAD showed a lower transcript level than that of 2074B at both 10 and 30 DPA but higher transcript level than that of 2074B at 40 DPA. GhENR showed a lower transcript level than that of 2074B at both 15 and 30 DPA. The highest transcript levels of GhKAR and GhENR were detected at 15 DPA in 10H1007, 10H1014, and 10H1041 compared with 2074B. From 5 to 45 days post anthesis (DPA) cotton seed, the oil content accumulated continuously in the developing seed. Oil accumulation reached the peak at 40 DPA to 45 DPA and slightly decreased in mature seed. In addition, GhKAR and GhENR showed different expression patterns in fiber and ovule development processes, in which they showed high expression levels at 20 DPA during fiber elongation stage, but their expression level peaked at 15 DPA during ovule development processes. These two genes showed the lowest expression levels at the late seed maturation stage, while GhHAD showed peak at 10 DPA of fiber development. Compared to 2074B, the oil contents of GhKAR and GhENR overexpression lines increased 1.05~1.08 folds. These results indicated that GhHAD, GhENR and GhKAR were involved in both seed oil synthesis and fiber elongation with dual biological functions in cotton.

HCC is a highly aggressive malignancy with limited treatment options. In this study, novel conjugates, of NSAIDs - Ibuprofen and Ketoprofen with oleanolic acid oximes derivatives (OAO) were synthesized and their activity as modulators of signaling pathways involved in HCC pathogenesis was evaluated in normal THLE-2 liver cells and HCC derived HepG2 cells. The results demonstrated that conjugation with OAO derivatives reduces the cytotoxicity of parent compounds in both cell lines. In THLE-2 cells treatment with conjugates resulted in increased activation of the Nrf2-ARE pathway. An opposite effect was observed in HepG2 cells. In the later reduction of NF-κB was observed along with modulation of MAPK signaling pathways (AKT, ERK, p38, p70S6K, and JNK). Moreover, STAT3, STAT5, and CREB transcription factors on protein levels were significantly reduced as a result of treatment with IBU- and KET-OAO derivatives conjugates. The most active were conjugates with OAO-morpholide. Overall, the findings of this study demonstrate that IBU-OAO and KET-OAO derivatives conjugates modulate the key signaling pathways involved in hepatic cancer development. Their effect on specific signaling pathways varied depending on the structure of the conjugate. Since the conjugation of IBU and KET with OAO derivatives reduced their cytotoxicity, the conjugates may be considered good candidates for the prevention of liver cancer.

The blackening of cut carrots decreases their shelf life and causes severe economic losses but the molecular and metabolic mechanisms that underpin this phenomenon remain poorly characterized. Studies were therefore undertaken to determine the molecular and metabolic causes of the blackening. The susceptibility of blackening was dependent on the period of time that the crop was stored underground prior to harvest. The structure of the cell walls in the black regions was substantially changed compared to the orange regions. The black regions of carrot batons had decreased immunodetection of xyloglucan, HG-pectin, RG-I pectin, galactan and arabinan but had higher levels of lignin and phenolic compounds compared to the orange regions. Transcript profiling analysis revealed that phytohormone signalling processes were activated in the black regions. Transcripts associated with auxin signalling and ethylene-responsive transcription factors were increased in the black regions. In contrast, the levels of transcripts encoding proteins associated with secondary metabolism were decreased in the black regions. These findings implicate ethylene and auxin-related processes in the control of the primary to secondary metabolism shift that results in lignification and cell wall disruption that underpin the blackening process.

Use of rhizosphere microorganisms provides an alternative or supplement to conventional plant breeding to improve water deficit tolerance of tomato plants. Experiment was carried out to explore the effect of two microbial species, AMF (Rhizophagus irregularis) and Bacillus subtilis, in single and co-application, on growth, colonization, and molecular aspects of tomato plants under drought stress. Co-inoculated plants showed less reduction in growth traits, photosynthetic pigments, colonization rate, and increased compatible solutes like proline which help in sustaining relative water content than non-inoculated plants. Inoculation considerably enhanced proline dehydrogenase activity, and significantly reduced both Δ1-pyrroline-5-carboxylate reductase Δ1-pyrroline-5-carboxylate synthetase activity causing lower proline accumulation in inoculated plants under drought stress. Co-inoculated plants showed obvious upregulation of antioxidant system, thus facilitating amelioration of oxidative stress through exclusion of reactive oxygen species. No inoculation under drought stress upregulated abscisic acid related genes expression but have no effect in plants inoculated either sole or mixed inoculation. Expression of aquaporin genes was upregulated in plants co-inoculated and with AMF alone under normal condition. However the expression of aquaporin genes were decreased or unaffected in plants inoculated with Bacillus subtilis but increased in non-inoculated plants. Co-applied AMF and bacillus subtilis substantially increase drought tolerance by upregulating proline metabolism, antioxidant enzymes and aquaporin genes. Therefore our results suggest that co-inoculation mediated drought tolerance is linked with increased proline accumulation, enhanced antioxidant enzyme activities and differential regulation of ABA biosynthetic and aquaporin genes, which is vital for osmotic adjustment of host plant.

One of the potential sources of rare-earth elements (REEs) is the solid waste from alumina industry - bauxite residue, known as “red mud” (RM). The main REEs from the raw bauxite are concentrated in RM after the Bayer leaching process. The earlier worldwide studies were focused on the scandium (Sc) extraction from RM by concentrated acids to enhance the extraction degree. This leads to the dissolution of major oxides (Fe2O3 and Al2O3) from RM. This article studies the possibility of selective Sc extraction from alkali fusion red mud (RMF) by diluted nitric acid (HNO3) leaching at pH ≥ 2 to prevent co-dissolution of Fe2O3. RMF samples have been analyzed by X-ray fluorescence spectrometry (XRF), X-ray diffraction (XRD), electron probe microanalysis (EPMA), and inductively coupled plasma mass spectrometry (ICP-MS). Sc extraction has been found to be 71.2 % at RMF leaching by HNO3 at pH=2 and at 80 °C during 90 min. The kinetic analysis of experimental data by the shrinking core model has shown that Sc leaching process is limited by the interfacial diffusion and the diffusion through the product layer. The apparent activation energy (Ea) was 19.5 kJ/mol. We have established that according to EPMA of RMF, Sc is associated with iron minerals; it could act as the product layer. The linear dependence of Sc extraction of magnesium (Mg) extraction has been revealed. This fact indicates that Mg can act as a leaching agent of Sc presented in RMF by ion-exchangeable phase.

Aim: the purpose of the present prospective, case series study were to report implant survival rate and marginal bone remodeling expected five years after loading using dental implants placed in in the daily practice. Material and Methods: this research was designed as an open-cohort, prospective case series study. Any completely or partially edentulous patients scheduled to receive at least one bone leve were considered eligible for this study. Primary outcomes were: cumulative implant (ISR) and prosthetic (PSR) survival rates, and any complications experienced up the five years follow-up. Secondary outcomes were: marginal bone remodeling, implant insertion torque, implant stability quotient (ISQ), and thickness of gingival biotype. Results: ninety consecutive patients (34 males and 56 females; mean age 53.2±15.4 years; range of 24–81 years), 243 implants were placed and followed for at least five years after loading (mean of 65.4±3.1 months; range of 60–72 months). The mean implant insertion torque was 42.9±4.8 Ncm (range from 15 to 45 Ncm). Overall, 83.5% of the implants (n=203) were placed with an insertion torque between 35 and 45 Ncm. At the one year follow-up, no drop-outs were recorded, but 17 patients (18.9%) with 18 restorations (12.6%) delivered on 34 implants (14%) were lost at the five years examination. At the five-year examination, six implants failed in six patients, resulting in a cumulative ISR of 97.5%. At the five-year follow-up, four prostheses failed (2.8%) resulting in a cumulative PSR of 97.2%. At the five-year examination, five complications were reported by five different patients, resulting in a prosthetic success rate of 96.5%, measured at patient level. Five years after loading, mean MBL was 0.41 ± 0.30 mm (95% CI: 0.26–0.34). Difference from the one year data was 0.04 ± 0.19 mm (95% CI: 0.01–0.07). The mean ISQ value at implant placement was 71.6 ± 5.5 (range of 45–88). Six months later, the mean ISQ was 76.7 ± 4.4 (range of 66–89). The difference was statistically significant (P=0.0001). Statistically significant higher MBL was found for smokers, and patient with thin gingival biotype. Conclusions: High implant survival and success rates could be expected with stable marginal bone remodeling up to five years after loading. Smoking and thin tissue biotype were the most important variabilities associated with higher MBL. Further research are needed to confirm these results.

Plukenetia volubilis is an underutilized oilseed crop native to the Amazon basin, where it has been utilised by humans since Incan times. The large seeds contain approx. 45–50 % lipid, of which approx. 35.2–50.8 % is α-linolenic acid (C18:3 n-3, ω-3) and approx. 33.4–41.0 % is linoleic acid (C18:2 n-6, ω-6), the two essential fatty acids required by humans. The seeds also contain 22–30 % protein and have antioxidant properties. Due to its excellent nutritional composition and good agronomic properties, it has attracted increasing attention in recent years, and cultivation is expanding. When considering current global challenges, a reformation of our food systems is imperative in order to ensure food security, mitigation of climate change, and alleviation of malnutrition. For this purpose, underutilized crops may be essential tools, which can provide agricultural hardiness and reduced need for external inputs, climate resilience, diet diversification, and improved income opportunities for smallholders. Plukenetia volubilis is a promising up and coming crop in this regard and has considerable potential for further domestication; it has an exceptional oil composition, good sensory acceptability, is well suited for cultivation, and has numerous potential applications in, e.g. gastronomy, medicine, and cosmetics.

Fumaric acid esters (FAEs) are small molecules with anti-oxidative, anti-inflammatory and immune-modulating effects. Dimethyl fumarate (DMF) is the best characterised FAE and is approved and registered for the treatment of psoriasis and Relapsing-Remitting Multiple Sclerosis (RRMS). Psoriasis and RRMS share an immune-mediated aetiology, driven by severe inflammation and oxidative stress. DMF, as well as monomethyl fumarate and diroximel fumarate, are commonly prescribed first-line agents with favourable safety and efficacy profiles. The potential benefits of FAEs against other diseases that appear pathogenically different but share the pathologies of oxidative stress and inflammation are currently investigated.

An elevated level of endoplasmic reticulum (ER) stress is considered an aggravating factor for inflammatory bowel disease (IBD). To develop an ER stress attenuator that is effective against colitis, 4-phenylbutyric acid (4-PBA), a chemical chaperone that alleviates ER stress, was conjugated with acidic amino acids to yield a 4-PBA-glutamic acid conjugate (PBA-GA) and a 4-PBA-aspartic acid conjugate (PBA-AA). The PBA derivatives were converted to 4-PBA in the cecal contents, where the conversion was greater with PBA-GA. After oral administration of PBA-GA (oral PBA-GA), millimolar levels of PBA were accumulated in the cecum, whereas 4-PBA was not detected in the blood, indicating the targeting of PBA-GA to the large intestine. At concentrations in the cecum achievable by oral PBA-GA, 4-PBA effectively attenuated ER stress in human colon epithelial cells. In 2,4-dinitrobenzenesulfonic acid-induced colitis in rats, oral PBA-GA alleviated the damage and inflammation in the colon. Moreover, oral PBA-GA substantially reduced the elevated levels of ER stress marker proteins in the inflamed colon. Moreover, PBA-GA was as effective as the currently used anti-IBD drug, sulfasalazine. In conclusion, PBA-GA is a colon-targeted prodrug of 4-PBA and is effective against rat colitis probably through the attenuation of ER stress in the inflamed colon.

Sol-gel route represents a valuable technique to obtain functional materials, in which organic and inorganic members are closely connected. Herein four hybrid materials, containing caffeic acid entrapped in a silica matrix at 5, 10, 15 and 20 wt%, were synthesized and characterized through FT-IR and UV-Vis spectroscopy. FT-IR analysis was also performed to evaluate the ability to induce the hydroxyapatite nucleation. Despite some structural changes occurred on the phenol molecular skeleton, hybrid materials showed scavenging properties vs DPPH and ABTS+ radicals, which was dependent on the tested dose and on the caffeic acid wt%. Finally, the SiO₂/caffeic acid materials have been proposed as valuable antibacterial agents against Escherichia coli and Enterococcus faecalis.

Acute ischemic strokes are the third leading cause of death and the leading cause of neurological disability worldwide. The oxygen and glucose deprivation associated with ischemic strokes not only leads to neuronal cell death, but also increases the inflammatory response and decreases functional output of the brain. The only intervention approved by US Federal Drug and Food Administration for treatment of ischemic strokes is tissue plasminogen activator (tPA), however, such treatment can only be given within 4.5 hours of the onset of stroke-like symptoms. This narrow time-range limits its application, and it also might induce detrimental rather than beneficial effects to stroke patients by treatment of the tPA. In order to reduce the infarct volume of an acute ischemic stroke while increasing the time period for treatment, emerging therapies reveal great potential by targeting inflammation, growth factors, ion channels, and neurotransmitter receptors with monoclonal antibody (MAB). With successfully application in the treatment of cancer patient by MAB, in this review, we will focus on recent advances on stroke therapy by using MAB on the treatment of stroke by targeting inflammation, growth factors, ion channels, and neurotransmitter receptors. Therefore, developing specific MAB targeting the signaling pathway of stroke will contribute to stroke therapy.

Butyric acid as a histone deacetylase (HDAC) inhibitor was produced by a number of periodontal and root canal microorganisms (such as Porphyromonas, Fusobacterium etc.). Butyric acid may affect the biological activities of periodontal/periapical cells such as osteoblasts, periodontal ligament cells etc., and thus affect periodontal/periapical tissue destruction and healing. The purposes of this study were to study the toxic effects of butyrate on matrix and mineralization markers’ expression of MG-63 osteoblasts. Cell viability and proliferation were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Cellular apoptosis and necrosis were analyzed by propidium iodide/Annexin V flow cytometry. Protein and mRNA expression of OPG, and RANKL were analyzed by western blotting and RT-PCR. OPG, soluble RANKL (sRANKL), 8-isoprostane, pro-collagen I, MMP-2, osteonectin (SPARC), osteocalcin and osteopontin secretion into culture medium were measured by enzyme-linked immunosorbant assay. Histone H3 acetylation levels were evaluated by immunofluorescent staining (IF) and western blot. We found that butyrate induced morphologic changes of growing MG-63 cells, with bigger and flattened in appearance. Butyrate activated histone H3 acetylation of MG-63 cells. Exposure of MG-63 cells to butyrate partly decreased cell number with no marked increase in apoptosis and necrosis. Butyrate stimulated RANKL protein expression, whereas it inhibited OPG protein expression. Butyrate also inhibited the secretion of OPG in MG-63 cells, whereas sRANKL level was below detection limit. Butyrate stimulated 8-isoprostane, MMP-2 and osteopontin secretion, but not procollagen I, osteonectin, osteocalcin in MG-63 cells. In conclusion, butyric acid generated by periodontal and root canal microorganisms may potentially induce bony destruction and impair bone repair by alteration of OPG/RANKL expression/secretion, 8-isoprostane, MMP-2, and osteopontin secretion, and affect cell proliferation. These effects are possibly related to increased histone acetylation. These events are important in the pathogenesis of periodontal and periapical destruction.

Background. Transferrin receptor 1 (TfR1), glucose transporter 1 (GLUT1), and CD98hc are candidates for targeted therapy at the blood-brain barrier (BBB). Our objective was to challenge the expression of TfR1, GLUT1, and CD98hc in brain capillaries by the histone deacetylase inhibitor (HDACi) valproic acid (VPA). Methods. Primary mouse brain capillary endothelial cells (BCECs) and brain capillaries isolated from mice injected intraperitoneally with VPA were examined using RT-qPCR and ELISA. Targeting to the BBB was performed by injecting monoclonal anti-TfR1 (Ri7217)-conjugated gold nanoparticles measured using ICP-MS. Results. In BCECs co-cultured with glial cells, Tfrc mRNA expression was significantly higher after 6 h VPA returning to baseline after 24 h. In vivo Glut1 mRNA expression was significantly higher in males, but not females', receiving VPA, whereas Cd98hc mRNA expression was unaffected by VPA. TfR1 increased significantly in vivo after VPA, whereas GLUT1 and CD98hc were unchanged. Uptake of anti-TfR1-conjugated nanoparticles was unaltered by VPA in spite upregulated TfR expression. Conclusions. VPA upregulates TfR1 in brain endothelium in vivo and in vitro. VPA does not increase GLUT1 and CD98hc proteins. The increase in TfR1 does not result in higher anti-TfR1 antibody targetability, suggesting targeting sufficiently occurs with available transferrin receptors without further contribution from accessory VPA-induced TfR1.

To clarify the risk factors for aggravation of esophagogastric varices (EGV) after hepatitis C virus (HCV) eradication with direct-acting antiviral (DAA) therapy, we enrolled 167 consecutive patients with HCV-related compensated cirrhosis who achieved a sustained virological response (SVR) after DAA therapy. During a median of 69 months, EGV was aggravated in 42 (25%) patients despite SVR. The cumulative 1, 3, 5, and 10-year aggravated EGV rates were 7%, 23%, 25%, and 27%, respectively. Multivariate analysis identified platelet count <11.0×10⁴/μL, LSM ≥18.0 kPa, total bile acid ≥33.0 μmol/L, and diameter of left gastric vein (LGV) ≥5.0 mm at HCV eradication as independent risk factors for EGV aggravation post-SVR. In groups that meet all of these risks, the cumulative EGV aggravation rates at 1, 3, and 5 years were 27%, 87%, and 91%, respectively. However, none of the patients who had only one or none of the risk factors experienced EGV aggravation. Platelet count, LSM, total bile acid, and diameter of LGV at HCV eradication were associated with aggravated EGV post-SVR. EGV tends to worsen as two or more of these risk factors increase.

Oral and parenteral delivery of first-line anticonvulsant Valproic cid (VA) are associated with serious adverse effects, high hepatic metabolism, high clearance, and low bioavailability in brain. GastroPlus program was used to predict in vivo performance of immediate (IR) and sustained release (SR) products in human. HSPiP software predicted excipients with maximum possible miscibility of the drug. Based on GastroPlus and HSPiP program, various excipients were screened for experimental solubility study and prepared cationic nanoemulsions and respective gels for nasal to brain delivery. These were characterised for size, size distribution, polydispersity index, zeta potential, morphology, pH, % transmittance, drug content, and viscosity. In vitro drug release, ex vivo permeation profile (goat nasal mucosa), and penetration studies were conducted. Result showed that in-vivo oral drug dissolution and absorption were predicted as 98.6 mg and 18.8 mg, respectively from both tablets (IR and SR) at 8 h using GastroPlus. The drug access to the portal vein was relatively predicted high in IR (115 mg) as compared to SR (82.6 mg). Plasma drug concentration-time profile predicted was in good agreement with published reports. The program predicted duodenum and jejunum as the prime site of drug absorption and no effect of nanonization on Tmax for sustained release formulation. Hansen parameters suggested suitable selection of excipients. The program recommended for nasal to brain delivery of the drug using cationic mucoadhesive product. The optimized stable CVE6 was associated with optimal size (113 nm), low PDI (0.26), high zeta potential (+34.7 mV), high transmittance (97.8%), and high strength (0.7 %w/w). In vitro release and ex vivo permeation of CVE6 were found to be substantially high as compared to anionic AVE6 and respective gels. Penetration study executed high fluorescence intensity with CVE6 and CVE6-gel as compared to suspension and ANE6 which may be attributed to electrostatic interaction between mucosal membrane and nanoglobules. Thus, cationic nanoemulsion and respective mucoadhesive gel are promising strategy for delivery of VA to brain through intransal administration for the treatment of seizure and convulsion.