The study examines the integration of postbiotics in food products through the use of attenuated probiotics, specifically lactic acid bacteria (LAB) in bread. Postbiotics, non-viable microorganisms or their metabolites, offer health benefits similar to probiotics without the risks associated with live bacteria. This research evaluates the regulatory aspects and safety of LAB in sourdough bread production, highlighting their historical and significant use in Europe before 1997. The study includes microbial quantification and Next-Generation Sequencing (NGS) to identify LAB in traditional sourdough, comparing them with historical and current EFSA Qualified Presumption of Safety (QPS) lists. Findings show that the LAB present in sourdough have been extensively and safely used in bread making, supporting their classification as non-novel foods under EU regulations. The stability and consistency of LAB metabolites in sourdough bread are also confirmed, ensuring quality and safety in each batch. The study concludes that LAB in sourdough, when inactivated through bread-making processes, are not considered novel foods, aligning with historical, scientific, and regulatory evidence.

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.

Bladder cancer (BC) possesses distinct molecular profiles that influence progression depending on its biological nature and delivered treatment intensity. Muscle-invasive BC (MIBC) and non-MIBC (NMIBC) demonstrate great intrinsic heterogeneity regarding different prognoses, survival, progression, and treatment outcomes. Transurethral resection of bladder tumor (TURBT) is the standard of care in treating NMIBC and serves both diagnostic and therapeutic purposes, despite the prevalent recurrence and progression among many patients. In particular, flat urothelial car-cinoma in situ and urothelial carcinoma with lamina propria invasion are the major precursors of MIBC. A new‐generation photosensitizer, 5‐Aminolevulinic acid (5-ALA), demonstrates high tumor specificity by illuminating the tumor lesion with a specific wavelength of light to produce fluorescence, and has been studied for photodynamic diagnosis to detect precise tumor areas by TURBT. Additionally, it has been applied for treatment by producing its cytotoxic reactive oxygen species, as well as screening for urological carcinomas by excreting porphyrin in the blood and urine. Moreover, 5-ALA may contribute to screening before and after TURBT in NMIBC. Here, we summarize the updated evidence and ongoing research on photodynamic technology for NMIBC, providing insight into the potential for improving patient outcomes.

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.

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.

The use of Lactic Acid Bacteria (LAB) for probiotic enrichment of minimally processed fruit is a well-established practice in literature. In addition, several LAB demonstrated a strain-specific ability to control harmful microorganisms and decay agents, improving shelf-life, maintaining quality and promoting the safety of fruits and vegetables. Edible coatings can help modulate phenomena of gas exchange and water loss by fruits, representing protection from physical damage and spoilage phenomena linked to oxidation and the development of undesired microorganisms. At the same time, the coating can represent an innovative delivery matrix for the LAB strains of potential interest to improve safety and quality in the postharvest management of fruits. In this work, five Lactiplantibacillus plantarum strains, previously characterized for their probiotic and antifungal activity, have been incorporated into a sodium alginate coating to develop edible probiotic coatings with antifungal properties for table grapes cv. Italia. The transfer of probiotics and their survival were evaluated by comparing coated and uncoated table grapes during 14 days of cold storage at 4 °C. The alginate edible coating increased the number of probiotics transferred to the surface of the berries from about 5 to more than 7 Log CFU/g, with a crucial impact on the potential functional attributes of the final product. The ability of the functionalised coatings to counteract the decay development was evaluated on table grapes berries artificially contaminated with Aspergillus niger CECT 2805. A significant reduction of lesion diameter was observed in alginate coating with L. plantarum 11-A. The lesion diameter reduction was also accompanied by the reduction of the symptoms of infection, such as browning around the wound. These results suggest the application of selected strains of L. plantarum as promising bio-resources to enhance the overall value of ready-to-eat fruits and vegetables, particularly in combination with edible coating as a carrier matrix. While a strain-dependent effect was not detected with respect to the improvement of the number of cells in the edible coating, a variability depending on the biotype used was detected for the properties linked to biocontrol, suggesting that the inclusion in edible packaging may represent an innovative criterion in the selection of lactobacilli to be applied postharvest.

The central nervous system (CNS) is the final frontier in drug delivery because of the blood-brain barrier (BBB), which poses significant barriers to the access of most drugs to their targets. Kynurenic acid (KYNA), a tryptophan (Trp) metabolite, plays an important role in behavioral functions and abnormal KYNA levels have been observed in neuropsychiatric conditions. The current challenge lies in delivering KYNA to the CNS owing to its polar side chain. Recently, C-3 side chain modified KYNA analogs have been shown to cross the BBB; however, it is unclear whether they retain the biological functions of the parent molecule. This study examined the impact of KYNA analogs, specifically SZR-72, SZR-104, and the newly developed SZRG-21, on behavior. The analogs were administered intracerebroventricularly (i.c.v.), and their effects on the motor domain were compared with those of KYNA. Specifically, open field (OF) and rotarod (RR) tests were employed to assess motor activity and skills. SZR-104 increased horizontal exploratory activity in the OF test at a dose of 0.04 μmol/4 μL, while SZR-72 decreased vertical activity at doses of 0.04 and 0.1 μmol/4 μL. In the RR test, however, neither KYNA nor its analogs showed any significant differences in motor skills at either dose. Side chain modification affects affective motor performance and exploratory behavior, as the results show for the first time. In this study, we showed that KYNA analogs alter emotional components such as motor-associated curiosity and emotions. Consequently, drug design necessitates the development of precise strategies to traverse the BBB while paying close attention to modifications in their effects on behavior.

The modification of GFP-CaaL sensor proteins by geranylgeranyl groups in plants requires an active plastidial mevalonate (MVA)-independent pathway. As a consequence, fosmidomycin, a specific inhibitor of 1-deoxy-D-xylulose (DX)-5 phosphate reductoisomerase/DXR, the second enzyme in this so-called methylerythritol phosphate (MEP) pathway, impedes protein prenylation, which results in GFP-labeling of nuclei instead of the plasma membrane. In tobacco cells, a visual screen of conditions that allowed membrane localization of GFP-CaaL proteins in the presence of fosmidomycin, pinpointed jasmonic acid methyl esther (Me-JA) as a chemical able to overcome the inhibition in a gradual manner. Using Arabidopsis protein prenyltransferase loss-of-function mutant lines expressing GFP-CaaL proteins, we demonstrated that Me-JA induces a modification in protein substrate recognition by protein farnesyltransferase (PFT). Similar to Me-JA, farnesol and MVA also alter the protein substrate specificity of PFT, whereas DX and geranylgeraniol have limited or no effect. Our data indicate that stimulation of the MVA pathway adjusts the protein substrate specificity of PFT, which is corroborated with metabolic cross-talk of the origin of the prenyl group used to modify the protein. To illustrate how activation of the MVA pathway impacting PFT substrate specificity benefits a plant under stress conditions, a model is proposed.

Endophytic fungi colonize the inner tissues of plants and provide direct and indirect benefits to the plant. Although Mongolia is rich in medicinal plants, due to climatic and anthropogenic reasons the resources are being depleted and many species are under the threat of gradual extinction, while the endophytic fungi of Mongolian plants are largely unknown. Understanding the diversity and metabolic potential of endophytic fungi is of great significance in terms of the utilization of beneficial fungal strains in plant propagation and the discovery of bioactive compounds. In this study, a total of 24 culturable endophytic fungal strains were isolated from Cynomorium songaricum (Rupr.), a medicinal and vulnerable plant species of Mongolia. Based on the morphological characteristics and the sequences of the rDNA internal transcribed spacer (ITS) region, the isolates were identified to 6 genera: Fusarium (8), Clonostachys (7), Penicillium (6), Alternaria (1), Aspergillus (1), and Madurella (1). The antimicrobial activity was assessed by agar-diffusion method, revealing that 15 strains were able to inhibit the growth of at least one of the test organisms. Among them, 1 strain showed inhibitory activity against Escherichia coli, 12 against Bacillus subtilis, 13 against Staphylococcus aureus, 8 against Aspergillus niger, respectively. All fungal strains were screened for their ability to solubilize complex phosphorus and zinc minerals and for their production of indole-3-acetic acid (IAA). The strains were preserved in the national culture collection for further sustainable exploitation of their biotechnological potential.

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.

: The primary objective of this study was to investigate the association of certain genetic alterations and intraoperative fluorescent activity of 5-aminolevulinic acid (ALA) in brain metastasis (BM) of lung adenocarcinoma. A retrospective cohort study was conducted among 72 patients who underwent surgical resection of BM from lung adenocarcinoma at our institute for 5 years. Cancer cell infiltration was estimated by the intraoperative fluorescent activity of 5-ALA, and genetic alterations were analyzed by next-generation sequencing (NGS). The sensitivity and specificity for detecting cancer cell infiltration using 5-ALA were 87.5% and 96.4%, respectively. Genes associated with cell cycle regulation (p = 0.003) and cell proliferation (p = 0.044) were significantly associated with positive fluorescence activity of 5-ALA in the adjacent brain tissue. Genetic alterations in cell cycle regulation and cell proliferation were also associated with shorter recurrence-free survival (p = 0.013 and p = 0.042, respectively) and overall survival (p = 0.026 and p = 0.042, respectively) in the multivariate analysis. The results suggest that genetic alterations in cell cycle regulation and cell proliferation are associated with positive fluorescence activity of 5-ALA in the adjacent infiltrative brain tissue and influence the clinical outcome of BM of lung adenocarcinoma.

The synthesis and characterization of the multicomponent crystals formed by 2,2’-thiodiacetic acid (H2tda) and 2,6-diaminopurine (Hdap) or N9-(2-hydroxyethyl)adenine (9heade) are reported. The crystals are in the salt rather than cocrystal form, as witnessed by single crystal X-ray diffractometry where a structural analysis revealed their ionic nature, confirming the proton transfer from the 2,2’-thiodiacetic acid to the basic groups of the coformers. The new multicomponent crystals have molecular formulas [(H9heade+)(Htda)] (1) and [(H2dap+)2(tda2)]·2H2O (2), and were also characterized by FTIR, elemental analysis as well as thermogravimetric/differential scanning calorimetry (TG/DSC) analyses. In the crystal packing the ions interact with each other via O–H···N, O–H···O. N–H···O and N–H···N hydrogen bonds generating cyclic hydrogen bonded motifs with graph-set notation of R22(16), R22(10), R32(10), R33(10), R22(9), R32(8) and R42(8), to form different supramolecular homo- and hetero-synthons. In addition, in the crystal packing of 2, pairs of diaminopurinium ions display an strong anti-parallel ,-stacking interaction, with short inter-centroids and interplanar distances (3.39 and 3.24 Å respectively) and fairly tight angle (17.5°). These assemblies have been further analyzed energetically by using DFT calculations, MEP surface analysis and QTAIM characterization.

This study is based on the fatty acid and amino acid profile of 7 edible insect species: Acheta domesticus, Alphitobius diaperinus, Blaptica dubia, Galleria mellonella, Locusta migratoria, Tenebrio molitor and Zophobas morio. The fatty acid distribution within lipid classes (neutral lipids, glycolipids and phospholipids) was studied, while the amino acid profile was used to calculate the species-specific nitrogen-protein conversion factor (Kp). The profiles were used to evaluate the nutritional quality of the lipids and proteins. Oleic acid was the predominant fatty acid in all insects except for A. domesticus, in which a larger percentage of linoleic acid was found. The majority of the lipids were neutral lipids. L. migratoria showed a remarkably high content of α-linolenic acid in its phospholipid fraction, while T. molitor phospholipids were the only fraction in which a measurable amount of docosahexaenoic acid was found. Overall, in most insects, the phospholipid fraction had the highest polyunsaturated fatty acid content compared to the other classes, which may be protective in terms of autoxidative stability. Kp values in the range of 4.17 to 6.43 were obtained. Within the nutritional quality indices, all insects showed healthy fatty acid and high quality amino acid profiles.

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.

The use of biolubricants as an alternative for petroleum-based products has played an important role in the last decade. Thus, due to the encouragement of global policies, which mainly support green chemistry and circular economy, there has been an increasing interest in bio-based products, including biolubricants, from scientific and industrial points of view. Due to the different applications of biolubricants for a wide range of practical uses, the raw materials, production, and characteristics might vary, making this field a continuously changing subject of study by researchers. The aim of this research work was to focus on biolubricant production from vegetable oil crops in a bio-refinery perspective, paying attention to the main raw materials used, the corresponding production methods (with special focus on double transesterification), the role of catalysts and techno-economic studies. Thus, the main factors affecting quality parameters such as viscosity or oxidative stability have been covered, including catalyst addition, reaction temperature or the use of raw materials, reagents or additives were also analyzed. The latest research trends were included, updating previous studies about this matter, considering current conclusions and future research.

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.

Anti-islet autoantibodies serve as key markers in immune-mediated type 1 diabetes (T1D) and slowly-progressive T1D (SPIDDM), also known as latent autoimmune diabetes in adults (LADA). Autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA), tyrosine phosphatase-like protein IA-2 (IA-2A), and zinc transporter 8 (ZnT8A) are currently employed in the diagnosis, pathological analysis, and prediction of T1D. GADA can also be detected in non-diabetic patients with autoimmune diseases other than T1D and may not necessarily reflect insulitis. Conversely, IA-2A and ZnT8A serve as surrogate markers of pancreatic β-cell destruction. Combinatorial analysis of these four anti-islet autoantibodies demonstrated that 93-96% of acute-onset T1D and SPIDDM cases were diagnosed as immune-mediated T1D, while the majority of fulminant T1D cases were autoantibody-negative. Evaluating the epitopes and immunoglobulin subclasses of anti-islet autoantibodies help distinguish between diabetes-associated and non-diabetes-associated autoantibodies and is valuable for predicting future insulin deficiency in SPIDDM (LADA) patients. Additionally, GADA in T1D patients with autoimmune thyroid disease reveals the polyclonal expansion of autoantibody epitopes and immunoglobulin subclasses. Recent advancements in anti-islet autoantibody assays include nonradioactive fluid-phase assays and the simultaneous determination of multiple biochemically defined autoantibodies. Developing a high-throughput assay for detecting epitope-specific or immunoglobulin isotype-specific autoantibodies will facilitate more accurate diagnosis and prediction of autoimmune disorders.

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.

The research and development of non-viral gene therapy has been extensive over the past decade and has received a big push thanks to the successful approval of non-viral gene therapy products in recent times. Despite these developments, gene therapy applications in cancer have been limited. One of the main causes of this has been the imbalance in development of delivery vectors as compared to nucleic acid payloads. This paper reviews non-viral vectors that can be used to deliver nucleic acids for cancer treatment. It discusses various types of vectors and highlights their current applications. Additionally, it also discusses perspective on regulatory landscape to facilitate commercial translation of gene therapy.

The fatty acid elongase ELOngation of Very-Long-chain fatty acids protein 2 (ELOVL2) controls the elongation of polyunsaturated fatty acids (PUFA) producing precursors for omega-3, do-cosahexaenoic acid (DHA), and omega-6, docosapentaenoic acid (DPAn6) in-vivo. Expectedly, Elovl2-ablation drastically reduced the DHA and DPAn6 in liver mitochondrial membranes. Unexpectedly, however, total PUFAs levels decreased further than could be explained by Elovl2 ablation. The lipid peroxidation process was not involved in PUFAs reduction since malondial-dehyde-lysine (MDAL) and other oxidative stress biomarkers were not enhanced. The content of mitochondrial respiratory chain proteins remained unchanged. Still, membrane remodeling was associated with high voltage-dependent anion channel (VDAC) and adenine nucleotide trans-locase 2 (ANT2), a possible reflection of the increased demand on phospholipid transport to the mitochondria. Mitochondrial function was impaired despite preserved content of the respiratory chain proteins and the absence of oxidative damage. Oligomycin-insensitive oxygen consumption increased, and coefficients of respiratory control were reduced by 50%. The mitochondria became very sensitive to fatty acid-induced uncoupling and permeabilization, where ANT2 is involved. Mitochondrial volume and number of peroxisomes increased as revealed by transmission elec-tron microscopy. In conclusion, the results imply that endogenous DHA production is vital for the normal function of mouse liver mitochondria and could be relevant not only for mice but also for human metabolism.

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

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.

A face serum composed of a combination of biologically active compounds was evaluated for safety and efficacy in vitro, in a repeat insult patch test and in a human clinical efficacy trial. The serum inhibited tyrosinase activity modestly, decreased collagenase activity and exhibited notable free radical scavenging activity in vitro. It is gentle to the skin, as the serum did not irritate the skin or produce symptoms of allergic contact dermatitis in the 55 healthy adults that participated in the repeat insult patch test. In the efficacy trial, daily application of the face serum for 30 days significantly increased skin hydration, with all 35 volunteers experiencing improvement. Substantial improvements in skin elasticity, roughness (fine lines and wrinkles), and brightness also occurred during the trial. Dermatological examination also revealed a trend for reduced comedone count with use of the serum. Self-assessment responses revealed that all volunteers experienced improvements in multiple skin quality parameters and that participant perceptions are consistent with the results of the instrumental analyses. These findings indicated that the measured improvements in skin quality are not only statistically significant but are also clinically relevant as they were great enough for users of the face serum to feel and recognize.

The development of platinum group metal-free (PGM-free) electrocatalysts derived from cheap and environmentally friendly biomasses for oxygen reduction reaction (ORR) is a topic of relevant interest, particularly from the point of view of sustainability. Fe-nitrogen-doped carbon materials (Fe-N-C) have attracted particular interest as alternative to Pt-based materials, due to the high activity and selectivity of Fe-Nx active sites, the high availability and good tolerance to poisoning. Recently, many studies focused on developing synthetic strategies, which could transform N-containing biomasses into N-doped carbons. In this paper chitosan was employed as a suitable N-containing biomass for preparing Fe-N-C catalyst in virtue of its high N content (7.1%) and unique chemical structure. Moreover, the major application of chitosan is based on its ability to strongly coordinate metal ions, a precondition for the formation of Fe-Nx active sites. The synthesis of Fe-N-C consists in a double step thermochemical conversion of a dried chitosan hydrogel. In acidic aqueous solution, the preparation of physical cross-linked hydrogel allows to obtain sophisticated organization, which assure an optimal mesoporosity before and after the pyrolysis. After the second thermal treatment at 900 °C, a highly graphitized material was obtained, which has been fully characterized in term of textural, morphological and chemical properties. RRDE technique was used for understanding the activity and the selectivity of the material versus the ORR in 0.5 M H2SO4 electrolyte. Special attention was put in the determination of the active site density according to nitrite electrochemical reduction measurements. It was clearly established that the catalytic activity expressed as half wave potential linearly scales with the number of Fe-Nx sites. It was also established that the addition of the iron precursor after the first pyrolysis step leads to an increased activity because of both an increased number of active sites and of a hierarchical structure, which improves the access to active sites. At the same time, the increased graphitization degree, and a reduced density of pyrrolic nitrogen groups are helpful to increase the selectivity toward the 4e- ORR pathway.

This study deals with computational analysis of dominant fatty acid ethyl esters characterized from the biodiesel produced from waste beef tallow by means of KOH catalyzed ethanol based transesterification. Ethyl palmitate, Ethyl Oleate, Ethyl Stearate and Ethyl Myristate were identified as dominant fatty acid esters and were computed for molecular analysis in Gaussian 09 software using Density Functional Theory (B3LYP method) with 6-31G* as basis set. Geometric parameters were in accordance with existing experimental values and population analysis exhibited negative charge for oxygen atoms, both positive & negative charge for carbon atoms in all ester molecules. The molecular dipole moment was higher for unsaturated ester molecule and quadruple moment proposed electronic dislocation in X+Y direction. Also, energy gap decreased slightly with increasing carbon chain but reduced drastically with increase in unsaturation. Electrostatic potential mapping displayed negative electrostatic potential for oxygen atoms in ester linkage of all ester molecules.

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.

Chlorotoxin (CTX) is a 36–amino acid peptide with 8 Cys residues that forms four Cys-Cys bonds. It has high affinity for the glioma-specific chloride channel and matrix metalloprotease-2. Structural and binding properties of CTX analogs with various Cys residue substitutions with L-a-aminobutyric acid (Abu) have been previously reported. Using 4.2 ìs molecular dynamics, we compared the conformational and essential space sampling of CTX and analogs [Abu/Ser^2,19]CTX, [Abu/Ser^5,28]CTX, [Abu/Ser^16,33]CTX, [Abu/Ser^20,35]CTX, and [Abu/Ser^{2,5,16,19,20,28,33,35}]CTX. The native and substituted peptides maintained a high degree of a-helix propensity from residues 8 through 21, with the exception of [Ser^5,28]CTX and [Abu^16,33]CTX. In agreement with previous circular dichroism spectropolarimetry results, the C-terminal b-sheet content varied less from residues 25 through 29 and 32 through 36 and was well conserved in all analogs, except: [Abu^16,33]CTX, [Ser^20,35]CTX, [Abu^{2,5,16,19,20,28,33,35}]CTX, and [Ser^{2,5,16,19,20,28,33,35}]CTX. The Cys¹⁶-Cys³³ and Cys²⁰-Cys³⁵ Cys-Cys bonds appear to be required to maintain the ab-motif of CTX. Their selective substitution with Ser^16,33 however, may mitigate the destabilizing effect of Cys¹⁶-Cys³³ substitution by the formation of an inter residue H-bond from OgH of Ser¹⁶ to OgH of Ser³³ bridged by a water molecule. All peptides shared considerable sampled conformational space, which explains the retained receptor binding of the nonnative analogs.

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.

Salinity is considered as one of the most important abiotic challenges that affect crop productivity. Plant hormones, including salicylic acid (SA), are key factors in the defence signalling output triggered during plant responses against environmental stresses. We have previously reported in peach a new SA biosynthetic pathway from mandelonitrile (MD), the molecule at the hub of the cyanogenic glucoside turnover in Prunus sp. In this work, we have studied whether this new SA biosynthetic pathway is also present in plum and the possible role this pathway plays in plant plasticity under salinity, focusing on the transgenic plum line J8-1, which displays stress tolerance via an enhanced antioxidant capacity. The SA biosynthesis from MD in non-transgenic and J8-1 micropropagated plum shoots was studied by metabolomics. Then the response of J8-1 to salt stress in presence of MD or Phe (MD precursor) was assayed by measuring: chlorophyll content and fluorescence parameters, stress related hormones, levels of non-enzymatic antioxidants, the expression of two genes coding redox-related proteins, and the content of soluble nutrients. The results from in vitro assays suggest that the SA synthesis from the MD pathway demonstrated in peach is not clearly present in plum, at least under in vitro conditions. Nevertheless, in J8-1 NaCl-stressed seedlings, an increase in SA was recorded as a result of the MD treatment, suggesting that MD could be involved in the SA biosynthesis under NaCl stress conditions in plum plants. We have also shown that the plum line J8-1 was tolerant to NaCl under greenhouse conditions, and this response was somewhat different in MD-treated plants. In that regards, the MD treatment produced an increase in SA, jasmonic acid (JA) and reduced ascorbate (ASC) contents as well as in the coefficient of non-photochemical quenching (qN) and the gene expression of Non-Expressor of Pathogenesis-Related 1 (NPR1) and thioredoxin H (TrxH) under salinity conditions, suggesting a crosstalk between different signalling pathways (NPR1/Trx and SA/JA) leading to salinity tolerance in the transgenic plum line J8-1.

This study aimed to characterize the long non-coding RNA (lncRNA) expression in the bovine mammary gland and to infer their functions in dietary response to 5% linseed oil (LSO) or 5% safflower oil (SFO). Twelve cows (six per treatment) in mid lactation were fed a control diet for 28 days followed by a treatment period (control diet supplemented with 5% LSO or 5% SFO) of 28 days. Mammary gland biopsies were collected from each animal on day-14 (D-14, control period), D+7 (early treatment period) and D+28 (late treatment period) and were subjected to RNA-Sequencing and subsequent bioinformatics analyses. Functional enrichment of lncRNA was performed via potential cis regulated target genes located within 50 Kb flanking regions of lncRNAs and having expression correlation of >0.7 with mRNAs. A total of 4955 lncRNAs (325 known and 4630 novel) were identified which potentially cis targeted 59 and 494 genes in LSO and SFO treatments, respectively. Enrichments of cis target genes of lncRNAs indicated potential roles of lncRNAs in immune function, nucleic acid metabolism and cell membrane organization processes as well as involvement in Notch, cAMP and TGF-β signaling pathways. Thirty-two and 21 lncRNAs were differentially expressed (DE) in LSO and SFO treatments, respectively. Six genes (KCNF1, STARD13, BCL6, NXPE2, HHIPL2 and MMD) were identified as potential cis target genes of six DE lncRNAs. In conclusion, this study indicated potential roles for lncRNAs in mammary gland immune functions and development and provided potential candidate genes and pathways via which lncRNAs can function in diet responses.

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.

The present article describes the synthesis of an isonicotinate-derived meso-arylporphyrin, that has been fully characterized by spectroscopic methods (including fluorescence spectroscopy), as well as by elemental analysis and by HR-MS. The structure of a n-hexane monosolvate has been determined by single crystal X-ray diffraction analysis. The radical scavenging activity of this new porphyrin against the 2,2-diphenyl-1-picrylhydrazyl (DDPH) radical has been measured. Its antifungal activity against three yeast strains (C. albicans ATCC 90028, C. glabrata ATCC 64677 and C. tropicalis ATCC 64677) has been tested, using the disk diffusion and the microdilution methods. Whereas the measured antioxidant activity was low, the porphyrin showed moderate but encouraging antifungal activity. Finally, a study of its effect on the germination of lentil seeds revealed interesting allelopathic properties.

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.

Nitraria tangutorum Bobrov is a berry shrub with white flowers and red fruits, which grows in the deserts in the Tibetan Plateau, Mongolia, and western China. Its fruit N. tangutorum fruit (NTF) contains various bioactive compounds, with anti-fatigue, anti-inflammatory, and neuroprotective functions. However, the high saccharide content of NTF makes it unsuitable for diabetic patients. In this study, we fermented NTF to obtain N. tangutorum fermented juice (NTJ), and N. tangutorum fermented residue (NTR), which are suitable for diabetics to consume. We characterized the bioactive compounds in NTF, NTR, and NTJ, and found that fermentation increased the diversity of bioactive compounds, and greatly reduced sucrose, glucose, and fructose content while generating trehalose, which has the potential to manage blood glucose levels. Further, NTJ displays anti-diabetic potential due to various compounds anti-diabetic properties. This study provides a basis for further clinical research on NTJ's anti-diabetic function in humans.

The subject of the conducted study was focused on the development of new type of technical blends reinforced with natural fillers. The study was divided into two parts, where in the firsts stage of the research unmodified POM was reinforced with different types of natural fillers: cellulose, wood flour and husk particles. In order to select the type of filler intended for further modification, the mechanical characteristics was assessed. The 20% wood flour (WF) filler system was selected as the reinforcement. The second stage of research involved the use of combination of polyoxymethylene POM and poly(lactic acid) PLA. POM/PLA blend (ratio 50/50 %) were modified with elastomeric compound (EBA) and chain extender as reactive compatibilized (CE). The microscopic analysis revealed that for POM/PLA system the filler-matrix interface is characterized by better wettability, which might suggest higher adhesion. The mechanical performance revealed that for POM/PLA-based composites the properties were very close to the results for POM-WF composites; however, there is still large difference in thermal resistance in favor of POM-based materials. The increase in thermomechanical properties for POM/PLA composites occurs after heat treatment. The increasing crystallinity of the PLA phase allows for an significant increase of the head deflection temperature (HDT), even above 125 °C.

The temperature effect plays an important role for an accurate determination of the polar free energy, polar thermodynamic parameters, and enthalpic and entropic Lewis’s acid base properties of oxides, polymers and composites polymers/oxides. The adsorption of polymers on other solid surfaces is crucial in many industrial applications, coatings, paints, catalysis, colloids and adhesion processes. (1) Background: Inverse gas chromatography at infinite was used for the physico-chemical characterization of solid substrates by determining the thermodynamic parameters of adsorption of model organic solvents on solid surfaces such as polymers, metallic oxides, carbon fibers, pharmaceutical or 3D/4D printing substrates. (2) Methods: A new method based on the London dispersion equation was applied with a new parameter associating the deformation po-larizability and the harmonic mean of the ionization energies of solvent. More accurate values of the dispersive and polar interaction energies of the various organic solvents adsorbed on PMMA in bulk phase and PMMA/silica at different recovery fractions were obtained as well as the Lewis acid-base parameters and the transition temperatures of the different composites. (3) Results: This new methodology gave very interesting results on the behavior of PMMA adsorbed on silica. An important effect of the temperature and the recovery fraction on the various physicochemical and thermodynamic properties was highlighted. The variations of all interaction parameters showed the presence of three transition temperatures for the different PMMA adsorbed on silica with the various coverage rates with a shift of these temperatures for a recovery fraction of 31% (4) Con-clusions: An important variation of the polar enthalpy and entropy of adsorption, the Lewis ac-id-base parameters and the intermolecular separation distance as a function of the temperature and the recovery fraction of PMMA on silica.

In order for the body to function properly, it needs not only food, but also nutrients and non-nutritive bioactive compounds that have an immunomodulating effect. This applies not only to healthy people, but especially to people with accompanying chronic diseases, including type 2 diabetes. Unfortunately, the current food industry and the use of highly processed food promote nutritional deficiencies. Many studies confirm their occurrence in patients with type 2 diabetes. The article presents the influence of selected nutrients on the functioning of the immune system, which ensures homeostasis of the body, with particular emphasis on type 2 diabetes. The role of macroelements, microelements, vitamins and selected substances, such as omega-3 acids, coenzyme Q10 and alpha-lipoic acid. The minimum scope of tests that should be performed in patients to directly or indirectly determine the degree of malnutrition in this group of patients is presented.

The effects of simulated acid rain (SAR) on the photosynthetic performance of subtropical coniferous species have not been thoroughly investigated. In this study, we treated two coniferous species, Pinus massoniana (PM) and Cunninghamia lanceolata (CL), with SAR and then analyzed photosynthetic activities via the simultaneous measurement of prompt fluorescence(PF), delayed fluorescence(DF), and modulated reflection at 820 nm(MR820). Following the low-pH SAR treatment, the I–P phase of the OJIP curves of PM and CL decreased significantly and then the K-band and L-band were detectable. The delayed fluorescence for both PM and CL decreased as the pH of the SAR solution decreased, with a more significant decrease in the I1 peak than in the I2 peak. According to the MR820 curve, the exposure to SAR stress inhibited the rapid decrease and slow increase in the MR820 transients of PM and CL. The gradients of the decreasing and increasing phases were lower for CL than for PM at pH 2.5. In addition, SAR decreased the light energy captured per unit area (ABS/CSm) and the quantum yield of electron transfer per unit area (ETO/CSm), but it increased the accumulation of QA−, thereby decreasing primary photochemical efficiency (TRO/CSm, φPO). These changes in photosystem II (PSII) resulted in a decrease in the maximum quantum yield of PSII (Fv/Fm) and the performance index (PIABS). Moreover, PSII was protected from thylakoid membrane photodamages through the increase in heat dissipation per unit area (DIO/CSm) in response to SAR. The increase in δRO as the pH of the SAR solution decreased was observed for PM, but not for CL. Considered together, the study findings suggest that SAR treatments can decrease chlorophyll contents and damage the OEC in PM and CL, which obstructs the transfer of electrons on the donor and acceptor sides of PSII. However, PM is better able to withstand SAR stress than CL, likely because of the activation of a protective mechanism (reflected by the change in δRO). Therefore, in coniferous forest areas severely affected by acid rain, CL may need to be protected more than PM.

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.

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.

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.

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.

Ribotoxin-like proteins (RL-Ps) are specific ribonucleases found in mushrooms that are able to cleave a single phosphodiester bond located in the Sarcin-Ricin Loop (SRL) of the large rRNA. The cleaved SRL interacts differently with some ribosomal proteins (P-stalk). This action blocks protein synthesis because the damaged ribosomes are unable to interact with elongation factors. Here, the amino acid sequence of eryngitin 3 and 4, RL-Ps isolated from Pleurotus eryngii fruiting bodies, was determined to: i) obtain structural information on this specific ribonuclease family from edible mushrooms; and ii) explore the structural determinants which justify their different biological and antipathogenic activities. Indeed, eryngitin 3 (exhibited higher toxicity with respect to eryngitin 4 against tumoral cell lines and model fungi. Structurally, eryngitin 3 and 4 consist of 132 amino acids, most of them identical and exhibit a single free cysteinyl residue. The amino acidic differences between the two toxins are: i) an additional phenylalanyl residue at the N-terminus of eryngitin 3, not retrieved in eryngitin 4; and ii) an additional arginyl residue at C-terminus of eryngitin 4, not retrieved in eryngitin 3. The 3D-models of eryngitins show slight differences at the N- and C-terminal regions. In particular, the positive electrostatic surface at C-terminal of eryngitin 4 is due to the additional arginyl residue not retrieved in eryngitin 3. This additional positive charge could interfere with the binding to the SRL (substrate) or with some ribosomal proteins (P-stalk structure), during substrate recognition.

The root extracts of Symphytum officinale (comfrey) are commonly used in traditional medicine to treat muscle, joint, skin and bone disorders. However, little information is available on the biomedical functions of comfrey leaves. In this study, sequencing results of Internal Transcribed Spacer and trnL-trnF genes showed that plants purchased from the local market were comfrey and named as S. officinale WL (WL). The optimal extraction conditions of WL leave with the highest extract yield and contents of total phenols and flavonoids by microwave-assisted extraction were identified. The antioxidative and anti-inflammatory activities and possible molecular mechanism(s) of the WL leaf extract (WLE) were evaluated. Furthermore, the major component of WLE was identified as rosmarinic acid by HPLC. Results showed that the optimal extract condition was obtained with 750W microwave power, 50℃, 75% methanol, the solid-to-solvent ratio of 1:10, and 15 minutes. Results of all DPPH, ABTS and superoxide radical scavenging activities, reducing power, ferrous ion chelating activity, and ferric reducing antioxidant power showed high antioxidative capacities of WLE. Furthermore, WLE showed obvious DNA protecting activity. WLE attenuated lipopolysaccharides-stimulated inflammation by suppressing iNOS, COX-2, IL-1β, IL-6, and TNF-α expressions in RAW264.7 macrophages. These attenuations involved in inactivations of lipopolysaccharides-induced NF-κB and MAPK signaling pathways.

There is an increasing interest in biomarkers of nitric oxide dysregulation and oxidative stress to guide management and identify new therapeutic targets in patients with chronic obstructive pulmonary disease (COPD). We conducted a systematic review and meta-analysis of the association between circulating metabolites within the arginine (arginine, citrulline, ornithine, asymmetric, ADMA, and symmetric, SDMA dimethylarginine), transsulfuration (methionine, homocysteine, and cysteine) and folic acid (folic acid, vitamin B6, and vitamin B12) metabolic pathways and COPD. We searched electronic databases from inception to 30 June 2023 and assessed the risk of bias and the certainty of evidence. In 21 eligible studies, compared to healthy controls, patients with stable COPD had significantly lower methionine (standardized mean difference, SMD=-0.50, 95% CI -0.95 to -0.05, p=0.029) and folic acid (SMD=-0.37, 95% CI -0.65 to -0.09, p=0.009), and higher homocysteine (SMD=0.78, 95% CI 0.48 to 1.07, p˂0.001) and cysteine concentrations (SMD=0.34, 95% CI 0.02 to 0.66, p=0.038). Additionally, COPD was associated with significantly higher ADMA (SMD=1.27, 95% CI 0.08 to 2.46, p=0.037), SDMA (SMD=3.94, 95% CI 0.79 to 7.08, p=0.014), and ornithine concentrations (SMD=0.67, 95% CI 0.13 to 1.22, p=0.015). In subgroup analysis, the SMD of homocysteine was significantly associated with the biological matrix assessed and the forced expiratory volume in the first second to forced vital capacity ratio, but not with age, study location, or analytical method used. Our study suggests the presence of significant alterations in metabolites within the arginine, transsulfuration, and folic acid pathways which can be useful for assessing nitric oxide dysregulation and oxidative stress and identifying novel treatment targets in COPD. (PROSPERO registration number: CRD42023448036)

This study propounds a sustainable alternative to petroleum-based polyurethane (PU) foams aiming to curtail this nonrenewable resource's continued and uncontrolled use. Coconut fatty acid distillate (CFAD) and crude glycerol (CG), both wastes from vegetable oil processes, were utilized for bio-based polyol production for rigid PU foam application. The raw materials were subjected to catalyzed glycerolysis with alkaline-alcohol neutralization and bleaching. The resulting polyol possessed properties suitable for rigid foam application with an average OH number of 215 mg KOH/g, acid number of 7.2983 mg KOH/g, and Gardner color value of 18. The polyol was used to prepare rigid PU foam, and its properties were determined using FTIR, TGA/DTA, and UTM. Additionally, the cell foam morphology was investigated by scanning electron microscope (SEM) in which most of its structure revealed an open-celled network and quantified at 92.71% open cell content using pycnometric testing. The PU foam thermal and mechanical analysis results showed an average compressive strength of 70.59 kPa, thermal conductivity of 46.50 mWm-1K-1, and density of 32.79 kgm-3. These properties showed its applicability as thermal insulating foam, thus, demonstrating the potential use of CFAD and CG in commercial polyol and PU foam production.

In globe artichoke both the edible portion and the waste biomass are recognized as valuable sources of bioactive compounds. For this study, heads with 30 cm-long floral stems, including 2-3 leaves, were harvested from five genotypes which included two traditional vegetatively-propagated varietal types (‘Brindisino,’ and ‘Violetto di Foggia,’) and three "seed"-propagated hybrids (‘Tempo,’ ‘Opal,’ and ‘Madrigal’). The study aimed to determine the total and individual polyphenolic concentrations (measured spectrophotometrically and by HPLC) and antioxidant activity (AA) in different artichoke parts, namely the "hearts" (H), head waste (HW), stem waste (SW), and leaf waste (LW). ‘Brindisino’ SW exhibited the highest accumulation of luteolin (26,317 mg kg−1 F.W.), while ‘Tempo’ H displayed the highest cynarin content (190 mg kg−1 F.W.). ‘Tempo’ HW and H showed the highest levels of apigenin (640 mg kg−1 F.W.), and the greatest source of chlorogenic acid was found in the HW of ‘Opal’ and the H of ‘Brindisino’ (4,300 mg kg−1 F.W.). The hybrids generally exhibited lower total polyphenolic concentrations than the traditional genotypes, particularly evident in the LW. The SW demonstrated the highest concentration of total polyphenols (18,000 mg kg−1 F.W.), followed by the edible H and non-edible HW (12,000 mg kg−1 F.W.), while the LW exhibited the lowest concentration (2,000 mg kg−1 F.W.). Interestingly, the AA did not precisely align with the total polyphenolic concentration, showing slight variations between the examined parts and genotypes.

Trans fatty acids (TFA) are a concern for public health due to their negative impact on cardiovascular health. This study aimed to assess the levels of TFA and other fatty acids in popular edible oils and fried foods commonly consumed in Tanzania. A total of 57 samples from 38 brands of edible oils and 20 samples of fried street foods and fast foods were collected in Dar es Salaam, Tanzania. Capillary gas chromatography was used to determine TFA levels, while nutritional labeling and other fatty acid classes were also evaluated. Among the analyzed edible oils, 21% exceeded the recommended TFA levels, primarily found in popular brands of margarine, industrially refined sunflower oils, animal butter, and peanut butter. Only two food items surpassed the 2% TFA limit, but a majority of the foods had high levels of saturated fatty acids and a fatty acid profile similar to palm oil. Additionally, only 22% of the edible oils provided TFA content information. These findings indicate the persistence of TFA levels beyond recommended limits and inadequate TFA nutritional labeling in Tanzanian food products. Urgent interventions are necessary to reduce TFA levels and improve nutritional labeling practices to safeguard public health.

The human respiratory syncytial virus (hRSV) poses a serious risk to global public health and is a significant cause of severe lower respiratory infections. There are currently only a few therapies available to treat RSV infections, as well as no RSV vaccinations. Therefore, there is an urgent demand for clinically feasible, safe, and affordable RSV prevention and treatment alternatives. In this study, an ion-activated in situ gel comprising broad-spectrum antiviral 18β-glycyrrhetinic acid (GA) for antiviral action on RSV was developed. In this content, mechanical properties, sprayability, drug content, pH, ex vivo mucoadhesive strength, in vitro drug release pattern, and stability were all examined. Rheological properties were also tested by utilizing in vitro gelation capacity and rheological synergism tests. Finally, the optimized in situ gel's cytotoxic and antiviral activities on RSV cultured in human laryngeal epidermoid carcinoma (HEP-2) cell line were evaluated. In conclusion, the optimized in situ gel prepared with a combination of 0.5%w/w gellan gum and 0.5%w/w sodium carboxymethylcellulose demonstrated good gelation capacity and sprayability (weight deviation between T0 and T14: 0.34%), desired rheological synergism (mucoadhesive force (Fb): 9.53), mechanical characteristics (adhesiveness: 0.300 mJ ± 0.05), ex vivo bioadhesion force (19.67 g ± 1.90), drug content uniformity (RSD%: 0.494), and sustained drug release over period of 168 h (101.57% ± 0.53). The antiviral activity test results showed that the optimized in situ gel had strong anti-HRSV activity (EC50 simultaneous = 0.05 µg/ml, SI = 306; EC50 preinfection = 0.154 µg/ml, SI= 100) which was significantly higher than that of ribavirin (EC50 =4.189 µg/ml; SI= 28) used as a positive control against hRSV. In conclusion, this research has demonstrated the formulation of an effective antiviral nasal spray that has the ability to possess both prophylactic and virucidal activity.

This paper presents the development of a cheap and rapid electrochemical sensor for ascorbic acid detection. In particular, the graphite ink working electrode of screen-printed cells was covered by a film of elecrosynthesized molecularly imprinted polypyrrole (e-MIP); differential pulse voltammetry (DPV) was the selected method for the analyte detection. The ascorbic acid molecules were suc-cessfully entrapped in the polypyrrole film, creating the recognition sites. The best results were obtained after polypyrrole overoxidation and performing the measurements in phosphate buffer solution 0.05 M/KCl 0.1M at pH 7.5. The comparison with the bare and the not imprinted polypyrrole-modified electrodes showed the highest selectivity and reproducibility of the e-MIP-based sensor. The developed method was applied to assess ascorbic acid in farmaceutical products obtaining values not significantly different from the declared content.

Acetic acid bacteria (AAB) form a bacterial film on the surface of alcoholic solutions and ferment ethanol to acetic acid while also producing bioactive compounds. To discover functional AAB for industrial use, we isolated and selected strains from farm-produced vinegars using a CaCO3-containing medium. The seven strains belonged to Acetobacter cerevisiae and A. pasteurianus. Physiological properties were determined, including ethanol tolerance at up to 12% (v/v). Acidification at a growth temperature of 40 ℃ was seen for GHA 7, GYA 23, JGB 21-17, and GHA 20 strains, which may be useful in vinegar production where thermotolerant AAB are required. The seven AAB isolates had strong antibacterial activity against Staphylococcus aureus. Antioxidant activity was 2- and 4-fold higher, respectively, for A cerevisiae and A. pasteurianus than for the control, 1% acetic acid. We also observed 91.3% inhibition of angiotensin-converting enzyme activity for the KSO 5 strain, higher than that for the positive control, 0.1% captopril (76.9%). All strains showed complete inhibition of α-glucosidase, except JGB 21-17 and GHA 7 with 98.3% inhibition. Our work suggests usefulness of the strains selected as seed strains for highly efficient production of functional vinegar and illustrates identification of useful functional characteristics on a scientific basis.

Vitamin C status is known to be associated with several demographic and lifestyle factors. These include gender, age, ethnicity, pregnancy/lactation, body weight, smoking status and dietary habits. In the present study, our aim was to interrogate the National Health and Nutrition Examination Survey (NHANES) 2017-2018 datasets to assess the impact of these factors on vitamin C dose-concentration relationships to establish if there are higher requirements for vitamin C in certain subpopulations and the possible extent of these additional requirements. The relevant data were extracted from the NHANES 2017-2018 datasets, the final cohort of which comprised 2828 non-supplementing adult males and females (aged 18 – 80+ years) with both vitamin C serum concentrations and dietary intake data available. The data was subsequently stratified by gender, age tertiles (≤36, 37-58, ≥59 years), ethnicity (non-Hispanic white, non-Hispanic black, and total Hispanic), socioeconomic tertiles (poverty income ratios: &gt;3.0, 1.36 – 3.0, ≤1.35), weight tertiles (≤72, 72-91, ≥91 kg), BMI tertiles (≤26, 26-32, ≥32 kg/m2) and smoking status. Sigmoidal (four parameter logistic) curves with asymmetrical 95% confidence intervals were fitted to the dose-concentration data. We found that males required vitamin C intakes ~1.2-fold higher than females to reach ‘adequate’ serum concentrations of 50 µmol/L. Males had both higher body weight and a higher prevalence of smoking than females. Smokers required vitamin C intakes ~2.0-fold higher than non-smokers to reach adequate vitamin C concentrations. Relative to adults in the lighter weight tertile, adults in the heaver weight tertile required ~2.0-fold higher dietary intakes of vitamin C to reach adequate serum concentrations. We did not observe any impact of ethnicity or socioeconomic status on the vitamin C dose-concentration relationship, and although no significant difference between younger and older adults was observed at vitamin C intakes &gt; 75 mg/day, at intakes &lt; 75 mg/day, older adults had an attenuated serum response to vitamin C intake. In conclusion, certain demographic and lifestyle factors, specifically gender, smoking and body weight, have a significant impact on vitamin C requirements. Overall, the data indicate that the general population must consume ~110 mg/day of vitamin C to attain adequate serum concentrations, smokers require ~165 mg/day relative to non-smokers, and heavier people (100+ kg) require ~155 mg/day to reach the same vitamin C concentrations. These findings have important implications for global vitamin C dietary recommendations.

SiO2-SO3H, with a surface area of 115 m2/g, pore volume of 0.38 cm3g-1 and 1.32 mmol H+/g, was used as a 20% w/w catalyst for the preparation of methyl salicylate (Wintergreen oil or MS) from acetylsalicylic acid (ASA). A 94% conversion was achieved in a microwave reactor during 40.0 minutes at 120 oC in MeOH. The resulting crude product was purified by flash chromatography. The catalyst could be re-used three times.

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.

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.

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.

Study of fungal antibiotics in their competitive interactions with arthropods may lead to development novel biorational insecticides. Extracts of Alternaria tenuissima MFP253011 obtained by various methods showed a wide range of biological activity, including entomotoxic properties. Analysis of their composition and bioactivity allowed to reveal several known mycotoxins and unidentified compounds that may be involved in entomotoxic activity of the extracts. Among them, tenuazonic acid (TeA), which was the major component of the A. tenuissima extracts, was found the most likely to have larvicidal activity against Galleria mellonella. In the intrahaemocoel injection bioassay, TeA was toxic to G. mellonella and of Zophobas morio with LT50 6 and 2 days, respectively, at the level of 50 µg/larva. Administered orally, TeA inhibited growth of G. mellonella larvae and caused mortality of Acheta domesticus imagines (LT50 7 days) at a concentration of 250 µg/g of feed. TeA showed weak contact-intestinal activity against the two phytophages, Tetranychus urticae and Schizaphis graminum, causing the 12 and 40% of mortality at a concentration of 1 mg/mL. TeA was cytotoxic to Sf9 cell line (IC50 25 µg/mL). Thus, model insect G. mellonella and cell line Sf9 could be used for a further toxicological characterization of TeA.

Endothelial cells form a powerful interface between tissues and immune cells. In fact, one of the underappreciated roles of endothelial cells is to orchestrate immune attention to specific sites. Tumor endothelial cells have a unique ability to dampen the immune responses and thereby maintain an immunosuppressive microenvironment. Recent approaches to trigger immune responses in cancers have focused on activating nucleic acid sensors such as cGAS/STING in combination with immunotherapies. In this review, we present a case for targeting nucleic acid sensing pathways within the tumor vasculature to invigorate tumor immune responses. We introduce two specific nucleic acid sensors, the DNA sensor TREX1 and the RNA sensor RIG-I and discuss their functional roles in the vasculature. Finally, we present perspectives on how these nucleic acid sensors in the tumor endothelium can be targeted in an antiangiogenic and immune activation context. We believe understanding the role of nucleic acid sensing in the tumor vasculature can enhance our ability to design more effective therapies targeting the tumor microenvironment.

Mitochondrial dysfunctions, e.g. abnormal handling of mitochondrial DNA in TFAM mutants or in altered mitophagy, activate innate immunity. Recent reports also showed that deletion of mitochondrial matrix peptidase ClpP in mice transcriptionally upregulates inflammatory factors. Here, we studied ClpP-null mouse brain at two ages and embryonal fibroblasts, to identify which signaling pathways are responsible, employing mass spectrometry, immunoblots, and reverse transcriptase polymerase chain reaction. Anomalies in the mitochondrial unfolded protein responses pathway were prominent for the co-chaperone DNAJA3, and for its known interactor STAT1. Their mitochondrial dysregulation affected also their extra-mitochondrial abundance, as possible innate immune modulators. Increased expression was observed not only for the transcription factors Stat1/2, but also for two interferon-stimulated genes (Ifi44, Gbp3). Inflammatory responses were strongest for RLR pattern recognition receptors (Ddx58, Ifih1, Oasl2, Trim25) and several cytosolic nucleic acid sensors (Ifit1, Ifit3, Oas1b, Ifi204, Mnda). They can be explained by the accumulation of mitoribosomes and mitochondrial nucleoids in ClpP-null cells, which may act as damage-associated molecular patterns. The consistent dysregulation of these factors from early age might influence also human Perrault syndrome, where ClpP loss-of-function leads to early infertility and deafness, with subsequent widespread neurodegeneration.

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.

Gut microbiota and its metabolites like short chain fatty acids (SCFAs) are linked with pathology of Alzheimer’s disease (AD)- a debilitating public health problem in older adults. However, strategies to beneficially modulate gut microbiota and its sensing signaling pathways remain largely unknown. Here, we screened, validated and established the agonists of free fatty acid receptor 2 (FFAR2) signaling, which senses beneficial signals from SCFAs produced by microbiota in the gut. We demonstrated that inhibition of FFAR2 signaling increases amyloid-beta (Aβ) stimulated neuronal toxicity. Thus, we screened FFAR2 agonists, using in-silico library of more than 144,000 natural compounds, and 15 compounds were selected based on binding with FFAR2 agonist sites. Further, cell culture toxicity and FFAR2 stimulatory experiments demonstrated that Fenchol (a natural compound commonly present in basil) was potent FFAR2 agonist in neuronal cells. Interestingly, we also demonstrated that Fenchol protects Aβ-stimulated neurodegeneration in FFAR2 dependent manner. In addition, Fenchol reduced AD like phenotypes such as Aβ-accumulation and, learning and memory behaviors in Caenorhabditis (C.) elegans. Fenchol increased Aβ-clearance by increasing proteasome/lysosome activity and reduced senescence in neuronal cells. These results demonstrated that the inhibition of FFAR2 signaling promotes Aβ-induced neurodegeneration, while activating it by Fenchol as a natural agonist reverse it by promoting Aβ-clearance and reducing cellular senescence; thus stimulation of FFAR2 signaling can be a therapeutic approach to prevent/ treat AD.

This study aimed to assess the response of 3D printed PLA scaffolds biomimetically coated with apatite on human primary osteoblast spheroids and evaluate the biological response to its association with Bone Morphogenetic Protein 2 (rhBMP-2) in rat calvaria. PLA scaffolds were produced via 3D printing, soaked in simulated body fluid (SBF) solution, and characterized by physical-chemical, morphological, and mechanical properties. The in vitro biological response was assessed with human primary osteoblast (HOb) spheroids. The in vivo analysis was conducted through the implantation of 3D printed PLA scaffolds either alone, covered by apatite (PLA-CaP) or PLA-CaP loaded with rhBMP-2 (PLA-CaP+rhBMP-2) on critical-sized defects (8 mm) of rat calvaria. Increased cell adhesion and in vitro release of growth factors (PDGF, bFGF, VEGF) was observed for PLA-CaP scaffolds when pre-treated with FBS. PLA-CaP+BMP2 presented higher values of newly formed bone (NFB) than other groups at all experimental periods (p&lt;0.05), attaining 44.85% of NFB after 6 months. These findings indicate that functionalization of PLA scaffolds with biomimetic apatite can improve its biological properties in the presence of complex biological media. Its association with BMP2 may enhance bone repair, suggesting this strategy as a promising candidate for bone tissue engineering.

Optical rotatory dispersion (ORD) is a beautiful analytical technique for the study of chiral molecules and polymers. In this study, ORD was applied successfully to follow the degree of polycondensation of l-(+)-lactic acid toward the formation of poly(lactic acid) oligomers (PLAO) and high molecular weight poly(l-lactic acid) (PLLA) in a simple esterification reaction equipment. PLLA is a biodegradable polymer obtainable from renewable raw materials. The racemization of the intrinsically isotactic PLLA through thermal treatment can be easily followed through the use of ORD spectroscopy. Organic or molecular electronics is a hot topic dealing with the combination of π-conjugated organic compounds and polymers with specific properties (e.g. chirality) which can be exploited to construct optoelectronic devices such as organic light-emitting diodes (OLEDs), organic photovoltaic (OPV) high efficiency cells, switchable chirality devices, organic field-effect transistors (OFETs), and so on. ORD spectroscopy was applied to study either the gigantic optical rotation of PLLA films as well as to detect successfully the excitonic coupling occurring in thin solid PLLA green film loaded with a combination of two dyes: SY96 (a pyrazolone dye) and PB16 (the metal-free phthalocyanine pigment). The latter compound PLLA loaded with SY96 and PB16 shows a really gigantic optical activity in addition to typical ORD signal due to exciton coupling and may be considered as a simple and easily accessible model composite of a chiral polymer matrix combined with π-conjugated dyes for molecular electronics studies.

The development of a highly specific drug delivery system (DDS) for anti-cancer therapeutics is an area of intense research focus. Chemical engineering of a “smart” DDS to specifically target tumor cells has gained interest, designed for safer, more efficient, and effective use of chemotherapeutics for the treatment of cancer. However, the selective targeting and choosing the critical cancer surface biomarker are essential for targeted treatments to work. The folic acid receptor alpha (FRalpha) has gained popularity as a potential target in triple-negative breast cancer (TNBC). We have previously reported on a functionalized folic acid (FA)-conjugated amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA) that has the essential features for efficient “smart” DDS. This biocompatible DDS self-assembles in a pH-dependent manner, providing stimuli-responsive, active targeting, extended-release of hydrophobic chemotherapeutic agents, and can effectively penetrate the inner core of 3-dimensional cancer spheroid models. The empty FA-DABA-SMA decreased spheroid volume, revealing a previously unknown mechanism of action. Upon further investigation, a size- and shape-dependent interaction FA-DABA-SMA with FR reduced the expression of p53, the product of the highly mutated TP53 gene, and additional oncogenic c-Myc and STAT3 proteins. Here, we investigated how this copolymer influences FR behavior and disrupting the receptor’s functions. Results indicate that FA-DABA-SMA increases FR expression levels in breast MDA MB-231 cancer cells and disrupting FR signaling by the reduction in HES1 and NOTCH1 protein expression levels. Also, FA-DABA-SMA induces apoptosis and further causes a change in the morphology of the MDA MB-231 cells, as well as significantly reduces their ability to migrate in a Scratch wound assay. Collectively, these findings provide a novel insight into the functionalized FA-DABA-SMA copolymer. The 350 kDa and 20 kDa copolymers actively target FRα to initialize internationalization. However, only the large size and sheet-shaped 350 kDa copolymers disrupt FRα signaling. The significance of these novel findings reveals the intracellular activity of the copolymer that is critically dependent on the size and structural shape. This report offers novel therapeutic insight into a dual mechanism of FA-DABA-SMA copolymer for its therapeutic potential for the treatment of cancer.

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

Pneumonia is a severe lower respiratory tract infection that is a common complication and a major cause of mortality of the vitamin C-deficiency disease scurvy. This suggests an important link between vitamin C status and lower respiratory tract infections. Due to the paucity of information on the vitamin C status of patients with pneumonia, we assessed the vitamin C status of 50 patients with community-acquired pneumonia and compared these with 50 healthy community controls. The pneumonia cohort comprised 44 patients recruited through the Acute Medical Assessment Unit (AMAU) and 6 patients recruited through the intensive care unit (ICU); mean age 68 ± 17 years, 54% male. Clinical, microbiological and haematological parameters were recorded. Blood samples were tested for vitamin C status using HPLC with electrochemical detection and protein carbonyl concentrations, a marker of oxidative stress, using ELISA. Patients with pneumonia had depleted vitamin C status compared with healthy controls (23 ± 14 µmol/L vs 56 ± 24 µmol/L, P <0.001). The more severe patients in the ICU had significantly lower vitamin C status than those recruited through AMAU (11 ± 3 µmol/L vs 24 ± 14 µmol/L, P = 0.02). The total pneumonia cohort comprised 62% with hypovitaminosis C and 22% with deficiency, compared with only 8% hypovitaminosis C and no cases of deficiency in the healthy controls. The pneumonia cohort also exhibited significantly elevated protein carbonyl concentrations compared with the healthy controls (P < 0.001), indicating enhanced oxidative stress in the patients. We were able to collect subsequent samples form 28% of the cohort (mean 2.7 ± 1.7 days; range 1-7 days). These showed no significant differences in vitamin C status or protein carbonyl concentrations compared with baseline values (P = 0.6). Overall, the depleted vitamin C status and elevated oxidative stress observed in the patients with pneumonia indicates an enhanced requirement for the vitamin during their illness. Due to the important roles that vitamin C plays in the immune system, low vitamin C status is possibly both a cause and a consequence of the disease. Therefore, these patients would likely benefit from additional vitamin C supplementation to restore their blood and tissue levels to optimal. This may decrease oxidative stress and aid in their recovery.

Succinic semialdehyde dehydrogenase deficiency (SSADH-D) is a genetic disorder that results from the aberrant metabolism of the neurotransmitter γ-amino butyric acid (GABA). The disease is caused by the impaired activity of the mitochondrial enzyme succinic semialdehyde dehydrogenase. SSADH-D manifests as varying degree of mental retardation, autism, ataxia and epileptic seizures, but the clinical picture is highly heterogeneous. So far, there is no approved therapy for this disease. In this review, we briefly summarize the molecular genetics of SSADH-D, the past and ongoing clinical trials and the emerging features of the molecular pathogenesis, including redox imbalance and mitochondrial dysfunction. The main aim of this review is to discuss the potential use of further therapy approaches that have so far not been tested in SSADH-D, such as pharmacological chaperones, read-through drugs and gene therapy. Special attention will also be paid to elucidating the role of patient advocacy organizations in facilitating research and in the communication between the researchers and the patients.

Alpha-fetoprotein (AFP) is a major embryo- and tumor-associated protein capable of binding and transporting variety of hydrophobic ligands including estrogens. AFP has been shown to inhibit estrogen receptor (ER)-positive tumor growth and this can be attributed to its estrogen-binding ability. Despite AFP has long been investigated, its three-dimensional (3D) structure has not been experimentally resolved and molecular mechanisms underlying AFP-ligand interaction remain obscure. In our study we constructed homology-based 3D model of human AFP (HAFP) with the purpose to perform docking of ERα ligands, three agonists (17β-estradiol, estrone and diethylstilbestrol) and three antagonists (tamoxifen, afimoxifene and endoxifen) into the obtained structure. Based on ligand docked scoring function, we identified three putative estrogen- and antiestrogen-binding sites with different ligand binding affinities. Two high-affinity sites were located in (i) a tunnel formed within HAFP subdomains IB and IIA and (ii) opposite side of the molecule in a groove originating from cavity formed between domains I and III, while (iii) the third low-affinity site was found at the bottom of the cavity. 100 ns MD simulation allowed studying their geometries and showed that HAFP-estrogen interactions occur due to van der Waals forces, while both hydrophobic and electrostatic interactions were almost equally involved in HAFP-antiestrogen binding. MM/GBSA rescoring method estimated binding free energies (ΔG_bind) and showed that antiestrogens have higher affinities to HAFP as compared to estrogens. We performed in silico point substitutions of amino acid residues to confirm their roles in HAFP-ligand interactions and showed that Thr132, Leu138, His170, Phe172, Ser217, Gln221, His266, His316, Lys453, and Asp478 residues along two disulfide bonds, Cys224-Cys270 and Cys269-Cys277 have key roles in both HAFP-estrogen and HAFP-antiestrogen binding. Data obtained in our study contribute to understanding mechanisms underlying protein-ligand interactions and anti-cancer therapy strategies based on ER-binding ligands.

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.

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.

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

Establishment of diagnostic methods with low detection limits plays a critical role in the maintenance of early diagnosis, prevention of serious neurological complications, and control of the spread of ZIKA. In this study, we established the micro-droplet digital polymerase chain reaction (ddPCR) and real-time fluorescent quantification PCR (qPCR) protocols for the detection of Zika virus based on the NS5 gene. For the Zika standard plasmid, the standard curve of R² was 0.999, and the amplification efficiency was 92.203%, as determined by qPCR. Both ddPCR and qPCR were positive for cell culture of Zika nucleic acid.The minimum detection limit of ddPCR is 1–2 times lower than qPCR. Moreover, all tests of Dengue virus (1–4 serotypes) were negative in cell culture. Overall, these results suggested than ddPCR may have a lower limit of detection than qPCR.

Ataxin-2 (ATXN2) acts during stress-responses, modulating mRNA translation and nutrient metabolism. Atxn2 knockout mice exhibit progressive obesity, dyslipidemia and insulin resistance. Conversely, the progressive ATXN2 gain-of-function due to polyGlutamine (polyQ) expansions leads to a dominantly inherited neurodegenerative process named spinocerebellar ataxia type 2 (SCA2), with early adipose tissue loss and late muscle atrophy. We tried to understand lipid dysregulation in a SCA2 patient brain and in an authentic mouse model. Thin layer chromatography of a patient cerebellum was compared to the lipid metabolome of Atxn2-CAG100-KnockIn (KIN) mouse spinocerebellar tissue. The human pathology caused deficits of sulfatide, galactosylceramide, cholesterol, C22/24-sphingomyelin and gangliosides GM1a/GD1b, despite quite normal levels of C18-sphingomyelin. Cerebellum and spinal cord from the KIN mouse showed a consistent decrease of various ceramides, with a significant elevation of sphingosine in the more severely affected spinal cord. Deficiency of C24/26-sphingomyelins contrasted with excess C18/20-sphingomyelin. Spinocerebellar expression profiling revealed consistent reductions of CERS protein isoforms, of Sptlc2 and Smpd3, but upregulation of Cers2 mRNA, as prominent anomalies in the ceramide-sphingosine metabolism. Reduction of Asah2 mRNA correlated to deficient S1P levels. In addition, downregulations for the elongase Elovl1, Elovl4, Elovl5 mRNAs and ELOVL4 protein explain the deficit of very-long-chain sphingomyelin. Reduced ASMase protein levels correlated to the accumulation of long-chain sphingomyelin. Overall, a deficit of myelin lipids was prominent in SCA2 nervous tissue at prefinal stage, not compensated by transcriptional adaptation of several metabolic enzymes. Myelination is controlled by mTORC1 signals, so our human and murine observations are in agreement with the known role of ATXN2 yeast, nematode and mouse orthologs as mTORC1 inhibitors and autophagy promoters.

This study comprehensively evaluates the DNA/RNA Defend Pro (DRDP) sample collection buffer designed to inactivate and stabilize patient samples. The primary objectives encompassed assessing DRDP's efficacy in ensuring sample stability, facilitating extraction-free polymerase chain reaction (PCR), and ensuring compatibility with rapid antigen testing.Ninety-five diagnostic nasopharyngeal swab samples tested for influenza A/B, RSV A/B, and/or SARS-CoV-2 were diluted 1/10 with DRDP and anonymized. Stability testing involved incubating 31 positive samples at 4 °C, 20 °C, and 37 °C for 7 days, with regular extraction-free nucleic acid amplification testing (NAAT).Results demonstrated that DRDP guaranteed viral RNA stability at all temperatures for influenza, SARS-CoV-2 and RSV showing stability up to 7 days at 4 °C. DRDP-diluted samples exhibited robust compatibility with direct PCR, as 72 out of 88 samples positive for cobas Liat also tested positive for direct PCR. Non-concordant results could be explained by the 200-fold lower input in the extraction-free NAAT.Compared to NAAT, rapid antigen testing demonstrated lower sensitivity, as expected, while maintaining perfect specificity. Clear cutoffs between positive and negative rapid antigen testing results were observed in both cobas Liat and direct PCR analyses, validating DRDP's compatibility with these techniques. In conclusion, DRDP is an effective stabilizing medium compatible with direct PCR and rapid antigen testing and shows great potential for optimizing diagnostic processes, particularly in resource-limited or time-sensitive scenarios.

The manufacturing method influences the properties of the produced components. This work investigates the influence of manufacturing methods such as fused filament fabrication (3D printing) and injection molding on water absorption, mechanical and thermal properties of the specimens produced from neat biobased poly(lactic acid) (PLA) polymer and poly(lactic acid)/wood composites. Acrylonitrile butadiene styrene (ABS) acts as the reference material due to its low water absorption and good functional properties. The printing layer thickness is one of the factors that affects the properties of a 3D printed specimen. The investigation includes two different layer thicknesses (0.2 mm and 0.3 mm) while maintaining uniform overall thickness of the specimens across two manufacturing methods. 3D printed specimens absorb significantly higher amounts of water than the injection molded specimens, and the increase in the layer thickness of the 3D printed specimens contributes to further increased water absorption. However, the swelling due to water absorption in 3D printed specimens decreases on increased layer thickness. Tensile, flexural and impact properties of all the specimens decrease after water absorption while the properties improve on decreasing the layer thickness. Higher porosity on increasing the layer thickness is the predominant factor. The results from dynamic mechanical analysis and microscopy validate the outcomes.

In an era of increasing interest in the potential health benefits of medicinal foods, the need to assess their safety and potential toxicity remains a critical concern. While these natural remedies have garnered substantial attention for their therapeutic potential, a comprehensive understanding of their effects on living organisms is essential. We examined 316 herbal extracts to determine their potential nematocidal attributes in Caenorhabditis elegans. Approximately 16% of these extracts exhibited the capacity to induce diminished survival rates and larval arrest, establishing a correlation between larval arrest and overall worm viability. Certain extracts led to an unexpected increase in male nematodes, accompanied by a discernible reduction in DAPI-stained bivalent structures and perturbed meiotic advancement, thereby disrupting the conventional developmental processes. Notably, Onobrychis cornuta and Veratrum lobelianum extracts activated a DNA damage checkpoint response via the ATM/ATR and CHK-1 pathways; hindering germline development. Our LC‒MS analysis revealed jervine in V. lobelianum and nine antitumor compounds in O. cornuta. Interestingly, linoleic acid replicated phenotypes induced by O. cornuta exposure, including an increased level of pCHK-1 foci, apoptosis, and the MAPK pathway. We observed that mutants in the MAPK pathway suppressed the reduction in worm survival, emphasizing its role in survivability, meiotic progression, and DNA damage checkpoint-mediated apoptosis. This study reveals complex interactions between herbal extracts and C. elegans processes, shedding light on potential antitumor effects and mechanisms. The findings provide insights into the complex landscape of herbal medicine's impact on a model organism, offering implications for broader applications.

The approval of sucrose fatty acid esters (SFAEs) as food additives/preservatives has triggered enormous interest in discovering new applications for these materials. Accordingly, many researchers reported that SFAEs consist of various sugar moieties, and hydrophobic side chains are highly active against certain fungal species. The combination of chain length and site of acylation is crucial in endowing the SFAE with high antimicrobial potency against Aspergillus species. Following several important studies, we herein present the synthesis and an assessment of the effects of acylation site and chain length (i.e., C-6 vs. C-2, C-3, C-4, and long-chain vs. short-chain) on the antimicrobial activity of mannopyranoside fatty acid esters. In vitro tests revealed that the fatty acid chain length in mannopyranoside esters significantly affects the antifungal activity where C12 chains are more potent against Aspergillus species. In terms of acylation site, mannopyranoside esters with a C8 chain substituted at the C-6 position are more active in antifungal inhibition. Molecular docking also revealed that these mannopyranoside esters had comparatively better stable binding energy, and hence better inhibition, with the fungal enzymes lanosterol 14-alpha-demethylase (3LD6), urate oxidase (1R51), and glucoamylase (1KUL) than the standard antifungal drug fluconazole. Additionally, the thermodynamic, orbital, drug-likeness, and safety profiles of these mannopyranoside esters were calculated and discussed, along with the structure-activity relationships (SAR). This study thus highlights the importance of the acylation site and lipid-like fatty acid chain length that govern the antimicrobial activity of mannopyranoside-based SFAE.

Vitamin C is an essential enzyme cofactor and antioxidant with pleiotropic roles in human physiology. Circulating vitamin C concentrations are lower in people with diabetes mellitus suggesting a higher dietary requirement for the vitamin. We interrogated the NHANES 2017/2018 and EPIC-Norfolk datasets to compare vitamin C requirements between those with and without diabetes mellitus using dose-concentration relationships fitted with sigmoidal (four parameter logistic) curves. The NHANES cohort (n=2828 non-supplementing adults) comprised 488 (17%) participants with diabetes (self-reported or HbA1c ≥6.5%). The participants with diabetes had a lower vitamin C status (median [IQR]) than those without (38 [17, 52] µmol/L vs 44 [25, 61] µmol/L, p&lt;0.0001), despite comparable dietary intakes between the two groups (51 [26, 93] mg/d vs 53 [24, 104] mg/d, p=0.5). Dose-concentration relationships indicated that the group without diabetes reached adequate vitamin C concentrations (50 µmol/L) with an intake of 81 (72, 93) mg/d, whilst the those with diabetes required an intake of 166 (126, NA) mg/d. In the EPIC-Norfolk cohort, comprising 20692 non-supplementing adults, 475 (2.3%) had self-reported diabetes at baseline. The EPIC cohort had lower a BMI than the NHANES cohort (26 [24, 28] kg/m2 vs 29 [25, 34] kg/m2, respectively). Correspondingly, the EPIC participants without diabetes required a lower vitamin C intake of 64 (63, 65) mg/d while those with diabetes required 129 (104, NA) mg/d to reach adequate circulating vitamin C status. C-reactive protein concentrations were strongly correlated with body weight and BMI and provided a surrogate biomarker for vitamin C requirements. In conclusion, people with diabetes have 1.4- to 1.6-fold higher requirements for vitamin C than those without diabetes. This corresponds to additional daily vitamin C intake requirements of ~30-40 mg for people with diabetes.

The diagnosis and management of cow's milk allergy (CMA) is a topic of debate and controversy. We aimed to compare the opinions of expert groups from the Middle East (n=14) and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) (n=13). These Expert groups voted on statements developed by the ESPGHAN group and published in a recent position paper. The voting outcome was compared. Overall, there was consensus amongst both groups of experts. Most experts agreed that symptoms of crying, irritability and colic, as single manifestations, do not suggest CMA. They agreed that amino-acid-based formula (AAF) should be reserved for severe cases (e.g. malnutrition and anaphylaxis) and that there is insufficient evidence to recommend a step-down approach. There was no consensus on the statement that a cow’s milk-based extensively hydrolysed formula (eHF) should be the first choice as a diagnostic elimination diet in mild/moderate cases. Although the statements regarding the role of hydrolysed rice formula as a diagnostic and therapeutic elimination diet were accepted, 3/27 disagreed. The votes regarding soy formula highlight the differences in opinion in the role of soy protein in CMA dietary treatment. Generally, soy-based formula is seldom available in the Middle East region. All ESPGHAN experts agreed that there was no added value of probiotics, prebiotics, and synbiotics to the efficacy of elimination diets, whereas 3/14 of the Middle East group thought there was sufficient evidence. Therefore, there is not a consensus on the optimal diagnostic and therapeutic elimination diet for CMA, but the first-choice elimination diet and the stepwise management approach reveal some differences.

The enteric nervous system is affected by inflammatory bowel diseases (IBD). Gut microbiota ferment dietary fibers and produce short-chain fatty acids, such as Butyrate, which bind to G protein-coupled receptors, such as GPR41, and contribute to maintaining intestinal health. This work aimed to study the GPR41 in myenteric neurons and analyze the effect of Butyrate in mice submitted to experimental ulcerative colitis. The 2, 4, 6 trinitrobenzene sulfonic acid (TNBS) was injected intrarectally in C57BL/6 mice (Colitis). Sham group received ethanol (vehicle). One group was treated with 100mg/kg of Sodium Butyrate (Butyrate), and the other groups received saline. Animals were euthanized 7 days after colitis induction. Analyzes demonstrated colocalization of GPR41 with neurons immunoreactive (-ir) to nNOS and ChAT-ir, and absence of colocalization of the GPR41 with GFAP-ir glia. Quantitative results demonstrated losses of nNOS-ir, ChAT-ir, and GPR41-ir neurons in Colitis group, and Butyrate treatment attenuated neuronal loss. The number of GFAP-ir glia increased in Colitis group, whereas Butyrate reduced the number of these cells. In addition, morphological alterations observed in Colitis group were attenuated in Butyrate group. The presence of GPR41 in myenteric neurons was identified and the treatment with Butyrate attenuated the damage caused by experimental ulcerative colitis.

Unmetamorphosed carbonaceous chondrites provide important information concerning the formation and evolution of organic matter, such as amino acids. However, terrestrial contamination remains a valid concern when investigating the organic inventory of meteorites that have fallen to Earth. Accordingly, JAXA’s Hayabusa2 and NASA’s OSIRIS-REx have been launched with the task of returning uncontaminated C-type asteroid material to Earth. The successful Hayabusa2 mission has a very limited sample size (5.4 g). Therefore, many conventional compound specific techniques will struggle to detect amino acids above detection limit with available sample amounts (~several mg to 10’s of mg) being much smaller than those typically used. Here a novel method utilizing ultrahigh performance liquid chromatography-Orbitrap-mass spectrometry is validated and applied to very small meteorite samples, thus providing an approach that can overcome the small sample size constraints of sample return missions. The method is highly sensitive, enabling the detection of amino acids in the carbonaceous chondrites Murchison (2.28 mg) and Orgueil (2.30 mg). Furthermore, quantitation was possible for many of the detected amino acids in Murchison and Orgueil. Using the data presented here, both the amino acid reservoirs of Murchison and Orgueil and the potential application of this method to sample return samples are discussed.

Traditional dry fermented meat products are obtained artisanally in many countries, where they represent a gastronomic heritage well distinguished from industrial counterparts. This food category is most often obtained from red meat, a food commodity that is under attack because of evidences of increased risk of cancer and degenerative diseases with high consumption. However, traditional fermented meat products are intended for moderate consumption and gastronomic experience and, as such, their production must be continued also to safeguard culture and economy of the geographical areas of origin. In this review, the main risks attributed to these products are considered and how these risks are minimized by following precise production norms, respectful of the ancient manufacturing processes is described. Moreover, results obtained in studies reporting use of autochthonous microbial cultures of lactic acid bacteria (LAB), coagulase negative staphylococci (CNS), Debaryomyces hansenii and Penicillium nalgiovense to improve safety and quality of traditional fermented meats are summarized. The role of these products as a source of microorganisms that can be beneficial to the host are also considered. From the results of the studies reviewed here it appears that the development of autochthonous cultures for these foods ensure safety and stabilize sensory characteristics with possibility to be extended to the large variety of traditional productions.

This study is the first report of the successful cultivation of Dinophysis norvegica isolated from Japanese coastal waters (7 of 48 isolated cells were established as the clonal cultures, 14.5%) and their toxin content and production. The strains were maintained at relatively high abundance (>2,000 cells mL-1) for more than one year when fed on Mesodinium rubrum with the addition of Teleaulax amphioxeia. At the end of the one-month incubation, the total amounts of pectenotoxin-2 (PTX2), dinophysistoxin-1 (DTX1) and okadaic acid (OA) were 132.0-375.0 ng mL-1 (n = 7), 0.7-3.6 ng mL-1 (n = 3) and trace level OA (n = 1), respectively. Similarly, the cell quota of PTX2 and DTX1 were 60.6-152.4 pg cell-1 (n = 7) and 0.5-1.2 pg cell-1 (n = 3), respectively. These data indicated that toxin production varies depending on the strains in this species. In the growth experiment, D. norvegica grew, but it was very slow first 12 days. However, after that they grew exponentially with the maximum growth rate of 0.56 divisions day-1 (during Day 24-27), reaching a maximum concentration of 3,000 cells mL-1 at the end of incubation (Day 36), suggesting that they have a long lag phase. In the toxin production, OA was not at a detectable level (≤ 0.010 ng mL-1) during the 36 days of incubation except for Day 6. The concentration of DTX1 and PTX2 showed similar patterns as described for vegetative growth, but the toxin production still increased on Day 36 (1.3 ng mL-1 and 154.7 ng mL-1 in DTX1 and PTX2, respectively). The findings of this study provide novel information on the toxin content and production in D. norvegica as well as details on the culturing and maintenance of the species.

This work presents the results of a comprehensive physico-chemical and biological study of hu-mic substances samples – an extract of humic and fulvic acids. The performed loss on drying test showed a 22 times different dry matter content between EHS and FA. The morphology and dis-tribution of particles in the dry residue of the samples assessed using the methods of optical and digital microscopy demonstrated differences in the qualitative features of the microstructures of their surfaces and granulometries. Shimadzu X-ray fluorescence spectrometry revealed Si (8.1 and 1.7%), P (33.5 and 2.7%), S (4.3 and 59.5%), K (1.35 and 2.5%), Ca (10.9 and 3.2%), Mn (0.27 and 0.06%), Fe (11 and 0.05%), Cu (0.16 and 0.45%), Zn (0.06 and 0.02%) in the dry residues of the EHS and FA samples, respectively. A high intensity of the X-ray fluorescence signal for Fe atoms in the EHS sample was demonstrated. The FT-IR spectra for EHS and FA are characterized by simi-lar vibration frequencies that are characteristic of the chromone derivatives (1-benzopyran-4-one). The UV absorption spectrum is characterized by max = 281 nm for FA. The EHS solution showed a fluorescence maximum at em = 560 nm at ex = 280 nm. Using the DLS method, nanoparticles of 1 nm and 200 nm were detected in EHS and FA diluted solutions, which are likely to condition the biochemical and physical properties of humic acids. Using the Spiro-tox-test method, the absence of the toxic effect of humic acids on the cell model of ciliates Sp. am-bigua was established. When the cell model was incubated in a solution of a toxicant of the fluo-roquinolone group, a decrease in toxicity was demonstrated when diluted with the EHS solu-tion. The results of the study of the antiviral activity of EHS and FA showed that the study ob-jects in the culture of Vero-E6 cells, in doses non-toxic to cells, suppress the reproduction of the SARS-CoV-2 virus both in the study of the virucidal effect and in the study of the antiviral activ-ity according to the therapeutic and prophylactic model scheme of injection. The results obtained suggest that standardized drugs based on humic acids may open up new perspectives in their biomedical application as antiviral drugs.

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

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the etiological agent of the current pandemic worldwide. The pathological condition induced by this pathogen is known as COVID-19 disease. SARS-CoV-2 associated pandemic has been defined as a “public health emergency of international concern” by the International Health Regulation Emergency Committee of the World Health Organization. To date, considerable efforts are in progress to develop more advanced strategies against SARS-CoV-2. Despite the numerous scientific studies published, our knowledge regarding this pathogen is still incomplete, as this virus has been identified only recently. Therefore, scientific investigation of the SARS-CoV-2 has been possible only for a short period of time and effective management of the serious forms of this disease is still lacking. Considerable efforts are in progress worldwide with the purpose to develop more advanced strategies against this pathogen. In this review, we have analyzed the structural and the biological SARS-CoV-2 characteristics and those of other well-known RNA viruses, with the aim to identify possible similarities and analogies between all these pathogens, may be a very useful approach. These infectious agents have been widely studied since several years ago and, a large series of scientific reports are available in the literature regarding this topic. Therefore, focusing on the Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV) and Influenza viruses (IVs), we have collected their historical data, clinical manifestations, pathogenetic mechanisms and related infections. Taking advantage of the results of our research, we have assembled this narrative review, with the aim to get useful insights and lessons from HIV, HCV and IVs characteristics and, consequently, to transfer the obtained knowledge to the study of SARS-CoV-2 biology. There are well known differences between all these pathogens. In particular, they present a distinct mode of transmission, as SARS-CoV-2 and Influenza viruses are airborne pathogens, whereas HIV and HCV are bloodborne infectious agents. However, these viruses exhibit some potential common clinical manifestations and pathogenetic mechanisms and their understanding may contribute to establishing preventive measures and new therapies against SARS-CoV-2. Accordingly, we have analysed and discussed the following points: 1) the biology, the pathogenesis and the clinical manifestations of SARS-CoV-2, HIV, HCV and IVs in mankind; 2) the onset and spreading of pandemics caused by respiratory viruses according to a perspective historical point of view; 3) the possible development of a persistent SARS-CoV-2 reservoir worldwide; 4) the possibility of SARS-CoV-2 reinfection/reactivation; 5) the possible involvement and impact of climatic factors in increasing the risk of SARS-CoV-2 spreading.

The major auxin, indole-3-acetic acid (IAA), is associated with a plethora of growth and developmental processes including embryo development, expansion growth, cambial activity, and the induction of lateral root growth. Accumulation of the auxin precursor indole-3-acetamide (IAM) induces stress related processes by stimulating abscisic acid (ABA) biosynthesis. How IAM signaling is controlled is, at present, unclear. Here, we characterize an ami1/rooty double mutant, that we initially generated to study the metabolic and phenotypic consequences of a genetic blockade of the indole glucosinolate and IAM pathways in Arabidopsis thaliana. Our mass spectrometric analyses of the mutant revealed that the combination of the two mutations is not sufficient to fully prevent the conversion of IAM to IAA. The detected strong accumulation of IAM was, however, recognized to substantially impair seed development. We further show by genome-wide expression studies that the double mutant is broadly affected in its translational capacity, and that a small number of cell proliferation and plant growth regulating transcriptional circuits are repressed by the high IAM content in the seed. In accordance with the previously described growth reduction in response to elevated IAM levels, our data support the hypothesis that IAM is a growth repressing counterpart to IAA.

FoxP3 is a transcription factor essential for the differentiation and function of T regulatory cells (Tregs). There are two major subsets of Tregs: natural Tregs (nTregs) generated in thymus and inducible Tregs (iTregs) produced in peripheral immune system. It has been documented that iTreg development is dependent on soluble mediators including interleukin 2 (IL2), transforming growth factor β (TGFβ) and all-trans-retinoic acid (ATRA). In our experiments we performed a gene expression array, followed by Real-time PCR experiments, to study the expression of genes regulated by 1,25-dihydroxyvitamin D (1,25D) or ATRA in cells of myeloid origin. Our experiments revealed that ATRA alone, but also a cocktail of mediators consisting of IL2, TGFβ and ATRA, upregulate the expression of FOXP3 gene in lymphoid cells, but also in normal and leukemic myeloid cells. The FoxP3 expression is followed by a phenotypic changes in cells of myeloid origin. Our results indicate that signaling pathways which are used in the late stages of T cell differentiation, are also active in the cells of myeloid lineage

High fructose and sugar-sweetened soft drink (SSSD) intakes are associated with elevated blood uric acid concentrations and increased risk of gout and cardiovascular disease. Fruits are naturally high in fructose but their effect on cardiometabolic risk is unknown. We examined the effect on serum uric acid and cardiometabolic risk factors of consuming fructose from either fruit or SSSD in overweight adults. 48 healthy, overweight (BMI≥ 28 kg/m²) men (n=21) and women (n=20) were randomised to either a fruit (n = 19) or SSSSD (n = 22) intervention for 4 weeks. The fruit group received 6 items of fresh and dried fruit per day and the SSSD group received 955ml of SSSD per day with treatments matched for energy and fructose content. Serum uric acid concentrations were significantly reduced in men in the fruit group compared to the SSSD group (difference 57.2 μmol/L [95% CI: 16.4, 98.0], p= 0.008) but there was no difference amongst women (1.3 μmol/L [95%CI: -9.5, 6.9], p= 0.295). There differences in weight change or other cardiometabolic risk factors. These findings suggest no need to restrict fruit intake in individuals with elevated serum uric acid concentrations, such as those with gout.

A large diversity of epigenetic factors, such as microRNAs and histones modifications, are known to be capable of regulating gene expression without altering DNA sequence itself. In particular, miR-1 is considered the first essential microRNA in cardiac development. In this study, miR-1 potential role in early cardiac chamber differentiation is analyzed through specific signaling pathways. For this, we performed in chick embryos functional experiments by means of miR-1 microinjections into the posterior cardiac precursors -of both primitive endocardial tubes- committed to sinoatrial region fates. Subsequently, embryos were subjected to whole mount in situ hybridization, immunohistochemistry and RT-qPCR analysis. As a relevant nov-elty, our results revealed that miR-1 increases Tbx5, Gata4 and AMHC1, while this microRNA diminishes Mef2c expression, during early differentiation of cardiac sinoatrial region. Further-more, we observed in this developmental context that miR-1 upregulates CRABPII and RARß, and downregulates CRABPI, which are three crucial factors in retinoic acid signaling pathway. Interestingly, we also noticed that miR-1 directly interacts with HDAC4 and Calmodulin, as well as with Erk2/MAPK1, which are three key factors actively involved in Mef2c regulation. Our study shows, for the first time, a key role of miR-1 as an epigenetic regulator in early differenti-ation of cardiac sinoatrial region through orchestrating opposite actions between retinoic acid and Mef2c, fundamental to properly assign cardiac cells to their respective heart chambers. A better understanding of those molecular mechanisms modulated by miR-1 will definitely help in fields applied to therapy and cardiac regeneration and repair.

The global increase in population has placed significant pressure on food security, leading to the emergence of aquaculture as a vital source of aquatic foods. However, rising costs and the limited availability of fishmeal in aquafeeds have spurred the search for alternative protein sources. While plant-based ingredients have been integrated into commercial aquafeeds, they come with challenges, including low protein content, palatability issues, and the presence of antinutritional factors. In this context, fish silage, derived from fish waste and discarded fish, stands out as a promising alternative technology due to its cost-effectiveness and sustainability attributes. The production of fish silage involves the addition of organic/inorganic acids or lactic acid bacteria to homogenized fish waste. This process yields a valuable mixture rich in peptides, free amino acids, and partially hydrolyzed proteins, offering significant nutritional benefits for animal diets. Beyond its nutritional advantages, fish silage contributes to environmental sustainability by reducing the impact of waste disposal and enhancing the value of fish waste. The objective of this review is to promote sustainable practices in the aquaculture industry in response to the increasing demand for high-quality feed nutrients. To achieve this, it includes an analysis of research results related to silage technology, an appraisal of the advantages and disadvantages of using fish silage as a feed additive, and a focus on emerging trends in this field.

This work presents noble composites of AAILs@MCM-48 by functionalizing ordered mesopo-rous silicon MCM-48 with two amino acid-based ionic liquids (AAILs) ([Emim][Gly] and [Em-im][Ala]) to improve carbon capture and selectivity of CO2 over nitrogen. Thermogravimetric and XRD analyses of the composites show that the MCM-48 support's thermal and structural in-tegrity was preserved after the AAILs were encapsulated. An N2 adsorption-desorption study at 77 K also confirms AAIL encapsulation in the porous support. Under post-combustion flue gas conditions, both [Emim][Gly]@MCM-48 and [Emim][Ala]@MCM-48 demonstrated improved CO2 adsorption in comparison to unmodified MCM-48, with a CO2 partial pressure of around 0.15 bar. In terms of maximal CO₂ uptake, the 40wt%-[Emim][Gly] composite outperformed the others at 303K, with values of 0.74 and 0.82 mmol g-1, respectively, at 0.1 and 0.2 bar. These numbers show a 10x and 5x increase, respectively, as compared to the pure MCM-48 under iden-tical conditions. In addition, the selectivity of the composites was improved significantly, at 0.1 bar, the selectivity of composites containing 40wt% [Emim][Ala] increased to 17, compared to 2 for pristine MCM-48.

This study presents the encapsulation of two amino acid-based ionic liquids (AAILs), 1-Ethyl-3-methylimidazolium glycine [Emim][Gly] and 1-Ethyl-3-methylimidazolium alanine [Emim][Ala], in a highly porous metal organic framework (MOF-177), to generate state-of-the-art composites for post-combustion CO2 capture. The thermogravimetric analysis (TGA) demonstrated a successful encapsulation of the AAILs, consequently dramatically reducing the composites' surface area and pore volume. Both [Emim] [Gly]@MOF-177 and [Emim][Ala]@MOF-177 had close to 3 times the CO2 uptake of MOF-177 at 20 wt.% loading, 0.2 bar, and 303 K. Additionally, 20-[Emim][Gly]@MOF-177 and 20-[Emim] [Ala]@MOF-177 enhanced their CO2/N2 selectivity from 5 (pristine MOF-177) to 13 and 11, respectively.

The present article describes a one-pot and cascade mode process using biocompatible/biodegradable reagents, for directly and simply obtaining surfactant compositions of mixtures of D-mannuronic acid and L-guluronic acid directly from oligoalginates or semi-refined alginates (mixtures of alginate, cellulose, hemicellulose, laminaran and fucan). Simple treatments of partial purification of the reaction crudes (elimination of the salts and/or the residual fatty alcohols) or isolation of the surfactant compositions result in derived compounds and in compositions having performance levels appropriate to applications in detergency. In addition, the challenging extension of this cascading one-pot synthesis technology to crude milled brown seaweeds was successfully carried out to provide promising surface-active compositions made up of alkyl uronate and alkyl glycoside monosaccharides.

Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated without drugs by using artificial diets in which the levels of specific amino acids (AAs) are manipulated. In this work, after showing that AA manipulation induces selective anticancer activity in renal cell carcinoma cells in vitro, we evaluated the anticancer activity of 17 artificial diets in a challenging animal model of renal cell carcinoma. The model was stablished by injecting murine renal cell carcinoma (Renca) cells into the peritoneum of immunocompetent BALB/cAnNRj mice. Mice survival was markedly improved when their normal diet was replaced with our artificial diets. Mice fed a diet lacking six AAs (diet T2) lived longer than mice treated with sunitinib or anti-PD-1 immunotherapy; several animals lived very long or were cured. Controlling the levels of several AAs (e.g., cysteine, methionine and leucine) and lipids was important for the anticancer activity of the diets. Additional studies are needed to further evaluate the therapeutic potential of this simple and inexpensive anticancer strategy.

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

PHLNs (polymeric lipid hybrid nanoparticles) are core–shell nanoparticle structures made up of polymer cores and lipid shells that have properties similar to both polymeric nanoparticles and liposomes. Methotrexate (MTX) loaded PLHNPs containing tween 80, phosphatidylcholine, poly D, L-lactic-co-glycolic acid (PLGA) & glyceryl tripalmitate prepared using solvent injection & homogenization method for glioblastoma treatment option. The MTX loaded PLHNPs optimized by Box–Behnken design to minimize particle size, higher entrapment efficacy, and maximize MTX concentration in the brain at 4h. The particle size, entrapment efficacy, concentration of drug in brain at 4h, zeta potential and AUC(Brain)/AUC(Plasma) ratio were in the range of 173.51-233.37nm, 70.56-86.34%, 6.38-12.38 μg/mL, 25.78-36.31mV & 1.02-5.32. in-vitro drug release studies, cellular internalization of optimized formulation against U-87 MG shows good anticancer effects.

Long-chain omega-3 fatty acid status during pregnancy may influence newborn anthropometry and duration of gestation. Evidence from high-quality trials from LMICs is limited. We conducted a double-blind, randomized, placebo-controlled trial among 957 pregnant women (singleton gestation, 14-20 weeks’ gestation at enrollment) in India to test the effectiveness of 400 mg/d algal docosahexaenoic acid (DHA) compared to placebo provided from enrollment through delivery. Among 3379 women who were screened, 1171 were found eligible; 957 enrolled and were randomized. The intervention was two microencapsulated algal DHA (200 X 2= 400 mg/d) or two microencapsulated soy and corn oil placebo tablets to be consumed daily from enrollment (20 weeks) through delivery. The primary outcome was newborn anthropometry (birth weight, length, head circumference). Secondary outcomes were gestational age and 1 and 5 min Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score. The groups (DHA; n=478 and placebo; n=479) were well balanced at baseline. There were 902 live births. Compliance with the intervention was similar across groups (DHA: 88.5%; placebo: 87.1%). There were no significant differences between DHA and placebo group for birth weight (2750.6 ± 421.5 vs. 2768.2 ± 436.6 g, p=0.54), length (47.3 ± 2.0 vs. 47.5 ±2.0 cm, p=0.13) or head circumference (33.7 ± 1.4 vs 33.8 ± 1.4 cm, p=0.15). The mean gestational age at delivery was similar between groups (DHA: 38.8 ± 1.7 placebo: 38.8 ± 1.7 wk, p= 0.54) as were APGAR scores at 1 and 5 min. Supplementing mothers through pregnancy with 400mg/d DHA did not impact the offspring birthweight, length or head circumference.

A New monogalactosyldiacylglycerol (MGDG), a known monogalactosylmonoacylglycerol (MGMG) and a known polyunsaturated fatty acid methyl ester (PUFAME) were isolated from the marine dinoflagellate Karenia mikimotoi. The planar structure of the glycolipids was elucidated using MS and NMR spectroscopic analyses and comparisons to the known glycolipid to confirm its structure. The isolation of PUFAME strongly supports the polyunsaturated fatty acid fragment of these glycolipids. The relative configuration of the sugar was deduced by comparisons of 3JHH values and proton chemical shifts with those of known glycolipids. All isolated compounds MGDG, MGMG and PUFAME (1-3) were evaluated for their antimicrobial and anti-inflammatory activity. All compounds modulated macrophage responses, with compound 3 exhibiting the greatest anti-inflammatory activity.

Distinctive strains of Pantoea are used as soil inoculants for their ability to promote plant growth. Pantoea agglomerans strain C1, previously isolated from the phyllosphere of lettuce, can produce indole-3-acetic acid (IAA), solubilize phosphate, and inhibit plant pathogens, such as Erwinia amylovora. In this paper, the complete genome sequence of strain C1 is reported. In addition, experimental evidence is provided on how the strain tolerates arseniate up to 100 mM, and on how secreted metabolites like IAA and siderophores act as biostimulants in tomato cuttings. The strain has a circular chromosome and two prophages for a total genome of 4,846,925-bp, with a GC content of 55.2%. Genes related to plant growth promotion and biocontrol activity, such as those associated with IAA and spermidine synthesis, solubilization of inorganic phosphate, acquisition of ferrous iron, and production of volatile organic compounds, siderophores and GABA, were found in the genome of strain C1. Genome analysis also provided better understanding of the mechanisms underlying strain resistance to multiple toxic heavy metals and transmission of these genes by horizontal gene transfer. Findings suggested that strain C1 exhibits high biotechnological potential as plant growth-promoting bacterium in heavy metal polluted soils.