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

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.

Regulation (EU) No 305/2011 lays down harmonized conditions for marketing construction products in the European Union. One of its consequences has been the introduction of the product standard EN 50575 and standard EN 130501-6, concerning power, control, and communication cables permanently installed in buildings to prevent the risk of a fire and its consequences. EN 13501-6 provides the reaction to fire classifications for cables, the test methods to be performed, the requirements to meet a specific reaction to fire, and additional classifications for smoke production, flaming droplets, and acidity. EN 60754-2 is the technical standard used to assess acidity, and it defines three classes: a1, a2, and a3 (the less performant), based on pH and conductivity measurements. Due to the release of hydrogen chloride during the combustion, acidity is the weak point of PVC cables, which are not yet capable of achieving the a1 or a2 classes required in specific locations according to a fire risk assessment. EN 13501-6 does not include EN 60754-1. Both EN 60754-1 and EN 60754-2 are common standards for determining halogen gas content, acidity, and conductivity, respectively. They involve the same type of tube furnace but with different heating regimes, final temperatures, and detection methods. EN 60754-2 must be performed at temperatures between 935 – 965 °C. The paper demonstrates that, when EN 60754-2 is carried out with the thermal profile of EN 60754-1 or at 500 °C in isothermal conditions, the evolution of hydrogen chloride changes significantly if potent acid scavengers are utilized in the PVC compounds. The reason lies behind the kinetic of hydrogen chloride release during the combustion of PVC compounds: the higher the temperature or faster the heat release, the quicker hydrogen chloride evolution and the lower the probability for the acid scavenger to trap it. That further highlights the "fragility" of EN 60754-2 as a tool for assessing the risks associated with the release of hydrogen chloride in case of fire

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 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 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 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.

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.

This work investigates how the user-controlled parameters of the 3D printing process define temperature conditions on the boundary between layers of the part being fabricated and how these conditions influence the structure and strength of the part. The process studied is fused filament fabrication with a desktop 3D printer and the material utilized is PLA (polylactic acid). As a characteristic of the part strength the fracture load in the case of a three-point bend and calculated related stress were used. During the printing process parts were oriented with the long side along the Z axis, thus, in the bend tests, the maximum stress occurred orthogonally to the layers. During the fabrication process, temperature distribution on the sample surface was monitored with thermal imager. Sample mesostructure was analyzed using SEM. The influence of the extrusion temperature, the intensity of part cooling, the printing speed and the time between printing individual layers were considered. The influence of all the parameters can be expressed through two generalizing factors: the temperature of the previous layer and the flow efficiency, determining the ratio of the amount of extruded plastic to the calculated. A regression model was proposed that describes the effect of the two factors on the printed part strength. Along with interlayer bonding strength, these two factors determine the formation of the part mesostructure (the geometry of the boundaries between individual threads). It is shown that the optimization of the process parameters responsible for temperature conditions makes it possible to approximate the strength of the interlayer cohesion to the bulk material strength.

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.

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.

Copper-containing materials are attracting attention as self-desinfecting surfaces, suitable for helping healthcare settings in reducing healthcare associated infections. However, the impact of repeated exposure to disinfectants frequently used in biocleaning protocols on their antibacterial activity remains insufficiently characterized. This study aimed at evaluating the antibacterial effi-ciency of copper (positive control), a brass alloy (AB+®) and stainless steel (negative control) after repeated exposure to a quaternary ammonium compound and/or a mix of peracetic acid/hydrogen peroxide routinely used in healthcare settings. A panel of 6 antibiotic-resistant strains (clinical isolates) was selected for this assessment. After a short (5 min) exposure time, the copper and brass materials retained significantly better antibacterial efficiencies than stainless steel, whatever the bacterial strain or disinfectant treatment considered. Moreover, post-treatment with both disinfectant products, copper-containing materials still reached similar levels of antibacterial efficiency as those obtained before treatment. Antibiotic resistance mechanisms such as efflux pump overexpression did not impair the antibacterial efficiency of copper-containing materials, neither did the presence of one or several genes related to copper homeostasis/resistance. In light of those results, surfaces made out of copper and brass remain interesting tools in the fight against dissemination of antibiotic-resistant strains that might cause healthcare associated infections.

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.

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.

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.

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.

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.

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.

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.

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.

The current paper is studying the influence of geometrical parameters of the FDM (FFF) 3D printing process on printed part strength for open source desktop 3D printers and the most popular material used for that purpose, i.e. PLA (polylactic acid). The study was conducted using a set of different nozzles (0.4, 0.6 and 0.8 mm) and a range of layer heights from the minimum to maximum physical limits of the machine. To assess print strength, a novel assessment method is proposed. A tubular sample is loaded in the weakest direction (across layers) in a three-point bending fixture. To explain the results obtained, a mesostructure evaluation through SEM scans of the samples were used. A significant influence of geometric process parameters was detected on sample mesostructure and, consequently, on sample strength.

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.

Adeno-associated viruses (AAVs, genus dependoparvovirus) are promising gene therapy vectors. In strains AAV1-12, the capsid gene VP1 encodes a recently discovered protein, MAAP, in an overlapping frame. MAAP binds the cell membrane by an unknown mechanism. We discovered that MAAP is also encoded in bovine AAV and in porcine AAVs (which have shown promise for gene transfer into muscle tissues), in which it is probably translated from a non-canonical start codon. MAAP is predicted to be mostly disordered except for a predicted C-terminal, membrane-binding amphipathic α-helix. MAAP has a highly unusual composition. In particular, it lacks internal methionines, and is devoid of tyrosines in most strains. Unexpectedly, we discovered that the N-terminus of VP1 also lacks several amino acids. In all AAVs that encode MAAP, the first 200 aas of VP1 are devoid of internal methionines, probably owing to a selection against ATG codons that could prevent translation of MAAP and of capsid isoforms (VP2, VP3). The N-terminus of VP1 also lacks cysteines, likely to avoid the formation of disulfide bridges when it becomes exposed outside of the capsid during post-endocytic trafficking. Finally, the region common to VP1 and VP2 lacks tyrosine in the vast majority of AAVs that encode MAAP. Avoiding these "forbidden" aas in MAAP and VP1 when creating recombinant AAV capsids might increase the efficiency of capsid design. Conversely, the presence of "forbidden" aas in some rare strains probably indicates that they have unusual properties that could help us understand the viral cycle.

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.

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.

The mortality rate of women during the gestation period or after delivery is very high worldwide. ToRCH pathogens [Toxoplasma gondii (T.gondii), Rubella Virus (RV), Cytomegalovirus (CMV), and Herpes Simplex Virus (HSV)] are transmitted vertically and are associated with mortality and complications both in the mother and the fetus or children. Therefore, this study is designed to investigate the ToRCH pathogen-induced histopathological changes in placental tissues and associated post-obstetric complications in Pakistani women. Women (N = 68) included in this study were divided into Group A (women with current abortion and bad obstetric history-BOH) and Group B (women with normal delivery and BOH). The venous blood collected was analyzed for ToRCH antibodies through ELISA. A small piece of placenta tissue taken after delivery or abortion was subjected to nucleic acid (NA) detection through PCR using ToRCH pathogen-specific primers. The placental tissue was analyzed for histopathological changes under a microscope. The data obtained were analyzed using percentages and the Chi square test. Overall ToRCH antibody positivity was 64.70% (44/68). Of these, IgM (Immunoglobulin M) was found in 17.65% (12/68), IgG (Immunoglobulin G) in 45.59% (31/68), and one case (1.47%) was seropositive for both IgM and IgG. The NA was detected in 66.18% (45/68) of the placental tissues of the study population. The higher prevalence of antibodies for T.gondii and RV (23.53% each) and NA for RV, CMV, and HSV (17.99% each) was observed in the study population. The ToRCH infection (antibodies and NA) with BOH complications was statistically found to be non-significant (p> 0.05). Overall discrepancies in ToRCH antibodies and NA positivity were found in 86.76% (59/68) of cases, especially for RV (26.47%). Chorionic villitis (CV) in placental tissues was observed in 20.59% (14/68), i.e., 13.23% of Group A and 7.35% of Group B. Of the total, four women with T.gondii, six with RV, and three each with CMV and HSV infection were found with CV. The most common BOH complications observed were recurrent spontaneous abortions (RSAs) (47.05%, 32/68), stillbirth (22.05%, 15/68), congenital abnormalities (14.70%, 10/68), etc. It was observed that RSAs were associated with CV (10.29%) in the study population. The BOH complication and CV were found to be statistically non-significant (p> 0.05). It is concluded that ToRCH pathogens are prevalent in the study population, and CV was the only histopathological change found and associated with BOH complications.

Obesity is one of the most prevalent chronic diseases and has become a global epidemic. Obesity leads to a greater risk of breast cancer (BC), metastases, recurrence, and decreased survival. For sustained weight loss, bariatric surgery is effective as a long-term solution. Bariatric surgery is associated with improved outcomes of several cancers including BC, although the mechanisms mediating this protection are unknown. We hypothesized that elevated bile acid pools detected after bariatric surgery may be factors that contribute to improved BC outcomes. Indeed, patients with greater expression of the bile acid receptor FXR displayed improved survival in specific BC subtypes. Patients with tumors that are estrogen receptor negative (ER-) displayed significantly elevated survival with higher FXR (NR1H4) expression compared to lower expression. FXR is a nuclear hormone receptor activated by bile acids. Therefore, we posited that activating FXR using an established FDA-approved agonist would display anticancer effects. Indeed, FXR agonism by the bile acid mimetic known commercially as OCALIVA (“OCA”), or Obeticholic acid (INT-747), significantly reduced BC progression and overall tumor burden in a pre-clinical model. In human and murine BC analyses in vitro, agonism of FXR significantly and dose-dependently inhibited proliferation, migration, and viability. In contrast, synthetic agonism of another common bile acid receptor, the G protein-coupled bile acid receptor (GPBAR1, TGR5) which is mainly activated by secondary bile acids, failed to significantly alter cancer cell dynamics. In conclusion, agonism of FXR by primary bile acid memetic OCA yields potent anti-tumor effects potentially through inhibition of proliferation and migration and reduced cell viability. Findings suggest that FXR is a tumor suppressor gene with high potential for personalized therapeutic strategies for individuals with BC.

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

The root-colonizing endophytic fungus Piriformospora indica promotes root and shoot growth of its host plants. We show that growth promotion of Arabidopsis leaves is abolished when the seedlings are grown on media with nitrogen (N) limitation. The fungus neither stimulated the total N content nor did it promote 15NO3- uptake from agar plates to the leaves of the host under N-sufficient or N-limiting conditions. However, when the roots were co-cultivated with 15N-labelled P. indica, more label can be detected in the leaves of N-starved host plants, but not of plants supplied with sufficient N. Amino acid and primary metabolite profiles, as well as expression analyses of N metabolite transporter genes suggest that the fungus alleviates the adaptation of its host to the N limitation condition. P. indica alters the expression of transporter genes which participate in relocation of NO3-, NH4+ and N metabolites from the roots to the leaves under N limitation. We propose that P. indica participates in the plant´s metabolomic adaptation to N limitation by delivering reduced N metabolites to the host, alleviating metabolic N starvation responses, and reprogramming the expression of N-metabolism related genes.

The proton conductivity, phase composition and mechanical properties of (1-x)CsH2PO4–x fluoropolymer electrolytes (x-mass fraction, x=0-0.3) have been investigated firstly and discussed. UPTFE and PVDF-based polymers (F2M, F42, SKF26) with the high mechanical properties and thermal stability have been chosen as a fluoropolymer additive. According the XRD data, a monoclinic CsH2PO4 (P21/m) phase is retained in all compositions of the polymer electrolytes studied. The conductivity of (1-x)CsH2PO4-x fluoropolymer in the high-temperature phase decreases by approximately one order of magnitude compared with the pure CsH2PO4 for x~0.15-0.20. The size and shape of CsH2PO4 particles and their distribution have been shown to affect significantly the proton conductivity and mechanical properties of the membranes. The thin-film composite systems were produced by various methods of the obtaining salt particles, their mixing and applying to a polymer matrix. The uniform distribution of particles in the polymer systems with the size of ~300 nm was achieved by a pretreatment of the suspension in a bead mill. CsH2PO4-based mechanically strong membranes with the thickness ~50–100 μm were obtained for the soluble fluoropolymers (F2M, F42, SKF26). With an increase in the mass fraction of the polymer the ability of the membranes to resist the plastic deformation and the mechanical strength increases and comparable to the best low temperature membranes. The proton-conducting membranes (1-x)CsH2PO4 – x fluoropolymer with the optimal combination of the conductivity, mechanical and hydrophobic properties are promising for use in solid acid fuel cells.

Conventional chemotherapy for colorectal cancer (CRC) gives only a small increase in patient survival, since it is often diagnosed in late stages, when tumor has disseminated to other organs. Besides, it is common to observe that malignant cells acquire tumor escape mechanisms which leads to therapy resistance. Considering these facts, the discovery of new molecules with therapeutic potential has become an invaluable tool in chemoprevention. In this context, we previously evaluated two hybrids (SAC-CAFA-MET and SAC-CAFA-PENT) which exhibited selective cytotoxicity against SW480, with better results than the conventional chemotherapeutic agent (5-fluorouracil; 5-FU). Here, we investigated a little deeper in the possible mechanism of these molecules to identify potential therapeutic alternatives for the treatment of CRC. Both compounds induced cell damage and reduced ROS formation. Further evaluations showed that SAC-CAFA-MET induces cell death independent from caspases and p53, but probably mediated by the negative regulation of the proapoptotic Bcl-2. In addition, the lack of activation of caspase 8 and the positive regulation of caspase 3 induced by SAC-CAFA-PENT suggest this compound acts through an apoptotic mechanism, probably initiated by intrinsic pathway. Besides, the down regulation of IL-6 by SAC-CAFA-PENT suggests it also induces a significant anti-inflammatory process. In addition, docking studies would suggest caspase-3 modulation as the primary mechanism by which hybrids elicits apoptosis in human colorectal adenocarcinoma SW480. Meanwhile, DFT calculations suggest that hybrids would produce effects in modulation of ROS in SW480 cells via hydrogen atom transfer pathway (HAT). Finally, both, SAC-CAFA-MET and SAC-CAFA-PENT displayed a favorable pharmacokinetic profile. The current work highlights the potential of the lead compounds SAC-CAFA-MET and SAC-CAFA-PENT as potential agents for colorectal cancer chemoprevention.

The design of multifunctional microcarriers has attracted significant attention because they combine various functions within a single system. In this study, we developed a set of multi-layered hydrogel microcarriers, which were first loaded with chemotherapeutic curcumin (CUR), then using the layer-by-layer (LbL) technique, coated through a polyelectrolyte shell consisting of chitosan (CHIT) or poly(allylamine hydrochloride) (PAH). As an outer layer with antimicrobial function, newly synthesised alkylene quaternary ammonium salt functionalised polyelectrolytes (A-QAS-PEs) were applied. For this purpose, poly(acrylic acid) (PAA) was decorated with dif-ferent hydrophobic side chains (n-hexane and n-dodecane side entities) and different degrees of substitution (m) of quaternary ammonium groups (abbreviated as PAA-C(O)O-(CH2)n-N+(CH3)3(m); n=6,12; m=8-14%). The grafting approach of PAA with the al-kylene quaternary ammonium salt moiety was performed under mild reaction conditions using Steglich esterification followed by quaternisation. The structure of antimicrobial decorated PAA was confirmed by 1H NMR and FTIR, and the mean diameter of all multifunctional microparticles was characterised by SEM. The viscoelastic properties of the functional layers were studied using QCM-D. The release of CUR from the microcarriers was described using a hybrid model, i.e., a combination of first-order kinetics and the Korsmeyer-Peppas model. The antimicrobial activity of functionalised PAA and multilayered CUR-loaded hydrogel microcarriers with quaternary am-monium function was assessed against Staphylococcus aureus and Serratia marcescens by the agar diffusion assay method. Only a limited inhibition zone of PAA was observed, but in the case of both antimicrobial decorated PAA and the corresponding multilayered nanocarriers, the inhibi-tory activity increase was achieved against both strains of bacteria.

Myxobacteria represent a viable source of chemically diverse and biologically active secondary metabolites. The myxochelins are a well-studied family of catecholate-type siderophores produced by various myxobacterial strains. Here, we report the discovery, isolation and structure elucidation of three new myxochelins N1–N3 from the terrestrial myxobacterium Corallococcus sp. MCy9049, featuring an unusual nicotinic acid moiety. Precursor-directed biosynthesis (PDB) experiments and total synthesis were performed in order to confirm structures, improve access to pure compounds for bioactivity testing and to devise a biosynthesis proposal. The combined evaluation of metabolome and genome data covering myxobacteria supports the notion that the new myxochelin congeners reported here are in fact frequent side products of the known myxochelin A biosynthetic pathway in myxobacteria.

Peptide nucleic acid (PNA) is a synthetic DNA mimic that outperforms the properties of traditional oligonucleotides (ONs). On account of its outstanding features, such as remarkable binding affinity towards complementary DNA or RNA as well as high thermal and chemical stability, PNA has been proposed as a valuable alternative to the ON probe in gene-sensor design. In this study, a hybrid transducer made-up of graphene oxide (GO) nano-sheets covalently grafted onto a porous silicon (PSi) matrix has been investigated for the early detection of a genetic cardiac disorder, the Brugada syndrome (BS). A functionalization strategy towards the realization of a potential PNA-based device is described. A peptide nucleic acid (PNA), able to detect the SCN5A associated with the BS has been properly synthesized and used as a bioprobe for the realization of a proof-of-concept label-free optical PNA-biosensor. PSi reflectance and GO photoluminescence (PL) signals were simultaneously exploited for the monitoring of the device functionalization and response.

Residential dust is recognized as a major source of environmental contaminants, including polycyclic aromatic hydrocarbons (PAHs) and phthalic acid esters (PAEs). To characterize the thoracic dust fraction (PM10), a sampling campaign was carried out with an in-situ resuspension chamber in three rooms (kitchen, living room and bedroom) of four Spanish houses. Two samples per room were collected with, at least, a one-week interval. The PM₁₀ samples were analyzed for their carbonaceous content by a thermo-optical technique and, after solvent extraction, for 20 PAHs, 8 phthalate plasticizers (PAEs) and one non-phthalate plasticizer (DEHA) by gas chromatography-mass spectrometry. In general, higher dust loads were observed for parquet flooring compared with tile. The highest dust loads were obtained for rugs. Total carbon accounted for 9.3 to 51%wt of the PM₁₀ mass. Plasticizer mass fractions varied from 5 µg g-1 to 17 mg g^-1 PM₁₀, whereas lower contributions were registered for PAHs (0.98–116 µg g^-1). The plasticizer and PAH daily intakes for children and adults via dust ingestion were estimated to be 3–4 orders of magnitude higher than those via inhalation and dermal contact. Potential carcinogenic and negligible non-carcinogenic risks arising from exposure to PAHs were found.

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.

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 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.

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.

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.

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.

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.

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<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.

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.

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.

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.

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.

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.

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.

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.

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

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<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.

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 Influenza A Virus (IAV) represents an enveloped, positive-sense and single-stranded RNA-based virus that infects mammals mainly via the respiratory system, although other bodily systems are also infected and undergo various extents of inflammatory pathogenesis. There are two well-known strains of IAV that cause life-threatening disease in mammals; H1N1 and H5N1, and the first strain caused the 1918 IAV H1N1 pandemic that claimed between 30 and 50 million human lives. Due to the significant ability of IAV to evade important immune recognition, the virus was observed to favor the onset of secondary microbial infections (i.e. bacterial or fungal), as the overall performance of the immune system became transiently weakened during the viral infection. During the IAV H1N1 pandemic, many patients died as a result of bacterial pneumonia, as pathogenic bacteria, such as Streptococcus pneumoniae and Haemophilus influenzae, gained a wider opportunity to colonize and infect vital areas of the lower respiratory tract, and such a phenomenon led to the excessive, prophylactic usage of antibiotics due to the increased levels of panic, which in turn favored the natural selection of bacteria with genes that became resistant to such antibiotics. Antibiotics might be required for usage solely when bacteria are known to be colonizing vital areas of the human body, and this aspect is tricky, as colonization is asymptomatic and screening is consequently rare. Recently, new variants of the avian IAV H5N1 strain were transmitted from live, infected birds to mammals, including humans in some isolated cases, and given that there have already been several zoonotic spillover events overall since the beginning of 2023, we are rapidly approaching the time when a zoonotic spillover into humans will mark the first epidemic outbreak of the avian flu in humans. A lethality rate of 60% was projected by the World Health Organization, as the virus was shown to favor the development of life-threatening hyper-inflammatory responses at the levels of alveolar tissues constituted by Type II pneumocytes. There are hints that novel variants of H5N1 are capable of infecting the intestinal layer, as recently, two dolphins died as a result of ingesting infected birds within the area of the British Isles. IAV is known to suppress the production and transmission of Type I Interferons by expressing various non-structural proteins (NSPs), such as NSP1, which was found to be also packaged into exosomes and transmitted to neighboring uninfected cells, thereby preventing them from responding to the virus in the first place. Additionally, it was determined that NSP1 induces the apoptosis of the cells it is produced in and the neighbouring ones it enters via induced paracrine signalling, and such an aspect may only emphasise upon the critical role that early innate immune stimulation plays in preventing the development of severe respiratory illness afterward, given the context of increased viral ability of suppressing the production of first-line and second-line signals. A more pronounced rate of innate immune evasion would probably be observed in H5N1 IAV infection than in the infection caused by recent variants of H1N1 IAV. The H5N1 strain of IAV was also found to secrete a higher concentration of NSP1 than SARS-CoV-2, indicating the existence of an association to the greater mortality rate of H5N1 IAV infection. A direct, prophylactic stimulation of the interferon system using a reduced oral or nasal dosage of recombinant anti-inflammatory and anti-viral interferon glycoproteins may represent the most viable approach to prevent an emergence of a life-threatening H5N1 IAV pandemic. A similar non-invasive approach could be developed for an Marburg Virus (MARV) and a Nipah Virus (NiV) infection of humans, as risks of the emergence of a Marburg epidemic and also of a Nipah epidemic may be substantial at this stage as well. Clinical testing of clinical approaches as such could be of critical importance at the moment. Animals could also benefit from related clinical approaches. Somatic natural and adaptive lymphocytes treated with IFN I and III could also constitute a substantial approach of immunization and heavily favor an indefinite shift in the evolutionary battle between the host organism and microbes of public health concern, as IFN I and III could improve the immunity of T-lymphocytes against HIV infection and even improve the performance of the mentioned types of immune cells during other types of infections. Likewise, a combination of all intellectual and clinical efforts implicating a shift of scientific and medical focus toward natural immunity in vaccine-related research could be a wise method in making the best efforts to prevent or alleviate the effects of a possible future pandemic, given the highly significant and diverse abilities of microbial “intelligence” to effectively hijack the natural immune system, many times causing severe implications upon the quality of the overall immune response against such microbes.

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.

Acute kidney injury (AKI) following surgery with cardiopulmonary bypass (CPB-AKI) is common in pediatrics. Urinary liver-type fatty acid binding protein (uL-FABP) increases in some kidney diseases and may indicate CPB-AKI earlier than current methods. The aim of this systematic review with meta-analysis was to evaluate the potential role of uL-FABP in early predicting CPB-AKI. Databases Pubmed/MEDLINE, Scopus, and Web of Science were searched on November 12th, 2023, using the MeSH terms “Children”, “CPB”, “L-FABP”, and “Acute Kidney Injury”. Included papers were revised. AUC values from similar studies were pooled by meta-analysis, performed using random- and fixed-effect models, with p

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

Lactic acid bacteria are traditionally applied in a variety of fermented food products and have the capability to produce a wide range of bioactive ingredients during fermentation including vitamins, bacteriocins, bioactive peptides and bioactive compounds. The bioactivity and health benefits associated with these ingredients have gained interest in applications in the functional dairy market and have relevance both as components produced in situ and as functional additives. This review provides a brief description of the regulations regarding the functional food market in the European Union as well as an overview of some of the functional dairy products currently available in the Irish and European markets. A better understanding of the production of these ingredients excreted by lactic acid bacteria can further drive the development and innovation of the continuously growing functional food market.

Waterford Blaa is one of only seven Irish Protected Geographical Indication (PGI) products and the only Irish PGI bread. Currently, there are few published data characterising these products. This study aimed to determine whether any compositional or sensory markers could be used to differentiate between the three authorised producers of Waterford Blaa. Compositional testing was completed using AOAC standard methods; colour of top crust, bottom crust and crumb were identified with the Minolta Hunter lab colorimeter and texture profile analysis (TPA) was completed with an 80% compression test using the Instron 5544 to establish hardness, gumminess, and springiness. The fatty acid and aroma profiles were established in triplicate testing for the three authorised Blaa products using gas chromatography-flame ionisation detection and headspace-solid phase micro extraction-gas chromatography-mass spectrometry, respectively. As expected, results showed little variation in the overall composition of Waterford Blaa products. However, this study identified a unique fatty acid profile/volatile aroma profile for each Blaa. Specifically, the volatile profile showed potential differentiation between Blaa’s in terms of pentanal, furfural, 2-furanmethanol, 2-ethyl-1-hexanol and 2-pentyl furan. In addition, levels of hexanal and ethyl acetate were significantly different (p<0.05) in the crumb section of all three Blaa’s. This unique fingerprint has the potential to be used to identify fraudulent products claiming to be Waterford Blaa.

Cross-species investigations on cancer invasiveness are a new approach that identified new biomarkers potentially useful for improving tumor diagnosis and prognosis in clinical medicine and veterinary science. In this study, we combined proteomic analysis of four experimental rat malignant mesothelioma (MM) tumors with analysis of ten patient-derived cell lines to identify common features associated to mitochondrial proteome rewiring. The comparison of significant abundance changes between invasive and non-invasive rat tumors rat tumors gave a list of 433 proteins, including twenty-six proteins reported to be exclusively located in mitochondria. Next, we analyzed the differential expression of genes encoding the mitochondrial proteins of interest in five primary epithelioid and five primary sarcomatoid human MM cell lines, and the most impressive increase was observed in the expression of the long-chain acyl coenzyme A dehydrogenase (ACADL). To evaluate the role of this enzyme in the migration/invasiveness, two epithelioid and two sarcomatoid human MM cell lines derived from patients with the highest and lowest overall survival were studied. Interestingly, sarcomatoid vs epithelioid cell lines were characterized by higher migration and fatty oxidation rates, in agreement with ACADL findings. These results suggest that evaluating mitochondrial proteins in MM specimens might identify tumors with higher invasiveness.

Red mud (RM) is a residue obtained from the production of alumina. It contains a high concentration of metal oxides and waste concentrated sodium hydroxide solution (pH = 13). To increase the value of RM, an environmentally friendly process of transesterification using waste cooking oil (WCO), MeOH and concentrated sodium hydroxide solution (CSHS) from aluminum production was proposed. Triglycerides of WCO reacted with MeOH at 60 oC to yield mixtures of fatty acid methyl esters (FAMEs) in the presence of 2.03% (w/w) CSHS/WCO using the CSHS (0.204 mol L-1, predetermined by potentiometric titration) from aluminum production by the Bayer process or with the addition of 0.68% (w/w) fabric softener (3% w/w cetyltrimethylammonium chloride in solution) as a phase transfer (PTA) agent. The addition of PTA to the catalyst resulted in a better yield of the products (greater than 98% yield). A simplified mechanism is presented to account for the experimental results.

Non-viral gene carriers because of their limited side effects, biocompatibility, simplicity and taking the advantages of electrostatic interactions have shown noticeable potential in gene delivery. The low transfection rate of non-viral vectors under physiological conditions is a significant issue. Here, the aim of this study was to investigate the efficacy of hydrophilic and hydrophobic groups on gene carriers such as two synthesized amphiphilic polymer of dextran-stearic acid-spermine (DSASP) with verified lipid and amine conjugations that associated with Fe3O4 superparamagnetic nanoparticles to promote the target delivery and decrease the transfection time using static magnetic field. Our findings illustrate that magnetic nanoparticles are spherical with positive surface charges and superparamagnetic behaviors. The DSASP–pDNA/MNPs offered a strong pDNA condensation, protection against DNase degradation, significant cell viability in HEK 293T cells and. Although conjugations of spermine play a critical role in transfection efficiency, amphiphilic polymer with more derivatives of stearic acid showed better transfection yields. Therefore, DSASP amphiphilic magnetic carriers offer new insights for gene delivery due to the amine contents and ameliorate the uptake of complexes via cell membrane based on its hydrophilic surface.

The aim of this study was to develop a basic model to predict enteric methane emission from dairy cows and to update operational calculations for the national inventory in Norway. Basic models were developed using a database with 63 treatment means from 19 studies. The database included records for enteric CH4 production (MJ/day), dry matter intake (DMI), and dietary nutrient composition. The basic models were evaluated against an external database (n=36, from ten studies) along with other extant models. When evaluated by low root mean square prediction errors and high concordance correlation coefficients, the developed basic models that included DMI, dietary concentrations of fatty acids and neutral detergent fiber performed slightly better in predicting CH4 emissions than extant models. In order to propose country-specific values for the CH4 conversion factor Ym (% of gross energy intake partitioned into CH4) and thus to carry out the national inventory for Norway, the existing operational model was updated for the prediction of Ym over a wide range of feeding situations using energy corrected milk and dietary concentrate share as predictor variables. Input values of Ym were updated based on the results from the basic models. The predicted Ym ranged from 6.22 to 6.72%. In conclusion, the prediction of CH4 production from dairy cows was improved with the help of newly published data, which enabled an update of the operational model for calculating the national inventory of CH4 in Norway.

Biofilms are communities of microorganisms that can colonize biotic and abiotic surfaces playing a significant role in the persistence of bacterial infection and antibiotic resistance. About 65% and 80% of microbial and chronic infections are produced by biofilm formation. The increase in infections by multi-resistant bacteria draws attention to the discovery of new drugs based on natural inhibitory molecules. The inhibition of diguanylate cyclases (DGCs), the enzyme implicated in the synthesis of the second messenger, cyclic diguanylate (c-di-GMP), involved the biofilm formation, represents a potential method for preventing the biofilm development. It has been extensively studied using PleD protein as a model of DGC for in silico studies as virtual screening and as a model for in vitro studies in biofilms formation. In the present study 224205 molecules from natural products database, ZINC15 has been evaluated through molecular docking and molecular dynamic simulation, our result suggests trans-Aconitic acid (TAA) as a possible starting point for hit-to-lead methodologies to obtain new molecules capable of inhibiting the PleD protein and hence blocking the biofilm formation.

The lytic bone disease is a hallmark of multiple myeloma, being present in about 80% of patients with newly diagnosed MM, and in more during the disease course. The myeloma associated bone disease (MBD) severely affects the morbidity and quality of life of the patients. MBD defines treatment demanding MM. In recent years, knowledge of the underlying pathophysiology has increased, and novel imaging technologies, medical and non-pharmaceutical treatments have improved. In this review, we highlight the major achievements in understanding, diagnosing and treating MBD. For diagnosing MBD, low-dose whole-body CT is now recommended over conventional skeletal survey, but also more advanced functional imaging modalities, such as diffusion-weighted MRI and PET/CT are increasingly important in the assessment and monitoring of MBD. Bisphosphonates have, for many years, played a key role in management of MBD, but denosumab is now an alternative to bisphosphonates, especially in patients with renal impairment. Radiotherapy is used for uncontrolled pain, for impeding fractures and in treatment of impeding or symptomatic spinal cord compression. Cement augmentation has been shown to reduce pain from vertebral compression fractures. Cautious exercise programs are safe and feasible and may have the potential to improve the status of patients with MM.

The early diagnosis of mastitis represents an essential factor for a prompt detection of the animal for further actions. In fact, if not culled, infected cows must be segregated from the milking herd and milked last, or milked with separate milking units. Besides microbiological analysis, the somatic cell count (SCC) commonly used as predictor of intramammary infection, frequently lead to a misclassification of milk samples. To overcome these limitations, more specific biomarkers are continuously evaluated. Total amino acid content increases significantly in mastitic milk compared to normal one. Bovine mastitis can arise as a result of infection of the mammary gland by Staphylococcus aureus. Multiplication of this bacterium within the mammary gland is required for infection to persist. S. aureus requires branched-chain amino acids (BCAAs: isoleucine, leucine, valine) for protein synthesis, branched-chain fatty acids synthesis and environmental adaptation by responding to their availability via transcriptional regulators. The importance of BCAAs for S. aureus physiology necessitates that it either synthesize them or scavenge them from the environment. Increase of BCAAs in composite milk has been postulated to be linked to mammary infection by S. aureus. In the present work, we demonstrated, by a direct ion-pairing reversed-phase method based on the use of the evaporative light-scattering detector (IP-RP-HPLC-ELSD), applied to 65 composite cow milk samples, a correlation between the concentration of isoleucine and leucine and S. aureus load.

Alzheimer’s disease manifests itself as a complex pathological condition with neuroinflammation, oxidative stress and cholinergic dysfunction being a few of the many pathological changes. Due to the complexity of the disease current therapeutic strategies aim at a multitargeted approach often relying on a combination of sub-stances with versatile and complementary effects. In the present study, unique combination of α-lipoic acid, citicoline, extracts of leaves from olive tree and green tea, Vitamin D3, selenium and an immune supporting complex was tested in a scopolamine-induced dementia in rats. Using behavioral and biochemical methods we assessed the effects of this combination on learning and memory, and elucidated the mechanisms under-lying its effects. Our results showed that as compared to the components, experimental combination was most efficient in improving short- and long-term memory assessed by the step-through method as well as spatial memory, assessed by T-maze and Barnes maze underlying decrease in AChE activity and LPO, in-creases in SOD activity in cortex; activities of catalase and GPx, levels of BDNF and pCREB in the hippocam-pus. No significant histopathological changes or blood parameter changes were detected, making the experi-mental combination an effective and safe candidate in a multitargeted treatment of AD.

The study of the surface thermodynamic properties of solid materials is primordial for the determination of the dispersive surface energy, polar enthalpy of adsorption and Lewis’s acid base properties of solid particles. Inverse gas chromatography technique (IGC) at infinite dilution is the best surface technique for the determination of the surface physicochemical properties of materials. (1) Background: This paper was devoted to study the surface properties of solid materials such as alumina particles by using IGC technique. (2) Methods: Different methods and molecular models such as spherical, cylindrical, van der Waals, Redlich-Kwong, Kiselev and geometric models, were used to determine the London dispersive surface energy of solid surfaces. Hamieh model was also used and highlighted the thermal effect on the surface area of solvents. (3) Results: The variations of the dispersive surface energy and the free energy of adsorption were determined for alumina particles as a function of the temperature as well as their Lewis’s acid base constants. Alumina surfaces were proved to exhibit a strong Lewis amphoteric character three time more basic than acidic (4) Conclusions: The new methodology based on Hamieh model gave the more accurate results of the physicochemical properties of the particle surfaces.

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

The seasonal variation in fatty acids and minerals concentrations was investigated through the analysis of Pecorino Romano cheese samples collected in January, April, and June. A fraction of samples contained missing values in their fatty acid profile. Probabilistic Principal component analysis coupled with Linear Discriminant Analysis was employed to classify cheese samples on a production season basis while accounting for missing data and quantifying the missing Fatty acids concentration for the sample in which they were absent. The levels of rumenic acid, vac-cenic acid and omega-3 compounds were positively correlated with the spring season, while the length of the saturated fatty acids increased throughout the production seasons. Concerning the classification performances, the optimal number of principal components (i.e., 5) achieved an ac-curacy in cross-validation equal to 98 %. Then, when the model was tasked to impute the lacking Fatty acid concentration values, the optimal number of principal components resulted in an R2 value in cross-validation of 99.53%

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.

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.

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.

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.

Animal products, in particular dairy and fermented products, are natural, major sources of lactic acid bacteria (LAB). Due to their antimicrobial properties, LAB are used in humans and in animals, with beneficial effects, as probiotics or in the treatment of a variety of diseases. In livestock production, LAB contribute to animal performance, health, and productivity. In the food industry, LAB are applied as bioprotective and biopreservation agents, contributing to improve food safety and quality. However, some studies have described resistance to relevant antibiotics in LAB, with the concomitant risks associated to the transfer of antibiotic resistance genes to foodborne pathogens, their potential dissemination throughout the food chain, and the environment. Here, we summarize the application of LAB in livestock and animal products, as well as the health impact of LAB in animal food products. In general, the beneficial effects of LAB on the human food chain seem to outweigh the potential risks associated with their consumption as part of animal and human diets. However, further studies and continuous monitorization efforts are needed to ensure their safe application in animal products and in the control of pathogenic microorganisms, preventing the possible risks associated with antibiotic resistance and, thus, protecting public health.

Several series of new polymers were synthesized: binary copolyesters of vanillic (VA) and hydroxybiphenylcarboxylic (HBCA) acids, as well as ternary copolyesters additionally containing hydroxybenzoic acid (HBA) and obtained via three different ways (in solution, in melt and in solid state). The high values of logarithmic intrinsic viscosities and insolubility of several samples proved its high molecular weights. It has been shown that the use of vanillic acid leads to the production of copolyesters with a relatively high glass transition temperature (about 130°C). Thermogravimetric analysis revealed onset of weight loss temperatures of ternary copolyesters occurred at 330-350 °C, the temperature of 5% mass loss is in the range of 390-410 °C. Two-stage thermal destruction is observed for all aromatic copolyester of vanillic acid: decomposition begins with VA units at 420-480 °C, and then decomposition of more heat-resistant units demonstrated above 520 °C. The copolyesters are thermotropic and exhibit a typical nematic type of liquid crystalline order. Mechanical characteristics of copolyesters are close to those for semi-aromatic copolyesters, but are much lower than typical values for fully aromatic thermotropic polymers. Thus, vanillic acid is a mesogenic monomer suitable for the synthesis of thermotropic fully aromatic and semi-aromatic copolyester, but resulting processing temperature must not exceed 280°C.

The microbiome is capable of modulating the bioavailability of chemotherapy drugs mainly due to metabolizing these agents. Multiple cytostatic bacterial metabolites were recently identified that have cytostatic properties on cancer cells. In this study we addressed the question whether the cytostatic bacterial metabolites (cadaverine, indolepropionic acid, indoxylsulfate) can interfere with the cytostatic effects of the chemotherapy agents used in the management of breast cancer (doxorubicin, gemcitabine, irinotecan, methotrexate, rucaparib, 5-fluorouracil, paclitaxel). The chemotherapy drugs were applied in a wide concentration range to which a bacterial metabolite was added in a concentration within its serum reference range and the effects on cell proliferation were assessed. There was no interference between doxorubicin, gemcitabine, irinotecan, methotrexate, rucaparib and the bacterial metabolites. Nevertheless, cadaverine increased the Hill coefficient of the inhibitory curve of 5-fluorouracil and indolepropionic acid increased the IC50 value of 5-fluorouracil that are either disadvantageous effects or effects of unknown significance. Nevertheless, indolepropionic acid decreased the IC50 value of paclitaxel that is a potentially advantageous combination.

Chronic Kidney Disease (CKD) is a major public health concern with an increasing proportion of sufferers progressing to renal replacement therapy (RRT). Early identification of those at risk of disease progression could be key in improving outcomes. We hypothesise that urinary liver-type fatty acid binding protein (uL-FABP) may be a suitable biomarker for CKD progression and can add value to currently established biomarkers such as urinary protein to creatinine ratio (uPCR) 583 participants with CKD 1-5 (not receiving renal replacement therapy) entered a 2-yr prospective longitudinal study. UPCR and uL-FABP were measured at baseline and CKD progression was defined as either i) a decline in eGFR of >5ml/min/1.73m2 or an increase in serum creatinine by 10% at 1-yr or ii) a decline in eGFR of >6 ml/min/1.73m2, or an increase in serum creatinine by 20% at 2-yrs or iii) the initiation of RRT. A combined outcome of initiating RRT or death was also included. Approximately 40% of participants showed CKD progression. UL-FABP predicted CKD progression at both years 1 and 2 (OR 1.01, p<0.01). Sensitivity and specificity were comparable to those of uPCR (AUC 0.623 v 0.706) and heat map analysis suggested that uL-FABP in the absence of significant proteinuria can predict an increase in serum creatinine of 10% at 1yr and 20% at 2yr. The risk of the combined outcome of initiating RRT or death was 23% higher in those with high uL-FABP (p<0.01) independent of uPCR. UL-FABP appears to be a highly sensitive and specific biomarker of CKD progression. The use of this biomarker could enhance the risk stratification of CKD and its progression and should be assessed further.

The expression of the Fasciola hepatica Carboxylesterase type B (CestB) gene is induced in response to the anthelmintic triclabendazole (TCBZ), resulting in a significant increase in enzymatic specific activity. Furthermore, the amino acid sequence of CestB exhibits variations that could lead to substantial amino acid substitutions at the ligand-binding site. These substitutions have the potential to affect the interaction between the ligand and the protein, as well as the catalytic properties of the enzyme. The objective of this study was to identify new CestB polymorphisms in TCBZ-resistant parasites using 3D modeling against the metabolically oxidized form of the anthelmintic TCBZSOX. Our aim was to observe the formation of TCBZSOX-specific binding pockets that could potentially explain the resistance to anthelmintic agents. We identified a CestB polymorphism in a TCBZ-resistant strain of parasites exhibiting three radical amino acid substitutions at positions 147, 215, and 243, resulting in the formation of a TCBZSOX-affinity pocket capable of binding the anthelmintic drug. Additionally, our 3D modeling analysis revealed that these amino acid substitutions also had an impact on the configuration of the CestB catalytic site, affecting the enzyme's interaction with chromogenic carboxylic ester substrates and altering its catalytic properties; however, the identified TCBZSOX-binding pocket was located far from the enzyme's catalytic site, making the enzymatic hydrolysis of TCBZSOX theoretically impossible. Nonetheless, the increased affinity for the anthelmintic may explain a drug-sequestration type of anthelmintic resistance and lays the foundation for the development of a molecular diagnostic tool for identifying anthelmintic resistance in F. hepatica.

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

Polycyclic aromatic hydrocarbons (PAHs) have been reported to cause oxidative stress in metabolic processes. This study aimed to evaluate the relationship between exposure to PAHs, including benzo[a]pyrene (BaP) and 1-nitropyrene (1-NP), in the atmosphere and oxidative stress levels in the human body. This study included 44 Korean adults who lived in Cheongju, South Korea. Atmospheric BaP and 1-NP concentrations and urinary 6-hydroxy-1-nitropyrene (6-OHNP), N-acetyl-1-aminopyrene (1-NAAP), and 1-hydroxypyrene (1-OHP) concentrations were measured. The oxidative stress level was assessed by measuring urinary thiobarbituric acid reactive substances (TBARS) and 8-hydroxydeoxyguanosine (8-OHdG) concentrations. Urinary TBARS and 6-OHNP concentrations significantly differed between winter and summer. BaP exposure was significantly associated with urinary 8-OHdG concentrations in summer. However, atmospheric 1-NP did not show a significant correlation with oxidative stress marker concentrations. Urinary 1-NAAP concentration was a significant determinant for urinary 8-OHdG concentration in summer. Oxidative stress in the body increases in proportion to inhalation exposure to BaP, and more 8-OHdG is produced in the body as the amount of 1-NP, which is metabolized to 1-AP or 1-NAAP, increases.

Recent studies have demonstrated an important role for vitamin C in the epigenetic regulation of cancer-related genes via DNA demethylation by the ten-eleven translocation (TET) methylcytosine dioxygenase enzymes. DNA methyltransferase (DNMT) reverses this, increasing DNA methylation and decreasing gene expression. Dual oxidase (DUOX) enzymes produce hydrogen peroxide (H2O2) in normal pancreatic tissue but are silenced in pancreatic cancer (PDAC). Treatment of PDAC with pharmacologic ascorbate (P-AscH-, intravenous, high dose vitamin C) increases DUOX expression. We hypothesized that inhibiting DNMT may act synergistically with P-AscH- to further increase DUOX expression and cytotoxicity of PDAC. PDAC cells demonstrated dose-dependent increases in DUOX mRNA and protein expression when treated with DNMT inhibitors. PDAC cells treated with P-AscH- + DNMT inhibitors demonstrated increased DUOX expression, increased intracellular oxidation, and increased cytotoxicity in vitro and in vivo compared to either treatment alone. These findings suggest a potential therapeutic, epigenetic mechanism to treat PDAC.

Duchenne muscular dystrophy (DMD), the severest form of muscular dystrophy, is characterized by progressive muscle weakness with fatal outcome most often before the fourth decade of life. Despite recent addition of molecular treatments, DMD remains a disease without a cure, and the need persists for the development of supportive therapies aimed to help improve patients’ quality of life. This review focusses on the therapeutical potential of amino acid and derivative supplements, summarizing results obtained in preclinical studies in the murine disease model. Several promising compounds have come forward, with L-arginine, N-acetylcysteine and taurine featuring among the most intensively investigated. Beneficial effects include improved muscle function and reduced muscle fiber necrosis and reduced inflammatory and oxidative damage to muscle tissues, however mild side effects have also surfaced. In order to identify amino acid formulae that are safe and of true benefit to DMD patients, more explorative, placebo-controlled and long-term clinical trials need to be conducted, documenting therapeutic outcomes.

Sporisorium scitamineum, the basidiomycetous fungus causing sugarcane smut that leads to severe losses in sugarcane quantity and quality, undergoes sexual mating to form dikaryotic hyphae capable of invading the host cane. Therefore, suppressing dikaryotic hyphae formation would potentially be an effective way to prevent host infection by the smut fungus, and the following disease symptom development. The phytohormone methyl jasmonate (MeJA) has been showed to induce plant defense against insects and microbial pathogens. In this study, we verified that exogenous addition of MeJA suppressed dikaryotic hyphae formation under in vitro culture condition, and effective in inhibiting maize smut disease symptom caused by Ustilago maydis. We constructed an Escherichia coli strain expressing plant JMT gene, encoding a jasmonic acid carboxyl methyl transferase that catalyzes conversion from jasmonic acid (JA) to MeJA. By GC-MS we confirmed that the transformed E. coli strain, designated as pJMT strain, was able to produce MeJA in the presence of JA and S-adenosylmethionine (SAM; as methyl donor). Furthermore, the pJMT strain was able to suppress S. scitamineum filamentous growth under in vitro culture condition. It waits to further optimize JMT expression under field condition, in order to utilize the pJMT strain as a biocontrol agent (BCA) of sugarcane smut disease. Overall, our study provides a potentially novel method for controlling crop fungal diseases by boosting phytohormone biosynthesis.

Amphetamine is a psychostimulant drug with a high risk of toxicity and death when misused. Abuse of amphetamines is associated with an altered organic profile, which includes omega fatty acids. Low omega fatty acid levels are linked to mental disorders. Using the Comparative Toxicogenomic Database (CTD), we investigated the chemical profile of the brain in amphetamine-related fatalities and the possibility of neurotoxicity. We classified amphetamine cases as low (0-0.5 g/ml), medium (&gt;0.5 to 1.5 g/ml), and high (&gt;1.5 g/ml) based on amphetamine levels in brain samples. All three groups shared 1-octadecene, 1-tridecene, 2,4-di-tert-butylphenol, arachidonic acid, docosahexaenoic acid (DHA), eicosane, and oleylamide. We identified chemical-disease associations using the CTD tools and predict an association between docosahexaenoic and arachidonic acids and curated conditions like autistic disorder, disorders related to cocaine, Alzheimer's disease, and cognitive dysfunction. An amphetamine challenge may cause neurotoxicity in the human brain due to a decrease in omega-3 fatty acids and an increase in oxidative products. Therefore, in cases of amphetamine toxicity, supplement therapy may necessitate preventing omega-3 fatty acid deficiency.

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

The changing dynamics in climate is the primary and important determinant of agriculture productivity. The effects of this changing climate on overall productivity in agriculture can be understood when we study the effects of individual components contributing to the changing climate on plants and crops. Elevated CO₂ (eCO₂) and drought due to high variability in rainfall is one of the important manifestations of the changing climate. There is a considerable amount of literature that addresses climate effects on plant systems from molecules to ecosystems. Of particular interest is the effect of increased CO₂ on plants in relation to drought and water stress. As it is known that one of the consistent effects of increased CO₂ in the atmosphere is increased photosynthesis, especially in C₃ plants, it will be interesting to know the effect of drought in relation to elevated CO₂. The potential of elevated CO₂ ameliorating the effects of water deficit stress is evident from literature suggesting that these two are agents are brothers in arms protecting the plant from stress rather than partnering in crime, specifically water deficit when in isolation. The possible mechanisms by which this occurs will be discussed in this minireview. Interpreting the effects of short-term and long-term exposure of plants to elevated CO₂ in the context of ameliorating the negative impacts of drought will show us the possible ways by which there can be effective adaption to crops in the changing climate scenario.

Reliable methods to confirm the diagnosis of COVID-19 are essential to the successful management and containment of the virus. Current diagnostic options are limited in type, supply, and reliability. This article explores the controversial unreliability of existing diagnostic methods and maintains that more reliable diagnostic methods, combinations, and sequencing are necessary to effectively assist in reducing the occurrence of discharge of the patient on false negative test results. This reduction would in effect reduce transmission of the disease.

Probiotics have been used to ameliorate gastrointestinal symptoms since ancient times. Over the past 40 years, probiotics have been shown to exert major effects on the immune system, both in vivo and in vitro. This interaction is clearly linked to gut microbes, their polysaccharide antigens, and key metabolites produced by these bacteria. At least four metabolic pathways have been implicated in mechanistic studies of probiotics, based on carefully studied animal models. Microbial-immune system crosstalk has been linked to short chain fatty acid production and signaling, tryptophan metabolism and the activation of aryl hydrocarbon receptors, nucleoside signaling in the gut, and activation of the intestinal histamine-2 receptor. Several randomized controlled trials have now shown that microbial modification by probiotics may improve gastrointestinal symptoms and multi-organ inflammation in rheumatoid arthritis, ulcerative colitis, and multiple sclerosis. Future work will need to carefully assess safety issues, selection of optimal strains and combinations, and attempts to prolong the duration of colonization of beneficial microbes.

The pleiotropic biochemical and antioxidant functions of Vitamin C (Vit C) have recently sparked interest in its application in intensive care. Vit C protects important organ systems such as the cardiovascular, neurologic and renal system during inflammation and oxidative stress. Vit C also influences the systems of coagulation and inflammation and its application might prevent the development of organ damage. The current evidence of Vit C’s effect on the pathophysiological reactions during various acute stress events, such as sepsis, shock, trauma, burn and ischemia-reperfusion injury imposes the question, if the application of Vit C might be especially beneficial for cardiac surgery patients, who are routinely exposed to ischemia/reperfusion and subsequent inflammation, systematically affecting different organ systems. This review covers current knowledge about the role of Vit C in cardiac surgery patients with focus on its influence on organ dysfunctions. The relationships between Vit C and clinical health outcomes are reviewed with special emphasis on its application in cardiac surgery. Additionally, this review pragmatically discusses evidence regarding the administration of Vitamin C in every day clinical practice, tackling the issues of safety, monitoring, dosage and most the appropriate application strategy.

Our previous in vitro reports showed that crude extract prepared with 50% ethanol (ethanol crude extract, ECE) from Mongolian oak cups possessed excellent antioxidant capacities as well as inhibitory activities against α-glucosidase, α-amylase and protein glycation caused by its enrichment in phenolics, including mainly ellagic acid, kaempferol and their derivatives. Nevertheless, few in vivo studies on antidiabetic activities of these phenolics were conducted. The present study investigated hypoglycemic effects with normal and diabetic rats being administrated orally without or with ECE at 200 and 800 mg/kg for 15 days. In normal rats, no significant differences were exhibited after ECE administration in body weight, fasting blood glucose level, levels of chelesterol, triglyceride, LDL and AST in serum, organ indexes, and levels of GSH and MDA in organs. In diabetic rats, the fasting blood glucose level, indexes of heart and liver, and levels of chelesterol and triglyceride in serum and MDA in heart tissue were significantly decreased. Moreover, HDL levels in serum and SOD activities in the four organs of diabetic rats were significantly improved after ECE administration at 800 mg/kg. Thus, in addition to inhibiting α-glucosidase, α-amylase and protein glycation reported previously, oak cups might contain novel dietary phytonutrients in preventing abnormal changes in blood glucose and lipid profile and attenuating oxidant stress in vivo. The results also implied that it is ellagic acid, kaempferol and their derivatives enriched in ECE that might play vital roles in managing type 1 as well as type 2 diabetes.

Antibody-mediated targeting is an efficient strategy to enhance the specificity and selectivity of polymer nanomedicines towards the target site, typically a tumor. However, direct covalent coupling of an antibody with a polymer usually results in a partial damage of the antibody binding site accompanied with a compromised biological activity. Here, an original solution based on well-defined non-covalent interactions between tris-nitrilotriacetic acid (trisNTA) and hexahistidine (His-tag) groups, purposefully introduced to the structure of each macromolecule, is described. Specifically, trisNTA groups were attached along the chains of a hydrophilic statistical copolymer based on N-(2-hydroxypropyl)methacrylamide (HPMA), and at the end or along the chains of thermo-responsive di-block copolymers based on N-isopropylmethacrylamide (NIPMAM) and HPMA; His-tag was incorporated to the structure of a recombinant single chain fragment of an anti-GD2 monoclonal antibody (scFv-GD2). Static and dynamic light scattering analyses confirmed that mixing of polymer with scFv-GD2 led to the formation of polymer/scFv-GD2 complexes; those prepared from thermo-responsive polymers formed stable micelles at 37 °C. Flow cytometry and fluorescence microscopy clearly demonstrated antigen-specific binding of the prepared complexes to GD2 positive murine T-cell lymphoma cells EL-4 and human neuroblastoma cells UKF-NB3, while no interaction with GD2 negative murine fibroblast cells NIH-3T3 was observed. These non-covalent polymer protein complexes represent a new generation of highly specific actively targeted polymer therapeutics or diagnostics.

The terpolymers of N-vinylpyrrolidone (VP) with acrylic acid and triethylene glycol methacrylate were synthesized with more than 90% yield by radical copolymerization in ethanol from monomeric mixtures of different composition (98 : 2 : 2, 95 : 5: 2 and 98 : 2: 5). Their physical and chemical characteristics such as monomer composition, absolute molecular masses and hy-drodynamic radii in aqueous media at different temperature were determined. The temperature effect on the behavior of terpolymers in water and aqueous saline buffer solution with pH 7.4 has been studied and the ability of a copolymer enriched with dimethacrylates units was discovered to respond to a temperature change in these media. On the basis of terpolymers and linear polyvi-nylpyrrolidone (PVP), polymer compositions of hydrophobic dye methyl pheophorbide a, MPP, that is fluorescent in the red region of the spectrum, were obtained; the sizes of the polymer nanostructures of MPP in water were determined. The structures based on terpolymers were demonstrated to be more stable than MPP-PVP ones. It was carried out the quantum-chemical modelling of the possible structures of MPP-copolymer that formed as a result of intermolecular interaction between MPP and terpolymer’s chains; the possibility of the formation of hydrogen bonds between the donors of the electrons of terpolymer units and the proton donors of the MPP molecule was shown. Using the MTT test, it was established that copolymers of various compositions are low toxic for non-tumor Vero cells and HeLa tumor cells. It was shown that the cytotoxicity of polymer particles loaded with MPP for FetMSC and HeLa cells increased. Using fluorescence microscopy, the accumulation and distribution of polymer particles in non-tumor (FetMSC) and tumor (HeLa) cells was studied and an increase in the accumulation of MPP with both types of particles was shown.

The demand for dietary supplements containing collagen has been growing for years. The speciality and uniqueness of the dietary supplement (DS) examined in our study is the presence of L-arginine and hyaluronic acid alongside collagen and vitamin C. The individual mechanisms of action and physiological role of these compounds are understood, but they have not yet been tested in the combination and amounts of the dietary supplement used in this study. In this study, we investigated the effectiveness of the DS in elderly patients with musculoskeletal complaints. Somatometric, body composition, physiotherapy and laboratory tests were performed at the beginning and at the end of the study. The two-month study involved 30 people, randomly divided into two groups: a control group (CG) and an experimental group (EG). All subjects consumed 25 ml DS per day and EG members also participated in physiotherapy 3 times a week. Alongside the DS, blood lipid levels changed: LDL decreased, HDL increased, LDL/HDL ratio significantly decreased in both groups. For EG, the results improved more markedly. In 3 items of the body composition test, there was a significant improvement in both groups, which was attributed to the use of the dietary supplement. For the EG, there were significant changes in 5 additional test items, which we attribute to the addition of regular physical activity. Knee and hip joint range of motion (ROM) showed significant improvements in the study group, while in the CG the DS can cause significant improvements in joint range of motion in a passive condition as well.

Two novel core-shell composites SiO2@PMDA-Si-Tb, SiO2@PMDA-Si-Tb-phen with SiO2 as the core and terbium organic complex as the shell, were successfully synthesized. The terbium ion was coordinated with organic ligand forming terbium organic complex in the shell layer. The bi-functional organosilane ((HOOC)2C6H2(CONH(CH2)3Si(OCH2CH3)3)2 (abbreviated as PMDA-Si) was used as the first ligand and phen as the second ligand. Furthermore, the silica-modified SiO2@PMDA-Si-Tb@SiO2, SiO2@PMDA-Si-Tb-phen@SiO2 core-shell-shell composites were also synthesized by sol–gel chemical route. An amorphous silica shell was coated around the SiO2@PMDA-Si-Tb and SiO2@PMDA-Si-Tb-phen core-shell composites. The core-shell and core-shell-shell composites both exhibited excellent luminescence in solid state. The luminescence of core-shell-shell composites was stronger than that of core-shell composites. Meanwhile, an improved luminescence stability property for the core-shell-shell composites was found in the aqueous solution. The core-shell-shell composites exhibited bright luminescence, high stability, long lifetime, and good solubility, which may present potential applications in the field of bio-medical.

This mini-review deals with some non-starter lactic acid bacteria (NSLAB) species with a controversial nature known to be both human and animal pathogens but also health-promoting and probiotic. The focus is put on Lactococcus garvieae, two Streptococcus species (Str. uberis and Str. parauberis), four Weissella species (W. hellenica, W. confusa, W. paramesenteroides and W. cibaria) and Mammalicoccus sciuri which worldwide are often found within the microbiotas of different kinds of cheese, mainly traditional artisanal ones made from raw milk and/or relying on environmental bacteria for their ripening. Based on literature data, their virulence and health-promoting effects are examined, and some of the mechanisms of these actions are investigated. Additionally, their possible roles in cheese ripening are also discussed. The analysis so far showed that, in general, the pathogenic and the beneficial strains, despite belonging to the same species, show pretty different genetic constitutions. Yet, when the safety of a given strain is assessed, genomic analysis on its own is not enough, and a polyphasic approach is needed including additional physiological and functional tests.

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.

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.