Miracle-dz/UniFAR-FTUs huggingface dataset:
Experimental and theoretical investigation of antioxidant activity and capacity of thiosemicarbazones based on isatin derivatives

GRAPHICAL ABSTRACT ABSTRACT The peroxidation of linoleic acid (LA) in the presence of copper (II) ions alone and with butylhydroxytoluene (BHT), gallic acid (GA), a BHT/GA pair, 5-methoxyisatin-3-(N-4-chlorophenyl) thiosemicarbazone (H25MI3ClPT), and 5-methoxyisatin-3-(N-phenyl) thiosemicarbazone (H25MI3PT) was investigated in aerated and incubated emulsions at 37°C and pH 7. Cu(II)-induced LA peroxidation followed pseudo-first-order kinetics with respect to the primary oxidation products (hydroperoxides), which were determined by the ferric thiocyanate (Fe(III)-SCN) method. It was observed that (H25MI3ClPT) and (H25MI3PT) showed antioxidant properties, but the percentage inhibition decreased as the concentration increased, contrary to the behavior of GA and BHT. In addition, they were investigated by the DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging method. The IC50 values were 69.60, 11.87, 88.71, 73.62, and 430.11 µM for the standard antioxidants BHT, GA, H25MI3ClPT, H25MI3PT, and bis(isatin-3-(4-iodophenyl)thiosemicarbazonato) zinc(II) (BI3ITZn), respectively. The bond dissociation enthalpy (BDE), adiabatic ionization potential (AIP), proton dissociation enthalpy (PDE), proton affinity (PA), electron transfer enthalpy (ETE), ΔHacidity, ΔGacidity descriptors and DPPH radical scavenging mechanisms of thiosemicarbazone were also determined with the B3LYP method. Furthermore, the energy values in the transition state form for the reactions of H25MI3PT and H25MI3ClPT with DPPH were calculated as 0.022278 and 0.021953 au, respectively.
Conformation of HIV-1 Envelope Governs Rhesus CD4 Usage and Simian-Human Immunodeficiency Virus Replication

Rhesus macaques are a critical animal model for preclinical testing of HIV-1 vaccine and prevention approaches. However, HIV-1 does not replicate in rhesus macaques, and thus, chimeric simian-human immunodeficiency viruses (SHIVs), which encode HIV-1 envelope glycoproteins (Envs), are used as surrogate challenge viruses to infect rhesus macaques for modeling HIV-1 infection. ABSTRACT Infection of rhesus macaques with simian-human immunodeficiency viruses (SHIVs) is the preferred model system for vaccine development because SHIVs encode human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins (Envs)—a key target of HIV-1 neutralizing antibodies. Since the goal of vaccines is to prevent new infections, SHIVs encoding circulating HIV-1 Env are desired as challenge viruses. Development of such biologically relevant SHIVs has been challenging, as they fail to infect rhesus macaques, mainly because most circulating HIV-1 Envs do not use rhesus CD4 (rhCD4) receptor for viral entry. Most primary HIV-1 Envs exist in a closed conformation and occasionally transit to a downstream, open conformation through an obligate intermediate conformation. Here, we provide genetic evidence that open Env conformations can overcome the rhCD4 entry barrier and increase replication of SHIVs in rhesus lymphocytes. Consistent with prior studies, we found that circulating HIV-1 Envs do not use rhCD4 efficiently for viral entry. However, by using HIV-1 Envs with single amino acid substitutions that alter their conformational state, we found that transitions to intermediate and open Env conformations allow usage of physiological levels of rhCD4 for viral entry. We engineered these single amino acid substitutions in the transmitted/founder HIV-1BG505 Envs encoded by SHIV-BG505 and found that open Env conformation enhances SHIV replication in rhesus lymphocytes. Lastly, CD4-mediated SHIV pulldown, sensitivity to soluble CD4, and fusogenicity assays indicated that open Env conformation promotes efficient rhCD4 binding and viral-host membrane fusion. These findings identify the conformational state of HIV-1 Env as a major determinant for rhCD4 usage, viral fusion, and SHIV replication. IMPORTANCE Rhesus macaques are a critical animal model for preclinical testing of HIV-1 vaccine and prevention approaches. However, HIV-1 does not replicate in rhesus macaques, and thus, chimeric simian-human immunodeficiency viruses (SHIVs), which encode HIV-1 envelope glycoproteins (Envs), are used as surrogate challenge viruses to infect rhesus macaques for modeling HIV-1 infection. Development of SHIVs encoding Envs from clinically relevant, circulating HIV-1 variants has been extremely challenging, as such SHIVs replicate poorly, if at all, in rhesus lymphocytes. This is most probably because many circulating HIV-1 Envs do not use rhesus CD4 efficiently for viral entry. In this study, we identified conformational state of HIV-1 envelope as a key determinant for rhesus CD4 usage, viral-host membrane fusion, and SHIV replication in rhesus lymphocytes.
Evaluation of polymeric PLGA nanoparticles conjugated to curcumin for use in aPDT

Antimicrobial photodynamic therapy (aPDT) involves the association of a photosensitizing agent with a light source with the goal of causing apoptosis or microbial lysing. The use of compounds with natural active principles is gaining prominence throughout the world. Several studies from groups that are linked to the development of innovations in the pharmaceutical market have used natural dyes, such as curcumin, the efficacy of which has been demonstrated in aPDT trials. Difficulties related to physicochemical stability, solubility and cell penetration are some of the challenges associated with this field. The present work aimed to prepare, investigate the characteristics and improve the photodynamic activity of PLGA-based nanoparticles loaded with curcumin for use in aPDT therapy. Using the simple technique of emulsion during the evaporation of a solvent, the particles were built, characterized and tested against microorganisms with importance for medicine and dentistry. The results revealed that the particles were able to protect the curcumin against degradation and eliminate some microorganism species at nanomolar concentrations.
The Impact of Host Genotype, Intestinal Sites and Probiotics Supplementation on the Gut Microbiota Composition and Diversity in Sheep

Simple Summary Given the fact that sheep serve as an increased meat product consumption in China, as well as a suitable model for fat deposition, their digestive tract microbiota has drawn growing attention. Our study depicted the gut microbiota community composition and diversity of sheep with varied genotypes but shared geography, with different sampling intestinal sites and probiotics supplementation time. The results indicated the great difference of the gut microbiota in samples from different sheep breeds, various intestinal sites, and different probiotics feeding times. Additionally, all results implied the dominance of the host factor in shaping unique microbiota under a certain environment, the greatest similarity of colonic and fecal microbiota, and the oral probiotic effectiveness for a given period of time for sheep. Abstract Three sampling strategies with a 16s rRNA high-throughput sequencing and gene expression assay (by RT-PCR) were designed, to better understand the host and probiotics effect on gut microbiota in sheep. Sampling: (1) colon contents and back-fat tissues from small-tailed Han sheep (SHS), big-tailed Hulun Buir sheep (BHBS), and short-tailed Steppe sheep (SHBS) (n = 12, 14, 12); (2) jejunum, cecum and colon contents, and feces from Tan sheep (TS, n = 6); (3) feces from TS at 4 time points (nonfeeding, 30 and 60 feeding days, and stop feeding 30 days) with probiotics supplementation (n = 7). The results indicated SHS had the highest Firmicutes abundance, the thinnest back-fat, and the lowest expression of C/EBPβ, C/EBPδ, ATGL, CFD, and SREBP1. Some bacteria orders and families could be potential biomarkers for sheep breeds with a distinct distribution of bacterial abundance, implying the host genotype is predominant in shaping unique microbiota under a shared environment. The microbiota diversity and Bifidobacterial populations significantly changed after 60 days of feeding but restored to its initial state, with mostly colonies, after 30 days ceased. The microbiota composition was greatly different between the small and large intestines, but somewhat different between the large intestine and feces; feces may be reliable for studying large intestinal microbiota in ruminants.
Theoretical Study of Radical Inactivation, LOX Inhibition, and Iron Chelation: The Role of Ferulic Acid in Skin Protection against UVA Induced Oxidative Stress

Ferulic acid (FA) is used in skin formulations for protection against the damaging actions of the reactive oxygen species (ROS) produced by UVA radiation. Possible underlying protective mechanisms are not fully elucidated. By considering the kinetics of proton-coupled electron transfer (PCET) and radical-radical coupling (RRC) mechanisms, it appears that direct scavenging could be operative, providing that a high local concentration of FA is present at the place of •OH generation. The resulting FA phenoxyl radical, after the scavenging of a second •OH and keto-enol tautomerization of the intermediate, produces 5-hydroxyferulic acid (5OHFA). Inhibition of the lipoxygenase (LOX) enzyme, one of the enzymes that catalyse free radical production, by FA and 5OHFA were analysed. Results of molecular docking calculations indicate favourable binding interactions of FA and 5OHFA with the LOX active site. The exergonicity of chelation reactions of the catalytic Fe2+ ion with FA and 5OHFA indicate the potency of these chelators to prevent the formation of •OH radicals via Fenton-like reactions. The inhibition of the prooxidant LOX enzyme could be more relevant mechanism of skin protection against UVA induced oxidative stress than iron chelation and assumed direct scavenging of ROS.
Genetic Parameters of Workability Traits in the Population of Polish Holstein-Friesian Cows Based on Conventional and Genomic Data

Simple Summary Workability traits are a group of functional traits that affect the economics of dairy production and are increasingly included in selection indexes. The most important of them include milking speed and temperament. The aim of this study was to estimate genetic and phenotypic parameters of workability traits. The estimation was carried out by considering two approaches: the first using pedigree data and the second using pedigree and genomic data. The obtained results indicate that workability traits belong to low heritable traits and are positively correlated genetically and phenotypically, which means a possibility of their effective improvement in the population, taking into account that the genomic information of sires did not have a significant effect on the estimated genetic parameters. Abstract Heritabilities of workability (WT) traits—milking speed (MS) and temperament (MT)—as well as genetic and phenotypic correlations between these traits in the population of Polish Holstein-Friesian (PHF) cows were estimated. The estimation of genetic parameters was performed twice: first with the use of pedigree data; and second with the use of pedigree and genomic data. Phenotypic data from routinely conducted MS and MT evaluations for 1,045,511 cows born from 2004 to 2013 were available; the cows were evaluated from 2011 to 2015. The main dataset was reduced based on imposed restrictions (e.g., on age of calving, stage of lactation and day of first trial milking). The dataset prepared in this manner comprised 391,615 cows. It was then reduced to daughters of 10% randomly selected sires for computational reasons. Finally, for genetic parameter estimation, 13,280 records of cows were used. The linear observation model included additive random effects of animal, fixed effects of herd-year-season of calving subclass (HYS) and lactation phase, fixed regressions on cow age at calving and the percent of HF breed genes in the cow genotype. Heritabilities estimated based on pedigree data were 0.12 (±0.0067) for MS and 0.08 (±0.0063) for MT, the genetic correlation between MS and MT was estimated at 0.05 (±0.0002) and the phenotypic correlation coefficient was estimated at 0.14 (±0.0004). The inclusion of genomic information of sire bulls had no clear effect on the size of the estimated WT genetic parameters. The heritabilities of MS and MT were 0.11 (±0.0065) and 0.09 (±0.0012), respectively. The genetic and phenotypic correlation coefficients were 0.07 (±0.0003) and 0.12 (±0.0005), respectively. The sizes of the obtained heritabilities of WT and of the genetic and phenotypic correlation between these traits indicate the possibility of effective population improvement for both WT traits.
Advances and Limitations of Antibody Drug Conjugates for Cancer

The popularity of antibody drug conjugates (ADCs) has increased in recent years, mainly due to their unrivalled efficacy and specificity over chemotherapy agents. The success of the ADC is partly based on the stability and successful cleavage of selective linkers for the delivery of the payload. The current research focuses on overcoming intrinsic shortcomings that impact the successful development of ADCs. This review summarizes marketed and recently approved ADCs, compares the features of various linker designs and payloads commonly used for ADC conjugation, and outlines cancer specific ADCs that are currently in late-stage clinical trials for the treatment of cancer. In addition, it addresses the issues surrounding drug resistance and strategies to overcome resistance, the impact of a narrow therapeutic index on treatment outcomes, the impact of drug–antibody ratio (DAR) and hydrophobicity on ADC clearance and protein aggregation.
Olfactory perceptual decision-making is biased by motivational state

Growing evidence suggests that internal factors influence how we perceive the world. However, it remains unclear whether and how motivational states, such as hunger and satiety, regulate perceptual decision-making in the olfactory domain. Here, we developed a novel behavioral task involving mixtures of food and nonfood odors (i.e., cinnamon bun and cedar; pizza and pine) to assess olfactory perceptual decision-making in humans. Participants completed the task before and after eating a meal that matched one of the food odors, allowing us to compare perception of meal-matched and non-matched odors across fasted and sated states. We found that participants were less likely to perceive meal-matched, but not non-matched, odors as food dominant in the sated state. Moreover, functional magnetic resonance imaging (fMRI) data revealed neural changes that paralleled these behavioral effects. Namely, odor-evoked fMRI responses in olfactory/limbic brain regions were altered after the meal, such that neural patterns for meal-matched odor pairs were less discriminable and less food-like than their non-matched counterparts. Our findings demonstrate that olfactory perceptual decision-making is biased by motivational state in an odor-specific manner and highlight a potential brain mechanism underlying this adaptive behavior.
Anthocyanins Promote Learning through Modulation of Synaptic Plasticity Related Proteins in an Animal Model of Ageing

Anthocyanin-rich foods, such as berries, reportedly ameliorate age-related cognitive deficits in both animals and humans. Despite this, investigation into the mechanisms which underpin anthocyanin-mediated learning and memory benefits remains relatively limited. The present study investigates the effects of anthocyanin intake on a spatial working memory paradigm, assessed via the cross-maze apparatus, and relates behavioural test performance to underlying molecular mechanisms. Six-week supplementation with pure anthocyanins (2% w/w), administered throughout the learning phase of the task, improved both spatial and psychomotor performances in aged rats. Behavioural outputs were accompanied by changes in the expression profile of key proteins integral to synaptic function/maintenance, with upregulation of dystrophin, protein kinase B (PKB/Akt) and tyrosine hydroxylase, and downregulation of apoptotic proteins B-cell lymphoma-extra-large (Bcl-xL) and the phosphorylated rapidly accelerated fibrosarcoma (p-Raf). Separate immunoblot analysis supported these observations, indicating increased activation of extracellular signal-related kinase (ERK1), Akt Ser473, mammalian target of rapamycin (mTOR) Ser2448, activity-regulated cytoskeleton-associated protein (Arc/Arg 3.1) and brain-derived neurotrophic factor (BDNF) in response to anthocyanin treatment, whilst α-E-catenin, c-Jun N-terminal kinase (JNK1) and p38 protein levels decreased. Together, these findings suggest that purified anthocyanin consumption enhances spatial learning and motor coordination in aged animals and can be attributed to the modulation of key synaptic proteins, which support integrity and maintenance of synaptic function.
Biologically Active Extracts from Different Medicinal Plants Tested as Potential Additives against Bee Pathogens

Honey bees (Apis mellifera) perform pollination service for many agricultural crops and contribute to the global economy in agriculture and bee products. However, honey bee health is an ongoing concern, as illustrated by persistent local population decline, caused by some severe bee diseases (e.g., nosemosis, AFB, EFB, chalkbrood). Three natural recipes are in development based on the bioactive compounds of different plants extract (Agastache foeniculum, Artemisia absinthium, Evernia prunastri, Humulus lupulus, Laurus nobilis, Origanum vulgare and Vaccinium myrtillus), characterised by HPLC-PDA. The antimicrobial activity of these recipes was tested in vitro against Paenibacillus larvae, Paenibacillus alvei, Brevibacillus laterosporus, Enterococcus faecalis, Ascosphaera apis and in vivo against Nosema ceranae. A mix of 20% blueberry, 40% absinthium, 10% oakmoss, 10% oregano, 10% Brewers Gold hops, 5% bay laurel and 5% anise hyssop extract showed the strongest antibacterial and antifungal activity. Combing several highly active plant extracts might be an alternative treatment against bee-disease-associated parasites and pathogens, in particular to replace synthetic antibiotics.
Investigating Ghanaian Allium Species for Anti-Infective and Resistance-Reversal Natural Product Leads to Mitigate Multidrug-Resistance in Tuberculosis

The bulbs of Allium species are a known source of antibacterial phytochemicals. Anti-infective, efflux pump and biofilm inhibitory activities of bulb extracts of selected Ghanaian shallots Allium cepa var aggregatum were evaluated using the HT-SPOTi assay and other whole-cell phenotypic screening techniques to determine their possible mechanisms of action. Ethanol and aqueous extracts of white A. cepa inhibited the growth of Mycobacterium smegmatis mc2 155 and Escherichia coli, respectively. The majority of the Allium extracts significantly (p < 0.05) exhibited efflux pump inhibitory activity against all the acid-fast, Gram-positive and Gram-negative strains used. Hexane and chloroform extract of the pink A. cepa and the aqueous extract of the white A. cepa significantly inhibited M. smegmatis biofilm formation. For Pseudomonas aeruginosa, the inhibition was observed at 250 µg/mL for the aqueous extract (~77.34%) and 125 µg/mL for the hexane extract (~76.51%). The results suggest that Ghanaian shallots could potentially be useful when further developed to tackle antimicrobial resistance, particularly in tuberculosis (TB).
Usnic Acid and Usnea barbata (L.) F.H. Wigg. Dry Extracts Promote Apoptosis and DNA Damage in Human Blood Cells through Enhancing ROS Levels

Nowadays, numerous biomedical studies performed on natural compounds and plant extracts aim to obtain highly selective pharmacological activities without unwanted toxic effects. In the big world of medicinal plants, Usnea barbata (L) F.H. Wigg (U. barbata) and usnic acid (UA) are well-known for their therapeutical properties. One of the most studied properties is their cytotoxicity on various tumor cells. This work aims to evaluate their cytotoxic potential on normal blood cells. Three dry U. barbata extracts in various solvents: ethyl acetate (UBEA), acetone (UBA), and ethanol (UBE) were prepared. From UBEA we isolated usnic acid with high purity by semipreparative chromatography. Then, UA, UBA, and UBE dissolved in 1% dimethyl sulfoxide (DMSO) and diluted in four concentrations were tested for their toxicity on human blood cells. The blood samples were collected from a healthy non-smoker donor; the obtained blood cell cultures were treated with the tested samples. After 24 h, the cytotoxic effect was analyzed through the mechanisms that can cause cell death: early and late apoptosis, caspase 3/7 activity, nuclear apoptosis, autophagy, reactive oxygen species (ROS) level and DNA damage. Generally, the cytotoxic effect was directly proportional to the increase of concentrations, usnic acid inducing the most significant response. At high concentrations, usnic acid and U. barbata extracts induced apoptosis and DNA damage in human blood cells, increasing ROS levels. Our study reveals the importance of prior natural products toxicity evaluation on normal cells to anticipate their limits and benefits as potential anticancer drugs.