Global warming poses a threat to plant survival, impacting growth and agricultural yield. Protein turnover, a critical regulatory mechanism balancing protein synthesis and degradation, is crucial for cellular response to environmental changes. We investigated the effects of elevated temperature on proteome dynamics in Arabidopsis thaliana seedlings using 15N-stable isotope labeling and ul-tra-performance liquid chromatography-high resolution mass spectrometry, coupled with the ProteinTurnover algorithm. Analyzing different cellular fractions from plants grown under 22°C and 30°C growth conditions, we found significant changes in the turnover rates of 571 proteins, with a median 1.4-fold increase, indicating accelerated protein dynamics under thermal stress. Notably, soluble root fraction proteins exhibited smaller turnover changes, suggesting tissue-specific adap-tations. Significant turnover alterations occurred with redox signaling, stress response, protein folding, secondary metabolism, and photorespiration, indicating complex responses enhancing plant thermal resilience. Conversely, proteins involved in carbohydrate metabolism and mito-chondrial ATP synthesis showed minimal changes, highlighting their stability. This analysis high-lights the intricate balance between proteome stability and adaptability, advancing our under-standing of plant responses to heat stress and supporting the development of improved thermo-tolerant crops.

In order to understand the defense response of Sanchezia nobilis to biotic and abiotic stresses, this study investigated the phenomenon of S. nobilis under biotic of feeding by Achatina fulica, and measured the temporal changes of malondialdehyde content, catalase and peroxidase activities under biotic of feeding by Achatina fulica and abiotic stress of garden pruning conditions on S. nobilis. The results showed that: 1) S. nobilis was seriously damaged by A. fulica and the average hourly food intake of A. fulica is 0.22 ± 0.01 g. 2) Leaf cutting stimulation and snail feeding stress significantly affected the content of malondialdehyde, the activities of catalase and peroxidase in the leaves of S. nobilis. 3) Compared with the control group, the snail feeding and leaf cutting stimulated stress could induce the leaf of S. nobilis to synthesize more malondialdehyde under varying durations, and the activities of catalase and peroxidase were significantly enhanced in a short time, and the induction response of snail feeding biological stress was faster than that of leaf cutting stimulated abiotic stress. 4) After the defense enzyme was strengthened, the activities of catalase and peroxidase in the feeding stress group of snails showed a gradual downward trend, while the activities of catalase and peroxidase in the leaf cutting stimulation stress group showed a first upward and then downward trend, indicating that abiotic stress had more lasting effects on plants than biological stress. It can be seen that biotic stress and abiotic stress significantly affect the defense response of plants, and the defense-related substances malondialdehyde, catalase and peroxidase play an important role in plants' response to biotic and abiotic stress. This study has important production guidance significance for carrying out stress resistance breeding or cultivation management of garden plants.

Medicinal plants have been a cornerstone of traditional medicine systems for centuries, offering a vast array of bioactive compounds with therapeutic potential. However, the identification, characterization, and elucidation of the pharmacological properties of these plants have often been challenging due to their complex chemical composition and diverse biological activities. Bioinformatics, with its interdisciplinary approach combining biology, computer science, and information technology, presents a powerful toolkit for the systematic study of medicinal plants. This review provides an overview of bioinformatics methodologies and resources that can facilitate the identification, phytochemical analysis, pharmacological investigation, and conservation of medicinal plants. It highlights the integration of omics technologies, computational algorithms, database resources, and molecular modeling techniques in advancing our understanding of medicinal plants' therapeutic potential and their applications in drug discovery and development.

"Suero costeño" a type of sour cream, is a traditional dairy product made mainly in the Colombian Caribbean region and has a variety of uses. The objective was to characterize the physicochemical and rheological properties of “suero costeño” produced in department of Córdoba-Colombia. Samples of " suero costeño " were obtained from local producers, characterized physicochemically (protein, fat, crude fiber, moisture, ash, carbohydrates, chlorides, pH and acidity), and rheologically (stationary tests), adjusting their behavior to the power-law model. The results show great variability in the physicochemical characteristics of the “suero costeño” made by the different artisanal producers, classifying it as a full-fat sour cream or light sour cream, and values of protein, pH and acidity similar to similar traditional dairy products from other countries, such as Reindeer sour cream and Curd or cottage cheese. “Suero costeño” can be classified as a pseudoplastic fluid and depending on the raw materials used and the production process, some present thixotropy, which may be the product of interactions between proteins and fats, which cause changes in the internal structure. Due to this great variability in its physicochemical and rheological characteristics, it is necessary to standardize the process of producing to improve the marketing of this Colombian culinary product.

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

Sinojackia Hu. comprises five to eight Chinese endemic species with high ornamental and medicinal value. However, the generic limits, interspecific relationships and evolutionary history of the genus remain unresolved. In this study, we newly sequenced and assembled three plastomes of S. oblongicarpa and compared them with those of the other congeneric species to explore the taxonomic delimitation of the species and the evolutionary history of the genus. Plastomes structure of Sinojackia species were extremely conserved in terms of number of genes, sequence length and GC content. Codon usage patterns revealed that natural selection may be the main factor shaping codon usage bias. Our phylogenetic tree shows that Sinojackia is monophyletic and can be divided into two clades. Sinojackia oblongicarpa as a distinct species is supported for it is distantly related to S. sarcocarpa. The evolutionary analysis of morphological features indicates that woody mesocarp is an ancestral feature, while mesocarp undeveloped, spongy and fleshy are the later derived. Sinojackia originated in Central-Southeast China during the early Miocene. In this period, it experienced elevated diversification and migrated from the Central-Southeast China to Hunan Province and Sichuan Province with the development of the Asian monsoon and East Asian flora. Sinojackia experienced elevated diversification at intraspecies levels that mainly occurred in the Quaternary. Glacial-interglacial interactions with the monsoon climate may provide favorable expansion conditions for Sinojackia on a small-scale.

Skeletal muscle (SKM), despite comprising ~40% of body mass, is rare. This review explores the mechanisms that help to explain this rarity, including unique SKM architecture and function, which prohibits development of new cancer as well as negates potential metastasis to SKM. SKM also presents a unique immune environment that may magnify the anti-tumorigenic effect. Moreover, the SKM microenvironment manifests characteristics such as decreased extracellular matrix stiffness and altered lactic acid, pH, and oxygen levels that may interfere with tumor development. SKM also secretes anti-tumorigenic myokines and other molecules. Collectively, these mechanisms help account for the rarity of SKM cancer.

In bovine embryos, microRNA (miRNA) expression has been profiled at each stage of early development in-vitro. miRNAomic analysis of spent media has the potential to reveal characteristics of embryo health, however, applications are limited without categorizing miRNA profiles by embryo quality. Time-lapse imaging has shown the timing of embryo development in-vitro may be indicative of their developmental potential. The aim of the study was to profile miRNAs in the spent media of slow and fast-growing bovine embryos throughout the pre-implantation period. Bovine cumulus-oocyte-complexes were aspirated from ovaries, fertilized, and cultured to blastocyst stage of development. At 2-cell, 8-cell, and blastocyst stage, each microdrop of 30 presumptive-zygotes were classified as slow or fast-growing based on the percentage of embryos that had reached the desired morphological stage. Following hybridization on a GeneChip miRNA 4.0 array, comparative analysis was conducted between spent media of slow and fast-growing embryos. In total, 34 differentially expressed miRNAs were identified between the comparison groups, with 14 of the miRNAs detected in the 2-cell samples, 7 miRNAs detected in the 8-cell samples, and 12 miRNAs detected in the blastocyst samples. The results demonstrate distinct miRNAs populations can be identified between slow and fast-growing embryos, highlighting novel biomarkers of developmental potential at each stage of pre-implantation development.

The flowering period of rice significantly impacts variety adaptability and yield formation. Properly shortening the reproductive period of rice varieties can expand their ecological range without significant yield reduction. Targeted genome editing, like CRISPR/Cas9, is an ideal tool to fine-tune rice growth stages and boost yield synergistically. In this study, we developed a CRISPR/Cas9-mediated multiplex genome editing vector containing five genes related to three traits: Hd2, Ghd7, and DTH8 (flowering stage genes), along with the recessive rice blast resistance gene Pi21 and the aromatic gene BADH2. This vector was introduced into the high-quality Geng rice variety in Zhejiang province, Jiahe212 (JH212), resulting in 34 T0 plants with various effective mutations. Among the 17 mutant T1 lines, several displayed diverse flowering dates, but most exhibited undesirable agronomic traits. Notably, three homozygous mutant lines (JH-C15, JH-C18, and JH-C31) showed slightly earlier flowering dates without significant differences in yield-related traits compared to JH212. Through special Hyg and Cas marker selection of T2 plants, we identified 7, 6, and 2 fragrant glutinous plants devoid of transgenic components, respectively. These single plants will serve as sib lines of JH212 and potential resources for breeding applications, including maintenance lines for Xian-Geng interspecific three-line hybrid rice. In summary, our research offers practical insights and potential resources for targeted improvement of Geng rice varieties, and would also promote the Geng rice varieties expending from the southward to the northward.

The opportunistic pathogen Pseudomonas aeruginosa is responsible for numerous chronic infections and has a case fatality rate of 50%. All P. aeruginosa strains express β–lactamase, an enzyme capable of inactivating β–lactam antibiotics, including penicillins. However, β–lactams are still considered desirable therapeutics by physicians due to their low toxicity. The short-term goal of this study was to create an optimal model for ampC expression in P. aeruginosa and determine the selecting antibiotic to be used during mutagenesis. In the long term, this study aims to renew effectiveness of β–lactams by identifying potential allosteric binding sites on β–lactamase for the development of novel β–lactamase inhibitors. To create a system for ampC expression, the chromosomal P. aeruginosa ampC gene encoding for β–lactamase was cloned into Escherichia coli, then conjugated into P. aeruginosa ∆ampC. β– lactamase assays on recombinant E. coli and P. aeruginosa detected much higher production of β–lactamase in pMMB67HE, which was confirmed with antibiotic susceptibility testing (AST) to numerous β-lactams. From AST, carbenicillin was chosen as the antibiotic to select functional β–lactamase production during mutagenesis. Future work includes conducting mutagenesis on ampC to identify allosteric binding sites on the β–lactamase enzyme that may enable the discovery of new β–lactamase inhibitors. This work allows for the development of novel β–lactamase inhibitors that could renew the utility of β–lactams and drastically reduce morbidity and mortality from chronic Pseudomonas infections.

Formidable and often seemingly insurmountable conceptual, technical, and methodological challenges hamper the measurement of oxidative stress in humans. For instance, fraught and flawed methods, such as the thiobarbituric acid reactive substances assay kits for lipid peroxidation, rate-limit progress. To advance translational redox research, we present ten comprehensive “cheat codes” for measuring oxidative stress in humans. The cheat codes include analytical approaches to assess reactive oxygen species, antioxidants, biomarkers of oxidative damage and redox regulation. They provide essential conceptual, technical, and methodological information inclusive of curated “do” and “don’t” guidelines. Given the biochemical complexity of oxidative stress, we present a research question-grounded decision tree guide for selecting the most appropriate cheat code (s) to implement in a prospective human experiment. Worked examples demonstrate the benefits of the decision tree-based cheat code selection tool. The ten cheat codes define an invaluable resource for measuring oxidative stress in humans.

Probiotics have emerged as a prominent alternative to antibiotics in antimicrobial-free broiler farming. To assess the effect of the probiotics Sphingomonas sp. Z392 isolated and identified by this this laboratory on broiler growth, we conducted a study to examine the changes in broiler body weight, EPI, intestinal histological structure and gut microbiota. The results showed that supplementation of broiler drinking water with 4 × 105 CFU/mL of Sphingomonas resulted in an increase in the relative abundance of Lactobacillus, Bacteroides, Lachnospiraceae, Aminobacterium, Oribacterium, Christensenellaceae, Faecalibacterium, Barnesiella, Ruminococcus, Parabacteroides, Phascolarctobacterium, Butyricicoccaceae, and Caproiciproducens, which were reported to be positively correlated with the digestion and absorption of broiler chickens. The relative abundance was increased of Odoribacter, Alistipes, Parabacteroides, and Rikenellaceae, which were reported to be negatively correlated with the occurrence of intestinal diseases. The relative abundance was decreased of Campylobacter, Shigella Castellani, Bilophila, Campylobacter, Clostridia, and Anaerotruncus, which were reported positively correlated with the occurrence of intestinal diseases. At the same time, it was increased in the integrity of small intestinal villus morphology, the number of goblet cells in small intestinal epithelial cells, the health of mitochondria in the cytoplasm of jejunal villous epithelial cells, and the number of lysosomes in the cytoplasm of goblet cells in small intestinal epithelium, ileal villous epithelial cells, mitochondria in the cytoplasm of large intestinal villous epithelial cells, the VH/CD of the ileum, digestive, absorption, and defense capabilities. Especially the final weight was increased by 4.33% and the EPI increased by 10.10%. Therefore, the supplementation of broiler drinking water with Sphingomonas generated better economic benefits for the broiler chickens.

Despite substantial evidence supporting the efficacy of prebiotics for promoting host health and stress resilience, few experiments present evidence documenting the dynamic changes in microbial ecology and fecal microbial-modified metabolites across time. Furthermore, the literature reports a lack of reproducible effects of prebiotics on specific bacteria and bacterial-modified metabolites. The current experiments examined whether consumption of diets enriched in prebiotics (galactooligosaccharides, GOS and polydextrose, PDX) compared to control diet, would consistently impact the gut microbiome and microbial-modified bile acids across time and between two research sites. Male Sprague Dawley rats were fed control or prebiotic diets for several weeks, and their gut microbiome and metabolome were examined using 16S rRNA gene sequencing and untargeted LC-MS/MS analysis. Dietary prebiotics altered beta diversity, relative abundances of bacterial genera, and microbially modified bile acids across time. PICRUSt2 analyses identified four inferred functional metabolic pathways modified by prebiotic diet. Correlational network analyses between inferred metabolic pathways and microbial-modified bile acids revealed deoxycholic acid as a potential network hub. All these reported effects were consistent between the two research sites supporting the conclusion that dietary prebiotics robustly changed the gut microbial ecosystem. Consistent with our previous work demonstrating that GOS/PDX reduces the negative impacts of stressor exposure, we propose that ingesting a diet enriched in prebiotics facilitates the development of a health-promoting gut microbial ecosystem.

A beverage made from a combination of Agave sap (AS) and prickly pear juice (PPJ) was ana-lyzed for its nutrients, bioactive and potentially health-promoting compounds. The beverage was evaluated for its ability to act as an antioxidant, regulate glycemic properties, and undergo gut bacterial fermentation in vitro. The major mono- and oligosaccharides present in the beverage were galacturonic acid (217.74±13.46 mg/100 mL), rhamnose (227.00±1.58 mg/100 mL), and fructose (158.16±8.86 mg/mL). The main phenolic compounds identified were protocatechuic acid (440.31±3.06 mg/100 mL) and catechin (359.72±7.56 mg/100 mL). It was observed that the beverage had a low glycemic index (

The skin beetle Reesa vespulae is regularly found beyond North America where it originated. The larvae cause considerable concern in museums as it damages hides or furs in addition to being a special source of damage to collections of dried plants in herbaria or collections of insects and other zoological specimens. It arrived in Europe in the mid-20th century and was associated mostly with stored food products, but over time it has become recognised as a museum pest. Although still uncommon and may only be observed in a small fraction of museums, where the insect is found in large numbers it can cause problems. As a single female can continue to breed because the beetle is parthenogenetic, presence can persist over long periods of time. Although small populations in museums are typically found as the adult, the larval forms are more common where a site is infested by high numbers, perhaps because the larvae and adults must range more widely for food. Although Reesa vespulae can be controlled using pesticides, it is also possible to kill the larvae within infested materials through freezing or anoxia.

The Drosophila spermatogenesis has the renewal of germline stem cells, meiosis of spermatocytes, and morphological transformation of spermatids into mature sperm. We previously demonstrated that Ocnus (ocn) plays an essential role in spermatogenesis. ValRS-m (Valyl-tRNA synthetase, mito-chondrial) gene was downregulated in ocn RNAi testes. By hatchability testing, we found that ValRS-m-knockdown induced complete sterility of male flies. We also concluded that ValRS-m-knockdown inhibited the transition from spermatogonia to spermatocytes and caused accumulated spermatogonia in testes. To understand the intrinsic reason for this destruction, we further conducted transcriptome sequencing analysis in ValRS-m RNAi testes. A total of 7710 dif-ferentially expressed genes (DEGs) were identified to have at least a 2-fold change with a p-value of

This comprehensive review delineates the extensive roles of Akkermansia muciniphila in various health domains, spanning from metabolic and inflammatory diseases to neurodegenerative disorders. A. muciniphila, known for its ability to reside in the mucous layer of the intestine, plays a pivotal role in maintaining gut integrity and interacting with host metabolic processes. Its influence extends to modulating immune responses and potentially easing symptoms across several non-communicable diseases, including obesity, diabetes, and inflammatory bowel disease. Recent studies highlight its capacity to interact with the gut-brain axis, suggesting a possible impact on neuropsychiatric conditions. Despite the promising therapeutic potential of A. muciniphila highlighted in animal and preliminary human studies, challenges remain in its practical application due to stability and cultivation issues. However, the development of pasteurized forms and synthetic mediums offers new avenues for its use in clinical settings, as recognized by regulatory bodies like the European Food Safety Authority. This narrative review serves as a crucial resource for understanding the broad implications of A. muciniphila across different health conditions and its potential integration into therapeutic strategies

Living systems are intricate repositories of biomolecules, where the interactions between these molecules play an important role in maintaining homeostasis. Interruptions in these interactions can lead to diseases, underscoring the significance of biomolecular interactions and their molecular basis. HUGENICS (Human Genetic Database) is a comprehensive biological database that focuses on molecular interactions between human and microbial proteins, particularly emphasizing protein-protein interactions (PPIs). This database offers insights into disease pathways by elucidating the interplay between microbial surface/secretory proteins and human disease-related proteins. This white paper highlights the significance, scope, and potential applications of HUGENICS in advancing biomedical research and improving human health.

This study was designed to examine the relationships among the impulsivity construct as a personality trait, the dehydroepiandrosterone sulfate (DHEA-S), and testosterone in a sample of 120 healthy middle-aged males. (Mage = 44.39; SD = 12.88). The sum of the three BIS-11 scales, the SR and the five UPPS-P scales correlated with DHEA-S .23 (p < .006) and testosterone .19 (p < .04), controlling for age. Partial correlations showed that DHEA-S is significantly related to Motor impulsivity (.24; p < .008), Sensitivity to Reward (.29; p < .002) and Lack of premeditation (.26; p < .05) and, to a lesser extent, Sensation Seeking (.19; p < .04) and Positive Urgency (.19; p < .04). Testosterone correlated with Attention impulsivity (.18; p < .04), Sensation Seeking (.18; p < .04), and Positive Urgency (.22; p < .01). Sensitivity to Reward, Negative Urgency and Positive Urgency were significant predictors of DHEA-S (R2 = .28), and Positive Urgency for testosterone (R2 = .09). Non-parametric LOESS graphical analysis for local regression allowed us to visualize the non-linear relationships between the impulsivity scales with the two androgens, including non-significant trends. We discuss the implications of these results for biological impulsive personality traits, the limitations of our analyses, and the possible development of future research.

Background: The rise of new SARS-CoV-2 mutations brought challenges and progress in the global fight against COVID-19. Mutations in spike and accessory genes affect transmission, vaccine efficacy, treatments, testing, and public health strategies. Monitoring emerging variants is crucial to halt virus spread. Methods: 44 nasopharyngeal/oropharyngeal swabs from Kenyan patients were sequenced with the Illumina platform. Galaxy's bioinformatic tools were used for genomic analysis. SARS-CoV-2 genome classification was done using PANGOLIN and mutation annotation with the COVID-19 Annotator tool. Results: The study showed 5 clades to be circulating in the region. 38(86%) were BA.1.1; 2(5%) were BA.1.1.1; 1(2%) was BA.1; 1(2%) was BA.1.14 and 2(5%) were AY.46. These clades had a cumulative of 173 mutations among them with 50 novel mutations. Forty-eight of these novel mutations occurred in a low frequency of 2.3% of the sequences tested while the other two, S:R214R, and NSP2:A555A, were for 43.2% and 18.2% of the cases respectively. Conclusions: The high-frequency novel mutations were synonymous mutations, a phenomenon that was previously viewed as phenotypically silent but recent studies indicate they can affect viral fitness with potential functional associations. These findings add to the understanding of the SARS-CoV-2 virus future evolutionary and immunological dynamics in the region

This study aimed to produce single-chain recombinant eel follicle-stimulating hormone (rec-eel FSH) analogs with high activity in Chinese hamster ovary DG44 (CHO DG44) cells. We recently reported that an O-linked glycosylated carboxyl-terminal peptide (CTP) of the equine chorionic gonadotropin (eCG) β-subunit plays contributes on high activity and time-dependent secretion in mammalian cells. We constructed a mutant (FSH-M) in which a linker including the eCG β-subunit CTP region (amino acids 115 to149) was inserted between the β-subunit and α-subunit of wild-type single chain eel FSH (FSH-wt). Plasmids containing eel FSH-wt and eel FSH-M were transfected into CHO DG44 cells. Single cells expressing each protein were isolated from 10 and 7 clones, respectively. Secretion increased gradually during the cultivation period and peaked at 4,000–5,000 ng/mL on day 9. The molecular weight of eel FSH-wt was 34–40 kDa, while that of eel FSH-M increased substantially, with two bands at 39–46 kDa. Treatment with PNGase F to remove the N glycosylation sites decreased the molecular weight remarkably to approximately 8 kDa. The EC50 value and maximal responsiveness of eel FSH-M were approximately 1.23- and 1.06-fold higher than those of eel FSH-wt, indicating that the mutant showed slightly higher biological activity. Phosphorylated extracellular regulated kinase (pERK1/2) activation exhibited a sharp peak at 5 min, followed by a rapid decline. These findings indicate that the new rec-eel FSH molecule with the eCG β-subunit CTP linker showed potent activity and could be produced in massive quantities using the stable CHO DG44 cell system.

Drug-induced liver injury (DILI) stands as a significant cause of drug attrition. To mitigate clinical DILI risks, assessing drugs using human liver models is crucial since animal studies may fall short due to species-specific liver pathway variations. Cell-based preclinical hepatotoxicity testing is often pertinent. In the present study, cells from a human liver cancer line (HepG2, HepaRG) were cultured in both formats of 2D and 3D spheroids to explore their responses to drugs. Liver-specific marker expressions across cell lines and culture formats were also examined to assess disparities in drug-induced liver injury marker expressions. In cytotoxicity assays, HepG2 cells exhibited heightened sensitivity to amiodarone HCl, while HepaRG cells showed greater sensitivity to acetaminophen. Generally, 2D cultures were more responsive to drugs than 3D cultures. Consistency was observed between cytotoxicity assays and liver injury markers AST and ALT. Variations were also noted in liver cell marker secretion, with albumin and urea concentrations declining post-drug treatment, particularly with higher baseline expression in HepaRG cells and 3D cultures. Additionally, mRNA expression levels of CYP enzymes involved in hepatocellular drug metabolism were compared following treatment with enzyme inducers. CYP1A2 and CYP2C9 were not expressed in HepG2 cells. On the other hand, CYP3A4 was expressed higher in 3D culture than in 2D culture. HepaRG cells exhibited significantly increased expression of all three enzymes post-treatment. Notably, enzyme expression was notably higher in 3D cultures than in 2D cultures. Collectively, these findings suggest that HepaRG cells and 3D cultures hold promise for evaluating DILI during early-stage drug development.

A two-year experiment was conducted with a local maize hybrid under full irrigation (F), deficit irrigation (D) and rainfed conditions (R) to estimate maize evapotranspiration in Bosnia and Herzegovina. Three approaches (Allen & Pereira (A&P), SIMDualKc (SD), and Vegetation Index (VI)) were used to estimate the actual crop coefficient (Kc act), actual basal crop coefficient (Kcb act), and actual crop evapotranspiration (ETc act) were applied with the dual crop coefficient method and remote sensing (RS) data. While Kcb act from all approaches matched FAO56 tabulated values, SD showed differences, in comparison to A&P, of up to 0.24 in D and R conditions, especially in initial and mid-season stages. VI demonstrated very good performance in all treatments. In F, the obtained Kc act for all approaches during the initial and end stages were higher than the tabulated values, ranging from 0.71-0.87 for Kc ini act and from 0.80-1.06 for Kc end act, while the mid-season period showed very good agreement with the literature. Maize crop evapotranspiration range is 769-813 mm, 480-752 mm, and 332-618 mm for F, D and R, respectively. The results confirmed the suitability of both approaches (SD and VI) to estimate maize crop evapotranspiration under F, with the VI approach demonstrating an advantage in calculating Kcb act, Kc act, and ETc act values under water stress conditions. The 67.6% increase in grain yields with irrigation emphasizes the need to transition from rainfed to irrigation-dependent agriculture, even for drought-resistant crops like maize.

The adipose tissue is responsible for fat storage and is the major producer of exosomes. Biological content transported by the exosomes provides information, such as immunometabolic alterations. This study aimed to isolate whole exosomes from plasma and supernatant of differentiated 3T3-L1 cells using three isolation techniques. Plasma from 120 individuals categorized by body adipose tissue proportion and differentiated 3T3-L1 cells were used in this study. The exosome isolation techniques were differential centrifugation (DC), size exclusion chromatography (SEC), and a commercial kit (Invitrogen), and characterized by cryo-TEM, TEM, and western blot for the tetraspanins CD9 and CD81. In the three isolation techniques, cryo-TEM and TEM analysis showed similar quality, quantity, and morphology of exosomes; at the same time, no difference was observed between individuals categorized by proportion of body fat. According to our results, the concentration of the circulating exosomes is not different between normal and high-fat percentage individuals, but rather their composition. The SEC and kit commercial proved that compile with most of the advantages of an exosome isolation technique, nerveless we emphasize the importance of selecting the appropriate methodology depending on the specific research objectives.

BackgroundThe present review summarizes the state-of-the-art of in silico methods and techniques that are the most useful in drug discovery, their relationship with data science, as well as the successful application of data science, machine learning (ML) and artificial intelligence (AI) applications. A meta-analysis of the various technologies available is furthermore proposed as a guideline for the non-expert, reader relative to the several subject areas is also discussed in this article. The scope of this meta-analysis is to rank the enlisted technologies by their field of applications and to depict the latter according to knowledge accessibility, from students to experts.Method The search strategy utilized for this review first produced a general collection of 900 papers without duplications, which were subsequently streamlined and divided into two independent collections: the top 300 most-cited papers of all time (since 2000) and the papers with the highest interest for a systematic review analysis (high-impact exciting papers). Results In Part 1, we discuss the most cited and quality 97 articles in these top 300 papers most relevant to the field of in silico drug discovery. The different disciplines are listed according to their industrial and economic incurred to society, independently from the “metric” results of how many new drug approvals (NDAs) each discipline has generated to date.ConclusionBig data, the ensemble of known items stored in publicly available databases, has improved our understanding of the many fates of a potential drug candidate during its development and even after its commercialization. Moreover, the combination of new screening techniques and “omics” with old drugs has led to a new paradigm in which the unknown knowledge of any biological molecule and its cellular structure, now plays an important role as a target for a series of yet-to-be-developed drugs: the chemical space. Furthermore, leveraging big data, data science, ML, and AI can revolutionize drug discovery by swiftly analyzing massive datasets, predicting efficacy and safety profiles, streamlining development, cutting costs, and boosting success rates for new drugs. AI also speeds up the search for promising drug candidates, advancing innovative therapies.

Vaccines are one of the most effective medical interventions, playing a pivotal role in treating infectious diseases. Although traditional vaccines comprising of killed, inactivated, or live attenuated pathogens have resulted in protective immune responses, negative consequences of their administration have been well-appreciated. Modern vaccines have evolved to contain purified antigenic proteins, epitopes, or antigen-encoding mRNAs, rendering them relatively safe. However, reduced humoral and cellular responses pose major challenges to modern vaccine platforms. Protein nanoparticle (PNP)-based vaccines have garnered substantial interest in recent years for their ability to present repetitive array of antigens for improving immunogenicity and enhancing protective responses. Discovery and characterization of naturally occurring PNPs from various living organisms such as bacteria, archaea, viruses, insects, and eukaryotes, as well as computationally designed structures and approaches to link antigens to the PNPs have paved the way for unprecedented advances in the field of vaccine technology. In this review, we focus on some of the widely used naturally occurring and optimally designed PNPs for their suitability as promising vaccine platforms for displaying native-like antigens from viral pathogens for protective immune responses. Such platforms hold great promise in combating emerging and re-emerging infectious diseases and enhancing vaccine efficacy and safety.

In mammals, Tripartite motif-containing (TRIM) proteins modulate the immune response by coordinating pro-inflammatory related processes such as antiviral restriction, cellular autophagy and inflammasome activation. In fish, TRIM proteins have been reported mainly in cyprinids (e.g., carp, zebrafish) and salmonids (rainbow trout). However, their molecular mechanisms and functions are still being described these animals. Our study focused on characterizing novel TRIM proteins involved in the innate immune response of gill cells from rainbow trout stimulated with LPS or poly(I:C). Also, a fish trial was performed to detect TRIM proteins of rainbow trout after a challenge with Flavobacterium psychrophilum, a salmonid bacterial pathogen. At in vitro level, the results showed that, among several TRIM proteins, OmTRIM25 triggered an LPS-induced expression of pro-inflammatory cytokines (TNF-α2 and IL-1β), suggesting a potential local modulatory function. Moreover, in the fish trial, while OmTRIM25 and finTRIM2 were up-regulated in the gills two days post infection (dpi), IL-1β and TNF-α2 reached their peaks of expression at four- and six-dpi. Finally, after delving into the function of OmTRIM25 by RNA interference (RNAi) gene-silencing, we propose that TRIM proteins such as OmTRIM25 are needed to induce the pro-inflammatory response in the gills of rainbow trout, which confirms their immunomodulatory function.

Citrus species essential oils (EOs) are significant sources of bioactive compounds and demonstrate diverse therapeutic effects. However, limited documentation exists regarding the phytochemicals associated with their biological activities. This study aims to assess the antioxidant activity, plant inhibitory properties, and brine shrimp cytotoxic effects of EOs derived from three Citrus species: C. sinensis, C. limon, and C. hystrix. Utilizing chemometric analysis and gas chromatography-mass spectrometry (GC-MS) fingerprints, the volatile components contributing to antioxidant activity were elucidated. The peels of the Citrus samples were hydro-distillated to obtain EOs, and subsequently subjected to antioxidant, plant inhibitory, and brine shrimp cytotoxic assays. The results indicated that C. limon EO exhibited the highest antioxidant activity, while C. hystrix and C. sinensis EOs demonstrated pronounced inhibitory effects against Aetrmia salina and Lactuca sativa, respectively. GC-MS analysis facilitated the identification of key compounds in each EO. Principal component analysis (PCA) and hierarchy cluster analysis (HCA) effectively categorized Citrus EOs based on their antioxidant properties, highlighting the proximity of C. limon and C. sinensis. Among the identified compounds, D-limonene, α-Terpineol, Caryophyllene, (+)-3-Carene, β-Pinene, (-)-Spathulenol, trans-p-Mentha-1(7),8-dien-2-ol, and trans-Verbenol were the most discriminating compounds affected the antioxidant activity of C.limon and C. sinensis EOs.

Oxidative neurodegeneration causes various neuronal diseases including Alzheimer's disease, Parkinson's disease, and Huntington's disease. This study aimed to demonstrate the protective effect of leaf extracts of Allium senescens on 6-hydroxydopamine (6-OHDA)-stressed SH-SY5Y cells, known as an optimal cell for neurotoxic research. Levels of apoptotic markers were evaluated using quantitative polymerase chain reaction (qPCR) and flow cytometry. The localization of apoptotic cells in vivo was analyzed using whole-mount immunochemistry and the terminal deoxynucleo-tidyl transferase dUTP nick end labeling assay. Additionally, reactive oxygen species (ROS) pro-duction was estimated using flow cytometry. 6-OHDA induced ROS production in neuroblast cells and in vivo, but treatment with the extract protected against the 6-OHDA-induced increase in ROS levels. Under oxidative stress, the extract performs three protective functions: decreases ROS production, prevents mitochondrial apoptosis, and protects the central and ventral nervous systems. These results also suggest that the extract can be useful for the development of functional foods for the prevention of neural damage due to oxidative stress.

Climate change related increases in frequency and intensity of heatwaves affect viticulture, leading to losses in yield and grape quality. We assessed whether canopy architecture manipulation mitigates the effects of summer stress in a Mediterranean vineyard. Muscat of Alexandria grapevines were monitored during 2019-2020. Two canopy shoot positioning treatments were applied: Vertical shoot positioning (VSP); and Modulated shoot positioning (MSP), the west side upper foliage released to promote partial shoot leaning, shading the clusters. Clusters were sampled at pea size (PS), veraison (VER) and full maturation (FM). Measurements included rachis anatomy and hydraulic conductance, and aquaporins (AQP) and stress-related genes expression in cluster tissues. Results show significant seasonal and interannual differences in Kh and vascular anatomy. At VER, Krachis , Krachis+pedicels, and xylem diameter decreased but were unaffected by treatments. The Phloem/Xylem ratio was either increased (2019) or reduced (2020) in MSP, compared to VSP. Most AQP were down-regulated at FM in pedicels, and up-regulated at VER in pulp. A potential maturation shift in MSP was observed, confirmed by the up-regulation of several stress-related genes in all tissues. The study pinpoints the role of canopy architecture in berry water relations and stress response during ripening.

Lipofuscin is indigestible garbage that accumulates in the autophagic vesicles and cytosol of post-mitotic cells with age. Drs. Brunk and Terman postulated that lipofuscin accumulation is the main or at least a major driving factor in aging. They even posited that the evolution of memory is the reason why we get lipofuscin at all, as stable synaptic connections must be maintained over time, meaning that the somas of neurons must also remain in the same locale. In other words, they cannot dilute out their garbage over time through cell division. Mechanistically, their position certainly makes sense given that rendering a large percentage of a post-mitotic cell’s lysosomes useless must almost certainly negatively affect that cell and the surrounding microenvironment. It may be the case that lipofuscin accumulation is the main issue with regard to current age-related disease. Degradation in situ may be an insurmountable task currently. However, a method of systemic lipofuscin removal is discussed herein.

Omsk hemorrhagic fever virus (OHFV) is a member of the tick-borne encephalitis virus (TBEV) complex of the Flaviviridae family. Currently, there is no data on cross-reactivity of antibodies to the NS1 proteins of OHFV and TBEV. Such data are of major interest for monitoring viral encephalitis of unknown etiology due to the increasing geographical distribution of OHFV. In this study, recombinant OHFV NS1 protein was produced using Escherichia сoli expression system and purified. The recombinant OHFV NS1 protein was recognized by specific mice immune ascetic fluids to the native OHFV NS1 protein. Western blot analysis and ELISA of recombinant NS1 proteins of OHFV and TBEV were used to study the cross-reactivity of antibodies from immune ascites fluid obtained from OHFV-infected mice and mAbs against TBEV NS1. Anti-TBEV NS1 mouse monoclonal antibodies (mAbs) have been shown not to be cross-reactive to OHFV NS1 protein. Sera from patients with confirmed tick-borne encephalitis (TBE) were examined by ELISA using recombinant OHFV NS1 and TBEV NS1 proteins as antigens. It was shown for the first time that cross-reactive antibodies to OHFV NS1 protein were not detected in the sera of TBE patients whereas the sera contained antibodies to TBEV NS1 protein.

Maternal diet plays a significant role in the fatty acid composition of breast milk. Natural trans fatty acids (TFAs) are generated through the biohydrogenation of unsaturated fatty acids (FAs) in the rumen of animals by bacterial isomerases and are consequently found in milk, dairy products, and meat from ruminant animals. Dietary products such as milk and meat are the primary sources of natural TFAs for humans, derived from rumen fermentations. These peculiar fatty acids hold nutritional significance as they not only lack the detrimental effects on endothelium characteristic of industrially produced trans fat, but also exhibit anti-inflammatory properties. The relationship between the presence in breast milk of eight fatty acids (including natural TFAs trans-vaccenic and conjugated linoleic acid) and maternal diet has been explored, and their abundance has been compared to that of infant formulas. Two cohorts of lactating women participated in this study, originating from a Spanish region adhered to the Southern European Atlantic Diet or Atlantic Diet. While the consumption of conventional meat or dairy products does not seem to increase the abundance of trans fatty acids in breast milk, trans-vaccenic and oleic acid are among the most distinctive features of breast milk fat in mothers consuming naturally improved dairy products, with an improved fatty acid profile. The most significant differences between natural breastfeeding and formula feeding lie in natural trans fatty acids, since formula are notably deficient, while overfortified in alpha-linolenic acid in comparison to breast milk.

The gut microbiota (GM) communicates with the brain via biochemical signaling constituting the gut-brain axis, which significantly regulates the body's physiological processes. The GM dysbiosis can impact the digestive system and the functioning of the central nervous system (CNS) linked to the onset of neurodegenerative diseases. In this review, the scientific data compiled from diverse sources primarily emphasizes the neuropathological characteristics linked to the accumulation of modified insoluble proteins (such as β-Amyloid peptides and hyperphosphorylated tau proteins) in Alzheimer’s Disease (AD) and the potential impact of gut microbiota (GM) on AD susceptibility or resilience. The specific GM profile of human beings may serve as an essential tool for preventing or progressing neurodegenerative diseases like AD. This review focuses mainly on the effect of gut microfauna on the gut-brain axis in the onset and progression of AD. The GM produces various bioactive molecules that may serve as proinflammatory or anti-inflammatory signaling, contributing directly or indirectly to the repression or progression of neurodegenerative disorders by modulating the response of the brain axis. Human studies must focus on further understanding the gut-brain axis and venture to clarify microbiota-based therapeutic strategies for AD.

Oil-Gan, also known as emblica, is the fruit of the genus Phyllanthus emblica L. The fruits of these trees are high in nutrients and have excellent effects on health care and development values. There are many methods for the management of diabetic nephropathy (DN). However, there is a lack of effective drugs for treating DN from throughout the disease course. The primary aim of this study was to examine the protective effects (including urine analyses, the measurement of inflammatory cytokine levels, and histological examination) and mechanisms of action of an ethyl acetate extract of P. emblica (EPE) on db/db mice, an animal model of diabetic nephropathy, as well as a secondary aim of examining the expression levels of protein kinase Cα (PKCα) in the kidney and its downregulation of vascular endothelial growth factor (VEGF) and fibrosis gene transforming growth factor-β1 (TGF-β1) by Western blot analyses. Eight db/m C57BLKS/J mice were used as the control group. Forty db/db mice were randomly divided into five groups. Treatments included vehicle, EPE1, EPE2, EPE3 (at doses of 100, 200, or 400 mg/kg EPE), or the comparative drug aminoguanidine for 8 weeks. After 8 weeks of treatment, blood samples were collected for analyses of blood glucose, insulin, and HbA1c levels, and pancreatic and kidney tissues were dissected for histological analyses. The present study indicated that the administration of EPE to db/db mice effectively controlled hyperglycemia and hyperinsulinemia by markedly lowering blood glucose, insulin, and glycosylated HbA1c levels. Administration of EPE to db/db mice decreased the levels of BUN and creatinine both in blood and urine and reduced urinary albumin excretion and the albumin creatine ratio (UACR) in urine. Moreover, EPE treatment decreased the blood levels of inflammatory cytokines, including kidney injury molecule-1 (KIM-1), C-reactive protein (CRP), and NLR family pyrin domain containing (NLRP3). Our findings showed that EPE not only had antihyperglycemic effects but also improved renal function in db/db mice. Histological examination of the kidney by immunohistochemistry indicated that EPE can improve kidney function by ameliorating glomerular morphological damage following glomerular injury; alleviating proteinuria by upregulating the expression of nephrin, a biomarker of early glomerular damage; and inhibiting glomerular expansion and tubular fibrosis. Moreover, the administration of EPE to db/db mice increased the expression levels of p- PKCα/t-PKCα but decreased the expression levels of VEGF and renal fibrosis biomarkers (TGF-β1, collagen IV, p-Smad2, p-Smad3, and Smad4), as shown by Western blot analyses. These results implied that EPE as a supplement has a protective effect against renal dysfunction through the amelioration of insulin resistance as well as the suppression of nephritis and fibrosis in a DN model.

Thyrotropin releasing hormone (TRH; pGlu-His-Pro-NH2) is an intercellular signal produced mainly by neurons. Among the multiple pharmacological effects of TRH, that on food-intake is not well understood. We review data that show that peripheral injection of TRH generally produces a transient anorexic effect, discuss the pathways that might initiate this effect, and explain its short half-life. In addition, central administration of TRH can produce anorexic or orexigenic effects, depending on the site of injection, that are likely due to interaction with TRH receptor 1. Anorexic effects are most notable when TRH is injected into the hypothalamus and the nucleus accumbens, while the orexigenic effect has only been detected by injection into the brain stem. Functional evidence suggests that TRH neurons that are prime candidate vectors for TRH action on food-intake include the caudal raphe nuclei projecting to the dorsal motor nucleus of the vagus, and possibly TRH neurons from the tuberal lateral hypothalamus projecting to the tuberomammillary nuclei. For other TRH neurons, the anatomical or physiological context and impact of TRH in each synaptic domain are still poorly understood. The manipulation of TRH expression in well-defined neuron types will facilitate the discovery of its role in food-intake control in each anatomical scene.

The fatty acid composition, biophenol, tocopherol, sterol and triterpenic dialcohol content and composition of the autochthonous Slovenian olive varieties 'Buga', 'Črnica' and 'Drobnica' were studied during a three-year period with the aim to valorise the characteristics of the three olive varieties. Standardized and accredited analytical methods were applied. The results of the investigation showed that the highest average amount of oleic acid (75.75%) was determined in oils of the variety 'Črnica', followed by 'Drobnica' (72.06%) and 'Buga' (68.73%). All the three varieties are a good source of total biophenols ('Buga' 616 mg/kg, 'Drobnica' 569 mg/kg and 'Črnica' 427 mg/kg) and α-tocopherol ('Buga' 378 mg/kg, 'Drobnica' 279 mg/kg and 'Črnica' 243 mg/kg). 'Buga' and 'Drobnica' are characterised by high amounts of total sterols, 2468 mg/kg and 2391 mg/kg, respectively, 'Črnica' oils, in comparison, showed a lower average value of total sterols (1351 mg/kg). The acquired data of the autochthonous Slovenian olive varieties 'Buga', 'Črnica' and 'Drobnica' are very important to valorise the characteristics of the produced oils. The studied varieties showed a great potential for further cultivation and valorisation of the traditional olive oil production of the region and are important for preserving the biodiversity and tradition of the territory.

Pig farms management is involved in multiple factors such as environmental conditions, animal behavior, weight gaining and others. In all those scenarios, it is fundamental to detect each individual and its development as it grows to reach the shipment phase. Therefore, the objective of this study was to apply an automatic individual pig detection algorithm using Deep Learning Techniques, in frames taken from videos recorded during the weaning phase in real production conditions of small and medium producers in tropical conditions in Colombia. The weaning phase was selected because individual detection in each cage is more difficult due to environmental adaptations that piglets undergo after nursing. Piglets tend to cluster together during this phase, making image processing more challenging compared to the fattening phase, where animals are more isolated. The You Only Look Once (YOLOv7) algorithm and VGG Image Annotator were used to detect individuals in two pens separated by gender. All animal postures, lighting conditions were considered. The Precision, Recall and mAP metrics were used to assess the model performance with different confidence values. A precision of 98.3% in a threshold of 0.9 was reached, Recall of 98.5% in a threshold of 0.85. Data augmentation techniques were important to increase the dataset and to have a more realistic model for individuals’ detection. The method used allowed us to identify all the complete pigs’ bodies under different posture and lighting situations.

The identification of an action principle for directing basic system energy exchanges can be used in a general framework for the study of dynamics in systems. The application of such action principles using Lagrangian procedures has become a very powerful methodology for the analysis of complicated problems in modern physics. This form of analytics has recently been considered as the mapping of the system state information in the context of system constraints. The process of translating perceived information into adaptive responses is considered to be the driving action dynamic for the living system. Reconciliation processes that provide for a minimization of the divergence of this information signature from a state of system stability are preferred. Such a state is naturally that of maximal entropy in the context of the operational constraints of the open living system. A mathematical expression incorporating inferential information entropy processing into biologic replicator dynamics describes the mechanics of the perception-action adaptive processes of living systems. From this framework, Kullback’s Principle of Minimum Information Discrimination is identified as the innate axiomatic action principle for guiding the dynamics of biological systems.

Pancreatic ductal adenocarcinoma (PDAC) is the fifth leading cause of cancer-related death in and presents the lowest 5-year survival rate for any form of cancer in the US. Only 20% of PDAC patients are suitable for surgical resection and adjuvant chemotherapy which remains the only curative treatment. Chemotherapeutic and genetherapy treatments are associated with adverse effects and lack specificity/efficacy. In this study we assess the oncolytic potential of immuno-oncolytic tanapoxvirus (TPV) recombinants expressing mouse monocyte chemoattractant protein (mMCP-1 or mCCL2), and mouse interleukin (mIL)-2, in human pancreatic BxPc-3 cells, using immunocompromised and CD-3+ T-cell reconstituted mice. Intratumoral treatment with TPV/∆66R/mCCL2 and TPV/∆66R/mIL-2 resulted in regression of BxPc-3 xenograft volume as compared to control in immunocompromised mice; mCCL-2 expressing TPV OV resulted in significant difference from control at p

This article explores the intricate dynamics of complexity and emergence through the lens of a graphical model representing hippocampal functions. Utilizing a series of overlapping curves that intersect at varying degrees and frequencies, we create a visual metaphor for the sophisticated processes to store information observed in the hippocampus. This model not only depicts the spatial and frequency-related interactions of these curves but also illustrates the emergent patterns that arise from these interactions. These patterns exemplify the principles of complexity and emergence, where the collective behavior of simple elements results in intricate and unexpected outcomes. This graphical representation serves as a bridge between the abstract mathematical concepts of complexity theory and the tangible biological processes observed in neuroscience. By drawing parallels to the hippocampus, known for its role in memory formation and spatial navigation, the article sheds light on how complex systems, such as neural networks, exhibit properties that are more than just the sum of their parts. The model thus offers a unique perspective on understanding complex systems, not only in neuroscience but in broader scientific inquiries where complexity and emergent phenomena are pivotal.

Verticillium dahliae (Vd) and Fusarium oxysporum f. sp. lycopersici (Fol) are two major fungal pathogens that infect tomato plants, causing significant challenges in their control since both pathogens can persist in the soil for several years even in the absence of a host plant and no effective fungicides are available at present. This study investigated the efficacy of two biocontrol formulations, Clonotri and Strepse, against Vd and Fol, and their impact on tomato fruit quality and yield under greenhouse conditions. Pathogenicity experiment demonstrated that the Clonotri formulation, containing Trichoderma and Clonostachys spores, significantly reduced Fusarium wilt disease by 32% compared to the control group. However, in Vd pathogenicity experiment, the formulations did not exhibit disease reduction, although the treatment with Strepse, containing Streptomyces and Pseudomonas microorganisms, resulted in preserved total fruit number when compared to uninfected plants. Analysis of fruit quality attributes revealed no significant differences among the various interventions. Furthermore, Fol infection in the first fruit set significantly increased fruit firmness, while Vd infection resulted in elevated levels of total soluble solids in fruits. These findings demonstrate that the evaluated biocontrol formulations provide a degree of protection against fungal wilt pathogens in tomato plants and can increase yield in greenhouse conditions, while having minimal impact on overall fruit quality attributes.

Rice prolamins are categorized into three groups by molecular size (10, 13, or 16 kDa), while the 13 kDa prolamins are assigned to four subgroups (Pro13a-I, Pro13a-II, Pro13b-I, and Pro13b-II) based on cysteine residue content. Here, we generated four knockout strains of rice using CRISPR-Cas9, each of which demonstrated selectively reduced expression of specific subgroups of the 13 kDa prolamins. These four mutant rice lines also demonstrated compensatory expression of glutelins and non-targeted prolamins, which resulted in low grain weight, altered starch content and atypically-shaped starch granules and protein bodies. Transcriptome analysis identified 746 transcripts that were differentially expressed in the mutant rice lines during development. These transcripts played roles primarily in RNA processing, protein synthesis, stress response, and transport. After selective suppression/knockout of genes in the Pro13a-I subgroup, compensatory upregulation of genes in the Pro13a-II and Pro13b-I/II subgroups was observed. Compensatory expression of 9 ER stress and 17 transcription factor genes was also observed in mutant rice in which expression of 13 kDa prolamin genes was suppressed. Our results provide valuable insight into the regulatory mechanisms underlying rice seed development and the specific roles played by 13 kDa rice prolamins and their target genes.

The advancement of sequencing technology and molecular breeding methods have provided technical support and assurance for accurate breeding. Genomic Selection (GS) utilizes genomic information to improve livestock breeding and, it is more accurate and more efficient than traditional selection methods. GS has been widely applied in domestic animals breeding, especially in cattle. However, there is still limited study on the application and research of GS in sheep and goat. In this paper, we outlined the principle, analysis methods, the influential factors of GS, and elaborated on the research progress, challenges, and prospects of applying GS in sheep and goat breeding. Through the review of these aspects this paper is expected to provide valuable references for the implementation of GS in the field of sheep and goat breeding.

Invasive fungal disease causes high morbidity and mortality among immunocompromised patients. Anti-fungal drug resistance and cytotoxicity highlight the need for effective antifungal therapeutics. In this study, the antifungal potential of the ethanolic extract of Anacardium occidentale (Cashew Leaf) leaves were evaluated against Candida albicans and C. auris. The antifungal activity was tested by the broth microdilution method and growth kinetic test. To further explore its antifungal action mode, spectrofluorophotometry, confocal microscopy and scanning and transmission electron microscopy were performed, Additionally, heterozygous knockout strains associated with resistance to oxidative stress were included in the study. We found that A. occidentale could inhibit the proliferation and growth of C. albicans at concentrations of 62.5 and 125 μg/mL. the doubling time was also drastically affected, going from 2.8 hours to 22.5 hours. Which was also observed in C. auris. The extract induced the accumulation of intracellular reactive oxygen species (ROS), resulting in endoplasmic reticulum stress and mitochondrial dysfunction, while it did not show cy-totoxicity or hemolytic activity at the concentrations evaluated. Our work preliminarily elucidated the po-tential mechanisms of A. occidentale against C. albicans on a cellular level and might provide a promising op-tion for the design of a new treatment for invasive candidiasis

The quantification of human DNA extracts from forensic samples plays a key role in the forensic genetics process. Quantification guarantees maximum efficiency and avoids repeated analyses, over amplified samples, or unnecessary examinations. Here, we present our experience using an extremely sensitive real-time-based method with the Quantifiler® Trio DNA quantification kit, which we have explored in the ISO/IEC17025 accredited test validation process conducted in our laboratory. In this study, our focus was on establishing a minimum threshold beyond which DNA typing is unnecessary, by defining the correlation of negative quantification results with the absence of genetic profiles resulting from DNA typing. We investigated the results in the range in which the technique is used (50-0.005 ng/μl). In the validation process of the internally accredited method, we used data from the commercial quantification system, based on the average values of the standard curve using a wide range of samples, including artificially degraded samples. This method was extensively used continuously for nine years to quantify the DNA extract coming from a wide range of samples from criminal cases. The validation allowed us to verify the limits of the technique, especially in the use of the minimum quantities necessary to obtain genetic profiles acceptable for sending to the Italian DNA database. This optimization of the protocol for analysing forensic samples allows us to optimise the protocol for analysing forensic samples. However, the technique is used in our laboratory with a completely manual preparative phase, and we have decided to investigate the contribution of human error more accurately. Thus, in our experience, we have found that it is preferable to use quantification ranges rather than exact limits before deciding how to analyse the extracts via PCR. In addition, here we present some preliminary data related to the analysis of certain samples that initially appeared negative during quantification, applying a concentration method for maximum yield from forensic samples of judicial interest. Our aim is to ensure that no source of evidence is lost in the reconstruction of a criminal event.

The recent consecutive economic and social crises impose sustainable “form farm to fork” food chain management to feed the global population. In this study we investigate young consumers (Gen Z) price perceptions in purchasing foods in Greece to find out the determinants ensuring sustainable, future food consumption. We used 8 overall price perceptions determinants, 5 with negative roles namely value &amp; price consciousness, coupon &amp; sales proneness, price mavenism and 3 with positive roles namely price-quality, price-value, and prestige-sensitivity for the formation of the study’s questionnaire. A total of 514 students (Gen Z by 85%) answered the questionnaire, promoted through the Google platform during September and October 2023. Data was analyzed with statistical tools, combining cross and chi-square tests. Between the negative determinants the “value consciousness” price perceptions (71.02%) were the most important parameters in purchasing food, followed by “price consciousness” (55.02%) parameters. “Coupon proneness” by 48.4% and “sales proneness” by 49% parameters were equally lower to the participants’ references, while “price mavenism” parameters were minimally preferred by only 26.4% by the participants. Participants exhibited major preference for “value to price” interconnection (66.7%) such as for good value for money, value exceeding its price, overvalued low priced foods, while their preference for “quality to price” interconnection was significantly lower (48.8%) such as for getting what you pay, more money for better quality, priced quality foods. The “prestige- sensitivity” price perception was out of their preference for food purchase (only 7.1%). Our findings indicate that young consumers (Gen Z) pay more attention to the value negative and positive parameters concerning price perceptions for food purchase rather than quality, coupons &amp; sales, low price, and mavenism or even prestige of the foods. This means that value issues such as the perceived environmental impact (green value), the climate crisis, the social signaling potential and others are high in their concerns for their future including their price perceptions for food purchase.

Strong-aroma Baijiu is a traditional Chinese spirit distilled from grains that undergo solid-state fermentation. At the end of each fermentation cycle, a significant quantity of Huangshui accumulates at the bottom of the fermentation pit, constituting one of the primary by-products in the brewing process of strong-flavor liquor. In this report, the chemical component analysis of Huangshui obtained from a strong-flavor liquor factory revealed a diverse array of organic acids, alcohols, esters, starch, reducing sugars, amino acids, and other compounds present in Huangshui. Additionally, two specialized solid-state fermentation models were developed to investigate the formation process of Huangshui. Our findings demonstrate a positive correlation between the yield of Huangshui and the initial moisture content of fermented grains. It is concluded that Huangshui is the percolate produced during the solid-state brewing process of strong-flavor liquor, with its water content originating from the initial moisture of fermented grains.

In Mexico there is a deficit in the production of pine resin, because it depends on natural forests. Therefore, it is necessary to select provenances and phenotypes of potential species such as P. oocarpa. The objective was to determine the difference between provenances and the variation of resin components and quality, as well as the effect of geographic and climatic factors. Resin from five provenances was collected from southern Mexico. The percentage of rosin, turpentine and water was obtained, as well as the acidity and saponification index. P. oocarpa resin had 80.94 % rosin, 7.7 % turpentine and 11.49 % water. The saponification and acidity index was 125.47 and 117.49 mg KOH.g_1, respectively. All variables showed differences (p≤ 0.0001) between provenances. The provenance contributed between 6.44 and 11.71 % to the total variance, the error contributed between 88.29 and 93.56 %. Geographic and climatic variables only had an effect on the percentage of turpentine; the correlation was negative with altitude and longitude, but positive with temperature and precipitation. The results allow defining seed collection sites for resin plantations and orienting the selection for a P. oocarpa improvement program.

The main objective is to offer a functionally coherent counter-narrative to the polarized views prevailing now about the complex ‘Eukaryogenesis problem’ versus the “primitive” nature ascribed to so-called “Prokaryotes” (termed Akaryotes herein). The paradigm shift presented aims at bridging the conceptual gap between the rudimentary beginnings of biomolecular cooperativity on a pristine Earth (the Origins of Life or OoL) and the beginnings of lineage-wise diversification toward Darwinean speciation in the Tree of Life (or ToL). Although the research field as a whole is not aware of a corresponding ‘Prokaryogenesis problem’, the evolutionary process resulting in the partly independent archaeal and bacterial cell types is not fully understood. The present paper provides an explanation for these problems based on coevolutionary complementarity at multiple levels. The unconventional model connects various stages from “neighborhood selection” in film-like layers of unbounded “surface protoplasm” based on short “statistical proteins”, via a closely knit “peptide/RNA partnership” in the “making of genes”, toward the “making of genomes” in several RNA-to-DNA transitions. Three virus-related plasmids carrying different DNA replicases may have initiated the vertical stability of hereditable lineages that led to the three “domains” of organismal life, with a fourth lineage ending in eukaryotic organelles. These partly independent transitions established DNA as a late-comer of fundamental biomolecules.

Introduction: Lipoyl transferase 2 is involved in biosynthesis of the lipoate. Lipoate is the cofactor for the glycine cleavage system and four dehydrogenase enzymes. Biallelic variants in LIPT2 causing severe neonatal encephalopathy was first described in 2017. Methods: Clinical data was collected by retrospective chart review after obtaining consent from parents. The pathogenicity of these variants was further delineated using a yeast model. The YEp352-LIPT2 plasmid was used as a template to generate the two patient variants using QuickChange Lightning Site-Directed Mutagenesis Kit. Results: Patient was a 15-month-old female who presented at 1 month with dystonia, developmental delay and feeding difficulties. MR Brain showed cortical malformations including colpocephaly, polymicrogyria and heterotopia. Patient had elevations in lactate (6.1 mmol/L) and glycine. Exome sequencing showed 2 variants of uncertain significance in trans in the LIPT2 gene: c.346 G>T and c.418C>T. Patient was started on lipoic acid, thiamine and COQ10. Yeast complementation experiments indicate that both patient mutation variants result in diminished function versions of the LIPT2 protein. Conclusion: We report the fourth case of LIPT2-related disorder. Proband shared significant overlap with previous patients, however had a distinct movement disorder and brain malformations which have not been previously described. Unlike most neurometabolic disorders where dystonia develops later after metabolic stroke in basal ganglia, LIPT2- related disorder seems unique due to early onset of dystonia due to energy deficit in the developing brain. Lipoic acid supplementation has not led to significant clinical improvement. Analyses in yeast indicate that novel variants are deleterious but have retained some functionality.

Understanding and controlling reproductive cycles and gonadal maturation in cultivated species are crucial in aquaculture. The sea urchin Paracentrotus lividus, known for its edible gonads, requires careful maturation control for both reproduction and commercialization. This study explores the impact of temperature, photoperiod, and diet on gonadal development to enhance year-round aquaculture practices. Using two independent cultivation systems, we manipulated environmental conditions to mimic different seasons. Sea urchins were exposed to natural or manipulated temperature and photoperiod conditions and fed either natural (Ulva spp.) or formulated diets. The gonadosomatic index (GI) and histological analysis assessed gonadal development. Results revealed a clear correlation between environmental conditions, diet, and gonadal maturation. Manipulated conditions accelerated maturation, with sea urchins showing advanced stages compared to natural conditions. Furthermore, sea urchins fed formulated diets exhibited higher GI values, indicating enhanced maturation. Histological analysis confirmed accelerated maturation, particularly in females. The study underscores the feasibility of controlling gonadal maturation through environmental manipulation and diet, enabling year-round marketable gonad production. Providing formulated diets rich in polyunsaturated fatty acids, notably docosahexaenoic acid (DHA), enhances commercial value. These findings optimize aquaculture practices for P. lividus, highlighting its adaptability to yield-maximizing production strategies. Understanding and controlling reproductive cycles and gonadal maturation in cultivated species are crucial in aquaculture. The sea urchin Paracentrotus lividus, known for its edible gonads, requires careful maturation control for both reproduction and commercialization. This study explores the impact of temperature, photoperiod, and diet on gonadal development to enhance year-round aquaculture practices. Using two independent cultivation systems, we manipulated environmental conditions to mimic different seasons. Sea urchins were exposed to natural or manipulated temperature and photoperiod conditions and fed either natural (Ulva spp.) or formulated diets. The gonadosomatic index (GI) and histological analysis assessed gonadal development. Results revealed a clear correlation between environmental conditions, diet, and gonadal maturation. Manipulated conditions accelerated maturation, with sea urchins showing advanced stages compared to natural conditions. Furthermore, sea urchins fed formulated diets exhibited higher GI values, indicating enhanced maturation. Histological analysis confirmed accelerated maturation, particularly in females. The study underscores the feasibility of controlling gonadal maturation through environmental manipulation and diet, enabling year-round marketable gonad production. Providing formulated diets rich in polyunsaturated fatty acids, notably docosahexaenoic acid (DHA), enhances commercial value. These findings optimize aquaculture practices for P. lividus, highlighting its adaptability to yield-maximizing production strategies.

Bats are natural hosts for a wide variety of viruses and could therefore be the reservoir, source and spillover for several mammalian viruses, including adenoviruses. We examined faecal samples from 12 bats (five species of the family Vespertilionidae) from central Russia (Moscow Region) and found that two of them (16%) were positive for mastadenoviruses. One of the identified viruses was isolated from faeces of Nyctalis noctule and named BatAdV/MOW15-Nn19. The genome of the BatAdV/MOW15-Nn19 was 37,915 bp in length. Comparative studies have shown significant divergence of the nucleotide sequence of the BatAdV/MOW15-Nn19 genome from European mastadenoviruses, the highest genome sequence similarity was to isolate WA3301 from an Australian bat. Phylogenetic analysis, as well as a comparative analysis of the protein coding genes to homologous available from public database, showed evidence of novel species within Mastadenovirus genus (preliminary named «K»). Analysis of the short part of the DNA polymerase gene of BatAdV/MOW15-Nn19 reveals few NCBI records from Europe with high identity to the new virus, i.e. mastadenoviruses related to the new species are circulating in European bats. The partial genome of another mastadenovirus from Pipistrellus nathusii was identified, it represented bat adenovirus species B, which is widely distributed in European Vespertilionidae bats. New data on the genetic diversity of bat adenoviruses may help to better understand how they evolved in mammals and spread across Europe.

Introduction: Gastric cancer (GC) is one of the most common cancers in the world. It is a very aggressive and heterogeneous tumor. GC does not cause symptoms, so it is often diagnosed in an advanced stage and associated with poor prognosis. Despite new treatment options, it still remains a therapeutic problem. An important element determining the method of treatment of locally advanced gastric cancer (LAGC) is the assessment of lymph node metastases in preoperative and postoperative imaging and/or histopathological examination.Aim: The assessment of lymphovascular invasion (LVI) in histopathological examination in patients with LAGC after gastrectomy. The groups of patients were divided into patients who received preoperative chemotherapy, patients without preoperative chemotherapy, and all patients. Additionally, we assessed the correlation between the presence of LVI and the number of lymph nodes collected during gastrectomy.Material and method: We collected patients with histologically confirmed GC after gastrectomy. The collected samples were divided into three subgroups: patients with neoadjuvant chemotherapy (NAC), patients without NAC, and all patients. Histopathological examination assessed the presence of LVI infiltration. We then assessed the correlation between the presence of LVI and the presence of lymph node metastasis in GC. Additionally, we assessed the correlation between LVI and the number of lymph nodes evaluated in patients in each group. The statistical analyses were performed using Statistica v13.3 and Microsoft Excel 2021. The significance limit was set at p<0.05.Results:The presence of LVI strongly correlated with node involvement, and the result was statistically significant in all patients and the group of patients treated with NAC. The difference was not statistically significant in the group not treated by NAC. Additionally, we did not observe a correlation between the presence of LVI and the number of metastatic lymph nodes in GC.Summary and Conclusions: The presence of LVI in a patient with GC indicates a high probability of lymph node metastasis, which should translate into therapeutic procedures. Assessment of LVI may help identify potential patients with lymph node metastases, particularly in patients undergoing endoscopic resection without planned lymphadenectomy. It is advisable to expand research on a larger scale in order to establish clear standards in this area.

The efficacy of an intranasal (IN) bovine respiratory syncytial virus (BRSV) administered in the face of passive immunity was assessed. Pooled colostrum was administered by intubation to fifty (50) beef-dairy crossbred calves the day they were born. The calves were transported to a research facility and were blocked by age and sex and randomly assigned into two groups, a sham-vaccinated intranasally with a placebo (sterile water) or vaccinated with a tri-valent modified live viral (MLV) vaccine. The calves were 92 days old when vaccinated (day 0). The calves were challenged by aerosolized BRSV on day 80 and day 81 as a respiratory challenge. The study was terminated on day 88. Lung lesion scores (LLS) were significantly lower for calves vaccinated with tri-valent MLV vaccine than those for calves that were sham-vaccinated. Serum neutralization (SN) antibody against BRSV in calves vaccinated with the tri-valent MLV vaccine demonstrated an anamnestic response on day 88. After challenge, the calves sham-vaccinated with the placebo lost weight while those vaccinated with the tri-valent MLV vaccine gained weight. In this study colostrum-derived antibodies did not interfere with the immune response or protection provided by one dose of the tri-valent MLV vaccine.

Chestnut is an interesting productive alternative for farmers in Southern Chile. However, cli-matic variability with the occurrence of late spring and early summer frost have cause damages on young trees. Glycine‒betaine (GB) spraying on shoots of sensitive chestnut induce an increase in tolerance during subsequent chilling stress. Experiment was performed on three years-old trees (cultivar Cittá di Castello) conducted in a leader training system and sprayed with com-mercial GB (120 g hL‒1). In summer trees treated with GB showed a better recovery after the frost (‒2.34°C) occurrence for 3.5 h compared to the control. Whereas trees obtained a 28% greater growth of central axis than untreated control (January). The trunk diameter measured in January showed the highest value under GB (27.2mm) compared with the control (25.7 mm). The GB ap-plication increased by 50 and 47% highest fresh and dry weight respectively in leaves. Under GB trees reached a 28% higher net photosynthesis (AN) compared to the AN in control (11.93 µmol CO2 m‒2 s‒1). Moreover, achieved higher stomatal conductance and transpiration rate was 44 and 31% with GB compared to control trees respectively. Antioxidant performance was differentially affected by GB activating non-enzymatic mechanisms and caused a reduced lipid peroxidation. Glycine‒Betaine has become as an interesting agronomic tool that aimed to increase tolerance to environmental stresses such as low temperatures that cause damage to herbaceous shoots and leaves in young chestnut trees.

The symbiotic interaction between leguminous and Bradyrhizobium sp. SUTN9-2 mainly relies on the nodulation process through Nod factors (NFs), while the type IV secretion system (T4SS) acts as an alternative pathway in this symbiosis. Two copies of T4SS (T4SS1 and T4SS2) are located on the chromosome of SUTN9-2. ΔT4SS1 reduces both nodule number and nitrogenase activity in all SUTN9-2 nodulating legumes. The functions of three selected genes (copG1, traG1, and virD21) within the region of the T4SS1 were examined. We generated deleted mutants and tested in Vigna radiata cv. SUT4. ΔtraG1 and ΔvirD21 exhibited lower invasion efficiency at the early stages of root infection but could be lately restored. In contrast, ΔcopG1 completely hindered nodule organogenesis and nitrogenase activity in all tested legumes. ΔcopG1 showed low expression of nodulation gene and ttsI, but exhibited high expression levels of T4SS genes, traG1 and trbE1. The secreted proteins from ΔT4SS1 were down-regulated compared to the wild type. Although ΔcopG1 secreted several proteins after flavonoid induction, T3SS (nopP and nopX) and C4-dicarboxylate transporter (dct) were not detected. These results confirm the crucial role of the copG1 gene as a novel key regulator in the symbiotic relationship between SUTN9-2 and legumes.

Fusarium stalk rot (FSR) caused by the Fusarium species complex is an economic threat to maize cultivation all over the world. We investigated the population structure and genetic diversity of Fusarium spp. obtained from five major maize-growing regions of India. The Tef-1α locus was used for phylogenetic analysis of geographically distinct isolates of Fusarium verticillioides, F. andiyazi, F. proliferatum, F. nygamai, and F. acutatum causing FSR. Geographical separation among four local populations contributed to 7.87% variance, whereas 92.12% of the variance was within popula-tions, suggesting a predominant influence of local adaptation or stochastic events like genetic drift within populations, with geographical separation playing a lesser but significant role in shaping genetic diversity. Genetic differentiation statistics between Fusarium species showed lower gene flow from haplotypes except in the population of F. acutatum and F. andiyazi having high GST values. In contrast, a high Kxy was reported, indicating elevated genetic differentiation between populations. The haplotype network analysis revealed the presence of eight distinct haplotypes which reflected pathogenic evolution and adaptive potential of Fusarium spp. The results offer a comprehensive framework for discussing the implications of genetic diversity in pathogen management and the evolutionary dynamics of the Fusarium spp. causing FSR of maize in the Indian subcontinent.

Mutations affecting codon 172 of the isocitrate dehydrogenase 2 (IDH2) gene define a subgroup of sinonasal undifferentiated carcinomas (SNUCs) with a relatively favorable prognosis and a globally hypermethylated phenotype. They are also recurrent (along with IDH1 mutations) in gliomas, acute myeloid leukemia, and intrahepatic cholangiocarcinoma. Commonly reported mutations, all associated with aberrant IDH2 enzymatic activity, include R172S, R172T, R172G, and R172M. We present a case of SNUC with a never-before-described IDH2 mutation, R172A. Our report compares the methylation pattern of our sample to other cases from the GEO database. Hierarchical clustering suggests a strong association between our sample and other IDH-mutant SNUCs and a clear distinction between sino-nasal normal tissues and tumors. Principal component analysis (PCA), using 100 principal components explaining 94.5% of the variance, shows the position of our sample within 1.02 standard deviation of the other IDH-mutant SNUCs. Molecular modeling analysis of the IDH2 R172A versus other R172 variants provides a structural explanation to how they affect the protein active site. Our findings thus suggest that the R172A mutation in IDH2 confers a gain of function similar to other R172 mutations in IDH2, resulting in a similar hypermethylated profile.

Purpose: The purpose of this study is to apply the Composite Radiographic Index modified (CRIm) in CBCT scans of patients with Medication related osteonecrosis of the jaws (MRONJ) in order to detect its validity, and corelate the radiologic findings with the clinical staging of the disease. Methods: This study included 43 patients with MRONJ diagnosis and CBCT scans performed in the School of Dentistry and approved by the Research Ethics Committee. Clinical staging for every patient (0-3) was provided according to AAOMS 2022 guidelines. In cases of patients with both jaws affected, each jaw was evaluated independently resulting to 52 CBCT scans. The 52 CBCT scans were assessed under standardized viewing conditions by 2 observers who evaluated independently the following 8 radiologic features: lytic changes, sclerosis, periosteal reaction, sequestration, non-healing extraction sockets and other findings (sinus implication, inferior alveolar canal involvement, jaw fracture). The CRIm index was constructed to assess the extent of osseous changes. The radiologic features were scored as absent (0), localized/single (1), extensive/multiple (2), yielding a theoretical range of 0–12. For statistical analysis Fisher’s exact test and Spearman’s correlation coefficient were performed. Results: A statistically significant association of clinical stage with lytic changes, sequestration and inferior alveolar canal involvement was found. Also, a statistically significant correlation of clinical stage with CRIm index classification was obtained. Conclusions: The CRIm index tends to increase as the clinical stages of MRONJ advance, suggesting a correlation between the clinical stage of MRONJ and the CRIm index.

Spontaneous tumours in higher plants can develop depending on plant genotype without any pathogen invasion. Spontaneous tumour formation on the taproots is consistently observed in certain inbred lines of radish (Raphanus sativus var. radicula Pers.). In this work, we have sequenced the genomes of two closely related radish inbred lines that differ in their ability to spontaneously form tumours. We have identified numerous single nucleotide variants (amino acid substitutions, insertions or deletions) that are likely to be associated with the spontaneous tumour formation. Furthermore, we performed the identification of CLE and WOX genes the genomic sequences of the radish inbred lines and, as a result, identified two unique radish CLE genes which probably encode proteins with multiple CLE domains. The results obtained provide a basis for investigating the mechanisms of plant tumour formation and also for future genetic and genomic studies of radish.

India, a megadiverse nation, harbors significant biodiversity, particularly in tropical moist deciduous forests. However, these forests and valuable medicinal plants face habitat loss and overexploitation threats. While indigenous knowledge of medicinal plants exists, a comprehensive ethnomedicinal study still needs to be included, especially for Uttar Pradesh's Terai region. This study focuses on the Suhelwa Wildlife Sanctuary, a haven for medicinal plants within the Terai. We aim to document the knowledge of local healers regarding wild medicinal plants used in phytotherapy. We will employ quantitative indices and compare our findings with data from other regions to identify novel medicinal plant uses. This enriched database can serve as a springboard for future pharmacological research. Suhelwa's diverse geography and climate contribute to its rich medicinal flora, making it a prime candidate for exploring the potential of traditional knowledge for drug discovery and sustainable income generation for local communities.

Glioblastoma multiforme (GBM) is one of the deadliest human cancers with very lim-ited treatment options available. The malignant behavior of GBM is manifest in a tu-mor which is highly invasive, resistant to standard cytotoxic chemotherapy and is strongly immunosuppressive. Immune checkpoint inhibitors have recently been in-troduced in the clinic and have yielded promising results in certain cancers. GBM however is largely refractory to these treatments. The immune checkpoint CD47 has recently gained attention as potential target for intervention as it conveys a “don’t eat me” signal to tumor associated macrophages via the inhibitory SIRP alpha protein. In preclinical models, administration of anti-CD47 monoclonal antibodies have shown impressive results with GBM and other tumor models. Several well characterized on-cogenic pathways have recently been shown to regulate CD47 expression in GBM cells and Glioma Stem cells (GSCs) include EGFR, beta catenin and LRIG2. Other macro-phage pathways involved in regulating phagocytosis including TREM2 and glycan binding proteins are discussed as well. Finally, Chimeric Antigen Receptor Macro-phages (CAR)-M could be leveraged for greatly enhancing phagocytosis of GBM and repolarization of the microenvironment in general. Here we comprehensively review the mechanisms that regulate about macrophage phagocytosis of GBM cells.

In the symptomatic treatment of gastrointestinal disorders, high dosages of zinc oxide (ZnO) were conventionally employed. However, concerns regarding the potential for microbial resistance and ecological detriment have arisen due to the excessive application of this compound. These concerns highlight the urgency to minimize the use of ZnO and to explore sustainable nutritional solutions. Hydrolysable tannins (HTs), known for their role in traditional medicine for acute gastrointestinal issues, emerge as a promising alternative. This study examined the combined effect of food-grade HTs and lower ZnO concentration on relevant biological functions of Caco-2 cells, a widely used model of the intestinal epithelial barrier. We found that, when used together, ZnO and HTs (ZnO/HTs) enhanced tissue repair and improved epithelial barrier function, normalizing the expression and functional organization of tight junction proteins. Finally, the ZnO/HTs combination strengthened enterocyte defence against oxidative stress induced by inflammation stimuli. In conclusion, combining ZnO and HTs may offer a suitable and practical approach for decreasing ZnO levels in veterinary medical applications.

Abstract Cerebral microbleed(s) (CMBs) are increasingly being viewed not only as a marker for cerebral small vessel disease (SVD) but also as having an increased risk for the development of stroke (hemorrhagic/ischemic) and aging-related dementia. Recently, brain endothelial cell activation and dysfunction and blood-brain barrier dysfunction and/or disruption have been shown to be associated with SVD, enlarged perivascular spaces, and the development and evolution of CMBs. CMBs are a known disorder of cerebral microvessels that are visualized as 3-5mm, smooth, round or oval, and hypointense (black) lesions seen only on T2*-weighted gradient recall echo or susceptibility-weighted sequences on MRI images. CMBs (a global problem) are known to occur with high prevalence in community-dwelling older individuals. Since our current global population is the oldest recorded in history and only expected to continue to grow, we can only expect the health care burdens associated with CMBs to also grow. CMBs should raise a red flag regarding the increased risk of large symptomatic neurologic intracerebral hemorrhages. Importantly, CMBs are also currently regarded as markers of diffuse vascular and neurodegenerative brain damage. Thus, it is essential that we try to learn as much as we can about their development, evolution, and their relation to impaired cognition, dementia, and neurodegeneration.

To mitigate pyrethroid resistance in mosquito vectors of emerging and re-emerging human pathogens, there is an urgent need to discover insecticides with novel modes of action. Natural alternatives, such as extracts derived from plants, may serve as substitutes for traditional synthetic insecticides if they prove to be sustainable, cost-effective, and safe for non-target organisms. Hemp (Cannabis sativa) is a sustainable plant known to produce various secondary metabolites with insecticidal properties, including terpenoids and flavonoids. The goal of this study was to assess the larvicidal activity of hemp leaf extract on 1st instar mosquito larvae from both pyrethroid-susceptible (PS) and pyrethroid-resistant (PR) strains of Aedes aegypti Another goal was to identify which components of the extracts were responsible for any observed larvicidal activity. We found that methanol extract of hemp leaves induced similar concentration-dependent larvicidal activity against PS (LC50: 4.4 ppm) and PR (LC50: 4.3 ppm) strains within 48 hours. Partitioning of the dried leaf extract between methanol and revealed that full larvicidal activity was restricted to the methanol fraction. Analysis of this fraction by gas chromatography-mass spectrometry and nuclear magnetic resonance showed it to be dominated by cannabidiol (CBD). Larvicidal assays using authentic CBD confirmed this compound was primarily responsible for the toxicity of hemp leaf extract against both strains. We conclude that hemp leaf extracts and CBD have the potential to serve as viable sources for the development of novel mosquito larvicides.

Understanding speech in noise is particularly difficult for individuals occupationally exposed to noise due to a to a mix between noise-induced auditory lesions and energetic masking of speech signal. For years, the monitoring of conventional audiometric thresholds has been the usual way to check and preserve the auditory function. But the highlighting of supra-threshold deficits, notably speech in noise understanding difficulties, has pointed out the need for new monitoring tools. The present study aims to identify the most important variables that predict speech in noise under-standing in order to suggest a new way of regular monitoring. Physiological (distortion products of otoacoustic emissions, electrocochleography) and behavioral (amplitude and frequency modula-tion detection thresholds, conventional and extended high frequency audiometric thresholds) variables were collected in a population of individuals presenting a relative homogeneous occu-pational noise exposure. Those variables were used as predictors in a statistical model (random forest) to predict scores of three different speech in noise tests and a self-report of speech in noise ability. The extended high frequency threshold appears to be the best predictor and therefore an interesting candidate for a new way of monitoring noise exposed professionals.

The 2020-2025 Dietary Guidelines for Americans recommends limiting intakes of saturated fat and added sugars (SF/AS) to 88% of the representative sample of U.S. adults. The top sources of SF were cheese, pizza, ice cream, and eggs. The leading sources of AS were soft drinks, tea, fruit drinks, and cakes and pies. This analysis reflects a parsimonious approach to reliably identify foods and beverages that contribute to SF/AS intakes in U.S. adults.

Invasive species are non-native organisms that are introduced to a particular environment with a potential to spread from the place of introduction and cause biodiversity loss. This research was done in Gullele Botanical Garden with the objective of advancing management strategies for invasive and potentially invasive species by examining their abundance, distribution, impacts. Proportional number of plots with a size of 10m by 10m was laid at each land use types to collect vegetation and environmental data. The impact rank was analysed as a data frame using the R-statics packages, which shows the lower and higher impact rate ranges for the sampled land use types. ArcGIS was used to map the spatial distributions of each species. A total of 2550 individuals from 12 families comprising 16 invasive and potentially invasive species have been recorded in 40 sample plots across all sampled land use types. The highest species abundance appeared near the roadside among the sampled plots. Acacia decurrens, Cyathula uncinulata, and Acacia melanoxylon were the three most predominant species, had a substantial contribution to the high impact on the native species. Either intentionally by planting for their advantageous qualities or unintentionally associated with other seeds or other vectors, invasive and potentially invasive species were introduced into the garden. Although there are various techniques to control invasive species, mechanical controlling mechanisms like hand-weeding, uprooting, cutting, and rehabilitation with native species, along with regular monitoring, are highly recommended for the current challenge in the garden.

The broad global distribution of freshwater clams belonging to the genus Corbicula is driven by multiple hermaphroditic lineages. These lineages, characterized by shared morphological traits and phenotypic plasticity, pose challenges to morphological identification. Genetic markers, such as the mitochondrial COI gene, play a crucial role in delineating these lineages and their ranges. Morphotypes represent observed phenotypic variations, while lineages are defined based on genetic markers. Here, we comprehensively review Corbicula's distribution in Argentina, dis-criminate extant lineages based on both morphological and genetic (COI) data, and describe variation in internal and external morphology using 15 Argentine populations. Haplotype net-works identified two mitochondrial lineages: A/R morphotype (FW5 haplotype) and C/S mor-photype (FW17 haplotype). Strikingly, despite having similar vectors, origins, and invasive stages, Corbicula lineages exhibit virtually segregated distributions. However, intermediate morphotypes and both mitochondrial haplotypes are found in sympatry in northeastern Argen-tina, suggesting the presence of hybrids due to maternal genome retention. These findings con-tribute to the clarification of the identity and distribution of Corbicula lineages in Argentina, where the genus has been found for over half a century. Similar studies are needed in other areas to better understand the invasion patterns of a successful and plastic group.

Frass generated during the production of black soldier fly larvae is taking the interest of scientists and horticultural producers because it is a material from the biotransformation of organic waste, it has several nutrients that can be used by plants, and its recent focus on its biostimulant capacity. The thermal-composting process is a stabilization that improves physical and chemical properties of treated wastes, allowing better performance in plants compared to its fresh state. In this research, thermocomposted frass was evaluated as a germination substrate for kale seeds (Brassica olerasea). To achieve this, it was evaluated the phytotoxicity in different concentrations on the seeds, and seedlings were grown in a germination substrates mixed with 20, 40, 60, 80 and 100% of frass. The treatment with 20% frass showed the highest values of seedling height, stem diameter, number of leaves, length, and width of first true leaf and length and width of cotyledons, reduced the content of phenols and tannins antioxidants but the content of flavonoids increased compared to the control and the rest of mixtures.

The effect of embryo reinsertion immediately after embryo flushing was studied to determine its effect on luteal function, pregnancy outcome, endometrial bacterial contamination, and embryo morphology. In Experiment 1, eight mares were used during 32 cycles (8 cycles in each group): for the first two groups, inseminated mares were flushed 8 days after ovulation and prostaglandin F2α was not administered: in group EF-ET (embryo flushing and embryo transfer) the embryo was reinserted in the same donor mare, while in the EF group, no further procedure was performed. In the third group (ET), non-inseminated mares (recipients) received a Day 8 embryo 5 to 8 days after ovulation. Progesterone concentration was measured before EF/ET and 72 h after in the 3 groups. Pregnancy diagnosis was performed within 6 days of transfer. In Experiment 2, twelve mares were used during 17 cycles in two groups: EF-ET (n=11) and ET (n=6), as in Experiment 1, except that every mare was flushed 24 h after embryo transfer to retrieve the embryo. Fewer pregnancies resulted after transfer in EF-ET cycles (0(8, 0%) than in the ET group (6/8, 75%). Progesterone concentration decreased significantly (p=0.05) 72 h after EF-ET, but not in EF or ET cycles (p>0.1). Three mares from the EF-ET showed full luteolysis and signs of endometritis. In Experiment 2, more (5/6; p=0.08) grade I embryos were recovered in the ET compared to the EF-ET group (3/7); 4 embryos were graded III-IV (were broken or had signs of degeneration) in the EF-ET group, but none in the ET group. In both groups, capsule fragments were obtained as indicative of the presence of a recently destroyed embryo in the EF-ET (n=3) and ET (n=1) groups. Positive bacterial cultures were obtained in 2/11 and 1/6 embryo flushes from the EF-ET and ET groups, respectively.

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

: Greenhouse plants are usually grown in containers filled with growing media. Peat is the main component of the growing media used in greenhouses. However, peat substrate is made from peat from drained peatlands, which is a limited resource. Wood fiber can be an alternative to use as a growing media for controlled-climate crops. The chemical properties of the growing media interact and change continuously due to the small volume of the growing media, which is limited by the vegetative container. Therefore, this study aims to gain new knowledge on the impact of nutrient changes in the microbial degradation of carbon compounds in wood fiber and mixtures with peat substrate on the content and uptake of nutrients required by plants. Cucumbers (Cucumis sativus L.) were cultivated in growing media of peat substrate and wood fiber: (1) peat substrate (PS); (2) wood fiber (WF); (3) wood fiber and peat substrate 50/50 v/v (WF/PS 50/50); (4) wood fiber and peat substrate 25/75 v/v (WF/PS 25/75). The rates of fertilization were the following: (1) conventional fertilization (CF); (2) N13; (3) N23; (4) N30. Fertilization of cucumbers with different rates of nitrogen influenced the nutrient uptake. Plants grown in WF/PS 50/50 and WF/PS 25/75 growing media had the best Cu uptake when fertilized with N23. When the plants grown in the wood fiber media and the 50/50 media were fertilized with N13, N23, and N30, the Mn content in the growing media at the end of the growing season was significantly lower than the Mn content in the media with conventional fertilization. Thus, nitrogen improved the uptake of Mn by plants grown not only in the wood fiber but also in combinations with peat substrate. Growing plants in wood fiber and fertilizing them with N13 can result in optimum uptake of micronutrients. The number and mass of cucumber fruits per plant were influenced by the amount of wood fiber in the growing media and the application of nitrogen fertilizer. The highest number of fruits and mass of fruits per plant was obtained significantly higher when cucumbers were grown on WF/PS 50/50 growing media with additional N13 fertilization.

The COLOSS research association has been assessing honey bee colony losses, associated risk factors and management, focusing on Western countries but with a progressive international expansion. Here, we report the first survey on the loss rates of colonies in 2022/23 in Ethiopia using COLOSS monitoring survey tools. A face-to-face interview questionnaire survey was conducted on 64 beekeepers selected from Oromia and Tigray regions. This covered 1,713 honey bee colonies distributed in 68 apiaries. The percentages of colonies lost were significantly different between Oromia (24.1%) and Tigray (66.4%) regions. Colony losses were attributed as unsolvable queen problems (8% in Oromia; 10% in Tigray), natural disaster (32%; 82%), and empty hives or dead colonies (60%; 8%). The loss rate was significantly affected by queen replacement (p

In recent years, the potential of insects has been explored as a sustainable protein alternative to sustain the growing world population. Differences in the way insects are processed can affect their proximate composition and digestibility. This work studies the effects of the combination of different types of slaughter methods and drying temperatures on the proximate composition, organic matter digestibility (OMd), hydrolysis degree (DH/NH2 and DH/100 g DM), total hydrolysis (TH) and hygienic sanitary study of BSFL (black soldier fly larvae). Four types of slaughter methods were used: frozen (F), blanched + frozen (B), Melacide® + frozen (M) and liquid nitrogen (N), each with three drying temperatures (50, 70 and 90 °C). A negative correlation between acid detergent fibre (ADF) and protein digestibility parameters was obtained. 70 °C was the most suitable drying temperature, as it reported higher values of protein digestibility (DH, TH), resulting in hygienic and sanitary conditions suitable for food use. Slaughtering with liquid nitrogen and blanching were more convenient than traditional freezing or the use of Melacide® to achieve higher protein digestibility results.

Abstract: (1) Background: We determined the prevalence of hepatitis B virus (HBV) amongst people without human immunodeficiency virus (HIV) in rural and peri-urban areas in Botswana. (2) Methods: We screened hepatitis B surface antigen (HBsAg) from archived plasma samples of people without HIV (n=2135) randomly selected from the Botswana Combination Prevention Program (BCPP) (2013–2018). We sequenced 415 bp of the surface region using BigDye sequencing chemistry. (3) Results: The median age of participants was 31 (IQR: 24–46) and 64% (1360/2135) were female. HBsAg prevalence was 4.0% (86/2135) [95% CI: 3.3 – 4.9]) and ranged between 0%–9.2%. Older participants (>35 years) had increased odds of HBsAg positivity (OR: 1.94; 95% CI: [1.32–2.86]; p = 0.001. Thirteen samples were sequenced and 7 (53.8%) were genotype A, 3 (23.1%) were genotype D and genotype E each. Clinically significant mutations were identified in the surface region, but no classic drug resistance mutations were identified. (4) Conclusions: We report an HBV prevalence of 4.0% (95% CI 3.3 – 4.9) among people without HIV in rural and pe-ri-urban communities in Botswana with varying rates in different communities. A comprehen-sive national HBV program is required in Botswana to guide HBV prevention, testing and management.

Camel milk occupies a pivotal and essential position in the dietary customs of individuals residing in semi-arid and arid areas. Historically, the promotion and distribution of camel milk have been negligible, primarily due to the absence of processing facilities in areas where camels are raised. Consequently, the consumption of untreated camel milk has been predominantly limited to nomadic households. However, owing to its exceptional medicinal properties and health-enhancing effects, a substantial surge in the global demand for camel milk and its derivatives has been observed over the past two decades. This growing demand has prompted the dairy sector to introduce a diverse range of camel milk products, which are distinguished by their enhanced nutritional and functional properties. In contrast to products derived from bovine milk, the current market offers only a limited selection of food items sourced from camel milk. Recent advances in food processing technologies have enabled the production of an array of both dairy and non-dairy products derived from camel milk. This includes a variety of items such as powdered milk, cheese, yogurt, ice cream. Moreover, in certain regions, camel milk is incorporated into customary cuisine, serving as a key ingredient in local culinary practices like fermented milk, camel milk tea, or as a fundamental component in various meals. This review underscores the possibility of transforming camel milk into a range of dairy products by addressing its intrinsic functional constraints. This objective can be realized by adjusting the processing parameters and modifying its chemical composition through enrichment techniques. Furthermore, further research avenues may focus on enhancing product quality and exploring innovative processing techniques.

In bacteria, enzymes usually comprise of enzymatic domains only. In eukaryotes/mammals, and here particularly in context of signal transduction, proteins with enzymatic functions contain additional modules promoting interactions with cooperating signaling proteins. Often such protein-protein interaction domains, such as SH2- and SH3-domains, help to localize the enzymatic function (e.g. kinase, phosphatase) to another protein, cellular compartment, or membrane nanodomain. In such cases, the interaction domain(s) serve(s) the enzymatic function. However, there are molecular situations in which an interaction domain fulfills its task completely independent of the protein´s enzymatic function and in this review, we call such function the adapter function of an enzyme. Though many stories can be told, we will concentrate on several proteins playing crucial roles in cells of the immune system, such as BTK, PI3K, and SHIP1, as well as in cancer cells, such as proteins of the RAS/ERK MAPK pathway. We will also discuss how these adaptor functions of enzymes determine or even undermine the efficacy of targeted therapy compounds, such as ATP-competitive kinase inhibitors, thereby highlighting the need to develop pharmacological approaches, such as PROTACs, that eliminate the entire protein. We also review how genetic kock-out and knock-in approaches can be leveraged to identify adaptor functions of signaling proteins.

The prevention of destruction caused by red flour beetle, Tribolium castaneum (Herbst), using essential oils derived from certain herbal plants presents an interesting alternative to synthetic insecticides, known for their harm to both consumers and the environment. The research aimed to investigate the chemical compositions and fumigating effects of essential oils derived from cardamom (Elettaria cardamomum (L.) Maton) and galangal (Alpinia galanga (L.) Willd) against T. castaneum. Chemical compositions were analyzed using GC-MS, while fumigation bioassay was conducted via a vapor-phase test. Experimental setup followed factorial design in CRD with 5 replications. Factor A encompassed 4 types of essential oils: the manually extracted essential oils from cardamom leaves (MCL) and galangal leaves (MGL), the commercially produced essential oils from cardamom seeds (CCS) and galangal rhizomes (CGR). Factor B consisted of 7 concentrations: 0, 50, 100, 150, 200, 250, and 300 µL/L air. Results indicated that MCL contained eucalyptol, trans-calamenene, and isospathulenol as its main compounds. Similarly, CCS was characterized by camphene and eucalyptol. MGL exhibited caryophyllene, aciphyllene, and α-bisanolene. Lastly, CGR was composed of methyl cis-cinnamate, safrole, and p-vinylphenyl isothiocyanate. Study noted that 250 µL/L air over 168 hours of CGR, demonstrated 94% fumigation efficiency against adult T. castaneum. These results suggest the potential of galangal rhizome derived essential oil as an insecticide for managing T. castaneum populations in agricultural product storage.

Myelolipoma is a benign, typically inert neoplasm of uncertain aetiology that is rarely reported in cats. Although commonly asymptomatic, in some cases, myelolipomas can cause abdominal discomfort or present with rupture and haemorrhage. Here, we describe a rare case of a splenic myelolipoma in a Domestic Long Hair cat in which, after extensive diagnostic investigations, clinical signs of hyporexia and weight loss were attributable to the presence of an intra-abdominal mass. The patient was treated by splenectomy and unexpectedly died during the post-operative period. Although splenectomy appears to be a sensible intervention in symptomatic patients, the optimal management of splenic myelolipomas in cats remains unknown. The risk-benefit ratio of surgical management needs to be carefully considered, and therapeutic intervention should be tailored individually to each patient.

Researchers are exploring solutions to meet the growing demand for protein due to the expected increase in global population by 2050. Interest in alternative protein sources like insects has risen, driven by concerns about environmental impact and the need for sustainable food production. This study aimed to develop and evaluate the physicochemical properties of soy protein-based burger enriched with insect protein from Alphitobius diaperinus. Three formulations were developed: a control (B0), and burgers with 5% (B5) and 10% (B10) insect protein - Whole Buffalo Powder (WBP). Results showed that adding insect protein decreased the burger analogue's pH. There was observed a clear trend of increasing total lipids and SFA, and decreasing MUFA and PUFA, as the WBP concentration increases from 0% to 10%. No significant differences with increasing WBP concentration in the protein content of the burger analogue, as well as the cooking yield, were noted. The WBP addition had a notable effect on the color change, especially decrease in brightness (L*). It was shown that as the WBP concentration increased, there were no significant differences in the texture profile of the burger analogues. The formulation with 5% WBP concentration was the most acceptable in sensory analysis.

At present, magnetic selection of genetically modified cells is mainly performed with surface markers naturally expressed by cells such as LNGFR, CD4 and H-2Kk. The disadvantage of such markers is the possibility of their undesired and poorly predictable expression by unmodified cells before or after cell manipulation, which makes it essential to develop new surface markers that would not have such a drawback. Earlier, modified CD52 surface protein variants with embedded HA and FLAG epitope tags (CD52/FLAG and CD52/HA) were developed by the group of Dr. Mazurov for selection of CRISPR-modified cells using FACS. In the current study, we tested whether these markers can be used for magnetic selection of transduced cells. For this purpose, appropriate constructs were created in MigR1-based bicistronic retroviral vectors containing EGFP and DsRedExpress2 as fluorescent reporters. Cytometric analysis of the transduced NIH 3T3 cell populations after magnetic selection evaluated the efficiency of isolation and purity of the obtained populations, as well as the change in the median fluorescence intensity (MFI). The results of this study demonstrate that the surface markers CD52/FLAG and CD52/HA can be effectively used for magnetic cell selection, and their efficiencies are comparable to that of the commonly used LNGFR marker. At the same time, the significant advantage of these markers is the absence of HA and FLAG epitope sequences in cellular proteins, which rules out spurious co-isolation of negative cells.

Neurofibromatosis type 2 (NF2) is a genetic syndrome characterized by the growth of benign tumors in the nervous system, particularly bilateral vestibular schwannomas, meningiomas, and ependymomas. This review consolidates the current knowledge on NF2 syndrome, emphasizing the molecular pathology associated with the mutations in the gene of the same name, the NF2 gene, and the subsequent dysfunction of its product, the Merlin protein. Merlin, a tumor suppressor, integrates multiple signaling pathways that regulate cell contact, proliferation, and motility, thereby influencing tumor growth. The loss of Merlin disrupts these pathways, leading to tumorigenesis. We discuss the roles of another two proteins potentially associated with NF2-deficiency as well as Merlin: Yes-associated protein 1 (YAP), which may promote tumor growth, and Raf kinase inhibitory protein (RKIP), which appears to suppress tumor development. Additionally, this review discusses the efficacy of various treatments, such as molecular therapies that target specific pathways or inhibit neomorphic protein-protein interaction caused by NF2-deficiency. This overview not only expands on the fundamental understanding of NF2 pathophysiology but also explores the potential of novel therapeutic targets that affect the clinical approach to NF2 syndrome.

The popular appreciation of dry white wines is most frequently directed to young wines. However, present consumption trends comprise the valorisation of aged dry white wines. Therefore, the present work was aimed at the sensory analysis of these wines with different ages to define their sensory space and to understand which factors drive their quality evaluation by experienced tasters (critics, oenologists and students). Individuals were asked to evaluate several synthetic and aesthetic attributes and to characterise the analytic sensory profile through a Check-All-That-Apply (CATA) methodology. The quality evaluations were differently correlated with wine synthetic parameters according to the taster group. For both critics and oenologists, overall quality scores were driven by persistence and complexity. Moreover, quality was also highly correlated with power for critics and with balance for oenologists. Quality scores were highly correlated with wine browning (absorbance at 420 nm) for critics. The tasting panel showed a homogeneous analytic description of aroma, taste and mouthfeel consistent with wine age. The different ages could be associated to a continuous sensory space characterised by a decreasing perception of freshness and increase in mature and mellowed descriptors. All wines shared an austere in-mouth perception elicited by their acidity, saltiness, bitterness, smoothness and dryness. The age prediction showed that most tasters failed to guess the age wines with more than roughly 13 years old, indicating that tasters were not familiar with the sensory features of white wines with 17 to 46 years old. In conclusion, experienced tasters consistently described the sensory space and recognised the high quality of aged dry white wines. Education programs may use the defined sensory spaces according to aging and to expand the range of quality perception by consumers.

Panax notoginseng (Burk.) F. H. Chen, a valuable Chinese herb in Yunnan Province, is susceptible to leaf spot caused by Boeremia linicola. Nonetheless, effective control methods against leaf spot in P. notoginseng are lacking. We surveyed understorey P. notoginseng bases in Lincang, Lancang, and Xundian, with incidence rate reaching 80% and an average disease index of 25 in severe cases. We found that pathogenic bacteria overwinter in infected leaves and soil, with conidia and conidiophores serving as the primary infection source. The strain B. linicola LYB-2 showed the best growth at 20°C and pH 5.0. We also screened control agents using the plate and face-off culture methods. Tetramycin exhibited 38.56–74.67% inhibition with an EC50 of 0.60 mg/L. Copper abietate showed 3.10–34.76% inhibition with an EC50 of 3,120.05 mg/L. Trichoderma atroviride and T. harzianum exhibited inhibition rates of 52.48% and 44.19%, respectively, while Bacillus subtilis reached 78.45%. Field tests demonstrated significant control effects with 20% copper abresinate, B. subtilis, T. virenceae BH-10 preparation, and 0.3% tetramycin, achieving 82.57%, 72.56%, 71.3%, and 70.2% inhibition, respectively. These findings support their eco-friendly use for preventing and controlling leaf spot disease in P. notoginseng forests; we provide vital scientific evidence for disease prediction and green control strategies.

Epidemiological studies point cholesterol as a possible key factor for both prostate cancer incidence and progression. So, it could represent a targetable metabolite as the most aggressive tumors also appear to be sensitive to therapies designed to decrease hypercholesterolemia, such as statins. However, whether and how cholesterol, through its dietary uptake and its metabolism, could be important for early tumorigenesis, remains unknown. Oncogene clonal induction in Drosophila melanogaster accessory gland allows to reproduce tumorigenesis from initiation to early progression, where tumour cells undergo basal extrusion to form extra-epithelial tumors. Here we show that these tumors accumulate lipids, and especially esterified cholesterol, as in human late carcinogenesis. Interestingly, high cholesterol diet displays limited effect on accessory gland tumorigenesis. On the contrary, cell-specific downregulation of cholesterol uptake, intracellular transport or metabolic response, impairs the formation of such tumors. Furthermore, in this context, high cholesterol diet suppresses this impairment. Taken together, these results reveal that during early tumorigenesis, tumour cells strongly increase their uptake and use of dietary cholesterol to specifically promote the step of basal extrusion. Interestingly, expression data from primary prostate cancer tissues indicate an early signature of redirection from cholesterol de novo synthesis to uptake. Altogether, these results suggest by which mechanism reduction of dietary cholesterol could lower the risk and slow down the progression of prostate cancer.

At the end of 2023 the Whole Mouse Brain Atlas was announced, revealing that there are about 5,300 molecularly defined neuronal types in the mouse brain. We ask whether brain models exist that contemplate how this is possible. The conventional columnar model, implicitly used by the authors of the Atlas, is incapable of doing so with only 20 brain columns (5 brain vesicles with 4 columns each). We argue that definition of some 1,250 distinct progenitor microzones, each producing over time minimally 4-5 neuronal types, may be sufficient. This is nearly achieved presently by the prosomeric model amplified by secondary dorsoventral and anteroposterior microzonation of progenitor areas, plus clonal variation of cell types produced on average by each of them.

Oxidative stress-mediated cell death is a major cause of dopaminergic neuronal loss in the substantia nigra (SN) of Parkinson’s disease patients. Ergothioneine (ET), a natural dietary compound, has been shown to have cytoprotective functions, but neuroprotective actions against PD have not been well established. 6-Hydroxydopamine (6-OHDA) is a widely used neurotoxin to simulate the degeneration of dopaminergic (DA) neurons in Parkinson's disease. In this study, we investigated the protective effect of ET on 6-OHDA treated iPSC-derived dopaminergic neurons (iDAs) and further confirmed the protective effects in 6-OHDA treated human neuroblastoma SH-SY5Y cells. In 6-OHDA treated cells, metabolic stress in the form of decreased mitochondrial membrane potential (ΔΨm), increased mitochondrial reactive oxygen species (mROS), reduced cellular ATP levels, and increased total protein carbonylation levels was observed. 6-OHDA treatment also significantly decreased tyrosine hydroxylase levels. These effects were significantly abrogated when ET was present. Verapamil hydrochloride (VHCL), a non-specific inhibitor of the ET transporter, OCTN1, abolished ET’s cytoprotective effects, indicative of an intracellular action. These results suggest that ET could be a potential therapeutic for Parkinson’s disease.

A central hypothesis on brain functioning is that plasticity regulates the signals transfer function by modifying the efficacy of synaptic transmission. In the cerebellum, granular layer has been shown to control the gain of signals transmitted through the mossy fiber pathway. Until now, the impact of plasticity on incoming activity patterns was analyzed by combining electrophysiological recordings in acute cerebellar slices and computational modeling, unraveling a broad spectrum of different forms of synaptic plasticity in the granular layer, often along with forms of intrinsic excitability changes. Here, we attempt to provide a brief overview of the most prominent forms of plasticity at excitatory synapses formed by mossy fibers onto principal neurons (granule cells, Golgi cells and unipolar brush cells) in the granular layer. Specifically, we will highlight current understanding of the mechanisms and their functional implications of the synaptic and intrinsic plasticity, providing valuable insights into how inputs are processed and reconfigured at the cerebellar input stage.

Dogs population increased exponentially in the past decade while the birth rate decreased gradually, especially in the developed countries. Due to dogs’ characteristics of loyalty and obedience, most pet owners treated their dogs as their family members or companions, therefore they are willing to select and purchase safe, high quality and nutrition dog food to their dogs. However, there is lack of regulation or standard to reinforce the production or distribution of dog food in Hong Kong. Consequently, this paper will first review the relationship between high dog population and declining birth rate, types of dog food and typical ingredients. Secondly, the potential health implications of various “toxic” food ingredients for dog, hazard analysis of dog food and its testing methods will be investigated. Lastly, this paper will summarize worldwide existing standards and regulations, quality and hygiene management system related to dog food safety to provide insights and suggestions to Hong Kong government about the importance and urgency of implementing regulations and policies to oversee the imported and local manufactured dog food.

Plants support numerous microorganisms within their tissues and the rhizosphere, and these microorganisms, known as the microbiota, can influence plant growth and health. Up to 40% of a plant's photosynthetic metabolism may be invested in the rhizosphere. The microbiota is considered an extra genome that can be modulated to meet plant needs. Researchers have identified a set of genes from these microorganisms, known as the microbiome, which can be manipulated to enhance plant growth and health, improve nutrient absorption, reduce the need for chemical fertilizers, increase resistance to pathogens and pests, and increase stress tolerance. In particular, fungi exhibit large genetic and metabolic diversity and are often used to promote plant growth. For example, the fungus Purpureocillum lilacinum has been employed primarily as a biocontrol agent to manage nematodes, but some studies have suggested that it may also promote plant growth by increasing the efficiency of the plant to absorb nutrients from the soil and provide phytohormones to plants. Therefore, the current review aims to summarize the existing literature on the use of this fungus in agriculture as nematodes control and discuss its potential as a plant growth promoter.

Soil management in orchards can have several economic and environmental implications. In this study, three different soil management systems were compared in a dry-farmed olive grove: conventional tillage (Tillage), glyphosate-based herbicide (Herbicide) and Sheep Walking. The experiment lasted eleven years (2011-2022) and was carried out after a previous trial conducted on the same plot with the same treatments and duration (2001-2011). However, in the earlier trial, the Herbicide and Sheep Walking treatments switched positions in the plot, while the tillage treatment remained in its original place. The average total accumulated olive yields between 2011 and 2022 were 225.1, 230.9, and 245.0 kg tree–1 for the Sheep Walking, Tillage, and Herbicide treatments, respectively. However, no significant differences were observed between the treatments. The levels of total organic carbon in the soil, measured in samples collected in the last year of the study, were 41.3, 33.7, and 37.3 g kg–1, respectively for the same treatments. These findings indicated that the Tillage treatment exhibited lower soil organic matter content and reduced bioavailability of some nutrients, which raises concerns about its sustainability. On the contrary, employing Sheep Walking with an appropriate stocking rate, effectively controlling vegetation in the spring, ensured favourable soil properties and olive yields comparable to the other treatments. Moreover, the Sheep Walking approach provides supplementary advantages to the farmer, including revenue from the sale of animal products and the opportunity to transition to organic farming systems, which better align with the preferences of contemporary societies.

The increased prevalence of obesity worldwide has been implicated for the alarming rise of the incidence of gestational diabetes and preeclampsia as well, both considered as threatening conditions for both mother and fetus. We studied gene polymorphisms of the proinflammatory cytokine Interleukin 6 (IL-6) and the gene expression levels of VEGF and VEGF-receptor all known to be involved in pregnancy complications aiming to identify possible predisposing risk factors in pregnancies with obesity. G allele of IL-6 was found to correspond with an increased risk for gestational diabetes and preeclampsia occurrence. Furthermore, in obese pregnant mothers with either gestational diabetes or pre-existing type 2 diabetes and to those developed preeclampsia it was confirmed that gene expression levels of VEGF were reduced while they were increased for VEGF receptor. We conclude that the genetic profile of the obese pregnant woman shares a common background with that of a pre-existing type 2 diabetes mellitus and therefore predisposes to complications in pregnancy.

Exosomes are nano-sized extracellular vesicles released by cells that contain nucleic acids, proteins, lipids, and other bioactive compounds that play a role in the body's physiological and pathological processes. Exosomes have significant and distinct benefits over synthetic carriers such as liposomes and nanoparticles in the realm of illness diagnostics and therapy due to their endogeneity and heterogeneity. Exosomes are classified as either natural or designed, depending on whether they have been deliberately altered. Natural exosomes are further classified as either animal-derived or plant-derived exosomes. Plant-derived exosome-like nanoparticles (PDENs) are comprised of numerous kinds of bioactive biomolecules. As an alternative cell-free therapeutic strategy, they have the ability to transfer nano-bioactive chemicals to the human body, resulting in diverse anti-inflammatory, antioxidant, and anti-tumour effects. This review focuses on the beneficial effects of plant-derived exosomes against a range of inflammatory conditions, including as periodontitis, inflammatory bowel disease (IBD), autoimmune skin disorders, and inflammation of the liver, lungs, and intestines. Inflammatory disorders are a major issue because of their widespread influence on both personal health and public healthcare systems. Since these illnesses are persistent, the affected people's quality of life is negatively impacted and long-term morbidity is exacerbated. The complicated interaction of genetic, environmental, and immunological variables in the development of various disorders makes effective prevention and therapy more challenging. Plant exosomes present a promising avenue for developing novel therapeutic strategies against inflammatory diseases, offering unique advantages over other alternatives. In order to exploit this efficient carrier, future research will concentrate on creating a PELNV delivery system with high stability, transdermal volume, and ease of administration. Plant exosomes have the potential to become reliable therapeutic agents for a range of common disorders if they are targeted and generated with interdisciplinary expertise.

Hepatitis B surface antigen (HBsAg) is not only the biomarker of hepatitis B virus (HBV) infection and expression activity in hepatocytes, but also contributes to viral specific T cell exhaustion and HBV persistent infection. Therefore, anti-HBV therapies targeting HBsAg to achieve HBsAg loss are key approaches for HBV functional cure. In this study, we found that YZH-106, a rupestonic acid derivative, inhibited HBsAg secretion and viral replication. Further investigation demonstrated that YZH-106 promoted the lysosomal degradation of viral L- and M-HBs proteins. Mechanistic study by Biacore and docking analysis revealed that YZH-106 bound directly to PreS2 domain of L- and M-HBsAg, thereby blocking their entry to the endoplasmic reticulum (ER) and promoting their degradation in cytoplasm. Our work thereby provide basis for design of novel compound therapy to target HBsAg against HBV infection.

Brain pathological changes impair cognition early in disease etiology. There is an urgent need for understanding aging-linked mechanisms of early memory loss to develop therapeutic strategies and prevent the development of cognitive impairment. Tusc2, also named Fus1, is a mitochondrial-resident protein regulating Ca2+ fluxes to and from mitochondria impacting overall health. We reported that Tusc2-/- female mice develop chronic inflammation and age prematurely, causing age- and gender-dependent spatial memory deficits at 5 m.o. Therefore, we investigated Tusc2-dependent mechanisms of memory impairment in mice, comparing changes in resident and brain-infiltrating immune cells. Interestingly, Tusc2-/- female mice demonstrated proinflammatory increase in astrocytes, IFN-γ expression in CD4+T cells and Granzyme-B in CD8+T cells. We also found fewer FOXP3+ T-regulatory cells and Ly49G+ NK and Ly49G+ NKT cells in female Tusc2-/- brain, suggesting a weakened anti-inflammatory response. Moreover, Tusc2-/- hippocampi exhibited Tusc2- and sex-specific protein changes associated with brain plasticity, including mTOR activation, and Calbindin and CamKII dysregulation affecting intracellular Ca2+ dynamics. Overall, data suggest that dysregulation of Ca2+-dependent processes and proinflammatory brain microenvironment heighten in Tusc2-/- mice could underlie cognitive impairment. Thus, strategies to modulate the brain’s Tusc2-, Ca2+, and mitochondria-dependent pathways should be explored to improve cognitive health.

Chlorella vulgaris has considerable promise as a raw material for biofuel production since it has a high productivity per unit area, has a minimum influence on the environment, and does not significantly affect food security. Nevertheless, the low fatty content of their biomass poses a considerable economic obstacle for commercialization. Increasing the amount of biomass and lipids produced by these algae is essential for improving the economic feasibility of using them as biofuel sources. This review highlights the significance of identifying appropriate algal strains, namely those found in local environments, and utilising mutagenesis and genetic engineering techniques to create 'platform strains'. Prior endeavours have primarily concentrated on altering environmental and dietary parameters to enhance the production of biomass and lipids. Here, we review a scientific literature that examines biotechnological approaches and develops methodologies designed to increase lipid production, emphasising the importance of aligning engineering efforts with breakthroughs in DNA manipulation tools. In addition, the review research evaluates the present economic and commercial situation of algal biorefineries, including any related disadvantages. In summary, this thorough research highlights the importance of using creative methods to tackle the intricacies of lipogenesis and enhance the economic viability of producing biofuels from algae.

After peripheral nerve injury, axon and myelin regeneration are key events for optimal clinical improvements. We have previously shown that early bone marrow mononuclear cell (BMMC) transplantation exerts beneficial effects on myelin regeneration. In the present study we analyze whether there is a temporal window in which BMMC migrate more efficiently to damaged nerves while still retaining their positive effects. Adult Wistar rats of both sexes, with sciatic nerve crush were systemically transplanted with BMMC at different days post injury. Vehicle-treated, naïve, and sham rats were also included. Morphological, functional, and behavioral analyses were performed in nerves from each experimental group at different survival times. BMMC transplantation between 0 and 7 days after injury resulted in the largest number of nested cells within the injured sciatic nerve, which supports the therapeutic value of BMMC administration within the first week after injury. Most importantly, later BMMC administration 7 days after sciatic nerve crush was associated with neuropathic pain reversion, improved morphological appearance of the damaged nerves, and a tendency toward faster recovery in the sciatic functional index and electrophysiological parameters. Our results thus support the notion that even delayed BMMC treatment may represent a promising therapeutic strategy for peripheral nerve injuries.

Chiroptera includes of over 1,400 bat species with at least 35 of these present in Italy. Due to their role as lyssavirus reservoirs, in Italy, dead bats and oral swabs are routinely submitted to the laboratory network of the Istituti Zooprofilattici Sperimentali within in the framework of the rabies national passive and active surveillance programme. Carcasses and biological samples collected from January to December 2021 in Latium and Tuscany Regions were further screened for the presence of Coronaviruses (CoVs) and Herpesviruses, using pan-family virus PCR tests and relative PCR products were Sanger sequenced. Subsequent to the viral investigations, genetic bat species was also carried out. Viral characterization detected AlphaCoVs in Miniopterus schreibersii and Beta- and Gamma-Herpesviruses in Tadarida Teniotis.