Malaria parasites increase their host erythrocyte’s permeability to obtain essential nutrients from plasma and facilitate intracellular growth. In the human P. falciparum pathogen, this increase is mediated by the plasmodial surface anion channel (PSAC) and has been linked to CLAG3, as encoded by one member of the conserved clag multigene family. Whether paralogs encoded by other clag genes also contribute to PSAC formation or serve unrelated roles remains unknown. Here, we generated transfectant lines carrying epitope-tagged versions of each CLAG. Each paralog colocalized with CLAG3, with concordant trafficking via merozoite rhoptries to the host erythrocyte membrane of newly-invaded erythrocytes. Each also exists within infected cells in at least two forms: an alkaline-extractable soluble form and a form integral to the host membrane. Like CLAG3, CLAG2 has a variant region cleaved by extracellular protease but CLAG8 and CLAG9 are protease-resistant. Paralog knockout lines, generated through CRISPR/Cas9 transfection, exhibited uncompromised growth in PGIM, a modified medium with more physiological nutrient levels; this finding is in marked contrast to a recently reported CLAG3 knockout parasite. CLAG2 and CLAG8 knockout lines exhibited compensatory increases in transcription of remaining clags and associated rhoph genes, yielding increased PSAC-mediated uptake to specific solutes. We also report distinct transport properties of these knockout lines, suggesting partially overlapping roles of CLAG paralogs in PSAC activity. We propose that the nutrient channel pore is formed by a higher order assembly of CLAG proteins at the host membrane.

Human papillomavirus (HPV) uses the cellular trafficking machinery to reach the cell nucleus and initiate a successful infection. The HPV capsid consists of two proteins: L1 (the major capsid protein) and L2 (minor capsid protein), and L2 is known to be responsible for trafficking the viral genome to the nucleus. From previous studies, we know that many cellular proteins interact with L2 and are involved in the trafficking process at different stages of the infectious entry process. To further investigate how HPV-16 achieves successful viral entry, we have performed a mass spectrometry analysis to identify novel interacting proteins that associate with incoming HPV-16 virions. We show that HPV-16 pseudovirions interact with a group of cellular cargo proteins (COPI), and here we confirm that this is mediated by the direct binding of L2, but not L1, to the COPB1 subunit. We also show that the ability of L2 to interact with COPB1 is conserved in both low- and high-risk HPV types. Furthermore, we also show that the interaction is essential for successful infection entry of multiple HPV types, thereby identifying a novel constituent of the infectious entry pathway of the HPV.

The use of endophytic microbes is increasing in commercial agriculture. This review will describe the endophyte-plant relationship and the fungi and bacteria involved. Their abilities to alleviate biotic (diseases and pests) and abiotic stresses (drought, salt and flooding), remediate pollution and increase photosynthetic capabilities will be described. Their mechanisms of action will be elucidated. These frequently result in increased plant yields. Finally, methods and practices for formulation and commercial use will be described.

Kisspeptin (KISS1) and its cognate receptor (KISS1R) are implicated in the progression of various cancers. However, a theranostic radiopharmaceutical targeting the KISS1 receptor (KISS1R) has yet to be explored. A gallium-68 labelled kisspeptin-10 (KP10) has potential as a pan-tumor radiopharmaceutical for the detection of cancers. Furthermore, a lutetium-177 labelled KP10 could find therapeutic application in treating oncological diseases. We attached DOTA to the NH2-terminus of KP10 as we posited that this modification would not impair biological activity and showed that receptor stimulation of inositol phosphate accumulation in HEK293 transfected with the KISS1R gene was similar for KP10 and DOTA-KP10. We describe optimization of radiolabeling with gallium-68 and lutetium-177 and stability in serum, plasma, and whole blood. Pharmacokinetics was established with µPET/CT and ex vivo measurements. Dynamic studies with µPET/CT demonstrated that background clearance for the radiopharmaceutical was rapid with a blood half-life of 18 ± 3 minutes. DOTA-KP10 demonstrated preserved functionality at KISS1R and good blood clearance. These promising results advocate the further development of KP10 structures which have high binding affinity along with proteolytic resistance.

Multiple sequence alignments and phylogenetic trees are rich in biological information and are fundamental to research in biology. PhyKIT is a tool for processing and analyzing the information content of multiple sequence alignments and phylogenetic trees. Here, we describe how to use PhyKIT for diverse analyses, including (i) constructing a phylogenomic supermatrix, (ii) detecting errors in orthology inference, (iii) quantifying biases in phylogenomic data sets, (iv) identifying radiation events or lack of resolution using gene support frequencies, and (v) conducting evolution-based screens to facilitate gene function prediction. Several PhyKIT functions that streamline multiple sequence alignment and phylogenetic processing—such as renaming FASTA entries or tree tips—are also discussed. These protocols demonstrate how simple command-line operations in the unified framework of PhyKIT facilitate diverse phylogenomic data analysis and processing, from supermatrix construction and diagnosis to gene function prediction.

The additional sex combs-like (ASXL) family, a mammalian homolog of the additional sex combs (Asx) of Drosophila, has been implicated in transcriptional regulation via chromatin modifications. Abnormal expression of ASXL family genes leads to myelodysplastic syndromes and various types of leukemia. De novo mutation of these genes also causes developmental disorders. Genes in this family and neighbor genes are evolutionary conserved in humans and mice. This review provides a comprehensive summary of epigenetic regulations associated with ASXL family genes. Their expression is commonly regulated by DNA methylation at CpG islands preceding transcription starting sites. Their proteins primarily engage in histone tail modifications through interactions with chromatin regulators (PRC2, trithorax complex, PR-DUB, SRC1, HP1α, and BET proteins), and with transcription factors, including nuclear hormone receptors (RAR, PPAR, ER, and LXR). Recently, non-coding RNAs have been identified following mutations in the ASXL1 or ASXL3 gene, along with circular ASXLs and microRNAs that regulate ASXL1 expression. The diverse epigenetic regulations linked to ASXL family genes collectively contribute to tumor suppression and developmental processes. Our understanding of ASXL-regulated epigenetics may provide insights into the development of therapeutic epigenetic drugs.

Carbapenems-resistant enterobacteria are considered multidrug-resistant, making the control of their nosocomial infections a major challenge in healthcare settings. It is important to know the incubation site and source of the spread of these strains, especially in neonatal intensive care units (NICU). Colonization of the colon of preterm neonates per se by multidrug-resistant bacterial strains could be the source of dissemination of these multidrug-resistant strains and their site of incubation. In this study, colonization of the colon of preterm neonates with enterobacteria and their multidrug-resistant strains was investigated. The presence of enterobacteria in the stool of preterm neonates was investigated on EMB (eosin-methylene blue) agar, followed by morphological and biochemical characterization and phylogenetic analysis of the 16S rRNA-encoding gene sequences. Antibiotic susceptibility of all isolated strains was tested using VITEK 2 technology. All cases examined at two weeks of age and older showed bacterial colonization of the colon. Klebsiella pneumoniae colonized the colon in 56.2% of the preterm neonates and Klebsiella quasipneumoniae was found in 6.3%, corresponding to 62.5% in total. The colonizing Klebsiella pneumoniae was multidrug-resistant in 2 of 9 cases. One strain of Klebsiella pneumoniae was resistant to carbapenems and another showed intermediate resistance to these antibiotics. These Klebsiella pneumoniae strains showed resistance to most of the other antibiotics tested. Some cases contained more than one genus, with Escherichia coli found in 50% of cases in preterm neonates. In contrast to Klebsiella pneumoniae, none of the E. coli strains colonizing the colon of preterm neonates in this study showed resistance to carbapenems. The results of this study suggest that Klebsiella pneumoniae and its carbapenems multidrug-resistant strains are well marked in preterm neonates colonizing their colon, which is the incubation site and source of such multidrug-resistant bacterial strains in NICU. This study highlights the importance of careful management of preterm neonates in the NICU and possible contamination with multidrug-resistant Klebsiella pneumoniae incubated in their colon. Further studies would be of interest to avoid the possibility of fecal-oral transmission and infection by these multidrug-resistant bacteria and their treatment in the colon, where their incubation site is located.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive sense single stranded RNA genome containing virus which has infected millions of people all over the world particularly China. The virus has been mutating rapidly enough resulting in the emergence of new variants and sub-variants which have reportedly been spread from Wuhan city of China, the epicenter of the virus, to the rest of China and all over the world. The occurrence of mutations in the viral genome especially in the viral spike protein region has resulted in the evolution of multiple variants and sub-variants which gives the virus benefit of host immune evasion and render the modern-day vaccines and therapeutics ineffective. Therefore, there is a continuous need to study the genetic characteristics and evolutionary dynamics of the SARS-CoV-2 variants. Hence, in this study, a total of 833 complete genomes of SARS-CoV-2 variants (including the wild-type or reference sequence) from Taiyuan and Wuhan cities of China were genetically characterized and studies their phylogenetic and evolutionary dynamics using phylogenetics, genetic similarity, and phylogenetic network analysis. Our results show a lot of useful information regarding the evolutionary dynamics of the viral variants, their genetic similarities/dissimilarities, and their phylogenetic relationships. It has been reported in this study that the SARS-CoV-2 variants have nine recombinant events which suggest very important information regarding the viral evolution. In addition, the phylogenetic network analysis shows the number of mutations resulting in emergence and clustering of the viral variants of both cities which reveal significant information regarding the phylodynamics of the virus. This study, to the best of our knowledge, is the first ever genetic comparative study of Taiyuan and Wuhan cities. This study will help better understand the virus, cope with the emergence, and spread of new variants at local level as well as at international level and inform the public health authorities to make better informed decisions in designing new viral vaccines and therapeutics.

Species of the genus Drosophila have served as favorite models in speciation studies; however, genetic factors of interspecific reproductive incompatibility are underinvestigated. Here we performed the analysis of hybrid female sterility by crossing Drosophila melanogaster females and Drosophila simulans males. Using transcriptomic data analysis, molecular, cellular, and genetic approaches, we analyzed differential gene expression, transposable element (TE) activity, piRNA biogenesis, and functional defects of oogenesis in hybrids. Premature germline stem cell loss was the most prominent defect of oogenesis in hybrid ovaries. Due to the differential expression of genes encoding piRNA pathway components, rhino and deadlock, the functional RDCmel complex in hybrid ovaries was not assembled. However, the activity of the RDCsim complex was maintained in hybrids, independent of the genomic origin of piRNA clusters. Despite the identification of a cohort of overexpressed TEs in hybrid ovaries, we found no evidence that their activity can be considered the main cause of hybrid sterility. We revealed a complicated pattern of Vasa protein expression in the hybrid germline, including partial AT-chX piRNA targeting of the vasasim allele and a significant zygotic delay in vasamel expression. We arrived at the conclusion that the hybrid sterility phenotype was caused by intricate multi-locus differences between the species.

Tomato is considered moderately sensitive to salinity, which detracts from the quality and yield of its fruit; therefore, wild populations have been used as a genetic resource. The aim of this research was to identify lines derived from wild tomato populations with tolerance to salinity during the germination and seedling stages. During germination, 52 wild lines and 2 commercial hybrids (Imperial®, Reserva®) were subjected to 150 mM and 0 mM NaCl and evaluated. The test was carried out for 20 days in a germination chamber with constant darkness, temperature of 25±2 °C and relative humidity of 80±4%. At the seedling stage, 22 wild tomato lines with the best performance in the germination test and 2 commercial hybrids (Imperial®, Topanga®) were evaluated for 12 days in a floating raft system. Concentrations of 175 mM and 0 mM NaCl were used. During germination, the saline condition decreased germination percentage (65.2%), speed of germination (88.2%), steam length (72.5%), root length (46.56%), normal plants number (59.5%), stem dry matter (68.78%), root dry matter (61.99%), and total dry matter (67.1%). At the seedling stage, this condition decreased (P<0.05) the aerial part dry matter (46.37%), leaf area (59.35%), root length (42.43%), final plant height (40.24%), and growth rate (71.42%). Seventeen tolerant genotypes were identified at one of both developmental stages, while one genotype showed tolerance at both stages. These results indicate that there are different response mechanisms in each developmental stage. Native tomatoes play an important role in the identification of tolerant genotypes since they can be used as genetic resources for obtaining commercial genotypes with salt tolerance.

Arbuscular mycorrhizal fungi are soil microorganisms that provide various benefits, such as increasing soil fertility and enhancing plant growth. The present study aimed to propagate arbuscular mycorrhizal fungal spores in trap plants. Soil sampling was carried out in October 2021 on five coffee farms in the central area of Veracruz, Mexico. Soil from coffee plantations and sterile sand were mixed in pots and used for the propagation of arbuscular mycorrhizal fungi, and Sorghum vulgare was used as a trap plant. The plants were kept in a greenhouse for 120 days. The abundance of spores in the sorghum trap plants increased significantly (p

Serine peptidases (SPs) of the chymotrypsin S1A subfamily are an extensive group of enzymes found in all animal organisms, including insects. Here we provide analysis of SPs in the yellow mealworm Tenebrio molitor transcriptomes and genomes datasets and profile their expression pattern at various stages of ontogeny. A total of 269 SPs were identified, including 137 with con-served catalytic triad residues, while others 125 lacking conservation were proposed as non-active serine peptidase homologs (SPHs). Seven deduced sequences exhibit a complex do-main organization with two or three peptidase units (domains), predicted both as active or non-active. The largest group of 84 SP and 102 SPH had no regulatory domains in the propep-tide, and the majority of them were expressed only in the feeding life stages, larvae and adults, presumably playing an important role in digestion. The remaining 53 SP and 23 SPH had differ-ent regulatory domains, showed constitutive or upregulated expression at eggs or/and pupae stages, participating in regulation of various physiological processes. The majority of polypep-tidases was mainly expressed at the pupal and adult stages. The data obtained expand our knowledge on SPs/SPHs and provide a foundation for further research on the functions of this gene family in T. molitor.

Originating in the Mediterranean, B. oleracea is grown all over the world and is highly valued for its nutritional value and variety in cooking. Its susceptibility to pests, diseases, and environmental stressors, however, poses significant challenges to sustaining consistent crop quality and productivity. The BASIC PENTACYSTEINE gene significantly impacts plant growth and responses to abiotic stresses. Nevertheless, little is known about its precise role and the underlying biological processes in B. oleracea. Eleven BPC genes in B. oleracea were identified by a thorough genome-wide investigation and categorized into three categories according to their structural traits and gene motifs. There were eight different chromosomes on which these BoBPCs were located. Comparative synteny analysis was used to reveal the evolutionary traits of potatoes, Arabidopsis, and B. oleracea. The BoBPC family genes in B. oleracea were found to have specific cis-elements linked to growth, stress responses, and hormone regulation when their promoter regions were studied. Cuticular wax synthesis expression revealed that all BoBZR1 genes, from wild to mutant, expressed at varied amounts in distinct types. Moreover, distinctive BoBPC gene expression patterns were found in the seven distinct tissues that were studied. Our thorough analysis shows that the BoBPC family is widely involved in B. oleracea developmental processes. The present findings provide an established theoretical basis for further exploration into the composition and roles of BoBPC in B. oleracea.

High pathogenicity avian influenza (HPAI) H5N1 clade 2.3.4.4b continues to have a substantial impact on wildlife, globally. A recent study has described the putative detection of HPAI in clinically healthy penguins, and those which were fitted with satellite tags reportedly engaged in apparently normal foraging behaviour in the months following sample collection. Herein we investigate the diagnostic approach utilised, and reveal that while the authors likely did detect subtype H5 influenza A virus, the most parsimonious conclusion is that they detected low pathogenicity H5 rather than HPAI H5N1. In response, we have provided an overview key considerations when selecting a diagnostic and outline published diagnostic assays that should be considered for future studies.

Retroviruses perpetuate their survival by incorporating a copy of their genome into the host cell, a critical step catalyzed by the virally encoded integrase. The viral capsid plays an important role during the viral life-cycle, including nuclear importation in case of lentiviruses and integration targeting events, hence, targeting the integrase and the viral capsid is a favorable therapeutic strategy. While integrase strand transfer inhibitors (INSTIs) are recommended as first-line regimens given their high efficacy and tolerability, lenacapavir is the first capsid inhibitor and the newest addition to the HIV treatment arsenal. These inhibitors are however designed for treatment of HIV-1 infection, and their efficacy against HIV-2 remains widely understudied and inconclusive, supported only by few limited phenotypic susceptibility studies. We therefore carried out inhibition profiling of a panel of second-generation INSTIs and lenacapavir against HIV-2 in cell culture, utilizing pseudovirion inhibition profiling assays. Our results show that the tested INSTIs and lenacapavir exerted excellent efficacy against ROD-based HIV-2 integrase, and interestingly, raltegravir also showed modest antiviral activity against the SARS-CoV-2 Omicron variant in antiviral assays carried out in Vero E6 cells.

Yellow pitahaya is a tropical fruit that has gained popularity in recent years. Natural elicitors are compounds that can stimulate the resistance and quality of fruits. The objective of this study was to evaluate the effects of natural elicitors: methyl salicylate (MeSa), methyl jasmonate (JaMe), salicylic acid (SA) and oxalic acid (OA) at concentrations of 0.1 mM (SaMe and JaMe) and 5 mM (SA and OA), applied to the yellow pitahaya fruits, under greenhouse conditions. After full blossom, 4 applications were made with a frequency of 15 days. At time of harvest and after storage, the following variables were evaluated: firmness (whole fruit), total soluble solids (TSS), total acidity (TA), phenolics and carotenoids (in the pulp), while phenolics, carotenoids, macronutrients and micronutrients were determined in the peel. The results showed that JaMe presented a delay of the ripening process, according to TSS, TA, firmness, and total phenolic compounds results, while MeSa advanced the fruit maturation. Regarding the alternative use of the peel as by-product, the application of natural elicitors significantly increased the content of polyphenols, carotenoids, macronutrients and micronutrients in the peel, which can be used as a bioactive compound in the food industry. In conclusion, the results indicate that natural elicitors can be an alternative to improve the quality and shelf life of yellow pitahaya fruits.

This article studies the morphological parameters of vegetative and generative organs of different age groups of Crataegus ambigua from four populations in Western Karatau (Mangistau region, Kazakhstan). The study examined four populations Pop 1 Sultan Epe, Pop 2 Karakozaiym, Pop 3 Emdikorgan, and Pop 4 Samal located in various gorges of western Karatau. Some phylogenetic inference methods were applied using six genetic markers atpF-atpH, ITS, matK, psbK-psbI, rbcL, and trnH-psbA. We also used a statistical analysis of the vegetative and generative organs of plants for three age groups of plants (virgin, young generative, and adult generative). According to the age structure, Samal populations have a high concentration of young generative plants - 42.3% and adult generative plants - 30.9%. Morphological analysis showed the significance of the parameters of the generative organs and separated the Samal population into a separate group according to the main PCoA coordinates. The results of the floristic analysis showed that the populations in the Samal have a high concentration of species diversity. The comparative dendrogram of UPGMA shows the informativeness of the use of genetic markers and the psbK-psbI region can be used to judge the difference between the fourth Samal population and the other three.

High-density olive groves, despite their interesting production potential, have several limitations, also due to the high fruit load and the irrigation requirements.The study aimed to evaluate the effects of fruit load and deficit irrigation on oil yield and fruit quality, and on olive chemical composition in a high-density olive grove (cv Sikitita). Our main hypothesis was that the primary metabolism, as influenced by crop load and stress, could modify the accumulation of different phenolic classes.Different fruit loads were generated through flower thinning (66%, 50%, 33%, 0%) and two deficit irrigation treatments (-60%, -75%) were compared to the well-watered control (920 m3/ha).Thinning treatments had a limited effect on oil yield, on the other hand, deficit irrigation caused considerably less oil accumulation in the fruit on all sampling dates.Thinning 66% and deficit irrigation 75% were considered with the control for untargeted metabolomic analysis, considering three sampling dates. 233 different phenolic compounds were annotated. Multivariate HCA results indicated the impact of harvest time on the phenolic profile of olive fruits, yielding two separate clusters grouping t1 and t2 together and apart from t3. Regarding agronomic techniques, they played a differential role in the phenolic profile (supervised OPLS – DA). Fruit load mostly affected flavonoid glycosides. In contrast, the phenolic response to deficit irrigation is more heterogeneous, with phenolic acids (35%), flavonoids (25%), LMW, and other phenols (25%).

Phenolic compounds represent a group of secondary metabolites that serve essential functions in plants. Beyond their positive impact on plant, these phenolic metabolites, often referred to as polyphenols, possess a range of biological properties that can promote skin health. Scientific research indicates that using phenolics derived from plants topically can be advantageous, but the activity and stability highly depend on storage of the source material and the extract method. These compounds have the ability to relieve symptoms and hinder the progression of different skin diseases. Because they come from natural sources and have minimal toxicity, phenolic compounds show potential in addressing the causes and effects of skin aging, skin diseases, and various types of skin damage, such as wounds and burns. Hence, this review provides an extensive information of the particular crops from which by-product phenolic compounds can be sourced, but pointing the need investigation according to a proper storage plant material and the choice of the best extracting method, along with an examination of their specific functions and the mechanisms by which they act to protect skin.

To investigate the effects of organic fertilizer combined with reduced chemical fertilizer on radish yield, quality, and soil environment in high mountainous areas (elevation: 1800 m), and to mitigate the environmental pollution caused by excessive use of chemical fertilizers. The field trial was conducted to study the effects of different fertilizer treatments. (Control:local fertilizer application rate: 375 kg·hm² reduction in chemical fertilizer + 4500 kg·hm² organic fertilizer; T1:12% reduction in chemical fertilizer + 4500 kg·hm² organic fertilizer; T2:20% reduction in chemical fertilizer + 4500 kg·hm² of organic fertilizer; T3:28% reduction in chemical fertilizer + 4500 kg·hm² organic fertilizer). Four different fertilizer ratios were studied to assess their impacts on radish quality, yield, and soil environment. The findings showed that T2 significantly increased radish yield by 12.92%. Moreover, it led to significant improvements in the content of vitamin C, soluble sugars, soluble solids, soluble proteins, titratable acidity, and glucosinolates, which increased by 10.62%, 2.15%, 50.00%, 26.90%, 43.90%, and 44.57%, respectively. Treatment T2 also significantly increased soil nutrient content, with a 7.69% and 14.29% increase in total nitrogen and total phosphorus content compared to the control (Control) treatment, and a significant reduction of 21.64% in soil bulk density . T2 treatment significantly enhanced soil urease activity, sucrase activity, alkaline phosphatase activity, and catalase activity, showing an improvement of 28.97%, 55.92%, 52.08%, and 17.47% compared to the control, respectively (p&lt;0.05). Moreover, treatment T2 resulted in a relative abundance increase of 12.25% and 10.43% in Proteobacteria and Actinobacteria respectively. Thus, the combined application of T2:20% reduction in chemical fertilizer + 4500 kg·hm² of organic fertilizer improved the quality and yield of radish while optimizing the soil environment. T2 effectively promoted radish growth, enhanced radish yield and quality, and improved the soil environment.

Compact solar-powered plasma water generator: enhanced on-site aged seed germination with the corona dielectric barrier discharger

Honey bee colonies rapidly decline when confined to greenhouses, increasing pollination rental costs as they need to be replaced frequently. We tested a hive system with entrances that can be manipulated to direct bees to inside or outside greenhouses containing a zucchini crop. In one greenhouse, the bees could only forage inside for 15 days; in another, bees were directed to the inside from 5 to 9 AM, after which they foraged outside. This procedure was repeated two more times in each greenhouse with new hives. Data was collected on how the number of bee flower visits affected fruit production, the frequency of flower visits, and the amount of bee brood and food in the hives. Flowers visited by bees four times or more set more and larger fruit. The frequency of flower visits by bees from the hives confined to the greenhouse was reduced after eight days; it was not reduced in the greenhouse with bees that could forage outside. Bee brood area was reduced in the colonies that were confined to the greenhouse, while it was maintained in the semiconfined hives. The hive system with controllable entrances proved effective for pollination, while causing less damage to the bees.

Bovine Respiratory Disease Complex, a complex respiratory ailment in cattle, results from a combination of viral and bacterial factors, compounded by environmental stressors such as overcrowding, transportation, and adverse weather conditions. Its impact extends beyond mere health concerns, posing significant economic threats to the cattle industry. This study presents an extensive investigation into viral pathogens associated with BRDC in Serbian cattle, utilizing serum samples and nasal swabs. A cross-sectional study was conducted in 2024 across 65 randomly selected dairy farms in Serbia, excluding vaccinated farms. Farms were categorized by livestock count: small (≤50 animals), medium-sized (51-200 animals), and large (&gt;200 animals). Serum samples from adult cattle older than 24 months were tested for antibodies against BVDV, BHV-1, BRSV, and BPIV3. Nasal swab samples from animals with respiratory signs were tested using PCR for viral genome detection. Results showed seropositivity for all four viruses across all farms, with BPIV3 exhibiting universal seropositivity. Medium-sized and large farms demonstrated higher seropositivity for BRSV and BHV-1 compared to small farms (p&lt;.05). True seroprevalence estimates at the animal level were 84.29% for BRSV, 54.08% for BVDV, 90.61% for BHV-1, and 84.59% for BPIV3. PCR analysis of nasal swabs revealed positive detections for BRSV (20%), BHV-1 (1.7%), BVDV (8%), and BPIV3 (10.9%). Influenza D virus was not found in any of samples. This study provides critical insights into the prevalence and circulation of viral pathogens associated with BRDC in Serbian cattle, emphasizing the importance of surveillance and control measures to mitigate the impact of respiratory diseases in cattle populations.

The global warming has caused poor grape skin coloration and reduced the production of high-quality berries. To overcome these problems, the effect of synephrine (Syn) on anthocyanin accumulation was investigated. Syn treatment above 1 mM increased anthocyanin content in cultured grape cells in a molecular-structure-specific and concentration-dependent manner, and increased only the anthocyanin without affecting the sugar/acid ratio in grape bunches. It increased the expression of genes linked to anthocyanin synthesis after 24 h of treatment, without affecting phytohormone levels. Syn treatment induced the expression of SOD3, elevating hydrogen peroxide (H2O2) production from 3 to 24 h after treatment in cultured cells. Subsequent increases in CAT and APX6 expression occurred, which encode H2O2-eliminating enzymes. In cultured grape cells, Syn and H2O2 treatments upregulated the H2O2-responsive gene Chit4 and the anthocyanin-biosynthesis-related genes mybA1 and UFGT 4 days after the treatments and promoted anthocyanin accumulation 7 days after the treatments. In berries, both treatments enhanced anthocyanin accumulation after 9 days. These results suggest that Syn promotes anthocyanin accumulation through the production of H2O2 without the upregulation of phytohormone biosynthesis. Syn treatment is expected to improve poor grape coloration and contribute to higher-quality fruit production.

This study used Dutch potatoes at the end of dormancy as the material to explore the impact of menthol (0.2 and 0.5 g/kg based on potato mass) treatment on sprouting inhibition and potato quality. The findings revealed that a menthol concentration of 0.5 g/kg effectively inhibited potato tuber sprouting and significantly reduced glucoside alkaloids production. After a storage period of 15 days, the sprouting percentage and glucoside alkaloids content of potatoes treated with 0.5 g/kg menthol were observed to be significantly lower at 4.17% and 68.63 mg/kg, respectively, compared to the control group which exhibited values of 100% and 282.01 mg/kg, respectively (P < 0.05). Throughout the storage period, 0.5 g/kg of menthol promoted respiration, reduced malondialdehyde production in potatoes, inhibited polyphenol oxidase activity, and slowed down tissue browning. Additionally, it mitigated the decline in starch and soluble protein content, inhibiting the accumulation of reducing sugars.

Papillary thyroid carcinoma (PTC) presents a significant health concern, particularly among Hispanic women in the United States, who exhibit a disproportionately higher chance of developing an advanced disease when compared to the non-Hispanic population. Emerging evidence suggests coagulation factor X, encoded by F10 gene, has a potential role in inhibiting cancer cell migration. However, comprehensive investigations into the differential expression patterns of F10 in Hispanic versus non-Hispanic females remain limited. RNA-sequencing data was acquired from the TCGA database for white female patients, 166 non-Hispanic and 25 Hispanic. A statistically significant (p &lt; 0.05) 2.06-fold increase in F10 expression levels was detected in disease-free tumors compared to recurrent PTC tumors. Furthermore, an increase in F10 gene expression levels was also observed corresponding to approximately a 1.74-fold increase in non-Hispanic patients compared to Hispanic patients. The probability of tumor recurrence was 1.82 times higher in the cohort with low expression of F10 compared to the high expression cohort, correlating with the lower disease-free rates observed in Hispanic patients’ cohort when compared to non-Hispanics. This finding underscores the relevance of ethnic disparities in molecular profiles for understanding cancer susceptibility. Identifying F10 as a potential prognostic biomarker highlights avenues for targeted interventions and contributes to improving diagnostic and treatment strategies for diverse patient populations.

Alpinia oxyphylla is a traditional Chinese medicinal plant, with a medicinal history of more than 1,700 years. Ring leaf blight (RLB) disease, caused by pestalotioid species, is an important disease of A. oxyphylla, seriously affecting the yield and quality of fruits. The causal agent of RLB disease has not been systematically identified and characterized so far. In this study, thirty-six pestalotioid strains were isolated from the leaves and stems of A. oxyphylla collected from 6 cities of Hainan province, China. Based on multi-locus phylogeny (ITS, tef-1α and tub2) and morphological characteristics analyses, seventeen species belonging to three genera (Neopestalotiopsis, Pestalotiopsis and Pseudopestalotiopsis) were identified and six new species (N. baotingensis, N. oblatespora, N. olivaceous, N. oxyphylla, N. wuzhishanensis and N. yongxunensis) were described. Pathogenicity tests revealed that strains of Neopestalotiopsis species caused more severe ring leaf blight on A. oxyphylla than strains of Pestalotiopsis and Pseudopestalotiopsis under wounded inoculation conditions.

Our study investigated the innate immune response to Toxoplasma gondii infection by assessing microglial phenotypic changes and sickness behavior as inflammatory response markers post-ocular tachyzoite instillation. Disease progression in Swiss albino mice was compared with documented outcomes in BALB/c mice using identical ocular route and parasite burden (2x105 tachyzoites), with saline as control. Contrary to expectations, Swiss albino mice displayed rapid, lethal disease progression, marked by pronounced sickness behaviors and mortality within 11-12 days post-infection, while survivors showed no apparent signs of infection. Comparative analysis revealed T. gondii-infected BALB/c mice exhibited reduced avoidance of feline odors, while in-fected Swiss albino mice showed enhanced avoidance responses. There was a significant increase in microglial cells in the dentate gyrus molecular layer of infected Swiss albino mice compared to BALB/c mice and their respective controls. Hierarchical cluster and discriminant analyses iden-tified three microglial morphological clusters, differentially affected by T. gondii infection across strains. BALB/c mice exhibited increased microglial branching and complexity, while Swiss al-bino mice showed reduced shrunk microglial arbors, diminishing morphological complexity. These findings highlight strain-specific differences in disease progression and inflammatory reg-ulation, indicating lineage-specific mechanisms in inflammatory responses, tolerance, and re-sistance. These elements are critical in devising control measures for toxoplasmosis.

Mild traumatic brain injuries (mTBIs) are highly prevalent and can lead to chronic behavioral and cognitive deficits, often associated with the development of neurodegenerative diseases. The formation of reactive oxygen species (ROS) and oxidative stress have been implicated in mTBI-mediated axonal injury and pathogenesis. However, the underlying mechanisms and contributing factors are not completely understood. In this study, utilizing a murine model of repetitive mTBI (r-mTBI) involving five closed-skull concussions in young adult C57BL/6J mice, we observed a significant elevation of Na+/H+ exchanger protein (NHE1) expression in GFAP+ reactive astrocytes, IBA1+ microglia, and OLIG2+ oligodendrocytes across various brain regions (including the cerebral cortex, corpus callosum, and hippocampus). This elevation was accompanied by astrogliosis, microgliosis and the accumulation of amyloid precursor protein (APP). Concurrently, r-mTBI mice displayed impaired motor learning and spatial memory deficits. However, post-r-mTBI administration of a potent NHE1 inhibitor, HOE642, attenuated locomotor and cognitive functional deficits as well as gliosis, oxidative stress, axonal damage, and white matter damage. These findings underscore the role of NHE1 upregulation in r-mTBI-induced oxidative stress, axonal damage, and gliosis, suggesting NHE1 as a promising therapeutic target to alleviate mTBI-induced injuries and restore neurological function.

BACKGROUND: Thromboembolic disorders including Myocardial infarction[ MI] and stroke represent the leading causes of death worldwide. Fibrinolytic enzymes extracted from microbial sources showed high efficacy in the dissolution of different blood clots. AIM OF THE STUDY: Screening and the bacterial recombinant DNA manufacture of bacterial fibrinolytic enzymes from different soil environments in Egypt. METHODOLOGY: A total of 50 soil samples were screened for their fibrinolytic enzyme production. The potent fibrinolytic enzyme-producing bacterial isolates were evaluated for their thrombolytic activities using the plasma plate method. The characterization of the enzyme activity and thermostability were carried out; also, the determination of molecular mass using a mass spectrometer and western blot technique was performed. The purification of the fibrinolytic enzymes was done through the affinity chromatography technique. On the other hand, the production of the purified bacterial fibrinolytic enzyme was achieved via bacterial recombinant DNA technology. Formulation of fibrinolytic enzymes in different dosage forms was tried. RESULTS: In the present study, the purified bacterial fibrinolytic enzyme was approximately 83% pure through affinity chromatography and SDS-PAGE assay. The predominating bacterial isolate secreting fibrinolytic enzymes was found to be Bacillus cereus. The fibrinolytic enzyme activities of 50 soil samples were found to be in the range of 0.167-1.853 U/ ml. The fibrinolytic activity of the extracellular enzyme refined from the culture supernatant of Bacillus cereus was relatively stable over the PH range from 7.4-10 for 18 hours and also it showed stability with the highest productivity at a temperature of 43 0C for nearly 60 minutes. The enzyme was called fibrin-proteinase[ FP] in the present study. The FP degraded the fibrin clots via direct thrombolysis. The specific activity and the molecular mass of the FP were estimated to be nearly 40.71 Units/ mg protein and nearly 30 KDa respectively. Protease activity was noticed to be slightly increased in the presence of Fe+3; While it was inhibited in the presence of EDTA. On the other hand, the FP fibrinolytic activity was enhanced greatly after the addition of monovalent cations such as K+1 and Na +1. The enzyme was also active over the temperature range of 20- 65 0C with the highest activity at 55 0C. The optimum temperature and PH of protease production was at 35-43 0C and PH 8.0-10. Conclusion: During the present study, the thermostable fibrinolytic enzyme FP purified from Bacillus cereus in different soil environments in Egypt was a promising fibrinolytic enzyme because it showed a broader efficacious fibrinolytic activity as well as less adverse effects than the current fibrinolytic enzymes globally. It is recommended in the future advanced exploration of the optimization of suitable formulation of bacterial fibrinolytic enzymes to aid in the dissolution of various blood clots and as a consequence overcoming the high rate of mortality globally.

Parkinson's disease (PD) is recognized as the second most prevalent primary chronic neurodegenerative disorder of the central nervous system. Clinically, PD is characterized as a movement disorder, exhibiting an incidence and mortality rate that is increasing faster than any other neurological condition. In recent years, there has been a growing interest concerning the role of the gut microbiome in the etiology and pathophysiology of PD. The establishment of a brain-gut microbiome axis is now real, with evidence denoting a bidirectional communication between the brain and the gut microbiota through metabolic, immune, neuronal, and endocrine mechanisms and pathways. Among these, the vagus nerve represents the most direct form of communication between the brain and the gut. Given the potential interactions between bacteria and drugs, it has been observed that the therapies for PD can have an impact on the composition of the microbiome. Therefore, in the scope of the present review, we will discuss the current understanding of gut microbiome on PD and whether this may be a new paradigm for treating this devastating disease.

Lactococcus lactis subsp. cremoris C60 is a probiotic strain of lactic acid bacteria (LAB) which induces various immune modifications in myeloid lineage cells. These modifications subsequently reg-ulate T cell function, resulting in enhanced immunity both locally and systemically. Here, we report that C60 suppresses tumor growth by enhancing macrophage function via metabolic al-terations, thereby increasing adenosine triphosphate (ATP) production in a murine melanoma model. Intragastric (i.g.) administration of C60 significantly reduced tumor volume compared to saline administration in mice. The anti-tumor function of intratumor (IT) macrophage was up-regulated in mice administered with C60, as evidenced by an increased inflammatory phenotype (M1) rather than an anti-inflammatory/reparative (M2) phenotype, along with enhanced anti-gen-presenting ability, resulting in increased tumor antigen-specific CD8+ T cells. Through this functional modification, we identified that C60 establishes a glycolysis-dominant metabolism, rather than fatty acid oxidation (FAO), in IT macrophages, leading to increased intracellular ATP levels. To address the question of why orally supplemented C60 exhibits functions in distal places, we found a possibility that bacterial cell wall components, which could be distributed throughout the body from the gut, may induce stimulatory signals in peripheral macrophages via Toll-like receptors (TLRs) signaling activation. Thus, C60 strengthens macrophage anti-tumor immunity by promoting a predominant metabolic shift towards glycolysis upon TLR-mediated stimulation, thereby increasing substantial energy production.

Background: given the various clinical manifestations that characterize coronavirus disease 2019 (COVID-19), the scientific community is constantly searching for biomarkers with prognostic value. Surfactant protein A (SP-A) and D (SP-D) play a crucial role in ensuring proper alveolar function and an alteration of their serum levels have been reported in several pulmonary diseases characterized by acute respiratory distress syndrome (ARDS) and pulmonary fibrosis. Consid-ering that such clinical manifestations can also occur during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we wondered if these collectins could act as prognostic markers. Methods: in this regard, serum levels of SP-A and SP-D were measured by enzyme immunoassay in patients with SARS-CoV-2 infection (n=51) at admission (T0) and after 7 days (T1) and compared with healthy donors (n=11). Results: SP-D increased in COVID-19 patients com-pared to healthy controls during the early phases of infection, while a significant reduction was observed at T1. Stratifying SARS-CoV-2 patients according to disease severity, increased serum SP-D levels were observed in severe compared to mild patients. Conclusions: In the light of these results SP-D, but not SP-A, seems to be an eligible marker of COVID-19 pneumonia and the early detection of SP-D serum levels could be crucial for a preventive clinical management.

Premalignant lesions in the bronchial epithelium represent early stages of squamous cell lung carcinoma, challenging to detect with conventional methods. While previous studies have focused on gene expression, here we examine transcriptomic alterations associated with lesion development with the emphasis on protein-coding transcripts. We reanalyzed publicly available RNAseq dataset on airway epithelial cells from 82 smokers with and without premalignant lesions. Transcript abundances were quantified using kallisto, and differential expression and transcript usage analysis was conducted using the sleuth and RATs packages. Functional characterization included overrepresentation analysis (clusterProfiler), weighted co-expression network analysis (WGCNA), and network analysis (Enrichr-KG). We detected 5,906 differentially expressed transcripts, with significant enrichment in pathways related to oxidative phosphorylation and mitochondrial function. Transcript-level WGCNA identified single module correlated with dysplasia status, enriched in cilium-related biological processes. Analysis of hubs within this module highlighted key genes including RABL2B, DNAH1, EFHC1 and VWA3A, and revealed transcription factors such as FOXJ1 and ZNF474 as potential regulators. Our findings underscore the value of transcript-level analysis in uncovering novel insights into premalignant lesion biology. By examining transcripts rather than genes, we identified potential biomarkers associated with early lung carcinogenesis.

Abstract: Abnormal growth of oligodendrocyte precursor cells (OPCs) importantly contributes to the progression of glioblastoma tumors. Hence, molecules that block OPC growth may be of therapeutic importance in treating gliomas. 2-methoxyestradiol (2ME), an endogenous tubulin interacting metabolite of estradiol is effective against multiple proliferative disorders. Based on its anti-carcinogenic and anti-angiogenic actions it is undergoing phase II clinical trials. We hy-pothesize that 2ME may prevent glioma growth by targeting OPC growth. Here we tested this hypothesis by assessing the impact of 2ME on growth of OPC cell line “Oli-neu” and dissected the underlying mechanism(s). Treatment with 2ME inhibited OPC growth in a concentra-tion-dependent manner and accompanied with significant upregulation in expression of p21 and p27, negative cell cycle regulators. Moreover, treatment with 2ME altered OPC morphology from multi-arm processes to rounded cells. At concentrations of 1uM and greater 2ME induced apoptosis with increased expression of caspase 3, PARP and caspase-7 fragments, externalized phosphatidylserine staining / apopercentage and increased mitochondrial activity. Flow-cytometry and microscopic analysis demonstrated that 2ME triggers endoreduplication in a concentration-dependent fashion. Importantly, 2ME induced cyclin E, JNK1/2 and p53 expres-sion as well as OPC cell fusion, key mechanisms driving endoreduplication or whole-genome duplication. Importantly, inhibition of p53 with pfithrin-α rescued 2ME-induced endoreduplica-tion. The pro-apoptotic and endoreduplication actions of 2ME were accompanied with upregula-tion of survivin, cyclin A, Cyclin B, Cyclin D2, ppRB. Taken together our findings provide evi-dence that 2ME not only inhibits OPC growth and triggers apoptosis, but also activates OPCs in a survival - fight or flight mode leading to endoreduplication. This inherent survival character-istic of OPCs may, in part be responsible for drug resistance in gliomas as observed for many tubulin interacting drugs. Importantly, the fate of OPCs after 2ME treatment may depend on cell-cycle status of the individual cells. Combining tubulin-interfering molecules with drugs, such as pfithrin-α, that inhibit endoreduplication may help inhibit OPC/glioma growth and lim-it drug resistance.

Transcription factors (TFs) are crucial in modulating gene expression and sculpting cellular and organismal phenotypes. The identification of TF-target gene interactions is pivotal for comprehending molecular pathways and disease etiologies but has been hindered by the demanding nature of traditional experimental approaches. This paper introduces a novel web application, utilizing the R programming language, which predicts TF-target gene relationships and vice versa. Our application integrates the predictive power of various bioinformatic tools, leveraging their combined strengths to provide robust predictions. It merges databases for enhanced precision, incorporates gene expression correlation for accuracy, and employs pan-tissue correlation analysis for context-specific insights. The application also enables the integration of user data with established resources to analyze TF-target gene networks. Despite its current limitation to human data, it provides a platform for exploring gene regulatory mechanisms comprehensively. This integrated, systematic approach offers researchers an invaluable tool for dissecting the complexities of gene regulation, with the potential for future expansions to include a broader range of species.

The safety of vegetable food is compromised by various factors, including the inefficient or excessive use of sanitizers. Instances of individuals falling ill after consuming raw vegetables have been reported, with outbreaks of diseases caused by pathogens on fresh vegetables becoming increasingly prevalent globally, attracting significant media coverage and impacting the economic viability of vegetable cultivation. Measures to enhance food safety in postharvest horticultural produce involve controlling microbial proliferation and minimizing cross-contamination. Sanitizers were utilized in the food safety arsenal for a variety of purposes, including pathogen elimination and microbe reduction, hand, tools, and vegetable contact surface cleaning, and produce shelf life extension. Choosing an appropriate sanitizer for all vegetables is difficult due to a lack of knowledge on which sanitizers are ideal for the many types of vegetables grown on farms under different environmental circumstances. Although chlorine-based sanitizers, such as sodium or calcium hypochlorite, have been widely used for the past 50 years, recent research has revealed that chlorine reacts with an organic compound in fresh vegetables to produce trihalomethane, a carcinogen precursor, and as a result, many countries have prohibited the use of chlorine in all foods. As a result, horticulture research groups worldwide are exploring for non-chlorine, ecologically friendly sanitizers for the vegetable industry. They also want to understand more about present procedures in the vegetable business for employing alternative sanitizers, as well as the efficacy and potential dangers to the food safety of fresh salad vegetables. This review-cum-research paper presented detailed information on non-chlorine sanitizers, such as their efficacy, benefits, drawbacks, regulatory requirements, and the need for additional research to lower the risk of marketed salad vegetable food safety.

Plant growth regulators (PGRs) and deficit irrigation (DI) play a crucial strategic role in sustaining agricultural yield and reducing water stress in drought prone areas. The study was carried out in 2021-2022 to assess the impact of various PGRs (SA & NAA) & irrigation levels (60% Epan, 80 % Epan, and 100 % Epan) with DI & partial root drying (PRD) irrigation strategies. PGR application boosted fruit yields and demonstrated its significance in reducing water stress by lowering canopy temperature, maintaining higher relative water content in the leaves, modifying stomatal opening, and increasing photosynthetic rate. PGRs were used to assess the increased accumulation of total phenols, flavonoids, and improved antioxidant activity. Results indicated that exogenous use of PGRs like SA+NAA in conjunction with 80% irrigation levels increased fruit yield (31.97 and 40.38%) and water productivity (64.92 and 75.39%) for DI and PRD treatments, respectively. Thus standardizing irrigation and crop management practices including PGR application can be recommended to boost pomegranate productivity particularly in water-scarce environments.

Thorough and precise gene structure annotations are essential for maximizing the benefits of genomic data and unveiling valuable genetic insights. The cucumber genome was first released in 2009 and updated in 2019. To increase the accuracy of predicted gene models, 64 published RNA-seq data and 9 new strand-specific RNA-seq data from multiple tissues were used for manual comparison with the gene models. The updated annotation file (version 2.0) contains increased 24,145 predicted genes from previous version (24317 genes) with a higher BUSCO value of 96.9%. 6231 and 1490 transcripts were adjusted and newly added, respectively, accounting for 31.99% of the overall gene tally. These newly added and adjust genes were renamed (CsaV3.1_XGXXXXX), while genes remaining unaltered preserve their original des ignations. A random selection of 21 modified/added genes were validated using RT-PCR analyses. Additionally, tissue-specific patterns of gene expression were examined using newly obtained transcriptome data with the revised gene prediction model. This improved annotation of cucumber genome will provide essential and accurate resources for studies in cucumber.

Background: Manoeuvres esbarrada and volta sobre patas are fundamental movements in equestrian activities, yet their kinematics remain largely unexplored. Objectives: This observational study aimed to kinematically describe the movements of esbarrada and volta sobre patas in Criollo breed horses. Methods: Kinematic analysis was conducted on 31 Criollo horses executing esbarrada and volta sobre patas manoeuvres. Results: The esbarrada maneuver covered a distance of 4.28 ± 0.99m in 1.15 ± 0.11s at a velocity of 3.77 ± 0.55m/s. Angular kinematic variables revealed specific joint angles during the maneuver. In volta sobre patas, significant differences were found in spin duration and thoracic limb suspension between the first and second spins. Conclusions: Volta sobre patas demonstrated prolonged spinning duration and increased thoracic limb suspension in the second spin. Additionally, static conformation did not correlate with limb protraction angles during esbarrada.

Cancer remains one of the main causes of death in the world due to its increasing incidence and treatment difficulties. Although several progresses have been done in this field, innovative approaches are needed to reduce tumor incidence, progression and spreading. In particular, the development of cancer vaccines is currently ongoing like both preventive and therapeutic strategy. This concept is not new, but few vaccines have been approved in oncology. Antigen-based vaccination emerges as a promising strategy, leveraging specific tumor antigens to activate the immune system response. However, challenges persist in finding suitable delivery systems and antigen preparation methods. Exosomes (EXs) are highly heterogeneous bilayered vesicles which carry several molecule types in the extracellular space. The peculiarity is that they may be released from different cells and may be able to induce a direct or indirect stimulation of immune system. In particular, EX-based vaccines may cause anti-tumor immune attack or produce memory cells recognizing cancer antigens and inhibit disease appearance. This review delves into EXs composition, biogenesis, and immune-modulating properties exploring their role as tool for prevention and therapy in solid tumors. Finally, here we describe future research directions to optimize vaccine efficacy and realize the full potential of EX-based cancer immunotherapy.

Despite impressive progress in quantum biology, many questions about perception, cognition, memory, and their relation to processing of information remain unanswered. Here is an attempt to draw a unified picture starting with the basic quantum-mechanical phenomenon of nano-superconductivity in the microtubules and extending it to quantum processing of information, and generation of coherent Josephson radiation. A model for the generation in the axons of neurons is suggested. Like in a symphony, but on frequencies ten orders of magnitude higher, the radiation forms resonant standing electromagnetic waves, which are defined by the anatomy, synchronize all the functions in organism, and are behind the memory, perception, and cognition of a living being. It is true that we are made of atoms, but we are coherent electromagnetic waves.

Amidst worsening climate change, drought stress imperils global agriculture, jeopardizing crop yields and food security, necessitating urgent exploration of sustainable methods like biopriming, harnessing beneficial microorganisms to bolster plant resilience. Recent research has revealed diverse biological compounds with versatile applications produced by Schizophyllum commune, rendering this fungus as a promising contender for biopriming applications. For the first time this study aimed to investigate,the potential of S. commune exo- (EPSH) and intra-PSH (IPSH), isolated from two strains: Italian (ITA) and Serbian (SRB) under submerged cultivation, in enhancing the resilience of Pisum sativum L. seeds through biopriming technique. Testing of seed quality of bioprimed, hydroprimed, and unprimed seeds was done using a germination test, under optimal and drought conditions. In optimal conditions, the IPSH SRB increased germination energy by 5.50% compared to the control, while the highest percentage of germination (94.70%) was shown after biopriming with PSH isolated from the ITA strain. Additionally, all assessed treatments resulted in a boost in seedling growth and biomass accumulation, where the ITA strain demonstrated greater effectiveness in optimal conditions, whereas the SRB strain showed superiority in drought conditions. The drought tolerance indices increased significantly in response to all examined treatments during the drought, with EPSH ITA (23.00%) and EPSH SRB (24.00%) demonstrating the greatest effects. Results demonstrate a significant positive influence of fungal PSH, indicating their potential as biopriming agents and offers insights into novel strategies for agricultural resilience in the face of changing environmental conditions.

.Various synthetic nematicides are currently used effectively in the control of plant parasitic nematodes. However, these nematicides have adverse effects on humans and the environment. Neem oil is eco-friendly alternatives to synthetic nematicides. The effectiveness of repeated neem oil application in suppressing the root-knot nematodes infestation in figs seedlings was therefore examined in this study, both in its natural form (10 ml/L) and in its nano-emulsion form (5 and 7 ml/L). The recorded reduction parameters of M. incognita were J2/250g soil, galls and egg masses / 5g roots of infected fig seedlings were measured at that time, and the effects of these natural additives were compared with the Fosthiazate (Krenkel 75%EC). The impact of such soil amendments on some typical plant parameters, the total microbial count of soil, and the overall enzymatic activity of the fig rhizosphere were also included. Obtained results revealed that the soil population density of root knot nematode suppressed by 80.3% , reduction of nematode egg masses (60.4%) due to the application of nano-emulsion of neem oil (at 7ml/L). Present work recommend the use of nano-emulsion of neem oil as one of the effective and eco-friendly means to reduce the root- knot nematode on fig .

Enterococcus faecalis is a growing cause of nosocomial and antibiotic-resistant infections. Treating drug-resistant E. faecalis requires novel approaches. The use of bacteriophages (phages) against multidrug-resistant (MDR) bacteria has recently garnered global attention. Biofilms play a vital role in E. faecalis pathogenesis as they enhance antibiotic resistance. Phages eliminate biofilms by producing lytic enzymes, including depolymerases. In this study, Enterococcus phage vB_Efs8_KEN04 (ФKEN04), isolated from a sewage treatment plant in Nairobi, Kenya, was tested against clinical strains of MDR Enterococcus faecalis. This phage had a broad host range against 100% (26/26) of MDR E. faecalis clinical isolates and cross-species activity against Enterococcus faecium. It was able to withstand acidic and alkaline conditions, from pH 3 to 11, as well as temperatures between -80ᵒC and 37ᵒC. It could inhibit and disrupt the biofilms of MDR E. faecalis. Its linear double-stranded DNA genome of 142,402 bp contains 238 coding sequences with a G+C content and coding gene density of 36.01% and 91.46%, respectively. Genomic analyses showed that ФKEN04 belongs to the genus Kochikohdavirus in the family Herelleviridae. It lacked antimicrobial resistance, virulence, and lysogeny genes, and its stability, broad host range, and cross-species lysis indicate strong potential for the treatment of Enterococcus infections.

In order to address the issue of nutrient deficiency in coconut coir-based nursery substrates, three materials with nutrient supplementation effects, namely pig manure, composted rice husks, and agricultural humic acid, were added in equal volumes to the coir-based substrate. The newly formulated substrates were then tested for their seedling growth effects on cucumber and rice. Results indicate that the substrate formulation consisting of "10% pig manure + 30% peat + 50% coconut coir + 10% vermiculite" was capable of satisfying the growth requirements of both cucumber and rice seedlings, with the highest acceptance among farmers.

Small interfering RNA (siRNA) holds significant therapeutic potential by silencing target genes through RNA interference. Current clinical applications of siRNA have been primarily limited to liver diseases, while achievements in delivery methods are expanding its applications to various organs, including the lungs. Cholesterol-conjugated siRNA emerges as a promising delivery approach due to its low toxicity and high efficiency. This study focuses on developing a cholesterol-conjugated anti-Il6 siRNA and the evaluation of its potency for the potential treatment of inflammatory diseases using the example of acute lung injury (ALI). The biological activities of different Il6-targeted siRNAs containing chemical modifications were evaluated in J774 cells in vitro. The lead cholesterol-conjugated anti-Il6 siRNA after intranasal instillation demonstrated dose-dependent therapeutic effects in a mouse model of ALI induced by lipopolysaccharide (LPS). The treatment significantly reduced Il6 mRNA levels, inflammatory cell infiltration, and the severity of lung inflammation. IL6 silencing by cholesterol-conjugated siRNA proves to be a promising strategy for treating inflammatory diseases, with potential applications beyond the lungs.

Mastitis-causing bacteria can establish persistent infections in the mammary gland of commercially important dairy animals despite the presence of strong specific humoral and cellular immune mechanisms. The aim of this study was to encapsulate vitamin D3 by complex coacervation with sulfur-saturated bovine lactoferrin-alginate using microbial transglutaminase-catalyzed crosslinking and investigate the oral administration of encapsulated vitamin D3 in blood serum biomarkers of the immune response in late-lactating dairy goats. Dairy goats (n = 18) in late lactation were randomly assigned to three experimental groups (n = 6), after balancing weight. Dairy goats were orally administered with 0.35 mg vitamin D3/day in the unencapsulated form and 0.35 mg vitamin D3/day in the encapsulated powder form. Another group received the basal diet. The experimental period lasted 6 weeks. The blood serum concentrations of 25-hydroxyvitamin D3 [25-(OH)-D3], lactoferrin, immunoglobulin A (IgA), and interferon-gamma (INF-γ) were measured. The delivery of vitamin D3 to dairy goats resulted in a marked increase of 25-(OH)-D3 concentration in serum while the serum level of lactoferrin also increased. Alternatively, the serum levels of IgA and the immunomodulatory cytokine INF-γ were elevated following supplementation with the encapsulated vitamin D3. Overall, the capsules in the powder form used in this study kept vitamin D3 highly bioavailable.

In this study, the microbial strain was isolated from the humus soil to ferment Sophora flavescens and Eleutherococcus sessiliflorus extracts. The isolated microbial was identified as Bacillus genus by 16S rRNA sequence analysis. The fermented plant extracts exhibited the antifungal effects against four types of the plant pathogens such as P. carotorum, B. cinerea, C. fructicola Sau-3, and C. gloeosporioides according to incubation time. Especially, the fermented plant extracts showed the most active activities for Colletotrichum genus to inhibit mycelium growth. Metabolite changes in fermented S. flavescens and E. sessiliflorus extracts were confirmed through LC-Q-TOF/MS. Flavonoid and peptide derivatives were improved in fermented S. flavescens and E. sessiliflorus extracts compared to their unfermented one, respectively. This study suggested that the isolated Bacillus microbial fermentation could be a valuable tool in improving the bioactivity of S. flavescens and E. sessiliflorus extracts to have potential with more environmentally-friendly antifungal agents.

The grain filling rate (GFR) plays a crucial role in determining grain yield. However, the regulatory and molecular mechanism of grain filling rate (GFR) in foxtail millet remains unclear. In this study, we found the GFR of 'Changnong No.47' (CN47) was significantly higher at 14 days after flowering (DAF) and 21 DAF in comparison to 'Changsheng 13' (CS13). Furthermore, CN47 also exhibited higher thousand grain weight and yield than CS13. Therefore, we conducted transcriptomics and metabolomics to analyze the biological processes and functional genes associated with GFR during two stages of grain filling in both cultivars. A total of 765 differentially expressed genes (DEGs) and 246 differentially accumulated metabolites (DAMs) were identified at the 14 DAF stage, while at the 21 DAF stage, a total of 908 DEGs and 268 DAMs were identified. The integrated analysis of co-mapped DAMs and DEGs revealed enriched pathways, including flavonoid biosynthesis, plant hormone signal transduction, tyrosine metabolism, ATP-binding cassette (ABC) transporters, beta-alanine metabolism, as well as stilbenoid, diarylheptanoid and gingerol biosynthesis. In order to elucidate their potential functions in the context of GFR, we developed a gene-metabolite regulatory network for these metabolic pathways. Notably we found some genes associated with ABC transporters and plant hormone signal transduction pathway were implicated in auxin transport and signal transduction, highlighting the crucial role of auxin during grain filling. The results provide initial insights into the regulatory and molecular mechanisms underlying GFR in foxtail millet, as well as offer valuable genetic resources for further elucidation of GFR in future studies. The findings have established a theoretical basis for improving the efficiency of yield breeding in foxtail millet.

Members of the SOX (SRY-related HMG-box) family of transcription factors are crucial for embryonic development and cell fate determination. This review investigates the role of SOX3 in cancer, as aberrations in SOX3 expression have been implicated in several cancers, including osteosarcoma, breast, esophageal, endometrial, ovarian, gastric, hepatocellular carcinomas, glioblastoma, and leukemia. These dysregulations modulate key cancer outcomes such as apoptosis, epithelial-mesenchymal transition (EMT), invasion, migration, cell cycle, and proliferation, contributing to cancer development. SOX3 exhibits varied expression patterns correlated with clinicopathological parameters in diverse tumor types. This review aims to elucidate the nuanced role of SOX3 in tumorigenesis, correlating its expression with clinical and pathological characteristics in cancer patients and cellular models. By providing a comprehensive exploration of SOX3 involvement in cancer, this review underscores the multifaceted role of SOX3 across distinct tumor types. The complexity uncovered in SOX3 function emphasizes the need for further research to unravel its full potential in cancer therapeutics.

The aim of this work was to describe the physiological limitations induced under drought conditions in young sweet orange trees, including the crop capability to recuperate its physiological status once re-watering, and after a water withholding. The trial was conducted during two consecutive months (July and August) in two-years old sweet orange trees. Three irrigation treatments were arranged: A full irrigation treatment; (FI); a low-frequency deficit-irrigation treatment (LFDI); and a sustained-deficit irrigation (SDI) treatment. The obtained results showed that for Stem values below -1.5 MPa, significant decreases in gas exchange rates, evidencing diffusive limitations to drought stress. Additionally, there was evidence of increased osmolyte synthesis, compatible as a defensive response to prevent oxidative damage. Likewise, the isohydric behaviour observed also resulted in significant decreases in gs even for moderate stress situations. In addition, it was observed that in the LFDI treatment, the stress levels reached caused a significant increase in the levels of Pro and MDA, which were not equal to those detected in FI during the recovery periods, which leads us to assume that potential values below -1.8 MPa would be causing significant oxidative damage with no capacity for subsequent recovery, and probably affecting the final yield.

The sperm heads of frozen/thawed horse spermatozoa were injected into ovulated mouse oocytes where they decondensed and formed paternal pronuclei in which the DNA damage has been evaluated. The motile spermatozoa exhibit none or minor level of DNA damage and the xenogenic zygotes cleave to the two-cell embryonic stage with regular nuclei and no micronuclei (MNs). On the other hand, the immotile spermatozoa exhibit typically high levels of DNA damage and blastomeres in two-cell stage embryos contain multiple MNs. Moreover, extremely high sperm DNA damage prevents even the cleavage to the two-cell stage.Keywords: keyword 1; keyword 2; keyword 3 (List three to ten pertinent keywords specific to the article yet reasonably common within the subject discipline.)

The substitution of chemical fertilizers by organic manure plays a critical role in sustainable crop production. Nevertheless, organic amendments promote the global warming potential (GWP) in rice paddies due to increased methane (CH4) emissions. Increasing evidence shows that lime application can reduce CH4 emissions from acidic paddy soils, while it is still not clear whether liming can reduce the GWP in rice fields under organic manure substitution. A two-year field experiment was conducted to investigate the impacts of pig manure substitution and lime application on grain yield, CH4 and nitrous oxide (N2O) emissions in a subtropical double-cropped rice field in China. The experiment consisted of three treatments: chemical fertilization (CF, 100% N from urea), 50% of chemical N substituted by pig manure (1/2N + M), and the 1/2N + M treatment plus lime amendment (1/2N + M + L). On average, 1/2N + M reduced rice yield by 5.65% compared to CF, while lime application had no effect on rice yield. Mean cumulative CH4 emissions were 218.8% higher in 1/2N + M than in CF, whereas 1/2N + M + L reduced CH4 emissions by 36.6% compared to 1/2N + M. Neither pig manure substitution nor lime application affected N2O emissions. Consequently, 1/2N + M increased the GWP and greenhouse gas intensity (GHGI) by 214.6% and 228.3%, respectively, compared to CF. In contrast, 1/2N + M + L reduced the GWP and GHGI by 36.4% and 36.5% compared to 1/2N + M. Lime application can mitigate CH4 emissions and GWP induced by pig manure amendment in double-cropped rice fields.

High resolution information on nucleotide arrangement in the genome of any or-ganism is critical to understand its genetic makeup, function, and evolutionary his-tory. For years, DNA sequencing has provided crucial breakthroughs in the field of genomics and molecular biology. With the advent of technology, Next Generation Sequencing has now transformed the whole genome sequencing prospects, thus unveiling the novel and interesting features of an organism genome that can behold. Next generation sequencing platforms offer realistic approach to identify and anal-yses whole genome with high throughput, accuracy, scalability in a very short time span. Information obtained can be further used in improving our existing healthcare systems, designing novel and personalized therapeutic modules, making the envi-ronment sustainable and proactively preparing ourselves for future pandemics and outbreaks. This article discusses the various NGS technologies and approaches, their advantages, drawbacks, and futuristic usage in different fields. Though still in nascent stages and marred with flaws, with ongoing advancement, NGS will indeed have promising impacts in the future.

Sirtuins (SIRTs) are a family of evolutionarily conserved enzymes, and the aim of this study was to disclose/re-annotate uncertain paralogs in gilthead sea bream, expanding from seven to ten the repertoire of Sirts in this Perciform fish. Such gene expansion revealed up to three copies of sirt3 (sirt3.1a/sirt3.1b/sirt3.2) and two of sirt5 (sirt5a/sirt5b). Phylogenetic and synteny attempts disclosed the duplication of SIRT3/Sirt3 branch as a process shaped by the 2R whole genome duplication (WGD) at the early vertebrate evolution, with still vestiges in all living fish, and some Sarcopterygii. In gilthead sea bream and other Percomorphaceae, this duplication was accompanied by short segmental duplications of sirt3.1 (clustered to the mammalian SIRT3 ortholog), making a conserved tandem-duplicated synteny block (psmd13-sirt3.1a/b-drd4-cdhr5-ctsd). Conversely, the expansion of the Sirt5 branch was shaped by the 3R WGD as a specific event of the teleost fish lineage. Intriguingly, gene expression profiling across tissues and developmental stages highlighted a conserved high expression of sirt3.1 and sirt5a in skeletal muscle, while the duplicated sirt3.2 and sirt5b displayed an overall muscle suppression of transcriptional activity, and an enhanced expression on immune-relevant tissues and gills, respectively. Altogether offers new insights about the function, regulation, and timing of Sirt expansion.

Nowadays, the identification and characterization of grapevine cultivars resilient to climate and water stress while preserving quality traits is crucial for the wine industry. Therefore, the objective of this work was to characterize according to their aromatic potential 9 white and 6 red minority cultivars recently recovered from Castilla-La Mancha region (Spain), subjected at two different water deficit regimes: rainfed, with subsistence irrigation, and irrigated. For this, the varietal aromatic potential index (IPAv) and the detailed aromatic composition were analyzed by HS-SBSE-GC/MS, in extracts of two different ph. For IPAv values, red varieties did not show a clear trend with respect to irrigation. However, in white minority varieties, higher values were obtained under irrigation conditions. Thus, a clear differentiation of the minority varieties in comparison to the references was observed, primarily attributed to the content of esters and acids, in both white and red varieties. A notable contrast was observed at different pH, indicating a greater extractability of certain compounds like linalool, under more acidic conditions. This suggests that some recovered minority cultivars could be promising for cultivation in semi-arid regions with limited water, contributing to the wine sector sustainability in the future.

Yeast, crucial in beer production, holds promise as a valuable by-product resource, known as brewer's spent yeast (BSY), with potentially beneficial physiological effects. This study aimed to compare the composition and soluble polysaccharide content of Brewer's spent yeast with those of pure cultured yeast strains, namely Saccharomyces cerevisiae (SC) and S. boulardii (SB), to facilitate the utilization of BSY as an alternative source of functional polysaccharides. BSY exhibited significantly higher carbohydrate content and lower crude protein content than SC and SB cells. The residues recovered through autolysis were 53.11%, 43.83%, and 44.99% for BSY, SC, and SB, respectively. Notably, the polysaccharide content of BSY residue (641.90 μg/mg) was higher than that of SC (553.52 μg/mg) and SB (591.56 μg/mg). The yields of alkali-extracted water-soluble polysaccharides were 40%, 30%, and 35% for BSY, SC, and SB, respectively, with BSY comprising a higher proportion of water-soluble saccharides than SC and SB, including 49.3% mannan and 20.1% β-glucan. Furthermore, BSY demonstrated antioxidant activities, including superoxide dismutase (SOD), ABTS, and DPPH scavenging potential, suggesting its ability to mitigate oxidative stress. BSY also exhibited a significantly higher total phenolic compound content, indicating its potential as an effective functional food material.

The majority of investigations on microbial communities from various environments are presently built on culture-independent methods. Many studies point to the pivotal, selective role of primers targeting hypervariable regions of 16S rRNA in the metabarcoding of bacteria, including cyanobacterial communities. The selectivity of primers designed to amplify targeted regions of the 16S rRNA gene, which has been highlighted by many authors, limited effective amplification. Moreover, the type and specificity of the studied material can also negatively influence the results of 16S metabarcoding. Most of the studies of cyanobacterial communities have been performed for planktonic microbial communities that are often represented by common, well-studied species. In this study, we present the results of 16S metabarcoding analysis using three primer pairs - two already well-known and a third designed in this study - that amplify divergent regions of the 16S rRNA gene (V3-V4, V4-V6, V6) for benthic, microbial mat-forming cyanobacteria communities. Such communities can be a source of toxigenic cyanobacterial taxa and should be monitored with adequate primers. The comparison of three primer pairs suggested that those designed within the present study describe the structure and composition of highly heterogeneous cyanobacterial mats’ communities better than the others

Cancer is a disease caused by the abnormal growth of cells in different parts of body is one of the top causes of death globally. Microarray gene expression data plays a critical role in the identification and classification of cancer tissues. Due to recent advancements in Machine Learning (ML) techniques, researchers are analyzing gene expression data using a variety of such techniques to model the progression rate &amp; treatment of cancer patients with great effect. But high dimensionality alongside the presence of highly correlated columns in gene expression datasets leads to computational difficulties. This paper aims to propose the use of ML classification techniques- Linear Discriminant Analysis (LDA) &amp; Random Forest (RF) for classifying five types of cancer (breast cancer, kidney cancer, colon cancer, lung cancer and prostate cancer) based on high dimensional microarray gene expression data. Principal component analysis (PCA) was used for dimensionality reduction, and principal component scores of the raw data for classification. Six distinct categorization performance measures were used to evaluate these approaches; RF method provided us with higher accuracy than LDA method. The method and results of this article should be helpful to researchers who are dealing with many genes in microarray data.

Previously, we described a 19-base pair double-stranded RNA with 3'-trinucleotide overhangs, acting as immunostimulatory RNA (isRNA). This molecule demonstrated notable antiproliferative effects on cancer cells, inhibited tumor growth, and elicited immunostimulatory and antiviral responses by inducing cytokine and interferon production. Within this study, we compared the efficiency of lung fibrosis development, initiated in mice by BLM or LPS using different schemes of induction. Then we compared the effect of isRNA used in a preventive or therapeutic regimen on the development of fibrosis in selected BLM- and LPS-induced mouse models and showed that isRNA can be used in pathological conditions accompanied by the development of inflammation and the risk of fibrosis formation, without adverse side effects. Prophylactic regimen of isRNA application is beneficial for prevention of the development of pulmonary fibrosis.

The FAS ligand (FASLG) is expressed on lymphocytes, which employ it to activated death receptors on targets cells. Cancer cells are generally resistant to apoptosis triggered by FASLG. In this work we found a way to circumvent this resistance by treatment with actinomycin D (ActD) and nutlin-3a (Nut3a). We selected this drug combination based on our transcriptomic data showing strong activation of proapoptotic genes, including the ones for receptor mediated apoptosis, in cells exposed to actinomycin D and nutlin-3a. To test our hypothesis, we pre-exposed cancer cell lines to this drug combination for 45h and next we treated them with recombinant FASLG. This almost instantaneously killed most cells. Actinomycin D and nutlin-3a strongly synergized in the sensitization because the effect of the drugs acting solo was not as spectacular as the drug combination, which together with FASLG killed more than 99% of cells. Based on the caspase activation pattern (caspase-8, caspase-9, caspase-10), we conclude that both extrinsic and intrinsic pro-apoptotic pathways were engaged. In engineered p53-deficient cells this pro-apoptotic effect was completely lost. Therefore, the combination of ActD+Nut3a activates p53 in an extraordinary way, which overcomes the resistance of cancer cells to apoptosis triggered by FASLG. Interestingly, other combinations of drugs, e.g., etoposide + nutlin-3a, actinomycin D + RG7112 and actinomycin D + idasanutlin had similar effect. Moreover, normal human fibroblasts are less sensitive to death induced by ActD+Nut3a+FASLG. Our findings create the opportunity to revive the abandoned attempts of cancer immunotherapy employing the recombinant FAS ligand.

More than 20 years after the discovery of the first anelloviruses (AVs), they still remain a mysterious group of viruses. To date, there is no clear understanding of their impact on the host organism, although information is emerging about their participation in various pathologies. However, it is well known that AVs are an important component of the human virome. In the current study we assessed the abundance of AVs in viromes from four nasal and pharyngeal samples from children with respiratory symptoms using a metagenomic approach. It is worth noting that three patients had known respiratory viruses and one did not have any. Regarding AVs, they were detected in all samples, namely Torque teno mini virus (TTMV). The greatest abundance and diversity of AVs (Torque teno virus (TTV), TTMV and Torque teno midi virus (TTMDV)) were shown in a diseased patient with an absence of respiratory viruses, which may indicate the potential involvement of AVs in the maintenance of respiratory symptoms. An activated immune system to combat the main pathogens, against the background of which the number of AVs decreases, is discussed as a possible reason for the reduced diversity of anellome in other patients. We also compared the results of the metagenomic approach and qPCR for major respiratory viruses, which were in agreement. In addition, metagenomic sequencing made it possible to obtain additional data on viral genomes in order to establish their taxonomic identification and characterize individual viral profiles in patients from the Siberian part of Russia.

The present study aimed to determine the genetic diversity of isolates of Mycobacterium tuberculosis (Mtb) from presumed drug resistant tuberculosis patients from several states of Brazil. The isolates had been submitted to conventional drug susceptibility testing for first- and second-line drugs. Multidrug-resistant (MDR-TB) (54.8%) was the most frequent phenotypic resistance profile, in addition to an important high frequency of pre-extensively resistant (p-XDR-TB) (9.2%). Using whole-genome sequencing (WGS), we characterized 298 Mtb isolates from Brazil. Besides analysis of genotype distribution and possible correlations between molecular and clinical data, we determined the performance of an in-house WGS pipeline with other online pipelines for Mtb lineages and drug resistance profile definition. Sub-lineage 4.3 (52%) was the most frequent genotype and the genomic approach revealed a p-XDR-TB level of 22.5%. We detected 20 novel mutations in three resistance genes, and six of these were observed in eight phenotypically resistant isolates. Cluster analysis of 170 isolates showed that 43.5% of the TB patients belonged to 24 genomic clusters, suggesting considerable ongoing transmission of DR-TB, including two interstate transmissions. The in-house WGS pipeline showed the best overall performance in drug-resistance prediction, presenting the best accuracy values to five of nine drugs tested. Significant associations were observed between suffering from fatal disease and genotypic p-XDR-TB (p = 0.03) and either phenotypic (p = 0.006) and genotypic (p = 0.0007) ethambutol resistance. The use of WGS analysis improved our understanding of the population structure of MTBC in Brazil, genetic and clinical data correlations and demonstrating its utility for surveillance efforts for spread of DR-TB, hopefully helping to avoid the emergence of even more resistant strains and to reduce TB incidence and mortality rates.

Amylose content (AC) stands as a pivotal determinant of rice grain quality, primarily governed by the Waxy gene (Wx), with its allelic diversity significantly influencing AC variation. In the current culinary landscape, soft rice varieties, known for their low AC and superior palatability, are particularly sought after by consumers. Notably, many soft japonica rice varieties cultivated in southern China, including the Nangeng series, are characterized by the presence of the Wxmp allele, derived from the ancestral Wxmq allele. While both alleles are associated with reduced AC, there remains a paucity of detailed understanding regarding the interplay between specific functional single nucleotide polymorphisms (SNPs) within these alleles and the overarching rice grain quality. Employing site-directed mutagenesis, we engineered three distinct transgenic rice lines, each harboring either the Wxmp, Wxmq, or Wxb-5c alleles, against the background of the glutinous rice cultivar Nip(wx). This suite of transgenic rice showcased a gradation ingrain transparency inversely correlated to AC, delineating a sequence from Wxmq, signifying the lowest, through Wxmp, to Wxb-5c, indicating the highest. Consequently, this gradation in AC precipitated variations in other rice grain physicochemical attributes, such as the taste value of cooked rice, gel consistency (GC), and starch pasting properties. Furthermore, analyses of gene expression and enzyme activity revealed that the functional SNPs, Ex4-53G/A and Ex5-53T/C, lead to a decline in the GBSSI enzyme activity without affecting expression levels. These findings underscore the potential of harnessing these SNPs in breeding programs aimed at developing soft rice varieties endowed with enhanced culinary qualities.

The replication of species A rotaviruses (RVAs) and other RNA viruses involves recruitment of and inter-action with the cellular organelles lipid droplets (LDs), both physically and functionally. Inhibition of en-zymes involved in the cellular fatty acid biosynthesis pathway or of cellular lipases that degrade LDs re-duces the functions of ‘viral factories’ (viroplasms for rotaviruses or replication compartments of other RNA viruses) and decreases the production of infectious progeny virus. Similarly, disturbance of the cellular lipid homeostasis in various ways blocks the replication of flaviviruses (hepatitis C viruses, Zikavirus, others), HIV-1, SARS-CoV-2, picornaviruses, noroviruses, influenza viruses and other negative-strand RNA viruses.

Salmonella infections can lead to intestinal inflammation and metabolic disorders in birds. However, whether ARA metabolism is involved in Salmonella-induced intestinal inflammation remains unclear. This experiment investigated the changes in cecal flora and arachidonic acid (ARA) metabolism in Hainan Wenchang chickens infected with S. Typhimurium using 16s rDNA sequencing and targeted metabolomics. The results showed that the levels of ARA metabolites were increased in the cecum tissue of Wenchang chickens after infection with S. Typhimurium, including prostaglandin E2, prostaglandin F2α, lipoxin A4, ±8(9)-EET, ±11(12)-EET, and ±8,9-DiHETrE. The content of key enzymes for ARA production and metabolism (PLA2 and COX-2) in chicken cecum tissues was increased after S. Typhimurium infection. The relative mRNA levels of inflammatory factors were also increased after infection, including IFN-γ, TGF-β1, IL-4, and IL-6. In HD11 cells, the use of a cyclooxygenase (COX) inhibitor reduced the increased levels of COX-2 and PGF2α induced by S. Typhimurium infection and effectively reduced the inflammatory response. In addition, the number of beneficial genera (e.g., Bifidobacterium, Lactobacillus, and Odorobacterium) in the cecum of Wenchang chickens was significantly reduced after infection with S. Typhimurium. In this study, we revealed the structure of the cecal flora of Wenchang chickens infected with S. Typhimurium and demonstrated that S. Typhimurium can mediate the onset and development of intestinal inflammation through the activation of the metabolic pathway of ARA cyclooxygenase in Wenchang chickens. The results can provide data support and theoretical support for the prevention and control of avian salmonellosis.

A single-center, randomized, double-blind, placebo-controlled clinical trial with two arms was conducted in 71 healthy subjects suffering from sleep disturbances, which were treated with a dietary supplement based on an extract of Aloysia citrodora (or Lippia citriodora, lemon verbena) (n = 33) for 90 days. Subjects in the placebo group (n = 38) received capsules of microcrystalline and maltodextrin with the same organoleptic properties. Between-group significant differences in favor of the experimental group were found in the visual analogue scale (VAS) score rating sleep quality; overall score, sleep latency and sleep efficiency of the Pittsburg Sleep Quality Index (PSQI); and sleep latency, sleep efficiency, wakefulness after sleep onset and duration of awakening assessed by actigraphy. Plasma nocturnal melatonin levels also increased significantly in the experimental group. Changes in anthropometric parameters and physical activity levels were not found. This study shows that the administration of a dietary supplement comprised lemon verbena administered for 3 months was associated with a significant improvement of sleep quality as compared with placebo in a population of healthy subjects with sleep problems. Improvements were also apparent at the mid-study visit after 45 days of supplementation.

The p53 tumor suppressor protein shows antiviral activity. The replication of viruses is also antagonized by interferons (IFNs) – cytokines, which control immunity genes by the STAT transcription factors. The best studied interferons belong to type I (e.g. IFNα) and type II (IFNγ) groups. IFNα and IFNγ both induce activating phosphorylation of STAT1 on Tyr701. Previously, we noticed that p53 activates SOCS1, which is a negative regulator of STAT1 phosphorylation. Thus, we hypothesized that p53 by activating SOCS1 expression reduces phosphorylation of STAT1 and attenuates activation of genes stimulated either by IFNα or IFNγ. To test this hypothesis, we exposed p53-proficient and p53-deficient cells to strong p53 activators, and either to IFNα or IFNγ. Subsequently, we estimated the phosphorylation status of STAT1 and the expression of genes regulated by either of these cytokines. Strong activation of p53 reduced the phosphorylation of STAT1 on Tyr701, however surprisingly it did not lead to reduced expression of most tested interferon-stimulated genes. On contrary, p53 and IFNγ synergized in the activation of CASP1, IFIT1 and IFIT3 genes. We conclude that the interactions between p53 and interferon-activated pathways are more complicated than initially expected, but the apparent cooperation between p53 and IFNγ deserves further studies.

Spinal muscular atrophy (SMA) is an orphan disease characterized by progressive degeneration of spinal alpha motor neurons. In recent years, nusinersen and several other drugs have been approved for the treatment of this disease. Transcutaneous spinal cord stimulation (tSCS) modulates spinal neuronal networks, resulting in changes in locomotion and posture in patients with severe spinal cord injury and stroke. We hypothesize that tSCS can activate motor neurons that are intact and restored by medication, slow the decline in motor activity, and contribute to the development of motor skills in SMA patients. Thirty-seven children and adults with SMA types 2 and 3 participated in the study. The median duration of drug treatment was over 20 months. Application of tSCS was performed during physical therapy for 20-40 minutes per day for ~12 days. Outcome measures were specific SMA motor scales, goniometry of contractured joints, forced vital capacity. Significant increases in motor function, improved respiratory function, and decreased contracture were observed in both types 2 and 3 SMA participants. The magnitude of functional changes was not associated with participants age. Further studies are needed to elucidate the reasons for the beneficial effects of spinal cord electrical stimulation in SMA.

“Pecorino” is a typical semi-hard cheese obtained with raw or heat-treated sheep milk using procedures to valorize the raw material's chemical and microbiological properties. In the present study, using a high throughput method of 16S rRNA gene sequencing, we assessed the evolution of the microbiome composition from milk to Pecorino cheese in artisanal processes using milk from Comisana and Lacaune sheep breeds. The comparative analysis of the bacterial com-munity composition revealed significant differences in the presence and abundance of specific taxa in the milk microbiome of the Comisana and Lacaune breeds. NGS analysis also revealed differences in the curd microbiome related to dairy farming practices, which have a relevant effect on the final structure of the Pecorino-cheese microbiome.

Molluscs are significant species in aquatic ecology. Molluscs are crucial for maintaining ecological balance as secondary consumers and serving as bioindicator species in biomonitoring systems. Molluscs are threatened by pesticides such as commonly used pyrethroid insecticides. Pyrethroids are typical insecticides used to control insects in agriculture and gardening. Pyrethroids are increasingly being utilized in both agricultural and human activities. Pyrethroids enter aquatic bodies through rainfall and drainage systems. The use of pyrethroids is becoming a significant concern for aquatic creatures, particularly molluscs. The discussion will focus on the increasing issue of pyrethroids becoming a nightmare for molluscs. Pyrethroids, due to their lipophilic nature, pose a significant risk to molluscs by affecting their metabolites, producing reactive oxygen species, and influencing neurotransmitter actions. Molluscs are crucial organisms in aquatic ecosystems, and their threats warrant significant discussion and attention. This review will delve into the behaviour of pyrethroids on molluscs.

This study introduces the MuhdoAge clock, a novel saliva-based epigenetic clock, designed to predict biological age with strong correlations in a healthy, disease-free cohort. Leveraging a comprehensive dataset from Muhdo Health, this research analyses saliva samples utilising the Illumina MethylationEPIC array. Through robust statistical methods, 237 significant CpG sites were identified that correlate with age-related methylation changes, exhibiting a coefficient of determination (R²) of 0.652 after outlier removal, with tiered algorithmic design improving this further to 0.726 in a new dataset that combined pathologic and healthy individuals (n=2682). Comparatively, the MuhdoAge clock was evaluated against other known epigenetic clocks, demonstrating high precision in predicting biological age within healthy individuals (R² = 0.878, n=1844), emphasising its potential utility in non-invasive, large-scale applications. The clock shows promise for integration into public health strategies for monitoring and potentially mitigating age-related decline, facilitated by its ease of use and accessibility through saliva sampling. Furthermore, this study highlights the impact of lifestyle and environmental factors on biological ageing, highlighting the importance of personalised health interventions. Future research is to focus on longitudinal studies to validate these findings and explore the mechanisms underlying epigenetic age acceleration.

The predatory mirids Macrolophus pygmaeus Ramber and Nesidiocoris tenuis Reuter (Heteroptera: Miridae) are used for the biological control of Tuta absoluta Meyrick (Lep.: Gelechiidae) and other pests in tomato greenhouses. The functional response of 1 (young) and 10 (old) days old adult females and males of M. pygmaeus and N. tenuis on eggs of T. absoluta, was determined on tomato at two temperatures (20° and 25°C) and LD 16:8 and found to be Type II. M. pygmaeus females exhibited higher predation efficiency, than males at both tested temperatures. Young M. pygmaeus females had a higher efficiency than old ones, whereas males had a low efficiency irrespective of age. The predation efficiency of N. tenuis was high (but lower than M. pygmaeus) in both young females and males, although old females had a higher efficiency than the respective males. Our results show that the two predatory species have different functional response characteristics to their prey depending mainly on sex and age which may affect their role as biological control agents.

Tunicate orthologs in the human genome comprise just 84 genes of the 19,872 protein-coding genes, yet they stand at the base of the Olfactores clade - which radiated to generate thousands of tunicate and vertebrate species. What were the powerful drivers among the 84 that enabled this process? Many of these orthologs are present in gene families. We discuss the biological role of each family and the orthologs’ quantitative contribution to the family. Most important was the evolution of a second type of cadherin. This, a Type II cadherin, had the property of detaching the cell containing that cadherin from cells that expressed the Type I class. The set of such Type II cadherins could now detach and move away from their Type I neighbours, a process which would eventually evolve into the formation of the neural crest, “ the fourth germ layer”, providing a wide range of possibilities for further evolutionary invention. A second important contribution were key additions to the broad development of the muscle and nerve protein and visual perception tool-kits. These developments in mobility and vision provided the basis for the development of the efficient predatory capabilities of the Vertebrata.

Functional genomics, a multidisciplinary subject, investigates the functions of genes and their products in biological systems to better understand diseases and find new drugs. Drug repurposing is an economically efficient approach that entails discovering novel therapeutic applications for already-available medications. Genomics enables the identification of illness and therapeutic molecular characteristics and interactions, which in turn facilitates the process of drug repurposing. Techniques like gene expression profiling and Mendelian randomization are helpful in identifying possible medication candidates. Progress in computer science allows for the investigation and modelling of gene expression networks that involve large amounts of data. The integration of data from DNA, RNA, and protein activities has resemblance to pharmacogenomics, which is of utmost importance in the development of cancer drugs. Functional genomics in drug discovery, particularly for cancer, is still not thoroughly investigated, despite the existence of a significant amount of literature on the subject. Next-generation sequencing and proteomics present highly intriguing opportunities. Publicly available databases and mining techniques facilitate the development of cancer treatments based on functional genomics. Expanding the study and application of functional genomics has great promise to advance the process of discovering and repurposing drugs, especially in the field of oncology.

The individual and combined effects of extracellular products (ECP) from Arthrobotrys oligospora (Ao) and A. musiformis (Am) growth in liquid media against Haemonchus contortus L3 (HcL3) were assessed. The following methodological steps were established: isolation, morphological (MI) and molecular identification (Mol-I), assessment of nematocidal activity (NA) of fungal liq-uid culture filtrates (LCF) produced in two liquid media alone and in combination and finally, the myco-compound profile identification (MCP). The MI of both isolates suggested that the fungi corresponded to the species Ao and Am. This result was confirmed by PCR analysis followed by sequencing, alignment and obtaining coverage and similarity with respect to isolates reported in the NCBI database. Likewise, the highest Hc mortalities were 91.4% with individual LCF of Am and 86.2% with those of Ao at the highest concentration (100 mg/mL) in Czapek-Dox Broth. The combination of both LCF resulted in a similarly high larval mortality with no statistical differ-ences in relation to individual activity (P>0.05). The MCP showed the presence of alkaloids in both fungi. Coumarins, triterpenes and saponins were found only in Ao. Both fungi produced ECP with a high NA that could be identified and assessed in future studies as potential natural an-thelmintic compounds.

Salt stress is a major limiting factor for alfalfa yield due to its relatively low salt tolerance. High soil salinity adversely impacts alfalfa growth and development, leading to reduced yield. Melatonin (MT) is known to play a significant role in enhancing plant resistance to abiotic stresses. However, the mechanisms underlying melatonin-mediated abiotic stress responses, particularly salt stress, are not well understood. To address this gap, we conducted a study focusing on germinating alfalfa seeds under salt stress. Physiological indexes and transcriptomics analyses were carried out on the germinated seeds to investigate the effects of melatonin on alfalfa seedlings under salt stress conditions. Our results revealed that the application of melatonin led to an increase in shoot length and fresh weight of alfalfa seedlings under salt stress. Moreover, key physiological indexes such as peroxidase (POD) activity and glutathione (GSH) content were enhanced, while levels of malondialdehyde and superoxide anions decreased. Transcriptomic analysis identified a total of 2,131 differentially expressed genes in the salt-treated group, with 726 up-regulated and 1,405 down-regulated genes, while the MT-treated group showed 2896 differentially expressed genes, of which 1,097 were up-regulated and 1,799 were down-regulated. Further, KEGG enrichment analysis highlighted the enrichment of differentially expressed genes in pathways including flavonoid biosynthesis, ABC transporter, glutathione metabolism, and the MAPK signaling pathway, with these pathways more significantly enriched in the MT-treated group. These findings collectively suggest that melatonin plays a crucial role in alfalfa's response to salt stress and offer new insights into the genomic mechanisms underlying melatonin-mediated salt tolerance in alfalfa.

Cell-to-cell distant mechanical communication has been demonstrated by using in-vitro and in-vivo models. However, the molecular mechanisms underlying long-range cell mechanoresponsive interactions remain to be more elucidated. This study further examined the roles of α-Catenin and Piezo in traction force-induced rapid branch assembly of airway smooth muscle (ASM) cells on Matrigel hydrogel containing type I collagen. Our findings demonstrate that siRNA-mediated downregulation of α-Catenin or chemical inhibition of Piezo activity significantly reduced both cell directional movement and branching assembly. In regarding the role of N-cadherin in regulating branch assembly but not directional migration, our results further confirmed that siRNA downregulation of α-Catenin caused a remarked reduction of focal adhesion formation, as assessed by focal Paxillin and Integrin α5 localization. These observations implied that mechanosensitive α-Catenin was involved in both cell-cell and cell-matrix adhesions. Additionally, Piezo showed partial localization with Paxillin in focal adhesions, which was inhibited by α-Catenin downregulation with siRNA. This provides a plausible clue for Piezo mechanosensing traction force in the hydrogel. Collectively, our findings highlight the significance of α-Catenin in regulating cell-matrix interactions along with possible interpretation for Piezo mechanosensation at focal adhesions during cell-cell distant mechanical communication.

This study aimed to investigate the potential of Cord Blood Stem Cell-derived exosome vesicles (CBSC-EVs) in regulating cancer growth and preventing cellular damage. The study aimed to examine the effects of CBSC-EVs on CHL1 cancer cells and healthy fibroblasts. The study results reveal that CBSC-EVs have an anti-cancer/antioxidant effect on CHL1 cancer cells without inducing any toxic effects on healthy lymphocytes. Further analysis of CBSC-EVs revealed the presence of seven miRNAs (noncoding RNA molecules), including three from the Let 7 family, two from the Let 5 family, and two novel miRNAs. The function of the novel miRNAs was the main focus of the study. To assess the efficacy of CBSC-EVs, CHL1 cells (a type of malignant melanoma cell line) and human fibroblasts were grouped into different treatments. One group of those cell lines were treated with CBSC-EVs, and in the second group, the cells were transfected with either miRNA inhibitor Novel 1 (miRNA IN1) plus CBSC-EVs or miRNA inhibitor Novel 2 (miRNA IN2) and CBSC-EVs to knock down those novel miRNAs in the CBSC-EVs. Therefore, by comparing these groups, the function of novel miRNAs is more understandable. In this study, the Comet assay was employed to evaluate cancer cells' DNA damage and CCK8 to measure cell viability. The findings revealed that CBSC-EVs caused an increase in DNA damage in CHL1 cells compared to cells without treatment (p

Avian influenza viruses (AIVs) are highly contagious respiratory viruses of birds, lead-ing to significant morbidity and mortality globally and causing substantial economic losses to the poultry industry. Since their first isolation in 2013, the Asian-origin H5N1 highly pathogenic avian influenza viruses (HPAI) of clade 2.3.4.4b have undergone unprecedented evolution and re-assortment of internal gene segments and have spread to Asia, Europe, Africa, and America, caus-ing outbreaks in all the poultry categories. Novel epidemiological and pathobiological character-istics, distinct from other clades, are specific of clade 2.3.4.4b viruses. Wild waterfowl, the natu-ral reservoir of AIVs, are frequently found infected with clade 2.3.4.4b viruses, which can also cause high morbidity and mortality in these birds. The sustained clade 2.3.4.4b virus circulation in waterfowl has also led to virus infection in other wild bird species, with implications for the conservation of endangered species. Furthermore, clade 2.3.4.4b viruses have been isolated in var-ious wild and domestic mammals worldwide, and critical mutations related to virus adaptation to mammalian species have been identified, raising concerns about virus spillover to humans. The main clinical signs, and anatomopathological findings associated to clade 2.3.4.4b virus infection in birds and non-human mammals are hereby summarized.

Candidiasis is considered an emerging public health concern because of the occurrence of drug-resistant Candida strains and the lack of available structurally diverse antifungal drug armamentariums. The indole alkaloid globospiramine from the anticandidal Philippine medicinal plant Voacanga globosa exhibits a variety of biological activities; however, its antifungal properties remain to be explored. In this study, we report the in vitro antifungal activities of globospiramine against Candida albicans and Candida tropicalis and explore its possible target proteins using in silico methods. The colony-forming unit (CFU) viability assay revealed time- and concentration-dependent anticandidal effects of the alkaloid by decreasing almost 50% of the viable CFUs 60 min after treatment. Results of the MIC and MFC assays indicated inhibitory and fungicidal effects of globospiramine against C. albicans (MIC = 8 µg/mL; MFC = 4 µg/mL) and potential fungistatic effects against C. tropicalis at lower concentrations (MIC = 4 µg/mL; MFC &gt; 64 µg/mL). The FAM-FLICA poly-caspase assay showed metacaspase activation in C. albicans cells at concentrations of 16 and 8 µg/mL, which agreed with the MIC and MFC values. Molecular docking and molecular dynamics simulation experiments indicated stable, strong binding of globospiramine with the target proteins 1,3-β-glucan synthase and Als3 adhesin enzymes, which are indirectly involved in apoptotic-driven candidal inhibition.

The River Habitat Survey (RHS) is a method for assessing the conditions of a river channel and valley, taking into account hydromorphological factors, and assessing the degree of naturalness or the degree of anthropogenic alteration within the channel and valley based on physical and landscape data. The hypothesis tested in this study was that the quality of river habitats demonstrated using the RHS should translate into the composition of their fauna. We investigated aquatic bugs (Heteroptera Aquatica), which are a group with considerable dispersal abilities and, at the same time, composed of stenotopic species associated with a particular environment as well as of eurytopic elements inhabiting a wide range of environments (REF). The research was carried out in a small lowland river, the River Krąpiel (north-western Poland) at 6 sites with 43 sub-sites included. Our analyses suggest the RHS method can predict the composition and quality of the aquatic bug fauna inhabiting a given river. Indicators of river habitat quality (HQA and RHQ) will be associated with different habitat types depending on the geographic location and type of river, once indicating habitats associated with the mainstream river and mineral substrate (mountain and small lowland rivers) and at other times habitats covered by vegetation with relatively slow water flow (large and medium lowland rivers). Therefore, RHS may be a good method for estimating the water bug fauna, linking it to the size and character of the river.

The article features the structure and functions of plant synthetic promoters frequently exercised to precisely regulate complex regulatory routes. The composition of plant native promoters together with interacting proteins is presented to provide a better understanding of tasks associated with synthetic promoter development. The production of synthetic promoters is conferred on relatively small libraries produced generally by basic molecular or genetic engineering methods such as cis-element shuffling or domain swapping. Moreover, the preparation of large-scale libraries supported by synthetic DNA fragments, directed evolution, and machine or deep learning methodologies is presented. A particularly interesting group of synthetic promoters are bidirectional forms that enable the putative expression of up to 6–8 genes by one regulatory element. The introduction and controlled expression of several genes after one transgenic event strongly decreases the frequency of such problems as complex segregation patterns and random integration of multiple transgenes. These complications are commonly observed during transgenic crop development through traditional, multistep transformation by genetic constructs containing a single gene. Another path to solving problems associated with the low complexity and homology of already tested DNA fragments is through orthogonal expression systems composed of synthetic promoters and trans-factors that do not occur in nature or arise from different species. Their structure, functions, and applications are rendered in the article.

Faba bean is an important legume crop wordwide, grown both for food and feed. As for many legume crops, postemergence weed control is difficult. The aim of this work was to assess potential of intercropping on weed management by assessing the effect of mixing faba bean with different crops (wheat, barley, and pea) on weeds in the South of Spain. Four field trials were conducted over four consecutive seasons, and results found that addition alternate intercropping of faba bean and barley achieved high levels of weed control, both for coverage and biomass (92.7% and 76.6%, respectively). Intercropping with wheat did not reduce weed coverage but did decrease weed biomass by 46.1% as compared to faba bean monocrop. Intercropping with pea did not provide significant reductions for weed coverage neither for weed biomass. The diversity of the weed community was not altered by the different crop combinations tested. Additional experiments under controlled conditions were carried out to determine a possible role of barley allelopathy in weed suppression. A strong allelopathic effect entailing a reduction in the number of plants and biomass was detected for four weeds: Sinapis arvensis, Polypogon monspeliensis, Matricaria camomilla, and Medicago trucatula. It can be concluded that intercropping faba bean with barley is an excellent strategy for weed control in the Southern Spain.

Precise monitoring of individual crop growth and health status is crucial for precision agriculture practices. However, traditional manual inspection methods are time-consuming, labor-intensive, and often lack the spatial resolution required for detailed analysis. This research addresses the need for efficient and high-resolution crop monitoring by leveraging Unmanned Aerial Vehicle (UAV) imagery and advanced computational techniques. The primary objective was to develop a methodology for precise identification, extraction, and monitoring of individual corn crops throughout their growth cycle. This was achieved by integrating UAV-derived data with image processing, computational geometry, and machine learning techniques. UAV imagery was ac-quired bi-weekly at altitudes of 40m and 70m, capturing the entire growth cycle of a corn crop from planting to harvest. A time-series Canopy Height Model (CHM) was generated by analyzing the differences between the Digital Terrain Model (DTM) and the Digital Surface Model (DSM) derived from the UAV data. Local spatial analysis and image processing techniques were em-ployed to determine the local maximum height of each crop. Subsequently, a Voronoi data model was developed to delineate individual crop canopies, successfully identifying 13,000 out of 13,050 corn crops in the study area. For enhanced accuracy in canopy size delineation, vegetation indices were incorporated into the Voronoi model segmentation, refining the initial canopy area esti-mates by eliminating interference from soil and shadows. The proposed methodology enables precise estimation and monitoring of crop canopy size, height, biomass reduction, lodging, and stunted growth over time, providing valuable insights for precision agriculture practices. This work contributes to the scientific community by demonstrating the potential of integrating UAV technology, computational geometry, and machine learning for accurate and efficient crop mon-itoring at the individual plant level.

Fungal infections caused by Candida spp. are responsible for high hospital morbidity and mortality rates. Therefore, there is a continuous search for new antifungal medicines, particularly ones with anti-Candida activity. This review analyzed articles published between 2002 and 2023 considering the anti-Candida activity of chemical compounds identified or isolated in plants of the Anacardiaceae family. In addition, the in-silico prediction of the isolated compounds described was performed. The analysis of 35 studies showed that extracts, essential oils, and compounds from the anti-Candida activity were frequently determined in vitro using the minimum inhibitory concentration (MIC). The most commonly tested species were Candida albicans, C. tropicalis, C. parapsilosis, C. glabrata, C. krusei, and C. guilliermondii, respectively. Essential oils were the most used form (37% of the studies). The isolated compounds with antifungal effects include cardanol, estragole, trans-anethole, β-caryophyllene, myrcene, catechin-3-o-rhamnoside, β-sitosterol-3-O-glucoside, 24Z-isomasticadienolic acid, oleanolic acid, and oleanolic aldehyde. The in-silico evaluation of those isolated compounds revealed the compounds' drug-likeness and possible antifungal activity. However, some of them showed high toxicity. In conclusion, compounds from the Anacardiaceae family show promise for developing new therapeutic antifungal drugs, especially in combination with conventional antifungals.

It has been proposed that procedures which up-regulate mitochondrial biogenesis and autophagy by replacing damaged mitochondria with healthy ones, may prevent the development of several heart diseases. A member of serine and threonine kinases, AMPK, could play essential roles in the autophagy and/or mitophagy. AMPK is widely distributed in various cells, which might play diverse regulatory roles in different tissues and/or organs. In fact, changes in the kinase function of AMPK due to alteration of activity have been linked with diverse pathologies including cardiac disorders. AMPK can regulate mitochondrial biogenesis via PGC1α signaling and also improve oxidative mitochondrial metabolism through inhibition of mTOR pathway, which may also modulate the autophagy/mitophagy through ULK1 and/or TGF-β signaling. Therefore, the modulation of AMPK in autophagy/mitophagy pathway might be considered as a therapeutic tactic for several cardiac disorders. As kinases are amongst the most controllable proteins, in general, the design of small molecules targeting kinases might be an eye-catching avenue to modulate the cardiac function. Some analyses of the molecular biology underlying mitophagy suggests that nutraceuticals and/or drugs including specific AMPK modulator as well as physical exercise and/or dietary restriction that could modulate AMPK may be useful against several heart diseases. In particular, some nutraceutical regimens may have encouraging potential for controlling some of cardiac disorders.

The photosystem I (PSI) of the green alga Chlamydomonas reinhardtii associates with 10 light-harvesting proteins (LHCI) to form the PSI-LHCI complex. Binding of LHCII to PSI may also occur and is controlled by a process called state transitions. Hereby, two LHCII trimers bind to the PSAL, PSAH and PSAO side of PSI to produce the PSI-LHCI-LHCII complex. In this work, we took advantage of chemical crosslinking of proteins in conjunction with mass spectrometry to identify protein-protein interactions between the light-harvesting proteins of PSI and PSII. We detected binding of LHCBM proteins to the LHCA1-PSAG side of PSI and identified protein-protein interactions of LHCSR3 with LHCA5 and LHCA3. Our data indicate that the binding of LHCII to PSI is more versatile as anticipated and reveal that LHCSR3 likely regulates excitation energy transfer to the PSI core via LHCA5/LHCA3.

Protein Kinase C delta (PKCδ) has emerged as a key protective molecule against systemic lupus erythematosus (SLE or lupus), an autoimmune disease characterized by anti-double stranded (ds) DNA IgGs. Although PKCδ deficient mice and lupus patients with mutated PRKCD genes clearly demonstrate the requirement of PKCδ for preventing lupus autoimmunity, this critical tolerance mechanism remains poorly understood. We recently reported that PKCδ selectively deletes anti-dsDNA B cells in the germinal center (GC), disclosing a key B cell tolerance mechanism that prevents lupus autoimmunity. PKCδ’s tolerance function is activated by sphingomyelin synthase 2 (SMS2), a lipid enzyme whose expression is generally reduced in B cells from lupus patients. Moreover, pharmacologic strengthening of the SMS2/PKCδ tolerance pathway alleviated lupus pathogenesis in mice. Here, we review relevant publications in order to provide mechanistic insights into PKCδ’s tolerance activity, and discuss the potential significance of therapeutically targeting PKCδ’s tolerance activity in the GC for selectively inhibiting lupus autoimmunity.

Considering the worldwide impact of heart failure, it is crucial to develop approaches that can help us comprehend its root cause and make accurate predictions about its outcome. This is essential for lowering the suffering and death rates connected with this widespread illness. Cardiomyopathies frequently result from genetic factors, and the study of heart failure genetics is advancing quickly. Dilated cardiomyopathy (DCM) is the most prevalent kind of cardiomyopathy, encompassing both hereditary and nongenetic abnormalities. It is distinguished by the enlargement of the left ventricle or both ventricles, accompanied by reduced contractility. The discovery of the molecular origins and subsequent awareness of the molecular mechanism is broadening our knowledge of DCM development. Additionally, it emphasizes the complicated nature of DCM and the necessity to formulate several different strategies to address the diverse underlying factors contributing to this disease. Genetic variations that can be transmitted from one generation to another can be a significant contributor to causing family or isolated DCM. Genetic variation also plays a significant role in determining susceptibility for acquired triggers for DCM. The genetic causes of DCM can have a diverse range of phenotypic expressions. It is crucial to select the most probable patients to have advantages from genetic testing. The purpose of this research is to emphasize the significance of identifying genetic DCM, the crucial relationships between genotype and phenotype, and the usefulness of genetic testing in the therapeutic care of both those affected and their relatives. This approach is expected to gain importance once treatment is guided by genotype-specific advice and disease-modifying medications.

Epithelial–mesenchymal transition (EMT) is defined as a cellular process during which epithelial cells acquire mesenchymal phenotypes and behavior following the downregulation of epithelial features. EMT and its reversed process, the mesenchymal-epithelial transition (MET), and the special form of EMT, the endothelial-mesenchymal transition (EndMT), have been thought as a universal dogma controlling developmental and pathological processes. More than half a century of EMT study has made it a large research field and a mainstream concept. However, discrepancies and disputes over EMT and EMT research have also grown over time. Particularly, neither the epithelial and mesenchymal states/properties nor their regulatory networks nor specific markers have been defined, rendering the EMT, MET and EndMT concepts groundless. Moreover, EMT and MET effects should not be a cause, but rather a consequence of or an accompanying effect during developmental and pathological processes. EMT and MET represented by the change in cell shapes or adhesiveness or symbolized by EMT factors are biased interpretation of the overall change in cellular property and regulatory networks during development and cancer progression. The true meaning of EMT effects in some developmental and pathological processes, such as fibrosis, needs re-evaluation. But the core EMT factors are actually a few components of the regulatory networks of neural stemness, which determines tumorigenicity and pluripotency. The EMT effects in cancer progression and neural crest formation are wrong attribution of the role of neural stemness during cancer progression and the cell-intrinsic property of neural crest cells to the unknown mesenchymal state. It is time to reassess the significance of EMT and its related concepts in scientific research.

Apple replant disease (ARD) is a complex issue caused by various fungal, oomycetes pathogens and parasites which can differ in their abundance between sites within a geographic region. Knowledge of the specific etiology of ARD at a particular site is required in order to develop commercially viable soil management strategies to combat specific/individual components of the disease. In this study we analyzed the soil from six ARD sites for the presence of fungal, bacterial and oomycetes communities and plant parasitic nematodes. Five fungal, and 17 bacterial classes were differentially represented in the microbiomes from different locations. Mortierellomycetes was the most abundant fungal taxa represented followed by Sordariomycetes. Mortierella exigua a fungal endophyte was the most abundant fungal amplicon sequence variant (ASV) in the core microbiome. Proteobacteria was the most prevalent phylum identified in orchard soils. Several potential phytopathogenic fungi involved in ARD and endophytes including Fusarium oxysporum, F. solani, Nectria ramulariae, Ilyonectria robusta and Nectriaceae were identfied in the orchard soil. Pythium attrantheridium (Globisporangium attrantheridium), P. monospermum and P. ultimum (Globisporangium ultimum) were the most abundant oomycete taxa identified in these soil samples. Six different groups of plant-parasitic nematodes were found across the six orchards soil. Root-lesion nematodes, Pratylenchus spp., which are commonly associated with ARD, were identified in all orchards soil at population densities ranging from 12 to 33/100 cm3 soil. This research contributes valuable understanding of the ARD complex as the apple industry needs alternative approaches to combat the disease.

The main focus of this review is to introduce readers to the fascinating class of lipid molecules known as norsteroids, exploring their distribution across various biotopes and their biological activities. The review provides an in-depth analysis of various modified steroids, including A, B, C, and D-norsteroids, each characterized by distinct structural alterations. These modifications, which range from the removal of specific methyl groups to changes in the steroid core, result in unique molecular architectures that significantly impact their biological activity and therapeutic potential. The discussion on A, B, C, and D-norsteroids sheds light on their unique configurations and how these structural modifications influence their pharmacological properties. The review also presents examples from natural sources that produce a diverse array of steroids with distinct structures, including the aforementioned A, B, C, and D-nor variants. These compounds, sourced from marine organisms like sponges, soft corals and starfish, as well as terrestrial entities such as plants, fungi, and bacteria. The exploration of these steroids encompasses their biosynthesis, ecological significance, and potential medical applications, highlighting a crucial area of interest in pharmacology and natural product chemistry. The review emphasizes the importance of researching these steroids for drug development, particularly in addressing diseases where conventional medications are inadequate or for conditions lacking sufficient therapeutic options. Examples of norsteroid synthesis are provided to illustrate the practical applications of this research.

Background: Progression of metabolic dysfunction associated steatotic liver disease (MASLD) to steatohepatitis (MASH) is driven by stress-inducing lipids that promote liver inflammation and fibrosis. MASH can lead to cirrhosis and hepatocellular carcinoma. We showed coordinated defenses regulated by transcription factors, nuclear factor erythroid 2 related factor-1 (Nrf1) and -2 (Nrf2), protect against hepatic lipid stress. Here, we investigated protective effects of hepatocyte Nrf1 and Nrf2 against MASLD-induced liver fibrosis and tumorigenesis. Methods: Using mice fed MASH diet for 24-52 weeks, we examined MASLD in mice with hepatocyte specific Nrf1, Nrf2, or combined deletion, and compared this to control. In a separate study, mice received weekly injections of carbon tetrachloride to induce liver fibrosis. From week 16-24, mice were treated with Nrf2 activating drug bardoxolone, hepatocyte overexpression of human NRF1 (hNRF1), or both, and groups were compared to control. Results: Hepatocyte Nrf2 deficiency had no effect. Hepatocyte Nrf1 and combined deficiency caused MASH but only hepatocyte Nrf1 deficiency in male mice increased tumor number. Bardoxolone reduced liver steatosis, fibrosis, inflammation, and proliferation, and this effect when combined with hNRF1 was greater than bardoxolone alone. Conclusion: Physiologic Nrf1 delays MASLD progression, Nrf2-induction alleviates MASH, and combined enhancement synergistically protects against steatosis.

Cholesterol, a crucial component of cell membranes, influences various biological processes, including membrane trafficking, signal transduction, and host-pathogen interactions. Disruptions in cholesterol homeostasis have been linked to congenital and acquired conditions, including neurodegenerative disorders such as Alzheimer’s disease (AD). Previous research from our group has demonstrated that herpes simplex virus type I (HSV-1) induces an AD-like phenotype in several cell models of infection. This study explores the interplay between cholesterol and HSV-1-induced neurodegeneration. The impact of cholesterol was determined by modulating its levels with methyl-beta-cyclodextrin (MβCD) using the neuroblastoma cell lines SK-N-MC and N2a. We have found that HSV-1 infection triggers the intracellular accumulation of cholesterol in structures resembling endolysosomal/autophagic compartments, a process reversible upon MβCD treatment. Moreover, MβCD exhibits inhibitory effects at various stages of HSV-1 infec-tion, underscoring the importance of cellular cholesterol levels not only in the viral entry pro-cess but also in subsequent post-entry stages. MβCD also alleviated several features of AD-like neurodegeneration induced by viral infection, including lysosomal impairment and intracellu-lar accumulation of amyloid-beta peptide (Aβ) and phosphorylated tau. In conclusion, these findings highlight the connection between cholesterol, neurodegeneration, and HSV-1 infection, providing valuable insights into the underlying mechanisms of AD.

Current microbiological methods for pneumonia diagnosis require invasive specimen collection and time-consuming analytical procedures. There is a need for less invasive and faster methods to detect lower respiratory tract infection. The analysis of volatile metabolites excreted by pathogenic microorganisms provides the basis for developing such a method. Given the synergistic role of Candida albicans in increasing the virulence of pathogenic bacteria causing pneumonia and the cross-kingdom metabolic interactions between microorganisms, we compare the emission of volatiles from Candida albicans yeasts and the bacteria Staphylococcus aureus using single and mixed co-cultures and apply that knowledge to human in vivo investigations. Gas-chromatography-mass spectrometry (GC-MS) analysis resulted in the identification of sixty-eight volatiles that were found to have significantly different levels in cultures compared to reference medium samples. Certain volatiles found in co-culture originated mainly from C. albicans metabolism (e.g., isobutyl acetate), whereas other volatiles primarily came from S. aureus (e.g., ethyl 2-methylbutyrate). Isopentyl valerate reflects synergic interactions of both microbes, as its level in co-cultures was found to be approximately three times higher than the sum of its amounts in monocultures. Hydrophilic-lipophilic balanced (HLB) coated meshes for thin-film microextraction (TFME) were used to pre-concentrate volatiles directly from bronchoalveolar lavage (BAL) specimens collected from patients suffering from ventilation-associated pneumonia (VAP) that was caused explicitly by C. albicans and S. aureus. GC-MS analyses confirmed the existence of in vitro-elucidated microbial VOCs in human specimens. Significant differences in BAL-extracted amounts respective to the pathogen causing pneumonia were found. The model in vitro experiments provided evidence that cross-kingdom interactions between pathogenic microorganisms affect the synthesis of the volatile compounds. The TFME meshes coated with HLB particles proved to be suitable for extracting VOCs from human material, enabling the translation of in vitro experiments on the microbial volatilome to the in vivo situation involving infected patients. This indicates the direction that should be taken for further clinical studies on VAP diagnosis based on volatile analysis.

MicroRNAs (miRNAs), particularly miR-16 and miR-21, play a crucial role in mul-tiple myeloma (MM) pathogenesis by regulating gene expression. This study evalu-ated the prognostic significance of circulating miR-16 and miR-21 expression levels in 48 patients with MM at diagnosis treated with lenalidomide/dexamethasone (LD) compared with 15 healthy individuals (HI). All patients were treated with LD, 13 at first line and 35 at relapse, of whom 21 were tested twice at diagnosis and before LD initiation. The results revealed significantly lower levels of miR-16 and miR-21 in patients than in HIs, both at diagnosis and relapse, with decreased miR-16 levels at diagnosis, indicating improved overall survival (OS) (p value 0.024). Furthermore, miR-16 and miR-21 levels were associated with disease markers, while both corre-lated with the depth of response and mir-16 with sustained response to LD treatment. The ratios of both miR-16 and miR-21 expression levels (prior to LD treat-ment/diagnosis) below 2 predicted a shorter time to response (P = 0.027) and a longer time to next treatment (P = 0.042), respectively. These findings suggested a prognostic value for serum miR-16 and miR-21 levels in MM, as their expression levels corre-lated with disease variables and treatment outcomes.

This study was conducted with the objective of investigating the enrichment of weaned piglet diets with organic selenium (proteinate selenium) and inorganic selenium (sodium selenite) with two addition levels (0.15 and 0.30 mg/kg). A total of 40 piglets (20 castrated males and 20 females) weaned at 28 days of age with an average initial weight of 6.60±1.06 kg were used. The treatments were: Control diet (Control diet); Selenium-enriched control diet proteinate with 0.15 mg/kg of selenium added (SeOrg-0.15); Selenium-enriched control diet proteinate with 0.30 mg/kg of selenium added (SeOrg-0.30); Control diet enriched with sodium selenite with 0.15 mg/kg of selenium added (SeInorg-0.15); and Control diet enriched with sodium selenite with 0.30 mg/kg of selenium added (SeInorg-0.30). The presence of selenium in the control diet came from the ingredients and the mineral supplement. The following data were analyzed: productive performance; digestibility of nutrients and energy; morphometry and intestinal integrity; serum biochemical parameters; and gene expression of selenoproteins in intestinal epithelium and liver tissue of piglets. The SeOrg-0.30 treatment caused a reduction (P

This retrospective study aimed to evaluate the performance of the hormone treatment protocols, determine the factors associated with pregnancy success after hormone treatment, and compare the cost-efficiencies of two types of hormone treatment among cyclic and noncyclic anestrous dairy cows. The clinical records of 279 anestrous cows who received hormone treatment for artificial insemination (AI) from 64 herds in the western region of Thailand were obtained from Kasetsart University Veterinary Teaching Hospital from January to August 2017. The performance of the hormone treatment protocols, fixed-time AI (TAI) and estrus detection before AI (EAI), showed that the pregnancy risk for the TAI protocol was higher than for the EAI protocol, but pregnancy per AI did not differ significantly between the two protocols in cyclic and noncyclic cows. Multivariate logistic regression analysis showed that cows receiving the TAI protocol were more likely to be pregnant compared to those treated with the EAI protocol. Cows with a 3.00 body condition score (BCS) &lt;3.75 after treatment and loose-housing cows were more likely to become pregnant. Treatment during winter showed higher pregnancy success than in the summer and rainy seasons. The cost-efficiency analysis showed that the TAI protocol was the most cost-efficient option for noncyclic cows, whereas the EAI protocol was the most cost-efficient option for cyclic cows.