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With increased use of agrochemicals to protect crops against phytopathogenic diseases, the environment is facing serious hazardous effects. The proven antimicrobial properties of nanomaterials may provide a new level of sustainable development and rapid research for the potential to replace chemical fungicides in crop protection. The objective of this study was to investigate the in vitro and in vivo antifungal activity of chitosan-copper nanocomposite (Ch-Cu NPs) against Rhizoctonia solani and Fusarium oxysporum to control root rot and wilt disease of marjoram plants. The chemically synthesized Ch-Cu NPs nanocomposite was characterized with respect to its morphological features and size, which were obtained by Transmission Electron Microscope (TEM) analysis, and the presence of functional chemical groups responsible for the synthesis of Ch-Cu NPs was determined using Fourier Transform Infrared (FTIR) spectrophotometer. Antifungal activity against the two pathogenic fungi was assessed using three concentrations (25, 50, and 100 mg/l) of Ch-Cu NPs. The laboratory evaluation showed that mycelial radial growth of F. oxysporum and R. solani was inhibited by 80.55% for two fungi at 100 mg/L of Ch-Cu NPs. The morphology of F. oxysporum and R. solani was investigated, and molecular identification was conducted to prove that F. oxysporum and R. solani were the causal agents of root rot and wilt disease of marjoram plants in Egypt. Pathogenicity test showed that both F. oxysporum and R. solani were virulent with the measured disease incidence was 59.14% and the disease severity was 28.47%, respectively. In this work, Ch-Cu NPs at 50 mg/L were found to be the appropriate concentration that could lead to a reduction in disease incidence by 23.67% and disease severity by 5.57% with induction of plant defense. The results of HPLC analysis revealed an increase in 7 out of 9 polyphenols in 50 mg/L Ch-Cu NPs application compared to the untreated control plants. Molecular studies using qRT-PCR technique on marjoram leaf tissue were done to determine the relationship between polyphenols biosynthesis and the expression of responsible genes affected by Ch-Cu NPs application. Genes such as CAD , C4H , TAT , FLS , EGS , HPPR , PAL , and RAS showed an upregulation of their expression in marjoram treated leaves compared to the control leaves. The release profile of Ch-Cu NPs also showed an important insight into the mode of disease control. The conclusion of this work is considered as an important step toward the application of nanomaterials in agriculture, where the biosynthesized and biodegradable Cu-chitosan NPs have better biological control compatibility as it can induce similar effects to natural plant defense elicitors and antioxidant defense to prime the crop for better resistance.

BackgroundRoot rot, wilt diseases, and rooting processes have been the major factors that constrain schefflera production. This study focuses on the impact of innovative applications of eco-friendly materials like chitosan nanoparticles loaded with l-proline or indole butyric acid to replace traditional chemical fungicides in controlling root rot and wilt diseases, as well as the vegetative propagation success of leafy stem schefflera cuttings.ResultsFusarium foeten (strain 1) and Fusarium falciforme (strains 2 and 4) were first identified as root rot and wilt pathogens of schefflera in Egypt based on morphological features and confirmed with molecular analyses. Fusarium foetens (strain 1) and F. falciforme (strain 2) have the most aggressive action, as the infection percentages significantly increased in the pathogenicity test. The disease incidence reached 38.88 and 44.44%, respectively, whereas the disease severity was 18.51 and 26.84%, respectively. Chitosan nanoparticles at a concentration of 25 mg/L were the most effective dose, leading to a significant reduction in disease incidence to 25.00%, disease severity to 4.17%, and playing a vital role in activating plant defense, which correlates well with improved growth characteristics. The novel strategy of L-proline loaded on chitosan nanoparticles (LP-CSNPs) application occupied the first rank at protective influence against root rot and wilt disease-induced oxidative stress, signaling a defensive function that was freelance verified. L-proline loaded on chitosan nanoparticles (LP-CSNPs) at 0.125–0.25 g/L had a significant impact on reducing the incidence and severity of root rot and wilt diseases, as well as improving photosynthetic pigments and free radical scavenging activities, which included strengthening plant defense and further validating the findings from the biochemical trait analysis. The TT biplot graph was an influential statistical tool to study the impacts of treatments on schefflera production and its attributes and to discover the interrelationships among them.ConclusionsApplying LP-CSNPs is one of the best techniques to manage schefflera root rot and wilt diseases, since it can be utilized as a growth stimulator and defense activator with sustainable increased efficiency.

Progressive multiple sclerosis (PMS) is an autoimmune demyelinating disease of the central nervous system (CNS) in humans. PMS is defined by neuroinflammation and axonal damage with advancing neurological disabilities, although the underlying molecular mechanisms remain uncertain. To gain insight into the proteomic aspects of PMS, we used mass spectrometry to investigate proteomic profiles and specific protein changes in matched CNS tissues (white matter, cortex, and lesions) from persons with PMS and age/sex-matched other disease controls (ODCs). These studies were examined further using proteomes of primary human neural cell types (e.g., neurons, astrocytes, microglia, oligodendrocyte progenitor cells/OPCs) and CNS tissues from PMS mouse models. Extracellular matrix (ECM) related proteins, including the annexin, S100, and AHNAK protein families, were significantly enriched in PMS white matter, especially within demyelinated lesions compared to ODC tissues. These enriched proteins showed increased abundance in astrocytes, microglia, and OPCs compared to neurons. Annexin, S100, and AHNAK family proteins were also increased in the CNS of the cuprizone and experimental autoimmune encephalitis mouse models. These findings highlight the importance of ECM protein induction in CNS glial cells during PMS while providing potential therapeutic targets for future investigation. The underlying molecular mechanisms of neuroinflammation and axonal damage in progressive multiple sclerosis remains unclear. Here, authors show proteomics results of human progressive multiple sclerosis brain tissues and found extracellular matrix proteins (annexin, S100, AHNAK families) were enriched in lesions and white matter.

Background In humans, two ubiquitously expressed N-myristoyltransferases, NMT1 and NMT2, catalyze myristate transfer to proteins to facilitate membrane targeting and signaling. We investigated the expression of NMT s in numerous cancers and found that NMT2 levels are dysregulated by epigenetic suppression, particularly so in hematologic malignancies. This suggests that pharmacological inhibition of the remaining NMT1 could allow for the selective killing of these cells, sparing normal cells with both NMTs. Methods and results Transcriptomic analysis of 1200 NMT inhibitor (NMTI)-treated cancer cell lines revealed that NMTI sensitivity relates not only to NMT2 loss or NMT1 dependency, but also correlates with a myristoylation inhibition sensitivity signature comprising 54 genes (MISS-54) enriched in hematologic cancers as well as testis, brain, lung, ovary, and colon cancers. Because non-myristoylated proteins are degraded by a glycine-specific N-degron, differential proteomics revealed the major impact of abrogating NMT1 genetically using CRISPR/Cas9 in cancer cells was surprisingly to reduce mitochondrial respiratory complex I proteins rather than cell signaling proteins, some of which were also reduced, albeit to a lesser extent. Cancer cell treatments with the first-in-class NMTI PCLX-001 (zelenirstat), which is undergoing human phase 1/2a trials in advanced lymphoma and solid tumors, recapitulated these effects. The most downregulated myristoylated mitochondrial protein was NDUFAF4, a complex I assembly factor. Knockout of NDUFAF4 or in vitro cell treatment with zelenirstat resulted in loss of complex I, oxidative phosphorylation and respiration, which impacted metabolomes. Conclusions Targeting of both, oxidative phosphorylation and cell signaling partly explains the lethal effects of zelenirstat in select cancer types. While the prognostic value of the sensitivity score MISS-54 remains to be validated in patients, our findings continue to warrant the clinical development of zelenirstat as cancer treatment.

The main protease of SARS-CoV-2 (Mpro) is the most promising drug target against coronaviruses due to its essential role in virus replication. With newly emerging variants there is a concern that mutations in Mpro may alter the structural and functional properties of protease and subsequently the potency of existing and potential antivirals. We explored the effect of 31 mutations belonging to 5 variants of concern (VOCs) on catalytic parameters and substrate specificity, which revealed changes in substrate binding and the rate of cleavage of a viral peptide. Crystal structures of 11 Mpro mutants provided structural insight into their altered functionality. Additionally, we show Mpro mutations influence proteolysis of an immunomodulatory host protein Galectin-8 (Gal-8) and a subsequent significant decrease in cytokine secretion, providing evidence for alterations in the escape of host-antiviral mechanisms. Accordingly, mutations associated with the Gamma VOC and highly virulent Delta VOC resulted in a significant increase in Gal-8 cleavage. Importantly, IC50s of nirmatrelvir (Pfizer) and our irreversible inhibitor AVI-8053 demonstrated no changes in potency for both drugs for all mutants, suggesting Mpro will remain a high-priority antiviral drug candidate as SARS-CoV-2 evolves.

Nicotine, a pervasive global environmental pollutant, is released throughout every phase of the tobacco’s life cycle. This study examined the probable ameliorative role of Chlorella vulgaris (ChV) extract against nicotine (NIC)-induced hepatic injury in Ehrlich ascites carcinoma (EAC) bearing female Swiss mice. Sixty female Swiss mice were assigned to four equal groups orally gavaged 2% saccharin 0.2 mL/mouse (control group), orally intubated 100 mg ChV /kg (ChV group), orally intubated 100 µg/mL NIC in 2% saccharin (NIC group), and orally intubated NIC + ChV as in group 3 and 2 (NIC+ChV group). The dosing was daily for 4 weeks. Mice from all experimental groups were then inoculated intraperitoneally with viable tumor cells 2.5 × 10 6 (0.2 mL/mouse) in the fourth week, and the treatments were extended for another 2 weeks. The results have shown that NIC exposure significantly altered the serum levels of liver function indices, lipid profile, LDH, and ALP in the NIC-exposed group. NIC administration significantly increased hepatic inflammation, lipid peroxidation, and DNA damage-related biomarkers but reduced antioxidant enzyme activities. NIC exposure downregulated SOD1 , SOD2 , CAT , GPX1 , and GPX2 but upregulated NF-κB hepatic gene expression. Notably, the presence of the EAC cells outside the liver was common in all mice groups. Liver tissue of the NIC-exposed group showed multifocal expansion of hepatic sinusoids by neoplastic cells. However, with no evidence of considerable infiltration of EAC cells inside the sinusoids or in periportal areas in the NIC + ChV groups. NIC significantly altered caspase-3, Bax, and BcL2 hepatic immune expression. Interestingly, ChV administration significantly mitigates NIC-induced alterations in hepatic function indices, lipid profile, and the mRNA expression of antioxidant and NF-κB genes and regulates the caspase-3, Bax, and BcL2 immunostaining. Finally, the in vivo protective outcomes of ChV against NIC-induced hepatic injury combined with EAC in female Swiss mice could suggest their helpful role for cancer patients who are directly or indirectly exposed to NIC daily.

Symptoms of infection okra plants (Abelmoschus esculentus L.) with Verticillium wilt were recorded during the summer of 2021 in Beni Suef Governorate specifically in Nasser, Beba, and El-Wasta Counties. The symptoms appeared on the external parts of plants, specifically through the alteration of color in the leaves of infected shoots, which transition from a normal color to a light green or yellow hue, had V-shaped chlorotic lesions, loss their turgidity and eventually desiccation, plant stunting and vascular discoloration. The presence of V. tricorpus on okra has not been previously documented. The isolated fungus was identified on the basis of morphological characteristics and molecular traits by utilizing sequencing techniques applied to the internal transcribed space (ITS region) of the ribosomal RNA gene. The analysis of the fungal sequencing data revealed a substantial genetic similarity and close ties between the fungus in question and V. tricorpus by 99.24–100% identity and 97–100% coverage with several strains of V. tricorpus, including the type strain CBS447.54 (NR_126128). The obtained sequences were submitted to the GenBank database and assigned the accession number MZ936483. Pathogenicity test confirmed that V. tricorpus had pathogenic properties, as shown by the appearance of disease symptoms that were similar to those previously noted on okra plants in the surveyed regions. This observation represents the initial documentation of V. tricorpus in relation to the occurrence of Verticillium wilt disease in okra. However, there is currently no information of host resistance to this disease among Egyptian okra cultivars, although it is essential for sustainable disease management. Our study indicate that cultivar of Balady green is more resistance to Verticillium wilt while the Iranian red cv. is more sensitive to infection.

BackgroundBeta vulgaris, known as beetroot, is renowned for its rich reserves of various biologically active compounds. Despite an extensive review of the available literature, there is a dearth of comprehensive information on the specific phytochemicals composition and biological belongings of beet leaves. Hence, the study aimed to examine the comprehensive chemical composition of red beet leaves and evaluate their potential as antidiabetic, anti-Alzheimer’s, and anti-inflammatory. ResultsLC–ESI–MS/MS in both positive and negative ionization modes identified eleven flavonoids, seven coumarins, seven pigments, four phenolic acids, four saponins, one sterol, and one fatty acid. Furthermore, eight flavonoidal compounds were successfully isolated using column chromatography technique. The ethanolic extract of Beta vulgaris leaves exhibited notable inhibitory effects on carbohydrate-metabolizing enzymes and moderate AChE inhibition, as well as a significant anti-inflammatory effect in a dose-dependent pattern. By employing molecular docking analysis, the interactions between the isolated compounds and the target proteins were examined and compared. Out of all the compounds, quercetin-3-methoxy-4-glucosyl-7-glucoside displayed the highest docking score, which was determined based on the binding free energy and the formation of hydrogen bonds. ConclusionsThe biological outcomes signpost that B. vulgaris leaves extract exhibits numerous advantageous belongings. Molecular docking analysis has supported these biological discoveries.Article HighlightsThe study examines the chemical composition of red beet leaves and their potential as antidiabetic, anti-Alzheimer's, and anti-inflammatory compounds. Results show that the ethanolic extract of Beta vulgaris leaves has inhibitory effects on carbohydrate-metabolizing enzymes, moderate AChE inhibition, and significant antiinflammatory effects.Quercetin-3-methoxy-4-glucosyl-7-glucoside displayed the highest docking score,supporting the biological findings that the extract of B. vulgaris leaves contains numerous beneficial properties.

This study evaluated the immunotoxic effects of thallium (Tl) in Nile tilapia fingerlings and the recovery role of dietary Astragalus membranaceus polysaccharides (ASs). An 8-week experiment was designed where 180 fishes were randomly and equally assigned in triplicates into the six groups: the control group (CNT) was reared in unpolluted water and fed a commercial diet, two groups were fed a well-balanced commercial diet plus 1.5 and 3.0 g AS/kg diet (AS0.15 and AS0.30), respectively, the fourth group was exposed to a sublethal dose of Tl (41.9 μg l −1 ) [equal to 1/10 of 96-h lethal concentration 50 (LC50)], and the last two groups were fed 0.15 and 0.3% AS, respectively, and concurrently exposed to Tl (41.9 μg l −1 ) (AS0.15+Tl and AS0.30+Tl). Fish hematobiochemical parameters, serum immunity [nitric oxide, total immunoglobulin M (IgM) levels, and lysozyme activity], transcription of hepatic interferon-γ (IFN-γ), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), and resistance to Aeromonas hydrophila ( A. hydrophila ) were assessed. Hematobiochemical parameters and serum immune indices were significantly decreased in the fish group exposed to sublethal Tl concentration compared to the CNT group. Furthermore, Tl exposure significantly induced overexpression of IL-1β, TNF-α, and IFN-γ genes (4.22-, 5.45-, and 4.57-fold higher, respectively) compared to CNT values. Tl exposure also increased the cumulative mortality (%) in Nile tilapia challenged with A. hydrophila . Remarkably, the groups fed AS0.15+Tl and AS0.30+Tl significantly ameliorated all the aforementioned parameters, but did not reach CNT values. Our findings suggest the possible immunomodulating roles of dietary AS in recovering the immunotoxic effects of Tl in Nile tilapia. We can conclude that dietary AS would be useful for maintaining the immunity of Nile tilapia fingerlings.

Mangrove forests in the Arabian Gulf are under continuous threat. To increase plantations of gray mangrove ( Avicennia marina ) in the United Arab Emirates (UAE), 27 endophytic actinobacterial isolates obtained from mangrove roots were in vitro pre-screened to detect the polyamines (PAs) [putrescine (Put), spermidine (Spd), and spermine (Spm)]. We also determined the abilities of the endophytic PA-producing actinobacterial isolates in enhancing the growth of A. marina under greenhouse conditions. Although three highly PA-producing isolates were recovered from inside mangrove root tissues, Streptomyces mutabilis UAE1 constantly colonized root and stem inner tissues for 12 weeks, suggesting an endophytic association between this actinobacterial isolate and mangrove seedlings. When roots were inoculated with S. mutabilis , mangrove growth was remarkably enhanced under gnotobiotic and greenhouse conditions. This was evident from the significant ( P < 0.05) increases in dry weight and length of root (66.7 and 65.5%, respectively) and shoot (64.8 and 58.0%, respectively), number of branches (64.3%), total leaf area (40.2%), and photosynthetic pigments (54.5% chlorophyll a ; 40.0% chlorophyll b ; and 53.1% carotenoids) of mangrove compared to the PA-non-producing Streptomyces sp. or control treatment. Growth promotion in plants treated with S. mutabilis was also supported by significant ( P < 0.05) elevations in the contents of mangrove in planta PAs, auxins, and cytokinins, accompanied by a decrease in abscisic acid levels. No difference was, however, detected in growth and amounts of PAs or any plant growth regulators (PGRs) in plants treated with or without the PA-non-producing isolate. Our findings indicate that plant growth parameters can be enhanced as a consequence of secretion of Put, Spd, and Spm by S. mutabilis resulting in regulation of endogenous PAs and other PGRs in mangrove tissues. This study is the first record that aims to improve sustainable agricultural management practices using plant growth promoting (PGP) actinobacteria, endophytic in mangrove tissues to promote mangrove growth under greenhouse conditions. Such research may allow this region to be a model to study the synergistic S. mutabilis –mangrove interactions and the future impacts on mangrove reforestation in the Arabian Gulf and elsewhere where mangrove forests are in threat.