Search Results (21,165)

Botrytis cinerea is a highly versatile pathogenic fungus, causing significant damage across a wide range of plant species. A central focus of this review is the recent advances made through proteomics, an advanced molecular tool, in understanding the mechanisms of B. cinerea infection. Recent advances in mass spectrometry-based proteomics—including LC-MS/MS, iTRAQ, MALDI-TOF, and surface shaving—have enabled the in-depth characterization of B. cinerea subproteomes such as the secretome, surfactome, phosphoproteome, and extracellular vesicles, revealing condition-specific pathogenic mechanisms. Notably, in under a decade, the proportion of predicted proteins experimentally identified has increased from 10% to 52%, reflecting the rapid progress in proteomic capabilities. We explore how proteomic studies have significantly enhanced our knowledge of the fungus secretome and the role of extracellular vesicles (EVs), which play key roles in pathogenesis, by identifying secreted proteins—such as pH-responsive elements—that may serve as biomarkers and therapeutic targets. These technologies have also uncovered fine regulatory mechanisms across multiple levels of the fungal proteome, including post-translational modifications (PTMs), the phosphomembranome, and the surfactome, providing a more integrated view of its infection strategy. Moreover, proteomic approaches have contributed to a better understanding of host–pathogen interactions, including aspects of the plant’s defensive responses. Furthermore, this review discusses how proteomic data have helped to identify metabolic pathways affected by novel, more environmentally friendly antifungal compounds. A further update on the advances achieved in the field of proteomics discovery for the organism under consideration is provided in this paper, along with a perspective on emerging tools and future developments expected to accelerate research and improve targeted intervention strategies. Full article

Background and Objectives: This study aimed to explore the risk factors of histopathological crescent formation in pediatric IgA vasculitis nephritis (IgAVN). Materials and Methods: Enrolled patients with biopsy-proven IgAVN from Zhejiang University’s hospital were split into two groups: 377 with no crescents on histopathology (Group 1) and 364 with crescentic nephritis (Group 2). Collected data included clinical features, lab indicators, histopathological grading, and factors causing glomerular sclerosis. Logistic regression was used to assess factors affecting crescent formation in IgAVN. Double-immunofluorescence assay was used to detect TGF-β1, MCP-1, α-SMA, Collagen I, and FN1 in kidney biopsy specimens. The relationship between kidney fibrosis factors and histopathological grade were analyzed using Chi-square and Pearson tests. Results: A total of 741 patients with IgAVN were included in the study. Univariate logistic regression identified potential factors related to crescent formation, including age, gender, clinical classification, hematuria grade, 24 h urine protein level, peripheral white blood cells (WBCs), serum albumin, Cystatin-C, APTT, and PT. Multivariate analysis revealed statistical significance for age, 24 h urine protein, and WBCs across pathological grades (p < 0.05). Mantel–Haenszel Chi-square tests indicated a linear relationship between IgAVN pathological grade and α-SMA, TGF-β1, MCP-1, and FN1. Pearson correlation analysis confirmed a positive correlation between pathological grade and these markers. Conclusions: Age, 24 h urinary protein, and blood WBCs are identified as risk factors for histopathological crescent formation in children with IgAVN. Additionally, a higher pathological grade is associated with more pronounced fibrosis indicators. Full article

In today’s oncology, immunotherapy arises as a potent complement for conventional cancer treatment, allowing for obtaining better patient outcomes. B7-H3 (CD276) is a member of the B7 protein family, which emerged as an attractive target for the treatment of various tumors. The molecule modulates anti-cancer immune responses, acting through diverse signaling pathways and cell populations. It has been implicated in the pathogenesis of numerous malignancies, including melanoma, gliomas, lung cancer, gynecological cancers, renal cancer, gastrointestinal tumors, and others, fostering the immunosuppressive environment and marking worse prognosis for the patients. B7-H3 targeting therapies, such as monoclonal antibodies, antibody–drug conjugates, and CAR T-cells, present promising results in preclinical studies and are the subject of ongoing clinical trials. CAR-T therapies against B7-H3 have demonstrated utility in malignancies such as melanoma, glioblastoma, prostate cancer, and RCC. Moreover, ADCs targeting B7-H3 exerted cytotoxic effects on glioblastoma, neuroblastoma cells, prostate cancer, and craniopharyngioma models. B7-H3-targeting also delivers promising results in combined therapies, enhancing the response to other immune checkpoint inhibitors and giving hope for the development of approaches with minimized adverse effects. However, the strategies of B7-H3 blocking deliver substantial challenges, such as poorly understood molecular mechanisms behind B7-H3 protumor properties or therapy toxicity. In this review, we discuss B7-H3’s role in modulating immune responses, its significance for various malignancies, and clinical trials evaluating anti-B7-H3 immunotherapeutic strategies, focusing on the clinical potential of the molecule. Full article

Sodium p-perfluorous nonenoxybenzenesulfonate (OBS) has been proposed as a substitute for perfluorooctanesulfonic acid (PFOS), yet it has garnered increasing attention due to its environmental persistence and potential toxicity. Despite these concerns, the neurotoxic mechanisms of OBS remain unclear. This study investigates and compares the neurotoxic effects and mechanisms of OBS and PFOS in Caenorhabditis elegans. L4-stage worms were exposed to OBS (0.1–100 μM) or PFOS (100 μM) for 24 h. Neurobehavioral analysis showed that OBS exposure induced concentration-dependent neurobehavioral deficits, with 100 μM OBS significantly reducing pharyngeal pumping rate (29.8%), head swing frequency (23.4%), and body bending frequency (46.6%), surpassing the effects of PFOS. Both compounds decreased the fluorescence intensity of dopaminergic, glutamatergic, and γ-aminobutyric acid neurons and downregulated neurotransmitter-associated genes. They also increased ROS generation and inhibited antioxidant gene expression. Molecular docking revealed that OBS had a stronger binding affinity to p38 MAPK key protein (PMK-1) than PFOS. OBS and PFOS upregulated pmk-1 and skn-1, modulating oxidative stress and neuronal function. pmk-1 mutation differentially affected OBS-induced neurobehavioral changes and gene expression alterations. Our findings indicate that OBS exhibits stronger neurotoxicity than PFOS in Caenorhabditis elegans, mediated through the PMK-1 pathway. These results highlight the need for further investigation into the safety of OBS as a PFOS alternative. Full article

The objectives of the present work were as follows: (i) the detection of cathelicidin biomolecules in the milk of individual goats during the early stages of mastitis and their potential use for the diagnosis of mastitis at its early stage and (ii) the evaluation of the presence of cathelicidin proteins in the bulk-tank milk from goat and sheep farms. In an experimental study, after inoculation of Staphylococcus simulans into a mammary gland of goats, bacteriological and cytological examinations of milk samples, as well as proteomics examinations [two-dimensional gel electrophoresis analysis (2-DE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS) analysis] were performed sequentially, from 4 to 48 h post-challenge. Cathelicidin-1 and cathelicidin-2 were detected consistently in milk samples obtained throughout the study, and spot optical densities obtained from PDQuest v.8.0 were recorded. Associations were calculated between the presence of mastitis in a mammary gland at a given timepoint and the detection of cathelicidin proteins in the respective milk sample. All inoculated mammary glands developed mastitis, confirmed by the consistent bacterial isolation from milk samples and the increased somatic cell content therein. Spot optical density of cathelicidin proteins was higher than in samples from contralateral mammary glands. There was a significant association between the presence of mastitis in a mammary gland and the detection of cathelicidin biomolecules in the respective milk sample; the overall accuracy was 81.8% (95% confidence interval: 70.4–90.2%). In a field investigation, the presence of cathelicidin proteins was evaluated in the bulk-tank milk of 32 dairy goat and 57 dairy sheep farms. In this part of the work, no cathelicidin proteins were detected in any bulk-tank milk sample of goat, 0.0% (95% confidence interval: 0.0–10.7%), or sheep, 0.0% (95% confidence interval: 0.0–6.3%), farms. Full article

Background and Objectives: The cytokine IL-6, methyltransferase NSD2, pro-protein convertase Furin, and growth factor receptor IGF-1R are essential factors in the proliferation of cancer cells. These proteins are involved in the tumor process by generating several cell-signaling pathways. However, the interactions of these oncogenic biomarkers, Furin, IL-6, and NSD2, and their links with the inhibitor SERPINA-1 remain largely unknown. Materials and Methods: Cell proliferation is measured by colorimetric and enzymatic methods. The genetic expressions of SERPINA-1, Furin, IL-6, and NSD2 are measured by qRT-PCR, while the expression of IGF-1R on the cell surface is measured by flow cytometry. Results: The proliferation of cells overexpressing SERPINA-1 (JP7pSer+) is decreased by more than 90% compared to control cells (JP7pSer-). The kinetics of the gene expression ratios of Furin, IL-6, and NSD2 show an increase for 48 h, followed by a decrease after 72 h for the three biomarkers in JP7pSer+ cells compared to JP7pSer- cells. The expression of IGF-1R on the cell surface in both cell lines is low, with JP7pSer- cells expressing 1.33 times more IGF-1R than JP7pSer+ cells. Conclusions: These results suggest gene correlations of SERPINA-1 overexpression with decreased cell proliferation and modulation of gene expression of Furin, IL-6, and NSD2. This study should be complemented by molecular transcriptomic and proteomic experiments to better understand the interaction of SERPINA-1 with IL-6, Furin, and NSD2, and their effect on tumor progression. Full article

Coffee silverskin (CS), a by-product generated during coffee roasting, contains high levels of xylan hemicellulose and protein, making it a promising substrate for functional ingredient production. This study developed an integrated bioprocess to simultaneously produce bioactive peptides and xylooligosaccharides (CS-XOS) from CS. Conventional alkaline extraction (CAE) under optimized conditions (1.0 M NaOH, 90 °C, 30 min) yielded 80.64 mg of protein per gram of CS and rendered the solid residue suitable for XOS production. Enzymatic hydrolysis of the extracted protein using protease_SE5 generated low-molecular-weight peptides (0.302 ± 0.01 mg/mL), including FLGY, FYDTYY, and FDYGKY. These peptides were non-toxic, exhibited in vitro antioxidant activity (0–50%), and showed ACE-inhibitory activities of 60%, 26%, and 79%, and DPP-IV-inhibitory activities of 19%, 18%, and 0%, respectively. Concurrently, the alkaline-treated CS solid residue (ACSS) was hydrolyzed using recombinant endo-xylanase, yielding 52.5 ± 0.08 mg of CS-XOS per gram of ACSS. The CS-XOS exhibited prebiotic effects by enhancing the growth of probiotic lactic acid bacteria (μ_max 0.100–0.122 h⁻¹), comparable to commercial XOS. This integrated bioprocess eliminates the need for separate processing lines, enhances resource efficiency, and provides a sustainable strategy for valorizing agro-industrial waste. The co-produced peptides and CS-XOS offer significant potential as functional food ingredients and nutraceuticals. Full article

Oxidative stress significantly contributes to the exacerbation of brain damage during cerebral ischemia-reperfusion injury (CIR/I). In our previous study, purified cornel iridoid glycoside (PCIG), consisting of morroniside (MOR) and loganin (LOG), showed neuroprotective effects against CIR/I. To further explore the antioxidative effects and underlying molecular mechanisms, we applied PCIG, MOR, and LOG to rats injured by middle cerebral artery occlusion/reperfusion (MCAO/R) as well as H₂O₂-stimulated PC12 cells. Additionally, the molecular docking analysis was performed to assess the interaction between the PCIG constituents and Kelch-like ECH-associated protein 1 (Keap1). The results showed that the treated rats experienced fewer neurological deficits, reduced lesion volumes, and lower cell death accompanied by decreased levels of malondialdehyde (MDA) and protein carbonyl, as well as increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). In H₂O₂-stimulated PC12 cells, the treatments decreased reactive oxygen species (ROS) production, mitigated mitochondrial dysfunction, and inhibited mitochondrial-dependent apoptosis. Moreover, the treatments facilitated Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) translocation into the nucleus and selectively increased the expression of NAD(P)H quinone oxidoreductase 1 (NQO-1) and heme oxygenase 1 (HO-1) through MOR and LOG, respectively. Both MOR and LOG demonstrated strong binding affinity to Keap1. These findings suggested that PCIG, rather than any individual components, might serve as a valuable treatment for ischemic stroke by activating the Nrf2/NQO-1 and Nrf2/HO-1 signaling pathway. Full article

Accurately estimating the radiation dose received by an individual is essential for evaluating potential damage caused by exposure to ionizing radiation. Most retrospective dosimetry methods require the time since exposure to be known and rely on calibration curves specific to that time point. In this work, we introduce a novel method tailored to the γ-H2AX assay, which is a protein-based biomarker for radiation exposure, that enables the estimation of both the radiation dose and the time of exposure within a plausible post-exposure interval. Specifically, we extend calibration curves available at two distinct time points by incorporating the biological decay of foci, resulting in a model that captures the joint dependence of foci count on both dose and time. We demonstrate the applicability of this approach using both real-world and simulated data. Full article

The purpose of this study was to determine the effect of breed and sex (3 × 2) on the basic chemical composition, concentration of some minerals, and physicochemical properties of edible giblets of farm geese. The study material consisted of edible giblets (livers, gizzards, hearts) obtained from 42 geese from three Polish native breeds (Rypin, Suwałki, Kartuzy) at 220 weeks of age. Edible giblets were obtained during goose evisceration from seven males and seven females of each breed. Each bird was an experimental unit. Goose breed and sex had a significant effect on the chemical composition and physicochemical properties of the edible giblets. Rypin geese had higher (p < 0.05) intramuscular fat content in the gizzard and heart, as well as higher protein content in the heart and lower water content in the gizzard, compared to Kartuzy and Suwałki geese. Kartuzy geese, in turn, had higher content of water in the heart, and higher concentrations of phosphorus, calcium, iron, manganese, sodium, and chromium in the liver, compared to Rypin and Suwałki geese. In turn, Suwałki geese had higher concentrations of phosphorus in the gizzard, and potassium, phosphorus, copper, and iron in the heart compared to the hearts of Rypin and Suwałki geese, while Kartuzy and Suwałki geese higher concentrations of sodium, magnesium, zinc, and manganese in hearts than the hearts of Rypin geese. In these studies, the highest lightness (L*) was observed in the liver and heart of Rypin geese, the lowest yellowness (b*) was observed in the gizzard of Suwałki geese, and the highest pH₂₄ and EC₂₄ were observed in the heart of Kartuzy geese. Regardless of breed, males had higher protein, collagen, and intramuscular fat contents in the heart, a higher water content in the gizzard, higher concentrations of potassium, and sodium in the liver and gizzard, copper in the heart and liver, and phosphorus in the gizzard, and less water in the heart and zinc in the liver, as well as higher (p < 0.05) concentrations of iron in the liver and heart compared with females. The breed by sex interaction was significant for intramuscular fat and water content in the gizzard and heart, and protein content in the heart. Significant differences were also noted for EC₂₄ in the liver and heart, yellowness of the gizzard, and concentrations of most labeled minerals in edible giblets. The obtained results indicate that the nutritional value and suitability of edible goose giblets for the poultry industry vary depending on breed and sex. Due to the limited research on the chemical composition and physicochemical properties of goose giblets, further research in this area is necessary in the future. Full article

Nitrogen (N) fertilizer management in winter wheat production faces challenges from volatilization losses and sub-optimal application strategies. This is particularly problematic in the Southern Great Plains, where environmental conditions during top-dressing periods favor N losses. This study evaluated the effects of a fertilizer placement method, enhanced-efficiency fertilizers, and application timing on grain yield and protein concentration (GPC) across six site-years in Oklahoma (2016–2018). Treatments included broadcast applications of untreated urea and SuperU^® (urease/nitrification inhibitor-treated urea). These were compared with subsurface placement using single-disc and double-disc drilling systems, applied at 67 kg N ha⁻¹ during January, February, or March. Subsurface placement increased the grain yield by 324–391 kg ha⁻¹ compared to broadcast applications at sites with favorable soil conditions. However, responses varied significantly across environments. Enhanced-efficiency fertilizers showed limited advantages over untreated urea. Benefits were most pronounced during February applications under conditions favoring volatilization losses. Application timing effects were more consistent for GPC than for the yield. Later applications (February–March) increased GPC by 0.8–1.2% compared to January applications. Treatment efficacy was strongly influenced by soil pH, equipment performance, and post-application environmental conditions. This indicates that N management benefits are highly site-specific. These findings demonstrate that subsurface placement can improve nitrogen use efficiency (NUE) under appropriate conditions. However, success depends on matching application strategies to local soil and environmental factors rather than adopting universal recommendations. Full article

Zinc finger proteins are frequently implicated in a wide range of neurodevelopmental disorders (NDDs). In this study, we report a case of mild intellectual disability (ID), global developmental delay (GDD), and developmental coordination disorder (DCD) in an individual with unaffected parents. Trio-based whole-exome sequencing (WES) identified a de novo variant (c.1530dup, p.Glu511ArgfsTer16) in the ZNF496 gene of the proband. According to ACMG guidelines, this novel variant is classified as pathogenic. It creates a frameshift that introduces a premature stop codon, resulting in a truncated protein of 525 amino acids (compared to the wild-type 587 residues). Notably, NMDEscPredictor analysis predicted that the transcript escapes nonsense-mediated decay (NMD) despite the frameshift. Computational analyses suggest the potential pathogenetic effects of the identified variant. As documented, ZNF496 interacts with JARID2, a gene associated with NDDs, ID and facial dysmorphism (MIM: #620098). In silico analyses suggest that the identified mutation disrupts this interaction by deleting ZNF496’s C2H2 domain, potentially dysregulating JARID2 target genes. To our knowledge, this is the first reported association between ZNF496 and NDDs, and the variant has been submitted to the ClinVar database (SCV006100880). Functional studies are imperative to validate ZNF496’s role in NDDs and confirm the mutation’s impact on ZNF496-JARID2 interactions. Full article

Alcalase was immobilized–stabilized on carrageenan beads following a previously described protocol. Then, the activities of free and immobilized enzymes were compared using different protein substrates (casein, (CS), bovine serum albumin (BSA), or hemoglobin (HG)) at different pH values and temperatures. The observed activity depended on the substrate protein and enzyme formulation used. The highest enzyme activity could be observed at pHs 5, 7, or 10, depending on the substrate protein and the Alcalase formulation. The effect of the temperature at these pHs on the activity versus the different substrate proteins showed a common pattern. At low temperatures, the immobilized enzyme presented higher (mainly at acidic-neutral pH values and using BSA) or similar specific activity than the free enzyme. At temperatures near the optimal for the free enzyme, it became the most active, while at higher temperatures, the immobilized enzyme recovered the lead, although differences in the optimal temperature were not very significant. This may be explained by the lower mobility of the immobilized–stabilized enzyme. The immobilized enzyme could be much more active than the free enzyme or slightly less active, even using mild conditions, depending on the substrate protein, pH, and temperature used to determine the enzyme activity. Full article

To enhance the effectiveness of sustainable preservation of modified corn wet distillers’ grains plus solubles (mcWDGS), various additives were tested under aerobic and anaerobic conditions. In Experiment I, the mcWDGS was stored under aerobic conditions for 5 days at 25 °C. Treatments included different organic acids applied at 0.3% or 0.6% of fresh matter (FM). In Experiment II, the mcWDGS was ensiled anaerobically for 8 weeks at 25 °C using organic acids, a commercial acid mixture, or a microbial inoculant at 0.2% FM. In aerobic conditions, the best preservability was achieved with propionic and formic acids at 0.6% FM, as indicated by the lowest temperature, pH, and microbial counts on days 3 and 5 (p ≤ 0.01). Under anaerobic storage, the highest lactic acid concentrations were recorded in the control, citric acid, and commercial acid mixture variants (p ≤ 0.01). Acetic acid levels were highest in the control (p ≤ 0.01). The highest NH3-N content was found in the formic acid variant and the lowest in the inoculant variant (p ≤ 0.01). Aerobic stability after ensiling was greatest in the control and propionic acid groups (p ≤ 0.01). Nutritional analysis showed that the citric acid group had the highest dry matter content (p ≤ 0.01), while the control group contained the most crude protein (p ≤ 0.01) and saturated fatty acids (p ≤ 0.05). The propionic acid and commercial acid mixture variants had the highest unsaturated fatty acids (p ≤ 0.05). Antioxidant capacity was also greatest in the control (p ≤ 0.01). In conclusion, mcWDGS can be effectively preserved aerobically with 0.6% FM of propionic or formic acid, and anaerobically via ensiling, even without additives. These findings support its potential as a stable and nutritious feed ingredient. Full article

Curli fimbriae are a major component of biofilm formation in Escherichia coli, and their expression is regulated by numerous transcription factors and small regulatory RNAs (sRNAs). The RcsD-RcsC-RcsB phosphorelay system, which is involved in the envelope stress response, plays a role in this regulation. In this study, we report that DNase-I footprinting analysis revealed that the response regulator RcsB interacts with the −31 to +53 region of the promoter region of csgD, which encodes a major regulator of biofilm formation, and thus contributes to its transcriptional repression. Additionally, overexpression of RcsB or RcsB D56A that could not be phosphorylated by the histidine kinases RcsC and D both significantly reduced csgD expression and suppressed Curli formation. This indicates that the phosphorylation of RcsB has an insignificant impact on its affinity for its operator sites. Furthermore, we confirm that RcsB binds cooperatively to the csgD promoter region in the presence of the nucleoid-associated protein H-NS. Our study also confirms that RcsB positively regulates the expression of an sRNA, RprA, which is known to reduce mRNA csgD mRNA translation RprA via its binding to the 5′-untranslated region (UTR) of csgD. These findings indicate that, in E. coli, the RcsBCD system suppresses csgD expression through both direct transcriptional repression by the regulator RcsB and translational repression by the sRNA RprA. Full article