Search Results (31,203)

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

Ready-to-eat meat products face quality challenges during storage and reheating. This study aimed to (i) characterize the physicochemical/microbiological changes in stewed mutton during storage (4 °C/−18 °C, 0–28 days) and (ii) evaluate reheating methods (boiling vs. microwaving) on day-7 samples. The nutritional analysis confirmed moisture reduction (57.32 vs. 72.12 g/100 g)-concentrated protein/fat levels. Storage at −18 °C suppressed microbial growth (the total plate count (TPC), 3.73 vs. 4.80 log CFU/g at 28 days; p < 0.05) and lipid oxidation (thiobarbituric acid reactive substances (TBARS): 0.14 vs. 0.19 mg/kg) more effectively than storage at 4 °C. The total volatile basic nitrogen (TVB-N) kinetics projected a shelf life ≥90 days (4 °C) and ≥120 days (−18 °C). Microwave reheating after frozen storage (−18 °C) maximized the yield (86.21% vs. 75.90% boiling; p < 0.05) and preserved volatile profiles closest to those in the fresh samples (gas chromatography–mass spectrometry (GC-MS)/electronic nose). The combination of freezing storage and subsequent microwave reheating has been demonstrated to be an effective method for preserving the quality of a precooked lamb dish, thereby ensuring its nutritional value. 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

Proteomic profiling using ultrafast chromatography–mass spectrometry provides valuable insights into plant responses to abiotic factors by linking molecular changes with physiological outcomes. Nanopriming, a novel approach involving the treatment of seeds with nanoparticles, has demonstrated potential for enhancing plant metabolism and productivity. However, the molecular mechanisms underlying nanoparticle-induced effects remain poorly understood. In this study, we investigated the impact of gold nanoparticle (Au-NP) seed priming on the proteome of wheat (Triticum aestivum L.) seedlings. Differentially regulated proteins (DRPs) were identified, revealing a pronounced reorganization of the photosynthetic apparatus (PSA). Both the light-dependent reactions and the Calvin cycle were affected, with significant upregulation of chloroplast-associated protein complexes, including PsbC (CP43), chlorophyll a/b-binding proteins, Photosystem I subunits (PsaA and PsaB), and the γ-subunit of ATP synthase. The large subunit of ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCo) exhibited over a threefold increase in expression in Au-NP-treated seedlings. The proteomic changes in the large subunit RuBisCo L were corroborated by transcriptomic data. Importantly, the proteomic changes were supported by physiological and biochemical analyses, ultrastructural modifications in chloroplasts, and increased photosynthetic activity. Our findings suggest that Au-NP nanopriming triggers coordinated molecular responses, enhancing the functional activity of the PSA. Identified DRPs may serve as potential biomarkers for further elucidation of nanopriming mechanisms and for the development of precision strategies to improve crop productivity. Full article

Quinoa (Chenopodium quinoa), a stress-tolerant pseudocereal ideal for studying abiotic stress responses, was used to systematically identify optimal reference genes for qPCR normalization under gradient stresses: low temperatures (LT group: −2 °C to −10 °C), heat (HT group: 39° C to 45 °C), and drought (DR group: 7 to 13 days). Through multi-algorithm evaluation (GeNorm, NormFinder, BestKeeper, the ΔCt method, and RefFinder) of eleven candidates, condition-specific optimal genes were established as ACT16 (Actin), SAL92 (IT4 phosphatase-associated protein), SSU32 (Ssu72-like family protein), and TSB05 (Tryptophan synthase beta-subunit 2) for the LT group; ACT16 and NRP13 (Asparagine-rich protein) for the HT group; and ACT16, SKP27 (S-phase kinase), and NRP13 for the DR group, with ACT16, NRP13, WLIM96 (LIM domain-containing protein), SSU32, SKP27, SAL92, and UBC22 (ubiquitin-conjugating enzyme E2) demonstrating cross-stress stability (global group). DHDPS96 (dihydrodipicolinate synthase) and EF03 (translation elongation factor) showed minimal stability. Validation using stress-responsive markers—COR72 (LT), HSP44 (HT), COR413-PM (LT), and DREB12 (DR)—confirmed reliability; COR72 and COR413-PM exhibited oscillatory cold response patterns, HSP44 peaked at 43 °C before declining, and DREB12 showed progressive drought-induced upregulation. Crucially, normalization with unstable genes (DHDPS96 and EF03) distorted expression profiles. This work provides validated reference standards for quinoa transcriptomics under abiotic stresses. Full article

The windowpane oyster (Placuna placenta) is common in coastal areas of the Philippines, thriving in brackish waters. Its shells underpin the local craft industries. While its meat is edible, only small amounts are consumed locally, most going to waste. Utilization of this potential nutrient source is hindered by the lack of information concerning its organic and mineral content, the possible presence of heavy metal ions, and the risk of microbial pathogens. We report extensive analysis of the meat from Placuna placenta, harvested during three different seasons to account for potential variations. This comprises proximate analysis, mineral, antioxidant, and microbial analyses. While considerable seasonal variation was observed, the windowpane oyster was found to be a rich source of protein, fats, minerals, and carbohydrates, comparing well with the meats of other shellfish and land animals. Following pre-cooking (~90 °C, 25–30 min), the standard local method for food preparation, no viable E. coli or Salmonella sp. were detected. Mineral content was broadly similar to that reported in fish, although iron, zinc, and copper were more highly represented, nevertheless, heavy metals were below internationally acceptable levels, with the exception of one of three samples, which was slightly above the only current standard, FSANZ. Whether the arsenic was in the safer organic form, which is commonly the case for shellfish, or the more toxic inorganic form remains to be established. This and the variation of arsenic over time will need to be considered when developing food products. Overall, the meat of the windowpane oyster is a valuable food resource and its current (albeit low-level) use should lower any barriers to its acceptance, making it suitable for commercialization. The present data support its development for high-value food products in urban markets. 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

Fasciola hepatica remains a global health and economic concern, and treatment still relies heavily on triclabendazole. At the parasite–host interface, F. hepatica calcium-binding proteins (FhCaBPs) have a unique EF-hand/DLC-like domain fusion found only in trematodes. This makes it a parasite-specific target for small compounds and vaccinations. To enable novel therapeutic strategies, we report the first elevated-resolution structure of a full-length FhCaBP4. The apo structure was determined at 1.93 Å resolution, revealing a homodimer architecture that integrates an N-terminal, calmodulin-like, EF-hand pair with a C-terminal dynein light chain (DLC)-like domain. Structure-guided in silico mutagenesis identified a flexible, 16-residue β4–β5 loop (LTGSYWMKFSHEPFMS) with an FSHEPF core that demonstrates greater energetic variability than its FhCaBP2 counterpart, likely explaining the distinct ligand-binding profiles of these paralogs. Molecular dynamics simulations and AlphaFold3 modeling suggest that EF-hand 2 acts as the primary calcium-binding site, with calcium coordination inducing partial rigidification and modest expansion of the protein structure. Microscale thermophoresis confirmed calcium as the major ligand, while calmodulin antagonists bound with lower affinity and praziquantel demonstrated no interaction. Thermal shift assays revealed calcium-dependent stabilization and a merger of biphasic unfolding transitions. These results suggest that FhCaBP4 functions as a calcium-responsive signaling hub, with an allosterically coupled EF-hand–DLC interface that could serve as a structurally tractable platform for drug targeting in trematodes. Full article

Objective: This study aimed to describe the perinatal and neonatal outcomes of chronic abruption oligohydramnios sequence in the Kanto region of Japan. Methods: This survey was conducted at 123 perinatal centers affiliated to this area. Data on the experience of managing chronic abruption oligohydramnios sequence between 1 January 2017, and 31 December 2022, were collected and analyzed. Results: Among the 82 cases of chronic abruption oligohydramnios sequence that were included in this study, there were seven miscarriages, five artificial abortions, and 70 deliveries beyond 22 gestational weeks (singleton: 68; twin: 2). In 82 patients, vaginal bleeding was the initial symptom of chronic abruption oligohydramnios sequence (88%). The mean gestational duration at the initial symptom onset was 17.3 ± 5.0 weeks. Of the 68 singleton pregnancies delivered after 22 gestational weeks, the mean gestational duration at delivery was 25.2 ± 2.8 weeks. In patients with chronic abruption oligohydramnios sequence, the mean white blood cell count at diagnosis and mean of the maximum white blood cell count during pregnancy were 11,589 ± 2885 and 15,357 ± 4745/μL, respectively; and the mean C-reactive protein at diagnosis and mean of the maximum C-reactive protein during pregnancy were 1.0 ± 1.2 and 2.0 ± 2.1 mg/L, respectively. Chorioamnionitis was identified in 43 patients (63%). All neonates were admitted to the neonatal intensive care unit. Of the 68 singleton neonates, 5 died immediately after birth. Conclusions: Chronic abruption oligohydramnios sequence is a rare perinatal complication that is possibly associated with infections, such as chorioamnionitis, and linked to adverse perinatal and neonatal outcomes. 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

Background/Objectives: The diminished efficacy of azoles in treating fungal infections is attributed to the emergence of resistance among pathogenic fungi. Employing a synergistic approach with other compounds to enhance the antifungal activity of azoles has shown promise, yet the availability of clinically valuable adjuvants for azoles and allylamines remains limited. Studies have demonstrated that the human host environment provides multiple carbon sources, which can influence the susceptibility of C. albicans to antifungal agents. Therefore, a comprehensive investigation into the mechanisms by which carbon sources modulate the susceptibility of C. albicans to azoles may uncover a novel pathway for enhancing the antifungal efficacy of azoles. Methods: This study explored the impact of various carbon sources on the antifungal efficacy of azoles through methodologies including minimum inhibitory concentration (MIC) assessments, super-MIC growth (SMG) assays, disk diffusion tests, and spot assays. Additionally, the mechanism by which galactose augments the antifungal activity of azoles was investigated using a range of experimental approaches, such as gene knockout and overexpression techniques, quantitative real-time PCR (qRT-PCR), Western blot analysis, and cycloheximide (CHX) chase experiments. Results: This study observed that galactose enhances the efficacy of azoles against C. albicans by inhibiting the translation of Erg1. This results in the suppression of Erg1 protein levels and subsequent inhibition of ergosterol biosynthesis in C. albicans. Conclusions: In C. albicans, the translation of Erg1 is inhibited when galactose is utilized as a carbon source instead of glucose. This novel discovery of galactose’s inhibitory effect on Erg1 translation is expected to enhance the antifungal efficacy of azoles. Full article

Background and Objectives: The uric acid to HDL-cholesterol ratio (UHR) has recently emerged as a promising biomarker reflecting systemic inflammation and metabolic disturbances. Elevated liver transaminases are clinical indicators of hepatic injury and underlying metabolic dysfunction. Many Middle Eastern countries face constrained clinical and laboratory resources, where access to comprehensive diagnostic tools may be limited. In such settings, identifying simple and easily accessible markers could offer significant practical value in detecting and monitoring health disorders. This study investigates the potential association between UHR and elevated liver transaminases levels in the Saudi general population. Materials and Methods: This retrospective cross-sectional study included 9618 subjects, and the association between the UHR and elevated liver transaminases, alanine transaminase (ALT), and aspartate transaminase (AST), was comprehensively analysed. In addition, the study assessed risk indicators including the prevalence ratio (PR) and odds ratio (OR) as well as the diagnostic accuracy of UHR and C-reactive protein (CRP) in detecting liver transaminases abnormalities, with analyses stratified by age and gender. Results: UHR was significantly elevated in subjects with increased ALT and AST activities, and this pattern was consistent across all age and gender categories. High UHR was significantly associated with elevated ALT (OR = 2.32, 95% CI: 2.12–2.53, p < 0.001) and AST (OR = 1.38, 95% CI: 1.25–1.52, p < 0.001), with stronger associations observed in males and for ALT activity. In addition, elevated UHR was more prevalent among individuals with increased liver transaminase activities. Receiver operating characteristic (ROC) analysis showed that UHR outperformed CRP in identifying elevated liver transaminases, with better discriminative ability for ALT than AST activity. Conclusions: These findings highlight a significant association between UHR and liver transaminase abnormalities in the general population, underscoring the potential utility of UHR as a simple and accessible indicator for liver function assessment in clinical settings. 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

The extensive use of pesticides has significant implications for public health and the environment. Breeding crop plants is the most effective and environmentally friendly approach to improve the plants’ resistance. However, it is time-consuming and costly, and it is sometimes difficult to achieve satisfactory results. Plants induce defense responses to natural elicitors by interpreting multiple genes that encode proteins, including enzymes, secondary metabolites, and pathogenesis-related (PR) proteins. These responses characterize systemic acquired resistance. Humic substances trigger positive local and systemic physiological responses through a complex network of hormone-like signaling pathways and can be used to induce biotic and abiotic stress resistance. This study aimed to assess the effect of humic substances on the activity of phenylalanine ammonia-lyase (PAL), peroxidase (POX), and β-1,3-glucanase (GLU) used as a resistance marker in various plant species, including orange, coffee, sugarcane, soybeans, maize, and tomato. Seedlings were treated with a dilute aqueous suspension of humic substances (4 mM C L⁻¹) as a foliar spray or left untreated (control). Leaf tissues were collected for enzyme assessment two days later. Humic substances significantly promoted the systemic acquired resistance marker activities compared to the control in all independent assays. Overall, all enzymes studied in this work, PAL, GLUC, and POX, showed an increase in activity by 133%, 181%, and 149%, respectively. Among the crops studied, citrus and coffee achieved the highest activity increase in all enzymes, except for POX in coffee, which showed a decrease of 29% compared to the control. GLUC exhibited the highest response to HS treatment, the enzyme most prominently involved in increasing enzymatic activity in all crops. Plants can improve their resistance to pathogens through the exogenous application of HSs as this promotes the activity of enzymes related to plant resistance. Finally, we consider the potential use of humic substances as a natural chemical priming agent to boost plant resistance in agriculture Full article

Background and Objectives: Clostridioides difficile infection (CDI) poses a major public health problem worldwide. Materials and Methods: In this retrospective study, we included 274 patients with CDI, who were hospitalized in Internal Medicine Departments in Evangelismos General Hospital in Athens, Greece, during the past decade. Demographic, clinical and laboratory parameters of the patients were recorded. Statistical analysis revealed an association between older age and mortality as well as heart failure and mortality among patients with CDI. Results: Notably, WBC (white blood count), neutrophils, NLR (neutrophil-to-lymphocyte ratio), dNLR (derived NLR), SII (systemic immune–inflammation index) and hs-CRP (high-sensitivity C-reactive protein) demonstrated a positive association with mortality, whereas serum albumin levels and PNR (platelet-to-neutrophil ratio) exhibited an inverse relationship with mortality. We propose that the aforementioned biomarkers may be used as prognostic parameters regarding mortality from CDI. Conclusions: Large scale studies among patients with CDI with the advent of AI (artificial intelligence) may incorporate demographic, clinical and laboratory features into prognostic scores to further characterize the global CDI threat. Full article