Search Results (7,207)

Continuous cropping obstacles (CCOs) severely restrict the sustainable development of the ginger industry, yet the response mechanisms of rhizosphere microbiome and metabolome to microbial fertilizer under different continuous cropping durations remain unclear. Here, a field experiment was conducted in ginger fields with 5-year (short-term) and 20-year (long-term) continuous cropping history under conventional chemical fertilization, with or without additional microbial fertilizer application. Rhizosphere soil samples were analyzed via metagenomic sequencing and UPLC–MS/MS. Long-term continuous cropping caused severe soil acidification (pH 5.18–5.26 vs. 6.82–6.98 in short-term) and pathogen enrichment. Microbial fertilizer reduced the disease index by 43.47% under long-term cropping and by 31.48% under short-term cropping. It also improved soil properties and enzyme activities (e.g., urease activity increased nearly 12-fold), enriched beneficial genera (Pedobacter, Flavobacterium, Pseudomonas), activated arginine and proline metabolism, and promoted 4-guanidinobutanoic acid accumulation, forming a positive feedback loop with beneficial microbes. In conclusion, microbial fertilizer alleviates ginger CCOs by reshaping the rhizosphere microbiome and metabolome in a continuous cropping duration-dependent manner. Full article

Intensive agricultural practices based on continuous monocropping and prolonged bare-soil fallows have contributed to soil degradation and loss of biological functioning. Replacing fallows with cover crops (CCs) is a promising strategy to restore soil quality, yet their legacy effects on rhizosphere fungal communities remain poorly understood. This study evaluated the legacy effects of Urochloa (syn. Brachiaria) brizantha cover cropping on rhizosphere fungal communities, as well as soil physicochemical and biological properties, in a degraded common bean system. A field experiment with a randomized complete block design included: bare fallow (BM), one (B1) or two (B2) CC cycles before bean, a perennial pasture (PB), and a pristine soil reference (PS). High-throughput sequencing showed that Urochloa-based treatments significantly shifted fungal community composition compared to BM, increasing saprotrophic and beneficial taxa (e.g., Mortierella, Penicillium, Coprinellus) and reducing potential pathogens such as Fusarium. These changes were associated with higher soil organic carbon, aggregate stability, microbial biomass, and enzyme activities, especially in B2 and PB. Indicator taxa identified by LEfSe were linked to organic matter decomposition and nutrient cycling. Multivariate analyses revealed strong associations between fungal community structure and soil properties. Overall, U. brizantha cover cropping induced measurable legacy effects, promoting soil biological recovery even after short-term implementation. Full article

The utilization of sugarcane molasses as a low-cost carbon source for riboflavin production is hindered by the reactive oxygen species (ROS) stress induced by its complex components, which suppresses microbial metabolism. To address this, we employed adaptive laboratory evolution (ALE) under progressively increasing stress to develop a sugarcane molasses-tolerant and high-yielding Ashbya gossypii. The adapted strain achieved a riboflavin titer of 298.39 ± 2.01 mg/L, representing a 99.4% increase over the parental strain (149.66 ± 4.97 mg/L), accompanied by a 96% increase in biomass (dry cell weight). Notably, the specific riboflavin production per unit biomass showed no significant difference between the two strains, indicating that the improved total yield was primarily driven by enhanced biomass accumulation. Transcriptomic analysis revealed the molecular basis for this enhanced biomass accumulation—the elevated expression of antioxidant enzymes (SOD1, PRDX5) mitigated ROS levels to support cellular growth, while the coordinated upregulation of the pentose phosphate pathway (E2.2.1.1) and purine metabolism genes (PPAT, ADE5, PFAS, ADSL) enhanced the supply of biosynthetic precursors, ribulose-5-phosphate (Ru5P) and GTP, for nucleotide biosynthesis and cell proliferation. These metabolic adjustments collectively enabled the adapted strain to achieve robust growth under sugarcane molasses stress, thereby driving the overall increase in riboflavin production. This study elucidates the molecular mechanism underlying ALE-improved riboflavin production and provides a promising strategy for its industrial fermentation using sugarcane molasses. Full article

Hepatocellular carcinoma is challenging to detect at an early stage, and its severity increases over time. Recently, the incidence of hepatocellular carcinoma has increased, partly due to lifestyle-related factors such as excessive alcohol intake, sedentary behavior, and diets high in fat, which contribute to the growing prevalence of fatty liver and hepatitis. Various therapeutic strategies are being explored for hepatocellular carcinoma, among which therapies targeting deubiquitinating enzymes (DUBs) have attracted growing attention. Ubiquitination acts as a crucial modulator in the regulation of intracellular signaling across many diseases. E3 ligase recognizes the target protein and transfers ubiquitin, received from the E2 enzyme, to the lysine residues of the substrate, thereby conferring specificity to the ubiquitination process. Once a ubiquitin chain is attached to a target protein by an E3 ligase, the protein is directed to the ubiquitin–proteasome system (UPS) for degradation. In this process, the 26S proteasome complex recognizes the ubiquitin chain and degrades the target protein, thereby serving as a major mechanism for maintaining protein homeostasis. Through this pathway, cells regulate signal transduction, eliminate abnormal proteins, and perform various essential functions. On the other hand, deubiquitinating enzymes (DUBs) recognize the ubiquitin chains on target proteins and remove them by hydrolyzing the isopeptide bonds of ubiquitin, thereby enabling the target proteins to evade degradation by the proteasome system. Furthermore, deubiquitinating enzymes independently remove ubiquitin from proteins and can serve as central regulators in signaling pathways related to hepatocellular carcinoma. Full article

Coniferyl alcohol and coniferyl aldehyde are precursors of lignin and are used in spices and the pharmaceutical industry. In this work, antioxidant, anticholinergic, antidiabetic, and antiglaucoma effects of coniferyl alcohol and aldehyde were evaluated and compared against the standards. To determine the antioxidant capacities of coniferyl alcohol and aldehyde, ABTS^•+, DMPD^•+ and DPPH^• scavenging abilities as well as cupric ion (Cu²⁺) reduction, ferrous ions (Fe²⁺) reduction and Fe³⁺-TPTZ reduction activities were studied. Butylated hydroxytoluene (BHT), ascorbic acid, α-Tocopherol, Trolox, and butylated hydroxyanisole (BHA) were used as the standard antioxidants. When the antioxidant effects of coniferyl alcohol and coniferyl aldehyde are compared to the standards, they exhibit significant antioxidant effects. In addition, it was determined that coniferyl alcohol and coniferyl aldehyde had a high degree of inhibition effect towards carbonic anhydrase (hCA) I and II isoforms purified from human erythrocytes, α-glycosidase, butyrylcholinesterase (BChE), acetylcholinesterase (AChE), and α-amylase as in vitro and in silico. Molecular docking studies revealed favorable binding affinities of coniferyl alcohol and coniferyl aldehyde toward all investigated enzymes, with key hydrogen bonding and π–π interactions identified at the active sites. The docking findings were found to be compatible with the in vitro enzyme inhibition results, supporting the proposed multi-target biological potential of both compounds. Molecular docking studies revealed favorable binding affinities of coniferyl alcohol and coniferyl aldehyde toward all investigated enzymes. Key hydrogen bonding and π–π interactions were identified within the active sites, particularly for AChE and hCA II. The docking results were consistent with the in vitro enzyme inhibition data, supporting their multi-target biological potential. Docking demonstrated that both compounds can effectively interact with the catalytic regions of the target enzymes. The identified binding modes and interaction patterns support the observed inhibitory activities and provide a molecular basis for their multi-target biological effects. Full article

Background/Objectives: Lavandula cariensis species is cultivated uncommonly in the western region of Turkey. The colloquial appellations avayianos, karabasi, and myra are used to refer to the L. cariensis plant. The essential oil of L. cariensis was studied for its potential antiglaucoma, antioxidant, antidiabetic, and acetylcholinesterase inhibitory effects. Methods: The inhibitory effect of the essential oil of L. cariensis on the acetylcholinesterase (AChE), carbonic anhydrase II (CA II), and α-amylase enzymes was determined. Therefore, chemical profiles of L. cariensis’ essential oil were identified using Gas Chromatography Mass Spectrometry (GC-MS) and as Chromatography with Flame Ionization Detection (GC-FID) analyses. Results: Camphor (39.73%), fenchone (19.49%), exobornyl acetate (6.81%), camphene (5.49%), and eucalyptol (5.49%) were the most abundant compounds in L. cariensis essential oil. Radical scavenging effect of the essential oil of L. cariensis was examined using 1,1-diphenyl-2-picrylhydrazyl (DPPH) (IC₅₀: 231.0 ± 0.094 μg/mL) and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) (IC₅₀: 7.45 ± 0.013 μg/mL) radicals. Also, the ferric ions (Fe³⁺), cupric ions (Cu²⁺), and Fe³⁺-2,4,6-tri(2-pyridyl)-S-triazine (TPTZ) complex reducing capabilities were studied. Additionally, essential oil of L. cariensis indicated a comparable level of inhibition towards hCA II (IC₅₀: 276.42 μg/mL), AChE (IC₅₀: 14.22 μg/mL), and α-amylase (IC₅₀: 475.63 μg/mL) enzymes. Conclusions: The evaluation of the antioxidant capabilities and enzyme inhibition profiling of the essential oil of L. cariensis will be made possible by this comprehensive study, which serves as a springboard for further research. The essential oil of L. cariensis demonstrated enzyme-inhibitory activities against target enzymes associated with Alzheimer’s disease, diabetes, and glaucoma. Also, this study’s in vitro inhibition suggests promising prospects. Full article

Background/Objectives: Sex-specific differences in the pharmacokinetics of psychotropic drugs are gaining increasing clinical relevance, but only limited data are currently available on sex-specific effects within genetically defined metabolizer phenotype categories. The objective of this study was to assess genotype-dependent sex differences in the metabolic capacity of the drug-metabolizing enzymes CYP2D6 and CYP2C19. Methods: Statistical analyses were performed using linear mixed-effects models with subject-level random intercepts to account for repeated therapeutic drug monitoring (TDM) measurements. Venlafaxine and risperidone were used as probe drugs to find differences in the metabolic capacity of CYP2D6 and escitalopram for CYP2C19. Pharmacokinetic surrogate parameters were the metabolite-to-parent ratio (MPR) for venlafaxine and risperidone and the dose-corrected serum concentration (CD) for escitalopram. Models included sex, metabolizer phenotype, and their interaction, adjusted for age and creatinine production rate (CPR). Sex-specific differences within phenotype groups were assessed using estimated marginal means. Results: Among venlafaxine samples (N = 117) and risperidone samples (N = 73), no significant sex-specific differences in MPR were observed within CYP2D6 metabolizer groups. For escitalopram samples (N = 51), a significant sex difference was observed among CYP2C19 normal metabolizers (NMs), with higher CD in males compared to females. Conclusions: Exploratory analyses suggested a higher metabolic capacity in CYP2C19 NM females treated with escitalopram. Due to the limited sample size, however, this finding should be considered hypothesis-generating. Future studies in larger samples are needed to corroborate whether sex and other factors modulate the metabolic capacity of CYP2C19, e.g., by epigenetic mechanisms. Full article

This study elucidates the multi-targeted antineoplastic mechanisms of Parkia speciosa empty pod extract (PSET) against HCT-116 and HT-29 colorectal cancer (CRC) cells through integrated transcriptomic and proteomic analyses. Phytochemical profiling indicates that PSET is rich in bioactive metabolites, notably quercetin, rutin, and pyrogallol, which orchestrate its profound ability to inhibit tumor proliferation, migration, and invasion. Transcriptomic data revealed that PSET profoundly suppresses the oncogenic Wnt/β-catenin signaling axis while simultaneously activating p53-mediated cell cycle arrest. Complementary proteomic profiling uncovered critical metabolic vulnerabilities, demonstrating that PSET abrogates the Warburg effect by disrupting key glycolytic enzymes (e.g., ENO1, GAPDH, LDHA), thereby inducing metabolic starvation. Furthermore, the extract precipitated a catastrophic collapse of the cytoskeletal architecture and downregulated epithelial–mesenchymal transition (EMT) markers, effectively paralyzing the cells’ metastatic machinery. The integrated transcriptomic and proteomic signatures also highlighted an irrecoverable state of cellular stress, characterized by an overwhelming unfolded protein response and dysregulated RNA splicing, ultimately driving the cells toward apoptosis. In conclusion, this integrated omics approach provides robust molecular validation that PSET systemically dismantles colorectal cancer survival networks, highlighting its strong potential as a natural, multi-targeted therapeutic agent. Full article

Aquatic organisms are exposed to multiple stressors, including microplastic pollution and rising temperatures. Bioplastics like Poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) are considered sustainable alternatives to conventional plastics, although their biological effects remain poorly understood. This study evaluated the effects of PHBV microplastics on Artemia franciscana under different temperature and exposure conditions. Organisms were exposed to 25 and 100 mg·L⁻¹ PHBV for 7, 14, and 21 days at 25 °C and for 14 days at 29 °C. Growth, development, antioxidant enzyme (CAT, GST) and esterase activities (ChE, CbE), lipid peroxidation (LPO), gut histology, fatty acid profiles and polymer particle length distributions were assessed. Growth and development increased with PHBV concentration, exposure time, and temperature. Enzymatic activities and LPO were significantly affected by these factors, although no evidence of oxidative damage was detected. Marked gut lesions were observed at 100 mg·L⁻¹ PHBV at 29 °C after 14 days. Fatty acid profiles were mainly influenced by time and temperature, while high PHBV levels were associated with additional, more subtle changes in long-chain polyunsaturated fatty acids. PHBV particle length distributions also varied depending on exposure conditions. These findings suggest that PHBV induces physiological responses distinct from those typically reported for conventional microplastics and highlight the importance of considering multiple stressors in ecotoxicological studies. Full article

High-Mobility Group Box (HMGB) proteins belong to the family of high-mobility proteins characterized by two DNA-binding domains and an unstructured, negatively charged C-terminal domain that modulates DNA–protein and protein–protein interactions. These proteins participate in multiple cellular processes, including DNA replication, transcription, recombination, and repair. The functional activity of HMGB proteins is associated with various physiological and pathological conditions, including malignant tumors and cardiovascular diseases, highlighting the need for strict regulation of their levels and activity to maintain cellular homeostasis. Such regulation can occur at multiple levels, including proteolytic degradation. In recent years, a number of E3 ubiquitin ligases that promote the degradation of HMGB proteins, as well as deubiquitinases (DUBs) that stabilize them by removing ubiquitin tags, have been identified. This review summarizes these enzymes and their proposed roles in controlling the functions of the HMGB family proteins, both through direct interaction with these proteins and via mediator proteins. Full article

Certain sacoglossan sea slugs, often known as “solar-powered sea slugs”, are a group of marine gastropods that have the unique ability to photosynthesize by stealing functional chloroplasts from algae. The sacoglossan Elysia papillosa can maintain functional chloroplasts for up to two weeks after feeding. The microbiome of these slugs may play a crucial role in their metabolism, immunity, development, but more importantly their photosynthesis. Shotgun metagenomic sequencing was conducted on four samples of E. papillosa in order to characterize their microbiome. Sequences were classified and relative abundance was quantified with Centrifuger and functional data was examined using SqueezeMeta. Bacteria were analyzed by taxonomic groups and hypothesized function to the sea slug was determined with literature analysis. All samples were dominated by phyla Actinomycetota, Bacillota, Patescibacteriota, and Pseudomonadota. The presence of the phyla Bacteroidota and Bacillota was notable in all samples, which contain species known to produce enzymes that break down polysaccharides. It is possible that these bacteria could assist in degradation of the polysaccharide xylan found in the cell walls of Penicillus, the algal food source of E. papillosa. One species that was found in all samples was Cutibacterium acnes which has been shown to be an important component of the gut microbiota in other marine invertebrates and may provide the host with vitamin B12 and other beneficial nutrients. Many of these bacteria may be opportunistic rather than commensal. As a result, more research is required to describe the interactions between the slug and its microbiome, but this preliminary report provides a valuable starting point for identifying the microbiome make-up to further understanding of these relationships. Full article

Mounting acaricide resistance in Tetranychus mexicanus (McGregor) (Acari: Tetranychidae), among the most damaging phytophagous mites in tropical and subtropical crops, has intensified the search for botanical alternatives. An oil-in-water nanoemulsion of Thymus vulgaris essential oil (TVEO-NE) was developed and evaluated for lethal and sublethal effects on adult females of T. mexicanus. TVEO, composed mainly of thymol (45%) and p-cymene (37%), was formulated by low-energy emulsification yielding stable dispersions (~200 nm; PDI < 0.25; zeta potential of −22.2 mV). At 30.0 mg a.i./mL, TVEO-NE caused 68.3% corrected mortality at 72 h and suppressed fecundity by ~44–52%; vehicle controls exerted only moderate effects, identifying the essential oil as the primary bioactive driver. Morphological examination revealed collapse of female idiosomata and disruption of excretory pellet architecture, corroborating the bioassay data. Molecular docking against a cathepsin L homology model revealed that thymol and p-cymene interact exclusively via hydrophobic contacts and display substantially lower ChemPLP fitness scores than the reference cysteine protease inhibitor E64, indicating weak predicted binding affinity and arguing against enzyme inhibition as the primary mechanism. Taken together, bioassay, morphological, and docking are consistent with supporting membrane partitioning as a plausible primary mode of action, positioning TVEO-based nanoemulsions as promising botanical tools for T. mexicanus management. Full article

Vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome is an adult-onset inflammatory disorder caused by acquired mutations in UBA1, the gene encoding the primary ubiquitin-activating enzyme. The recognition of VEXAS has transformed the current understanding of autoinflammatory disease by demonstrating that somatic alterations arising within hematopoietic stem cells can precipitate severe, multisystem inflammation in later life. While pathogenic UBA1 variants are essential to disease pathogenesis, many affected individuals also harbor additional somatic mutations associated with clonal hematopoiesis, most commonly involving DNMT3A and TET2. These concurrent mutations may contribute to clonal architecture; however, their independent impact on inflammatory phenotype and hematologic manifestations remains incompletely defined. Emerging evidence suggests that co-occurring clonal hematopoiesis mutations may be independently associated with poorer overall survival, though their causal role remains unestablished. This review examines the evolving genetic framework of VEXAS syndrome, emphasizing UBA1 as the obligate driver mutation while reviewing current evidence regarding non-Met41 UBA1 variants and co-occurring somatic mutations. Full article

Fungal infections pose diagnostic challenges in both human and veterinary medicine, as traditional detection methods such as fungal culture are time-consuming, microscopy is operator-dependent, and molecular detection assays often require specialized instrumentation and trained personnel, which can limit their routine clinical application. This study developed a sandwich immunoassay to detect β-1,3- and β-1,6-glucans, two major components of the fungal cell wall, based on two catalytically inactive glucanase mutants, LamA_E175Q and Neg1_E321Q. The sandwich ELISA exhibited higher detection sensitivity than conventional ITS-based PCR for Saccharomyces cerevisiae and Candida albicans under the conditions of this study. Using pre-coated plates, the sample-processing and detection workflow can be completed in approximately 40 min. It effectively detected a wide range of fungal species, including yeasts (Saccharomyces cerevisiae, Candida albicans) and filamentous fungi such as dermatophytes and non-dermatophyte molds. In a preliminary clinical cohort, the assay identified β-glucan signals in all 21 samples confirmed positive for dermatophytes, while no signal was detected in 20 negative samples, suggesting potential clinical applicability. This dual-enzyme sandwich immunoassay provides a rapid and low-cost complementary tool for broad-spectrum fungal screening, which may help guide further confirmatory diagnostics and timely clinical decision-making. Full article

The genetic and antigenic diversity of H5Nx HPAI Gs/GD lineage continues to be a great challenge facing conventional inactivated vaccines. To overcome this challenge, a recombinant herpes virus of turkey (rHVT) vaccine expressing the viral protein 2 (VP2) of infectious bursal disease (IBD) and H5, rHVT+IBD+H5, was developed using computationally optimized broadly reactive antigen (COBRA) technology. In the current study, the protective efficacy of a commercially available vector trivalent vaccine rHVT+IBD+H5 using COBRA technology was assessed. A total of 120 commercial broilers were divided equally into six groups (G1B–G6B). The chickens in G1B–G3B were challenged with the most recent circulating HPAI-H5N1 clade 2.3.4.4.b Egyptian isolate (GenBank accession No. OQ933425) at 28 days old (DO), while the chickens in G4B and G5B were kept as vaccinated (as G1B and G2B, respectively) and non-challenged, and G6B was the non-vaccinated non-challenged group. In G1B, the chickens were vaccinated with Vaxxitek^® rHVT+IBD+H5 at 1 DO and boostered with a commercially available subunit Baculovirus bivalent inactivated H5+ND (Volvac^® B.E.S.T AI+ND) at 10 DO and had a 100% survival rate. The standalone vaccinated chicken G2B, using rHVT+IBD+H5 at 1 DO, had a highly significant survival rate (90%) vs. 0% (100% mortality) in the non-vaccinated challenged control, G3B. All the vaccinated groups had higher seroconversion at 45 DO especially using H5-coated antigen plates for the enzyme-linked immunosorbent assay (ELISA) test. The viral shedding titers and time were evaluated using a quantitative real-time polymerase chain reaction (RT-qPCR) in the collected oropharyngeal and cloacal swabs at 3, 5, 7, and 10 days post-challenge (DPC). In conclusion, vaccination with rHVT+IBD+H5 either as a standalone or when boostered with subunit Baculovirus bivalent inactivated ND+H5 resulted in 90 and 100% protection, respectively, without significant difference in the quantity and duration of viral shedding between both groups against HPAI-H5N1 clade 2.3.4.4.b experimental challenge in broilers. Full article