搜索结果：Applied biochemistry and biotechnology

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters host cells when the spike receptor-binding domain (RBD) engages angiotensin-converting enzyme 2 (ACE2). Cannabinoid scaffolds have recently been reported to bind S1/RBD, block spike-mediated membrane fusion, and modulate host inflammatory pathways, making them attractive candidates for entry inhibition. Here, we applied an integrated computational pipeline to prioritize cannabis-derived compounds as interfacial blockers of the RBD-ACE2 complex across variants. Eleven phytocannabinoids were docked into the wild-type (WT) RBD-ACE2 interface, identifying three cavities, with ligands preferentially occupying pocket 1. Complexes were subjected to triplicate 200 ns all-atom molecular dynamics (MD) simulations for WT, Delta, and Omicron BA.1 RBD-ACE2. Binding energetics were quantified using molecular mechanics/generalized Born surface area (MM/GBSA) and solvated interaction energy (SIE), and per-residue contributions were analyzed together with solvent-accessible surface area (SASA) and residue interaction networks. Among all compounds, cannabidiol (CBD) and cannabinol (CBN) were the only ligands that remained stably bound in pocket 1 for all variants. CBN showed the most favorable ligand-complex binding in WT, whereas CBD preserved favorable binding in Omicron BA.1 despite reduced interface burial, indicating that van der Waals/electrostatic complementarity and solvation, rather than surface coverage alone, govern affinity. Both ligands weakened modeled RBD-ACE2 binding by perturbing hot-spot residues centered on Y505 or N501Y in RBD and E37, A387, and R393 in ACE2. Overall, our results highlight CBD and CBN as tractable, variant-spanning interface disruptors and illustrate how MD-based free-energy calculations can support computational drug discovery against evolving viral protein-protein interfaces.

Vision-threatening ocular diseases are impacted by aging-associated molecular changes, including mitochondrial dysfunction, cellular senescence, and chronic inflammation. Anti-VEGF therapies targeting VEGF-A/VEGFR2 signaling remain the frontline standard of care, but many patients exhibit suboptimal or nondurable responses, often due to compensatory and/or compromised antiangiogenic and anti-inflammatory pathways. We aimed to elucidate shared mechanisms underlying treatment failure and disease progression. We applied an integrative systems biology framework that combined multiomics datasets, network-based machine learning, and disease-specific pathway mapping. A comprehensive literature review of conditions, including diabetic retinopathy, age-related macular degeneration, retinitis pigmentosa, glaucoma, and aging, identified 14 core genes consistently associated with angiogenesis, inflammation, and immune signaling. Multialgorithm centrality and enrichment analyses reconstructed disease-specific interaction networks, revealing consensus mechanistic axes. Integration of cell-type-specific single-cell RNA sequencing data from AMD-RPE clusters identified cluster-specific gene hubs and vertical signaling axes, leading to VEGF blockade failure. EGFR, HSP90AA1, SIRT1, and STAT3 emerged as central resistance hubs linking angiogenesis and inflammatory processes. Pathway enrichment analyses revealed 21 conserved core signaling cascades, grouped into six functional categories, with AGE-RAGE, PI3K-Akt, HIF-1, MAPK, and chemokine pathways playing central roles. A MiRGD-based peptide nanocomplex delivering htsFLT01 achieved efficient RPE transfection and controlled gene activation under basal conditions. This systems-level framework clarifies mechanisms of VEGF blockade resistance and provides a rational basis for next-generation, combinatorial therapeutic strategies requiring validation in disease-relevant models.

The booming food and feed industries strongly promote the exploration of new resources, while Dendrocalamus brandisii presents a promising potential for application for the vigorous growth and abundant harvest in Southeast Asia. To further utilize and increase the value of Dendrocalamus brandisii, firstly, main different parts were comparatively analyzed, while digestive and nutritional indexes were evaluated. As a result, bamboo shoots and leaves contain 26.3% and 20.7% of crude protein, respectively. The relative feed values of bamboo leaves, leaf stems, shoots shells and shoots all exceed 80%. As analyzed, bamboo leaves were promising for producing feed. Afterwards, the silage fermentation of bamboo leaves was carried out, during which the effects of different additives and the changes in nutritive index of bamboo leaves were investigated. By fermenting with composite bacterial inoculum of Lacticaseibacillus paracasei, Saccharomyces cerevisiae and Bacillus subtilis, neutral-detergent fiber and acid-detergent fiber in leaves were decreased significantly by 22.68%~30.36% to produce 55.03 ~ 89.47 g/kg organic acids with over 60 g/kg domination of lactic acid, while crude protein was maintained well. The exogenous cellulase assisted Lacticaseibacillus paracesei fermentation exhibited the fastest decrease in pH (3.68) and the highest lactic acid content (78.68 g/kg). This study provides foundational data on Dendrocalamus brandisii's nutritive composition and demonstrates the feasibility of bamboo leaf-based feed production with potential for scaled implementation in bunkers. Moreover, this approach can facilitate the utilization of sustainable bamboo resource by converting it into high-value feed product and reduce pressure on conventional agricultural system.

Blood cancers, including leukemia, lymphoma, and myeloma, are complex malignancies influenced by genetic, environmental, and epigenetic factors. Among these, epigenetic modifications play a crucial role in cancer initiation and progression. This review explores the interplay between dietary patterns, epigenetic mechanisms, and blood cancer development, highlighting the potential of diet-based interventions in cancer prevention and therapy. A growing body of evidence suggests that dietary habits significantly impact epigenetic modifications such as DNA methylation and histone modifications, which regulate gene expression. Phytochemicals, including curcumin, resveratrol, quercetin, and epigallocatechin gallate (EGCG), exhibit promising epigenetic modulation in blood cancer. These compounds influence DNA methyltransferases (DNMTs) and histone deacetylases (HDACs), restoring normal epigenetic patterns and reactivating silenced tumor suppressor genes (TSGs). Individual variability in dietary response, bioavailability of bioactive compounds, and the complexity of epigenetic interactions necessitate further research in nutri-epigenomics. Future directions should focus on personalized nutrition strategies and clinical trials to validate the efficacy of dietary approaches in blood cancer prevention and therapy. In conclusion, diet plays a pivotal role in epigenetic regulation, influencing the risk and progression of blood cancer. Understanding the molecular mechanisms underlying dietary epigenetic modifications may open new avenues for preventive and therapeutic strategies.

The alarming contamination of aquatic ecosystems with toxic heavy metals and persistent organic dyes demands innovative nanotechnological solutions for simultaneous detection and remediation. In this research, 4-fluorobenzohydrazide-stabilized silver nanoparticles (4-FBH@AgNPs) were synthesized to serve as a versatile nanoplatform for the colorimetric detection of Cd(II), photocatalytic degradation of the methylene blue (MB) dye, and antimicrobial applications. The synthesized nanoparticles were characterized using various techniques, including UV-Visible spectroscopy, FTIR, XRD, TEM, XPS, DLS, zeta potential, and SEM to assess their structural and optical properties. The UV-Vis analysis displayed a distinct localized surface plasmon resonance (LSPR) peak at 435 nm, confirming nanoparticle formation. Colorimetric sensing tests revealed notable color changes for Cd(II), showing a linear response in the nanomolar range with a low limit of detection (LOD) of 37 nM, demonstrating high sensitivity and selectivity towards Cd(II) ions. Additionally, the 4-FBH@AgNPs exhibited impressive photocatalytic efficiency, achieving over 95% degradation of methylene blue (MB) in 60 min under visible light, attributed to improved electron-hole separation and enhanced charge transfer due to plasmon effects. The nanoparticles also exhibited considerable antibacterial properties against Escherichia coli and Staphylococcus aureus. Statistical analysis affirmed the reproducibility and reliability of the photocatalytic and antimicrobial results by response surface methodology. Collectively, these findings demonstrate that 4-FBH@AgNPs possess excellent multifunctional capabilities, making them a promising candidate for environmental remediation and biosensing applications.

Ambient tropospheric ozone is a pervasive air pollutant and an emerging threat to crop quality, food security, and agroecosystem sustainability. While ozone-induced yield losses are well documented, its impacts on crop nutritional quality and livestock feed value under field conditions remain poorly quantified. We investigated the effects of chronic ambient ozone exposure on nutrient uptake, grain micronutrient composition, and straw feed quality in six genotypes grown under field conditions in Bangladesh, one of the world's most ozone-exposed rice-growing regions. Ethylenediurea was applied to provide a diagnostic contrast for ozone-related responses under ambient field conditions across three consecutive growing seasons. Ambient ozone was associated with reduced plant carbon and nitrogen uptake and lower crop nitrogen-use efficiency in ozone-sensitive genotypes. Grain nutrient uptake declined, accompanied by a reduction in grain iron concentration (≈22%) and smaller declines in zinc, together with increased phytate levels, indicating reduced micronutrient bioavailability. In parallel, straw lignin content increased in sensitive genotypes, reflecting stress-induced carbon allocation to structural defenses and a deterioration in forage quality. Multivariate analyses demonstrated that ozone exposure weakened the association between nutrient-use efficiency and grain nutritional quality. In contrast, the tolerant genotype Kasalath maintained nutrient uptake, use efficiency, and grain micronutrient composition under ozone stress. Our findings demonstrate that field-level ambient ozone pollution is associated with declines plant physiological performance, degrade livestock feed value, and exacerbate human micronutrient risks, highlighting the need for integrated air-quality management and crop adaptation strategies in ozone-affected regions.

The antioxidant and antifungal activities of (Lavandula stoechas) L. stoechas aqueous extract were studied to examine their potential application against food and crop spoilage. Total phenolic (TPC) and flavonoids (TFC) contents were quantified and individual polyphenols were analyzed by high-performance liquid chromatography (HPLC). In vitro antioxidant assays including DPPH, ABTS, and Galvinoxyl radical scavenging, β-carotene bleaching assay, reducing power, CUPRAC, and phenanthroline were applied. The antifungal effect of the extract was evaluated against the two plant pathogenic fungi Aspergillus niger and Fusarium oxysporum using the agar diffusion method. High TPC (197.23 ± 0.12 µg GAE/mg) and TFC (166.93 ± 1.15 µg QE/mg) contents were recorded with the extract. In total, 36 compounds were identified by HPLC, of which 35 are phenolic compounds, with rosmarinic acid (25.2%), p-coumaric acid (7.7%) and luteolin-7-O-glucoside (7.6%) being the representative phenolic compounds. L. stoechas demonstrated strong antioxidant activity in all the methods used. The extract completely inhibited (100% inhibition) the growth of A. niger at a concentration of 5%, while at the same concentration the extract inhibited F. oxysporum with a percentage of 89.62%. These preliminary results suggest the possible use of L. stoechas extract as a potential alternative for preventing plant diseases, reducing post-harvest losses and for food preservation.

Ubiquitin carboxyl-terminal hydrolase L3 (UCHL3), a key deubiquitinating enzyme of the UCH family, has been implicated in DNA repair in breast cancer; however, its role in regulating cell migration and invasion in triple-negative breast cancer (TNBC) remains poorly understood. The expression pattern of UCHL3 across breast cancer subtypes was analyzed using TCGA data. In TNBC cells, UCHL3 mRNA levels were quantified by qRT-PCR, while its protein expression and epithelial-mesenchymal transition (EMT) markers (Vimentin, N-cadherin, SNAIL, E-cadherin, α-SMA, TWIST) were assessed by Western blot. Functional assays included: MTT and EdU incorporation assays for proliferation; wound healing and Transwell migration assays for migratory capacity. Transcriptomic changes induced by UCHL3 knockdown were profiled via RNA sequencing. Additionally, an in vivo mice model was used to evaluate the pro-invasive effects of UCHL3 overexpression in TNBC. UCHL3 was significantly overexpressed in TNBC and correlated with poor patient prognosis. Functional studies revealed that UCHL3 enhances the proliferative capacity of TNBC cells. Furthermore, UCHL3 was demonstrated to promote TNBC cell migration and invasion through modulation of epithelial-mesenchymal transition (EMT) markers. Mechanistically, knockdown of UCHL3 attenuated activation of invasion- and migration-related signaling pathways in TNBC cells. Pharmacological inhibition of UCHL3 effectively suppressed TNBC cell migration and invasion in vitro. In vivo studies further confirmed that UCHL3 overexpression drives metastatic progression of TNBC in mice. UCHL3 is significantly upregulated in TNBC and drives tumor progression by promoting cell proliferation and activating EMT-mediated migration and invasion. These findings identify UCHL3 as a potential therapeutic target for TNBC treatment.

Laccase is an environmentally friendly catalyst characterized by a wide substrate spectrum and clean reaction processes. It demonstrates the ability to efficiently oxidize various pollutants, with water being the sole by-product. Consequently, laccase holds significant potential for applications in diverse fields such as papermaking, environmental protection, food processing, and bioenergy production. In this study, crude laccase produced by Schizophyllum commune was immobilized within a composite material through chemical cross-linking to enhance the enzyme's activity and stability. Free laccase was immobilized using a gelatin/chitosan (GEL/CS) hydrogel, and the conditions for this process were optimized. Enzymatic properties of immobilized laccase (GEL/CS-laccase) were investigated to assess its potential applications. Results indicated that the maximum laccase activity by Schizophyllum commune reached 343.9 U·mL- 1 on day 6. Following optimization, GEL/CS-laccase achieved an activity recovery of 33.9% and an activity of 113.8 U·g- 1. Compared with free laccase, GEL/CS-laccase shows better adaptability to pH and temperature. Furthermore, GEL/CS-laccase demonstrates moderate reusability and excellent long-term storage stability: its activity remains above 34.7% after 5 cycles and exceeds 52.9% following 180 days of storage at -80 °C and vacuum. This study has developed an efficient enzyme immobilization method, enhancing its stability and operability, and laying a solid foundation for the practical application of laccase.

This study investigated the phenolic profile, antioxidant capacity, and anti-gout potential of methanolic extracts obtained from flowers, leaves, and stems of Diplotaxis harra subsp. crassifolia. Total phenolic and flavonoid contents were quantified spectrophotometrically, and individual phenolics were characterized by LC-MS/MS, revealing 15 compounds in flowers, 11 in leaves, and 7 in stems, with quinic acid as the predominant constituent. Antioxidant activity was evaluated using DPPH, ABTS, CUPRAC, FRAP, phosphomolybdenum, and metal-chelation assays, in which flower extracts consistently exhibited the highest antioxidant potential. Xanthine oxidase (XO) enzyme inhibition assay revealed that the flower extract exhibited the best inhibition activity, with an IC50 of 0.212 mg/mL, comparable to that of the positive control allopurinol (0.25 mg/mL). Consistently, molecular docking showed that gentisic and protocatechuic acids, most phenolics in the extract, bind XO with more favorable energies than allopurinol through extensive hydrogen-bonding and hydrophobic interactions at key active site residues. Overall, this initial organ-specific evaluation of D. harra provides strong support for its flower extracts as promising candidates for standardized anti-gout preparations and as scaffolds for future XO inhibitor development.

Marine-derived endophytic fungi have long been recognised as valuable sources of therapeutic metabolites. In the present study, the endophyte Penicillium rubens strain PrubVJ was studied for optimised production of bioactive compounds using Response Surface Methodology (RSM). Experimental data predicted that incubation time was identified as the most influential variable, with maximum protein yield (190 mg/L) observed at day 20, antioxidant activity (74%) at 10-15 days and total phenolics (1,724 ± 19 µg GAE g⁻¹ DW) at day 25. The optimal fermentation conditions (25 °C, pH 3.6, 4 g/L salinity, 10 days incubation) with a desirability of 0.92, yielding 158 ± 1.325 mg/L protein, 1,798 ± 18 µg GAE g⁻¹ DW phenolics, and 84.9% antioxidant activity were predicted from the RSM model. Experimental validation under these conditions achieved protein yield of 190 mg/L, phenolics of 1,724 µg GAE g⁻¹ DW, and 74% antioxidant activity, confirming the reliability and robustness of the model. The developed quadratic models exhibited strong statistical reliability with stochastic parameters such as F-value and p-value, and coefficients of determination (R², adjusted R² and predicted R²) above 80% for all responses, validating model adequacy. Collectively, these findings establish P. rubens strain PrubVJ as a promising microbial platform, providing a reliable framework for optimising fungal fermentation. This study recommends the optimized strategy for large-scale pharmaceutical bioprocessing of fungal metabolites, to reduce production costs and accelerate the discovery of novel bioactive metabolites with pharmaceutical relevance, particularly for anticancer, antimicrobial, and antioxidant applications.

This study explores the therapeutic potential of methanol extracts from the shells of the marine crab Portunus sanguinolentus, with a focus on inhibiting acetylcholinesterase (AChE) to enhance acetylcholine (ACh) levels, an essential strategy in the management of Alzheimer's disease (AD). GC-MS analysis identified 18 distinct zoochemicals, predominantly fatty acid derivatives, and HPLC analysis confirmed the presence of n-Hexadecanoic acid, while FT-IR spectroscopy confirmed the presence of functional groups typical of polyphenols, alkaloids, and terpenoids. The extract exhibited notable antioxidant activity, with IC50 values of 62.08 µg/mL (DPPH) and 68.05 µg/mL (ABTS), both showing strong dose-dependent responses (R2 = 0.90). AChE inhibition assays revealed dose-dependent effects with an IC50 of 161.49 µg/mL (R2 = 0.943). Molecular docking studies further supported the bioactivity, indicating strong interactions between identified zoochemicals and key targets, including AChE (1EVE), Peroxiredoxin 5 (1HD2), Myeloperoxidase (1DNU), and MraY (5CKR). Additionally, the extract demonstrated significant antibacterial efficacy, confirmed through MIC, MBC, zone of inhibition assays, cytoplasmic leakage (DNA and protein), and in silico predictions. These findings suggest that the P. sanguinolentus shell methanol extract contains bioactive zoochemicals with promising AChE-inhibitory, antioxidant, and antibacterial activities. Importantly, the use of crab shells not only contribute to drug development for Alzheimer's disease but also offers a sustainable approach to marine biowaste valorization.

The traditional extraction method of Lycium barbarum pigment has some problems, such as long extraction time, large solvent consumption, low extraction efficiency and serious environmental pollution, so it is necessary to develop a new extraction method with shorter treatment time, lower cost, easier operation and environmental friendliness than the traditional method. In this study, the pigment from Ningxia Lycium barbarum was extracted, purified and identified by deep eutectic solvents assisted by surfactant. The pigments from Lycium barbarum from Ningxia were extracted, purified and identified by surfactant-assisted deep eutectic solvents (DES). The maximal pigments extraction rate was obtained under optimal conditions (3% surfactant Tween 20 (v/v), menthol-lactic acid with water content of 50% (molar ratio of 1:4), 1% material-liquid ratio (m/v), the water bath at 30 ℃ for 2.5 h). The pigments extraction rate by surfactant-assisted DES was 6-folds higher than traditional extraction agents (ethanol), and reached 32.09 mg/g. The HPLC detection results showed that the main component of the pigments was corn lutein dipalmitate with 348.861 mg/g. Furthermore, the purified pigments exhibited excellent free radical scavenging activities for DPPH and ABTS+, and ·OH radicals, indicating its high antioxidant activity.

This study evaluated the biological properties of the essential oil (EO) from Cinnamomum camphora L. leaves, revealing eucalyptol, sabinene, and alpha-terpineol as major constituents. This EO exhibited potent antioxidant activity with an IC50 of 5.79 in DPPH and 36.71 µg/mL in ABTS assays. The anti-inflammatory potential reached 67.84% at a concentration of 1600 µg/mL. Antimicrobial assays revealed significant activity against several pathogenic strains, such as Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa, with MICs ranging from 31.25 to 500 µg/mL. The EO inhibited biofilm formation by up to 76.25%, reduced bacterial motility by up to 83.33%, and suppressed the production of the quorum sensing (QS)-regulated pigment pyocyanin by 60.81%. These results indicate a potent anti-virulence strategy targeting bacterial cell-to-cell communication. Molecular docking analysis targeting the FliC protein indicated that alpha-terpineol adopts a stable conformation within the active site, closely overlapping with the reference ligand. These findings support further investigation of the therapeutic potential of C. camphora L. as a natural alternative to counteract microbial resistance.

Small regulatory RNAs of Mycobacterium tuberculosis have emerged as important regulators of virulence and stress adaptation, with growing interest in their potential diagnostic biomarkers relevance. Among these, Mcr7, a PhoP-regulated sRNA that influences the twin-arginine translocation (Tat) secretion pathway by translational repression of tatC, is a well-studied regulatory molecule. Although its molecular significance in virulence control has been experimentally proven, its diagnostic utility is mainly unexplored. This review critically summarizes the current knowledge on sRNA -mediated regulation in Mycobacterium tuberculosis, with particular focus on Mcr7 and examines the feasibility of integrating sRNA detection into microfluidics Lab On Chip (LOC) platforms. In this, we discuss the current RNA-based TB diagnostic strategies which can be technically challengeable when particularly the detection is associated with small noncoding RNA and also the practical consideration for on-chip isolation and diagnosis based on antisense probe implement. Rather than presenting Mcr7 as a validated biomarker, we highlight its potential as a candidate target requiring exacting clinical evaluation. This interdisciplinary interaction aims to create a bridge between these sRNA concepts on TB disease diagnostics, with vastly emerging microfluidic technologies while outlining the limitations and validation steps necessary for Mcr7-specific diagnostics, and presents a conceptual framework for developing next-generation biosensing tools for TB with integrated microfluidic technology.

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