Search Results (8,183)

Translation of mRNAs is a tightly regulated process in gene expression. In mRNA, the 5′ untranslated region (5′ UTR) controls ribosome recruitment and frequently contains structured elements that modulate translation efficacy. This study investigates stable structural motifs within the 5′ UTR of DDX23 mRNA, encoding a protein relevant for anticancer therapy, as potential regulators and targets for antisense oligonucleotides (ASOs). Despite bioinformatic predictions and transcriptomic validations suggesting RNA G-quadruplex (rG4) formation, comprehensive structural analysis using a light-up assay and CD, UV, and NMR spectroscopy revealed that most putative rG4-forming sequences do not fold into stable rG4 structures, although one of them exists in an equilibrium between rG4 and an alternative, likely hairpin, conformation. Reporter assays using a robust G4 stabilizer also argue against the significant regulatory role of rG4s in DDX23 mRNA translation. Instead, we identified and characterized a stable hairpin structure with potential regulatory function. Based on these findings, we designed fully locked nucleic acid (LNA)-modified ASOs to target this hairpin and regions flanking the upstream open reading frame (uORF) and start codon of the coding sequence. A reporter assay demonstrated that cap-proximal targeting achieved robust translation inhibition up to 80%. In contrast, targeting the efficiently translated uORF was ineffective, presumably due to steric hindrances from the ribosomal complex. The study yields crucial design principles for translation-regulating ASOs: avoid targeting regions shielded by efficient uORF translation and carefully tune ASO-RNA duplex stability to surpass endogenous structures without disrupting regulatory mechanisms. These findings provide insights into the regulation of DDX23 expression and establish a framework for developing ASO-based therapeutics with broad implications for mRNA targeting in anticancer applications. Full article

Background: Timely recognition of sepsis remains a critical clinical challenge, particularly in cancer patients, who are at higher risk due to immunosuppression. Monocyte distribution width (MDW) has emerged as a biomarker with potential utility in the early detection of sepsis. Methods: This retrospective study analyzed 1167 patients who presented to the emergency department of a cancer specialty hospital in Republic of Korea. Patients were classified according to Sepsis-2 and Sepsis-3 criteria, and the diagnostic performance of MDW was compared with conventional biomarkers, including C-reactive protein (CRP) and procalcitonin (PCT). Subgroup analyses were conducted based on malignancy status, leukopenia, and initial signs of infection. Additionally, turnaround times (TATs) were compared among the biomarkers. Results: MDW demonstrated diagnostic accuracy comparable to or exceeding that of CRP and PCT for identifying sepsis and infection across both Sepsis-2 and Sepsis-3 criteria. In the context of diagnosing sepsis using the Sepsis-3 criteria, MDW yielded the highest area under the curve (0.869), sensitivity (91.0%), and negative predictive value (98%). Notably, in cancer patients, MDW maintained strong diagnostic reliability. It also demonstrated high diagnostic capability in patients with leukopenia or presenting with initial signs of infection. Moreover, the TAT was significantly shorter for MDW (median 59 min) than for CRP (105 min) or PCT (111 min). Conclusions: MDW is a rapid and accessible biomarker with demonstrated value for early sepsis detection in emergency settings. Its balanced diagnostic profile and consistent performance across diverse patient subgroups support its integration into routine clinical workflows, especially as part of multimodal sepsis screening strategies. Full article

This study aimed to describe a new broiler meat quality class—red, soft, and exudative (RSE) meat—and to propose novel classification criteria. Two-step cluster analysis assigned 132 broilers into five meat quality classes using ultimate pH, drip loss, and L* values: pale, soft, and exudative (PSE); pale, firm, and nonexudative (PFN); RSE; red, firm, and nonexudative (RFN); and dark, firm, and dry (DFD) meat. PSE meat showed the lowest plasma superoxide dismutase activity, highest malondialdehyde activity, greater live and carcass weights, higher breast and leg yields, the lowest initial and ultimate pH, highest initial temperature, the lightest colour (the highest L* and b* values, and the lowest a* value), and the greatest drip, thawing, and cooking losses. RFN meat had the highest superoxide dismutase activity, lowest malondialdehyde activity, and remained within the optimal range for ultimate pH, drip loss, and L* value, generally occupying a midpoint between PSE and DFD meat. RSE meat shared the poor water-holding capacity of PSE but differed by showing a colour similar to RFN and an optimal ultimate pH. PFN meat had firmness comparable to RFN, with appropriate water-holding capacity and optimal ultimate pH, but an undesirably pale colour resembling PSE. DFD meat displayed the highest initial and ultimate pH, lowest drip, thawing, and cooking losses, darkest colour (the lowest L* value), and lowest protein content. This study provides the first evidence of RSE meat in broilers and proposes a classification system based on ultimate pH, drip loss, and L* values to distinguish five quality classes. Further studies are required to validate these findings and develop preventive strategies. Full article

This study aimed to explore innovative sorbent materials for the remediation of contaminated marine environments, with a focus on metal removal from seawater. Adsorption tests were carried out to evaluate the performance of single-cell proteins (SCPs), a protein-rich biomass derived from industrial by-products, in comparison with commercial activated carbon (AC). Given the increasing need for sustainable and effective approaches in sediment remediation and water treatment, identifying alternatives to conventional sorbents is of particular relevance. Results showed that SCPs exhibited higher affinity for Cr than for Zn, while multi-metal solutions improved adsorption, suggesting synergistic interactions possibly linked to surface charge effects and ternary complex formation. Importantly, SCPs demonstrated competitive and, in some cases, superior performance compared to AC, highlighting their potential as an innovative and sustainable material. Moreover, when the absorbent materials were combined, SCP and AC mixes outperformed both the individual adsorbents and the expected additive efficiencies, achieving significantly higher removal yields for both metals, particularly at low concentrations. Overall, these findings suggest that SCPs, alone or in combination with AC, represent a promising strategy for the removal of heavy metals from marine systems, offering new opportunities for the treatment of contaminated sediments and seawater. Full article

Quinoa (Chenopodium quinoa Willd) is a nutrient-rich multipurpose crop. Its grains are used as a cereal, green leaves as a vegetable for humans, and the whole green plant as an alternate forage for livestock. Recently, whole-plant quinoa forage has been evaluated in several countries in Asia and Europe for its potential use as an alternative forage for livestock; however, this has not been performed in the United States. We investigated forage yield and related agronomic traits, nutritional composition, and feed quality-related traits in 60-day-old quinoa whole plants of four quinoa lines over a two-year period. The goal was to evaluate the feasibility of quinoa forage production in Missouri, a drought-prone midwestern state of the USA. Morphological traits (height and fresh and dry weight per plant), chemical composition (fiber contents), and nutritive quality (digestible nutrient contents) of forages were affected by quinoa genotype and year of planting. The crude protein content of quinoa forage averaged 16.23% and fiber 22.08%, which was similar to the values reported in Asia and Europe, but was slightly lower than that of alfalfa. Calcium (1.26%) and phosphorus (0.47% dry weight) were significantly higher than those reported in published quinoa forage results and are comparable to those in published alfalfa minerals. Lysine (0.98%) and methionine (0.25%) were higher than the published results for quinoa and alfalfa. Neutral detergent fiber (34.10%) and acid detergent fiber (25.01%) were lower than those of alfalfa, indicating better digestibility of the quinoa forage. The calculated digestible dry matter (69.40%), dry matter intake (3.56%), relative food value (192%), and total digestible nutrient (70.33%) were higher than those of alfalfa and comparable with published results for quinoa forage. Our preliminary results indicate that the quinoa lines evaluated in this study have excellent potential to be used as a non-traditional alternative forage, especially in environmentally stressed areas where the production of other forage crops is limited. Further research should explore the full multipurpose benefits of quinoa, including its use as grains, leafy green, and whole-plant forage. Full article

Background: Seed shattering enhances ecological adaptation in perennial grasses but severely limits harvestable seed yield in forage crops. Psathyrostachys juncea is an important perennial forage species in arid and cold regions, yet the genetic basis of its seed shattering remains largely unknown. Here we asked which genomic regions and biological pathways underlie natural variation in seed shattering in P. juncea, and whether cellulose synthase (CESA)-mediated cell-wall formation contributes to abscission-zone strength. Results: We evaluated seed shattering in a diverse association panel of P. juncea across four environment–-year combinations and performed a genome-wide association study (GWAS) using genotyping-by-sequencing single-nucleotide polymorphism (SNP) markers. The analysis identified 36 significant SNP loci distributed on multiple chromosomes, consistent with a highly polygenic and environment-responsive architecture. Candidate-gene annotation highlighted pathways related to cell-wall biosynthesis, hormone signaling and sugar transport. Notably, in the BT23SHT environment a cluster of association signals on chromosome 3D co-localized with several genes annotated as cellulose synthase (CESA). Abscission-zone transcriptome profiling and qRT-PCR at 7, 14, 21 and 28 days after heading revealed that CESA genes, including TraesCS3D02G010100.1 located near the lead SNP Chr3D_3539055, showed higher early expression in low-shattering lines and a decline toward baseline in high-shattering lines. Comparative analyses placed P. juncea CESA proteins within a broadly conserved but lineage-divergent framework among grasses. Conclusion: Together, these results define the genetic landscape of seed shattering in P. juncea and nominate cellulose-biosynthetic genes on chromosome 3D as promising targets for marker-assisted selection of low-shattering, high-seed-yield forage cultivars. Full article

Integrating positive welfare indicators into dairy science is gaining attention, yet the biological correlates of affective states in commercial herds remain poorly understood. This study explored associations between dairy cows’ emotional states quantified through the Positive Affect Index (PAI) derived from the Qualitative Behaviour (QBA) Assessment and milk biomarkers, yield, and udder health indicators across 37 commercial farms. Descriptive statistics, housing-adjusted linear regressions, and partial Spearman correlations were used to explore these relationships. Higher PAI values, indicating more positive herd-level emotional states, were significantly associated with lower SCC (22% reduction, p = 0.016) and lower odds of elevated DSCC (OR = 0.69, p = 0.002), reflecting improved udder health. Positive affect was also linked to a higher lactose concentration (p < 0.001) and an increased fat-to-protein ratio (FPR). A tendency for higher milk yield (+1.07 L per milking, p = 0.077) and slightly lower protein content was observed, consistent with a dilution effect. These associations remained robust after sensitivity analyses and were independent of housing type. The results demonstrate that milk composition and udder health biologically reflect positive emotional states, supporting the integration of behavioural assessments and milk biomarkers as a non-invasive framework for advancing welfare-oriented and precision dairy farming. Full article

Background/Objectives: In this work, a series of six new indazole-benzimidazole hybrids (M1–M6) were designed, synthesized, and fully characterized. The design of these compounds was based on the combination of two pharmacophoric units, indazole and benzimidazole, both known for their broad spectrum of biological activities. Methods: The molecular hybridization strategy was planned to combine these scaffolds through an effective synthetic pathway, using 6-nitroindazole, two 2-mercaptobenzimidazoles, and 1,3- or 1,5-dihaloalkanes as key precursors, affording the desired hybrids in good yields and with enhanced biological activity. Quantum chemical calculations were performed to investigate the structural, electronic, and electrostatic properties of M1–M6 molecules using Density Functional Theory (DFT) at the B3LYP/6-311++G(d,p) level. The antimicrobial activity efficacy of these compounds was assessed in vitro against four Gram-positive bacteria (Staphylococcus aureus, Enterococcus faecalis, Bacillus cereus, and Lactobacillus plantarum), four Gram-negative bacteria (Salmonella enteritidis, Escherichia coli, Campylobacter coli, Campylobacter jejuni), and four fungal strains (Saccharomyces cerevisiae, Candida albicans, Candida tropicalis, and Candida glabrata) using ampicillin and tetracycline as reference standard drugs. Results: Among the series, compound M6 exhibited remarkable antimicrobial activity, with minimum inhibitory concentrations (MIC) of 1.95 µg/mL against S. cerevisiae and C. tropicalis, and 3.90 µg/mL against S. aureus, B. cereus, and S. enteritidis, while the standards Ampicillin (AmB) (MIC ≥ 15.62 µg/mL) and Tetracycline (TET) (MIC ≥ 7.81 µg/mL) exhibited higher MIC values. To gain molecular insights into the compounds, an in silico docking study was performed to determine the interactions of M1–M6 ligands against the antimicrobial target beta-ketoacyl-acyl carrier protein (ACP) synthase III complexed with malonyl-COA (PDB ID: 1HNJ). Molecular modeling data provided valuable information on the structure-activity relationship (SAR) and the binding modes influencing the candidate ligand-protein recognition. Amino acid residues, such as Arg249, located in the solvent-exposed region, were essential for hydrogen bonding with the nitro group of the 6-nitroindazole moiety. Furthermore, polar side chains such as Asn274, Asn247, and His244 participated in interactions mediated by hydrogen bonding with the 5-nitrobenzimidazole moiety of these compound series. Conclusions: The hybridization of indazole and benzimidazole scaffolds produced compounds with promising antimicrobial activity, particularly M6, which demonstrated superior potency compared to standard antibiotics. Computational and docking analyses provided insights into the structure–activity relationships, highlighting these hybrids as potential candidates for antimicrobial drug development. Full article

Facing the significant challenges posed by global population growth and urbanization, plant factories, as an efficient closed cultivation system capable of precise environmental control, have become a key direction in the development of modern agriculture. However, high energy consumption, particularly lighting (which accounts for over 50%), remains a major bottleneck limiting their large-scale application. This study systematically explored the effects of dynamic light regulation strategies on lettuce (Lactuca sativa L.) growth, physiological and biochemical indicators (such as chlorophyll, photosynthetic, and fluorescence parameters), nutritional quality, energy utilization efficiency, and post-harvest shelf life. Four different light treatments were designed: a stepwise increasing photosynthetic photon flux density (PPFD) from 160 to 340 μmol·m⁻²·s⁻¹ (T1), a constant light intensity of 250 μmol·m⁻²·s⁻¹ (T2), a three-stage strategy with high light intensity in the middle phase (T3), and a three-stage strategy with sequentially increasing light (T4). The results showed that the T4 treatment exhibited the best overall performance. Compared with the T2 treatment, the T4 treatment increased biomass by 23.4%, significantly improved the net photosynthetic rate by 50.32% at the final measurement, and increased ascorbic acid (AsA) and protein content by 33.36% and 33.19%, respectively. Additionally, this treatment showed the highest energy use efficiency. On the 30th day of treatment, the light energy use efficiency (LUE) and electrical energy use efficiency (EUE) of the T4 treatment were significantly increased, by 23.41% and 23.9%, respectively, compared with the T2 treatment. In summary, dynamic light regulation can synergistically improve crop yield, chlorophyll content, photosynthetic efficiency, nutritional quality, and energy utilization efficiency, providing a theoretical basis and solution for precise light regulation and energy consumption reduction in plant factories. Full article

This study systematically explored the regulatory mechanisms of uterine function across four reproductive stages: sexual maturity sow (SMS), low-yield sow (LYS), high-yield sow (HYS), and culled sow (CS) in Large White (LW) pigs through integrated transcriptomic, proteomic, and metabolomic analyses. Twelve healthy LW sows were selected, and uterine tissues were collected for multi-omics detection. Combined with bioinformatics analysis, molecular regulatory networks were constructed. Results showed that transcriptomics identified 12 types of alternative splicing and 1243 novel genes, which were enriched in energy metabolism and signal transduction pathways. Proteomics revealed 430 differentially co-expressed proteins, indicating high protein synthesis activity in the SMS stage and extracellular inflammatory characteristics in the CS stage. Metabolomics detected numerous differential metabolites, among which XTP and DHA ethyl ester were associated with high fecundity and aging, respectively. Integrated multi-omics analysis identified hub genes such as PLA2G4A, which influence reproductive performance by regulating inflammatory and metabolic balance, and clarified stage-specific “gene–protein–metabolite” modules. This study provides a molecular map for understanding dynamic changes in uterine function in Large White pigs and offers a theoretical basis for optimizing reproductive lifespan and breeding strategies. Full article

The utilization of post-production and post-processing by-products aligns with current trends in sustainable fruit industry practices. Recovering valuable nutrients from such materials holds significant potential for the food, nutraceutical, pharmaceutical, and cosmetic sectors. Among these, cornelian cherry (Cornus mas L.) seeds represent a promising source of functional ingredients, particularly due to their oil’s rich nutritional and phytochemical profile. The seeds, accounting for approximately 9–10% of the fruit mass, yield an oil characterized by high levels of polyunsaturated fatty acids—mainly linoleic acid (≈67.5%) and oleic acid (≈20%)—alongside palmitic (≈5.8%) and stearic acids (≈2.1%). Linolenic acid content, however, shows notable variability (1.4–14.7%), influencing the oil’s omega-6/omega-3 ratio, which generally remains below 5:1. Cornelian cherry seed oil stands out among other stone fruit oils (e.g., rosehip, apricot, peach, cherry, plum) for its favorable fatty acid composition and absence of cyanogenic glycosides, making it safe for human consumption. Beyond its nutritional value, this oil exhibits biological activity and health-promoting potential, suggesting wide applicability in functional foods and nutraceutical formulations. Despite progress in characterizing seed composition—including proteins, lipids, carbohydrates, minerals, and tannins—knowledge gaps persist regarding the transfer of these compounds into the oil, particularly under cold-pressing conditions. Future studies should focus on optimizing extraction processes, assessing thermal treatment effects, and clarifying the variability of linolenic acid. Such research will support the sustainable exploitation of cornelian cherry by-products and the industrial-scale development of this high-value oil. Full article

Squaraine dyes are a class of organic compounds that exhibit some characteristics inherent to those of an “ideal photosensitizer”, such as high absorption at near-infrared-close wavelengths and to produce reactive oxygen species. The introduction of amines into their squaric ring, although known to increase the phototoxicity of squaraines, can improve dyes’ water solubility and induce bathochromic shifts compared to their unsubstituted derivatives, interesting effects in biological contexts. In this work, four new squaraines were synthesized and structurally, photophysically, and photochemically characterized (including absorption and aggregation, fluorescence, light stability, and singlet oxygen generation). Their potential as fluorescent probes for albumin detection was assessed through both in silico and in vitro approaches, as well as their suitability as potential photosensitizers for photodynamic therapy. For this last purpose, the 663 nm light-induced effects of the new dyes were evaluated against the PC-3 prostate cancer cell line, while their photocytotoxicity toward normal human dermal fibroblasts was also assessed using the MTT assay, to determine their potential tumor-selective effects. Low singlet oxygen quantum yields suggest that type I reactions predominate in generating cytotoxicity. Overall, the findings indicate that the designed squaraines exhibit moderate yet favorable interactions with albumin protein while demonstrating selective photodynamic effects toward prostate adenocarcinoma cancer cells, highlighting their potential as protein-assisted, tumor-targeted photosensitizers, providing a basis for further mechanistic studies. Full article

Melia azedarach L. (Meliaceae) exhibits potential as a source of bioactive antibacterial compounds. In this study, the effect of solvent polarity on ultrasound-assisted extraction of M. azedarach leaves and twigs was evaluated in relation to their phytochemical composition and antibacterial activity against both non-resistant and multidrug-resistant bacteria. The results showed that solvent polarity significantly affected the extraction yield, with methanol and water producing yields above 10%. The methanol extracts of twigs and leaves exhibited the strongest antibacterial activity, showing greater potency against Escherichia coli than Bacillus subtilis. Consistent with these findings, the methanol extracts inhibited the growth of multidrug-resistant enteropathogenic E. coli K1-1, resulting in inhibition zone diameters of 10.93 mm (leaf) and 7.73 mm (twig). Furthermore, the methanol extract contained the highest levels of phenolic, flavonoid, and hydroxyl-rich compounds, which were associated with its antibacterial properties. In silico analysis further revealed that isofucosterol, meliasenin, and melianone exhibited strong predicted binding affinities to key antibacterial proteins, particularly those involved in multidrug-resistant bacterial mechanisms. Full article

Sesame (Sesamum indicum L.) is one of the most important oilseed crops globally, valued for its high content of unsaturated fatty acids, proteins, and essential nutrients. However, weed infestation represents a major constraint on sesame productivity, competing for resources and releasing allelopathic compounds that can significantly reduce both yield and quality without timely control. To address the challenge of low detection accuracy in complex agricultural environments with dense weed distributions, this study proposes YOLOv12-BDA, a dynamic multi-scale architecture for small weed detection in sesame fields. The proposed architecture incorporates three key dynamic innovations: (1) an Adaptive Feature Selection (AFS) dual-backbone network with a Dynamic Learning Unit (DLU) module that enhances cross-branch feature extraction while reducing computational redundancy; (2) a Dynamic Grouped Convolution and Channel Mixing Transformer (DGCS) module that replaces the C3K2 component to enhance real-time detection of small weeds against complex farmland backgrounds; and (3) a Dynamic Adaptive Scale-aware Interactive (DASI) module integrated into the neck network to strengthen multi-scale feature fusion and detection accuracy. Experimental validation on high-resolution sesame field datasets demonstrates that YOLOv12-BDA significantly outperforms baseline models. The proposed method achieves mAP@50 improvements of 6.43%, 11.72%, 7.15%, 5.33%, and 4.67% over YOLOv5n, YOLOv8n, YOLOv10n, YOLOv11n, and YOLOv12n, respectively. The results confirm that the proposed dynamic architecture effectively improves small-target weed detection accuracy at the cost of increased computational requirements (4.51 M parameters, 10.7 GFLOPs). Despite these increases, the model maintains real-time capability (113 FPS), demonstrating its suitability for precision agriculture applications prioritizing detection quality. Future work will focus on expanding dataset diversity to include multiple crop types and optimizing the architecture for broader agricultural applications. Full article

Aflatoxin B1 (AFB1) is a highly toxic and carcinogenic compound produced by certain fungi (e.g., Aspergillus flavus and Aspergillus parasiticus). Rapid and ultra-sensitive detection methods for AFB1 in various commodities are in high demand. This study aimed to enhance the sensitivity of a competitive lateral flow immunoassay (LFIA) for AFB1 detection by leveraging a previously developed experimental design strategy, named 4S. This approach comprises four phases—START, SHIFT, SHARPEN, and STOP—and involves the analysis of two reference conditions: NEG (0 ng/mL AFB1) and POS (1 ng/mL AFB1). By generating and overlaying response surfaces, regions of optimal NEG signal and POS/NEG signal ratio (IC%) were identified. Four variables were optimized: two related to the labeled antibody (its concentration and antibody-to-label ratio) and two to the competitor antigen (its concentration and hapten-to-protein ratio). An initial design defined the parameter space, while three subsequent designs did not yield further improvements in sensitivity. A strong anti-correlation was observed between the IC% and competitor parameters. The optimized LFIA-1 exhibited enhanced sensitivity, achieving a limit of detection of 0.027 ng/mL compared to 0.1 ng/mL for the original device. Additionally, the amount of expensive antibody required for device fabrication was reduced by around a factor of four. Full article