Search Results (14,621)

This study presents a novel environmentally-friendly process for the selective extraction and enrichment of DHA/EPA-containing phospholipids (PL-DHA/EPA) from krill oil. The methodology leverages differential crystallization behavior between phospholipids and triacylglycerols in ethanolic solutions, exploiting their distinct freezing point thresholds to achieve precise fractionation. Response surface methodology optimization identified optimal extraction parameters: liquid-to-material ratio of 6:1 (v/w), freezing temperature of −20 °C, freezing duration of 25 h, and rotary evaporation temperature of 45 °C, yielding a final product with 39.40% PL-DHA/EPA content. Principal component analysis revealed substantial overlap in confidence ellipses among extraction methodologies, indicating effective preservation of core phospholipid signatures from the parent krill oil while maintaining critical structural characteristics and molecular species distribution. Comprehensive analysis of phospholipid fractions and heatmap analysis revealed distinctive molecular profiles compared to conventional organic solvent extraction, with selective enrichment of EPA-containing phospholipids, particularly PC-EPA and PI-EPA species. The green extraction method demonstrated comparable oxidative stability to conventional approaches, with superior protection against secondary oxidation as evidenced by significantly lower anisidine values. This sustainable approach achieves effective phospholipid enrichment while substantially reducing environmental impact through elimination of halogenated solvents, addressing the critical need for environmentally conscious technologies in marine lipid processing with potential applications in nutraceutical and functional food industries. Full article

Aralia chinensis L. has shown potential in breast cancer treatment, yet its pharmacodynamically active components and mechanisms remain undefined. To systematically identify the bioactive constituents absorbed into the bloodstream and elucidate their multi-target mechanisms against breast cancer, we employed ultra-high-performance liquid chromatography in conjunction with Q Exactive Orbitrap mass spectrometry (UHPLC-Q Exactive Orbitrap-MS) alongside serum pharmacochemistry to analyze the chemical constituents of total saponins derived from A. chinensis (TSAC) and to identify the blood-absorbed prototypes in a rat model. Network pharmacology predicted targets and pathways of serum prototypes, validated by molecular docking and in vitro experiments. We identified 38 triterpenoid saponins, 3 steroidal saponins, and 8 triterpenoids in TSAC, with 22 prototype compounds detected in serum. An integrative analysis encompassing 486 compound targets and 1747 genes associated with breast cancer elucidated critical pathways, notably the PI3K-Akt signaling pathway and resistance mechanisms to EGFR tyrosine kinase inhibitors. Molecular docking confirmed strong binding of araloside A and elatoside L to SRC, PIK3R1, PIK3CA, STAT3, and EGFR. In MCF-7 cells, TSAC suppressed proliferation and migration while downregulating Src, PI3K, and EGFR expression at the gene and protein levels. This study successfully identified TSAC’s serum-absorbed bioactive components and demonstrated their anti-breast cancer effects via multi-target mechanisms involving the Src/PI3K/EGFR axis, providing a crucial pharmacological foundation for developing A. chinensis-derived breast cancer therapies. Full article

Objective: To describe first-trimester maternal, biochemical, biophysical, and ultrasound characteristics in women with recurrent pregnancy loss (RPL) compared to women without RPL. Methods: This was a retrospective cohort study analyzing data from 4440 pregnant women, including 142 women with previous RPL. Maternal and pregnancy characteristics, first-trimester biochemical markers, biophysical assessments, early-onset preeclampsia (EOPE) risk, and perinatal outcomes were compared. Results: Women with RPL were older (37.8 vs. 34.0 years, p < 0.001) and had higher rates of antiphospholipid syndrome (4.9% vs. 0.9%, p < 0.001), other thrombophilias (5.6% vs. 0.8%, p < 0.001), and thyroid disorders (14% vs. 7.5%, p = 0.010) than women without RPL. First-trimester uterine artery pulsatility index (UtA-PI) values, pregnancy-associated plasma protein-A (PAPP-A) levels, mean arterial pressure, and final risk for EOPE were comparable between groups. However, the RPL group had higher rates of very high risk for PE (10.6 vs. 5.1, p = 0.011). Likewise, second-trimester UtA-PI was higher in this group (1.10 vs. 1.01, p = 0.045). Aspirin and low molecular weight heparin prophylaxis were more frequent in women with RPL (23.8% vs. 9.6%, p < 0.001; 14.7% vs. 0.1%, p < 0.001). Regarding perinatal outcomes, we found a higher incidence of second-trimester intrauterine demise in the RPL group (6.4% vs. 1.4%, p = 0.011), with no other differences observed in the remaining outcomes. Conclusions: Women with RPL exhibit distinct maternal characteristics and worse pregnancy outcomes, although first-trimester markers do not seem to significantly differ from findings in women without RPL. These findings underscore the importance of tailored screening and intervention protocols to improve perinatal outcomes in this high-risk population. Full article

Reactive oxygen species (ROS) act as double-edged swords in cancer biology—facilitating tumor growth, survival, and metastasis at moderate levels while inducing oxidative damage and cell death when exceeding cellular buffering capacity. To survive under chronic oxidative stress, cancer cells rely on robust antioxidant systems such as the glutathione (GSH) and thioredoxin (Trx), and superoxide dismutases (SODs). These systems maintain redox homeostasis and sustain ROS-sensitive signaling pathways including MAPK/ERK, PI3K/Akt/mTOR, NF-κB, STAT3, and HIF-1α. Targeting the antioxidant defense mechanisms of cancer cells has emerged as a promising therapeutic strategy. Inhibiting the glutathione system induces ferroptosis, a non-apoptotic form of cell death driven by lipid peroxidation, with compounds like withaferin A and altretamine showing strong preclinical activity. Disruption of the Trx system by agents such as PX-12 and dimethyl fumarate (DMF) impairs redox-sensitive survival signaling. Trx reductase inhibition by auranofin or mitomycin C further destabilizes redox balance, promoting mitochondrial dysfunction and apoptosis. SOD1 inhibitors, including ATN-224 and disulfiram, selectively enhance oxidative stress in tumor cells and are currently being tested in clinical trials. Mounting preclinical and clinical evidence supports redox modulation as a cancer-selective vulnerability. Pharmacologically tipping the redox balance beyond the threshold of cellular tolerance offers a rational and potentially powerful approach to eliminate malignant cells while sparing healthy tissue, highlighting novel strategies for targeted cancer therapy at the interface of redox biology and oncology. Full article

Downy mildew, caused by the oomycete Pseudoperonospora cubensis, is the most destructive foliar disease of cucumbers. While partially resistant slicer cultivars (with spined fruits) are commercially available, no resistant Beit Alpha cultivars (characterized by smooth, dark green fruit) have been developed to date. Here, we report the successful breeding of downy mildew-resistant Beit Alpha cucumber lines. Resistance was transferred from the wild Sikkim cucumber accessions PI 197088 and PI 330628 (characterized by round fruit, with heavily netted brown rind). The resistance and fruit phenotype were restored through backcrosses to elite commercial susceptible cultivars. Due to the recessive nature of the resistance genes and their distribution across multiple chromosomes, the breeding program required multiple backcrosses and stringent selections for both resistance and fruit type. Full article

Hederagenin, a pentacyclic triterpenoid saponin from various medicinal plants, shows immense therapeutic potential; however, its inherent low bioavailability severely hinders its clinical translation. This comprehensive review synthesizes recent studies on the health benefits of hederagenin and its glycosides, critically the chemical modification strategies and pharmacological mechanisms aimed at optimizing its bioactivity. Key findings reveal that its broad anticancer and anti-inflammatory activities largely stem from its capacity to modulate crucial cellular signaling pathways, including the NF-κB, PI3K/Akt, and MAPK. Structural modification, particularly intelligent derivatization at the C-28 position, is a central strategy to overcome its pharmacokinetic deficiencies and significantly boost cytotoxicity. Furthermore, its unique pro-oxidant function within cancer cells, achieved by inhibiting the Nrf2-ARE antioxidant pathway, offers a novel approach for selective chemotherapeutics. For the clinical translation of hederagenin, we propose a strategic focus on derivatization through multi-target hybrids and sophisticated delivery systems. This approach is essential for addressing its pharmacokinetic barriers while strategically leveraging its context-dependent pro-oxidant effects. Full article

This study aims to develop a gelatin methacryloyl (GelMA)-based ginsenoside Rb3 (G-Rb3) drug delivery system and investigate its application in the treatment of periodontitis and the underlying mechanisms. Periodontal ligament stem cells (PDLSCs) were obtained and identified. The appropriate concentration ranges of G-Rb3 and lipopolysaccharide (LPS) were investigated by the CCK-8 experiments. Quantitative RT-PCR, ELISA, and Western blot were performed to assess the effects of GelMA@G-Rb3 on LPS-treated PDLSCs. The possible mechanisms were determined through network pharmacology analysis and Western blot. The therapeutic effects of GelMA@G-Rb3 in rat periodontitis animal models were systematically evaluated using Micro-CT, H&E staining, Masson staining, and immunofluorescence staining. PDLSCs were successfully isolated and characterized. The in vitro results indicated that GelMA@G-Rb3 significantly alleviated LPS-induced inflammation in PDLSCs by inhibiting the p38/ERK signaling pathway and activating the PI3K/AKT signaling pathway. In vivo experiments confirmed that GelMA@G-Rb3 significantly reduced alveolar bone resorption, and promoted periodontal tissue regeneration, while simultaneously demonstrating significant regulatory effects on the MAPK signaling pathway. This study demonstrated the efficacy of the GelMA@G-Rb3 system in modulating the inflammatory responses of periodontitis and improving the periodontal tissue regeneration, which establish a solid foundation and proposed innovative therapeutic approaches for the treatment of periodontitis. Full article

This study investigates key factors affecting the adsorption behavior of proteins on the multimodal chromatographic adsorbent Capto MMC, aiming to enhance selective protein separation strategies. Batch equilibrium experiments were conducted using six model proteins to explore the combined effects of pH, ionic strength, and the nature of salts (kosmotropic and chaotropic) on protein–ligand interactions. Given that the Capto MMC ligand supports multiple interaction modes beyond cation exchange, particular focus was placed on acidic proteins (pI 4–5), which exhibited binding even at moderately elevated pH values—conditions ineffective for conventional cation exchangers. Hydrophobic interactions were identified as critical for stable binding of proteins like BSA and fetuin, while hydrophilic proteins such as ovalbumin showed minimal adsorption. Chromatographic column experiments were performed to evaluate elution performance under various buffer conditions, revealing that prolonged adsorption phases can reduce recovery yields for proteins with less stable tertiary structures. The findings highlight how salt type, pH, and protein hydrophobicity interplay to modulate multimodal binding mechanisms, providing practical insights for the design of tailored purification protocols. Full article

Sign language serves as a vital way to communicate with individuals with hearing loss, deafness, or a speech disorder, yet accessibility remains limited, requiring technological advances to bridge the gap. This study presents the first real-time Greek Sign Language recognition system utilizing deep learning and embedded computers. The recognition system is implemented using You Only Look Once (YOLO11X-seg), an advanced object detection model, which is embedded in a Python-based framework. The model is trained to recognize Greek Sign Language letters and an expandable set of specific words, i.e., the model is capable of distinguishing between static hand shapes (letters) and dynamic gestures (words). The most important advantage of the proposed system is its mobility and scalable processing power. The data are recorded using a mobile IP camera (based on Raspberry Pi 4) via a Motion-Joint Photographic Experts Group (MJPEG) Stream. The image is transmitted over a private ZeroTier network to a remote powerful computer capable of quickly processing large sign language models, employing Moonlight streaming technology. Smaller models can run on an embedded computer. The experimental evaluation shows excellent 99.07% recognition accuracy, while real-time operation is supported, with the image frames processed in 42.7 ms (23.4 frames/s), offering remote accessibility without requiring a direct connection to the processing unit. Full article

Background/Objectives: Chronic myeloid leukemia (CML) is a myeloproliferative neoplasm characterized by the BCR–ABL fusion gene, whose constitutive tyrosine kinase activity drives leukemogenesis. Although tyrosine kinase inhibitors (TKIs) have revolutionized treatment, drug resistance and leukemic stem cell persistence remain major challenges. Natural compounds such as polyphenols have shown potential in modulating key oncogenic pathways in CML. Results: Polyphenols such as resveratrol, quercetin, curcumin, and epigallocatechin gallate (EGCG) demonstrated significant antiproliferative and pro-apoptotic effects in CML cell lines, including imatinib-resistant models. These effects were mediated through the modulation of signaling pathways, including PI3K/Akt, STAT5, and MAPK; inhibition of BCR–ABL expression; induction of oxidative stress; and the enhancement of apoptosis via mitochondrial and caspase-dependent mechanisms. Some polyphenols also showed synergistic activity with TKIs, potentiating their efficacy and overcoming resistance. Conclusions: Preclinical evidence supports the role of polyphenols as potential adjuvants in CML therapy, particularly in drug-resistant contexts. Their pleiotropic molecular actions and low toxicity profile make them promising candidates for integrative oncology. Nonetheless, clinical translation requires further investigation through well-designed trials assessing efficacy, safety, and pharmacokinetics. Full article

Progress in clinical practice, research, and teaching needs a common language. Agreement among veterinary endocrinologists on definitions of concepts related to Cushing’s syndrome (CS) and hypoadrenocorticism is lacking. After a successful inaugural cycle on diabetes mellitus terminology, project Agreeing Language in Veterinary Endocrinology (ALIVE) held a second cycle, with simplified methodology, and brought together 10 experts of the European Society of Veterinary Endocrinology (ESVE) and the Society of Comparative Endocrinology (SCE). It employed a four-round modified Delphi Method to generate draft definitions and try and achieve consensus. A final round used an endorsement survey of the expert-generated definitions distributed to the ESVE and SCE memberships, seeking a simple majority endorsement. A minimum of 20% membership participation was sought. The 10 experts achieved 100% consensus on the definition of 35 adrenal disease-associated concepts, including disease definitions, diagnostic criteria, and test definitions, a disease classification system for CS and hypoadrenocorticism, and a clinical scoring system for CS. Definitions were subsequently assessed by 78 ESVE and SCE members (26% of combined memberships). All definitions achieved a simple majority, ranging from 83.1 to 100%. ALIVE proved effective in creating a body of terminology for adrenal disease in companion animals, which met the overall approval of a majority of those participating in the endorsement phase. The prospective use of these definitions could help improve comparability and standards for adrenal disease research, education, and clinics. Full article

Abrus bottae belongs to the subfamily Papilionoideae DC. and the family Fabaceae Lind., endemic to the Arabian Peninsula. This genus encounters numerous taxonomic issues concerning both the quantity of species within the genus and the systematic relationships among its species. Notably, there is a complete absence of sequence data in the GenBank database for this species. A molecular and phylogenetic study of the chloroplast genome of the species A. bottae was performed in this work. The chloroplast genome is 152,540 bp in size and exhibits a typical quadripartite structure, consisting of a substantial single-copy region of 83,507 bp, a small single-copy region of 17,681 bp, and a pair of inverted repeat regions of 25,676 bp each. The chloroplast genome of Abrus bottae encompasses 130 genes. An analysis of nucleoside diversity revealed 26 nucleotide polymorphism sites with Pi values (a measure of genetic variation within species) ≥ 0.04, serving as hotspots of variation. This work represents the first molecular phylogenetic study on the endemic species Abrus bottae and presents a comparative and phylogenetic analysis of the cp genomes of related taxa within the tribe Abreae. These outcomes can be used to develop DNA barcodes to study variation among the Abrus species. Full article

Background: Hepatocellular carcinoma is one of the leading causes of cancer-related deaths worldwide. Its high recurrence rate and limited treatment options underscore the urgent need for the development of new and highly effective drugs. Methods: This study systematically explores the molecular mechanism of cinnamic acid against hepatocellular carcinoma through integrated machine learning prediction, network pharmacological analysis and in vitro experimental verification. Results: The prediction of anti-tumor activity based on the random forest model showed that cinnamic acid has significant anti-tumor potential (probability = 0.69). Network pharmacology screened 185 intersection targets of cinnamic acid and liver cancer, of which 39 core targets (such as PIK3R1, AKT1, MAPK1) were identified as key regulatory hubs through protein interaction network and topological analysis. Functional enrichment analysis showed that these targets were mainly enriched in the PI3K/AKT signaling pathway (p = 2.1 × 10⁻¹²), the cancer pathway (p = 3.8 × 10⁻¹⁰), and apoptosis-related biological processes. Molecular docking validation revealed that the binding energies of cinnamic acid with the 19 core targets were all below −5 kcal/mol, a threshold indicating strong binding affinity in molecular docking. The binding modes to PIK3R1 (−5.4 kcal/mol) and AKT1 (−5.1 kcal/mol) stabilized through hydrogen bonding. In vitro, cinnamic acid dose-dependently inhibited Hep3B proliferation/migration, induced apoptosis, downregulated PI3K, p-AKT, and Bcl-2, and upregulated Bax and Caspase-3/8. Conclusions: This study systematically reveals, for the first time, that the multi-target mechanism of cinnamic acid exerts anti-hepatic cancer effects by targeting the PI3K/AKT signaling pathway, supporting its potential as a natural anti-tumor drug. Full article

The objective of this work was to analyse the genetic diversity of a population of Citrus spp. in the south of the State of Espírito Santo, Brazil, for pre-breeding studies. For that, a total of sixty genotypes were analysed, including ten citrus varieties from four species of the Citrus genus. The methodology involved DNA extraction, amplification via polymerase chain reaction, and the use of a set of 16 Simple Sequence Repeat markers. These markers identified 42 alleles, with a variation of one to four alleles per locus, an average heterozygosity value of 0.53, and an average polymorphic information content of up to 0.29 per species. After the analysis, a dissimilarity matrix was generated using Jaccard distance and a dendrogram, revealing the formation of two groups: Group I, comprising Citrus sinensis varieties, and Group II, comprising varieties of Citrus latifolia, Citrus aurantifolia, and Citrus reticulata. Our study demonstrated that the combination of these markers allowed for the differentiation of genotypes within the collection. The results obtained are valuable for the future management of the collection and the efficient use of genetic diversity estimation in Citrus spp. Full article

Loop shaping the controller for high-order systems, especially in the presence of flexible transmission components such as elastic shafts, gearboxes, and belts commonly found in servo systems, poses significant challenges. Therefore, developing a non-parametric, versatile tuning algorithm that adapts to multi-order systems is essential for general control applications. This article first obtains the frequency characteristics of plants through a frequency sweep. Then, based on preset frequency domain specifications, the boundaries representing disturbance rejection and stability constraints are defined in the complex plane with explicit mathematical and graphical expressions. Subsequently, a system of equations is developed based on the tangency between the open-loop curve of the system and the boundaries in the complex plane. On this basis, a versatile tuning algorithm is designed to calculate parameters of a PI controller cascaded with a low-pass filter that ensures the system meets the preset constraints. The proposed approach does not rely on parametric modeling, and the zeros and poles of the controller can be flexibly placed. Experimental validation is carried out on mechanical platforms. Full article