Search Results (13,417)

Background: Trans-resveratrol (3,5,4′-trihydroxystilbene) is a natural polyphenolic antioxidant widely used in anti-aging dermocosmetics for its strong radical-scavenging capacity and its activation of cell-protective pathways such as sirtuin 1 (SIRT1). However, its poor aqueous solubility, photochemical lability, and low bioavailability limit its incorporation into topical formulations and its delivery into the skin. Objective: In this study, ethosomal nanocarriers were designed as a phospholipid–ethanol vesicular system to solubilize, stabilize, and control the release of trans-resveratrol for dermocosmetic applications. Microfluidization is not a commonly used method; however, circulating the formulation through the interaction chamber under optimized pressure can produce ethosomes with desirable colloidal stability by this simple process. Methods: Resveratrol-loaded ethosomes were prepared with synthetic phosphatidylcholine (Lipoid P75), ethanol, and vitamin E. Microfluidization was optimized by varying the number of high-pressure homogenization cycles and the applied pressure. Vesicle size, size distribution and distribution uniformity, zeta potential, pH, conductivity, density, and long-term stability were monitored for up to 180 days; morphology was examined by cryogenic scanning electron microscopy (cryo-SEM) and molecular compatibility by Fourier-transform infrared (FTIR) spectroscopy. A trans-resveratrol high-performance liquid chromatography (HPLC) assay was developed and validated according to International Council for Harmonisation (ICH) Q2 guidelines for quantitative analysis. Encapsulation efficiency was determined by HPLC after ultracentrifugation, cytotoxicity was assessed in human keratinocytes (HaCaT), and in vitro release was evaluated using Franz diffusion cells with two different membranes. Results: All ethosome formulations yielded a nanoscale size distribution (median diameter around 190 nm for loaded and around 90 nm for unloaded) and good colloidal stability, with absolute zeta potentials above the 30 mV threshold at early time points and a skin-compatible pH (around 6.5). The optimized formulation (T16; 1.5% w/w trans-resveratrol, 5% w/w phosphatidylcholine (Lipoid P75), 0.3% w/w vitamin E and 30% w/w ethanol, processed with seven microfluidization cycles) achieved a high encapsulation efficiency (EE) of 95.5% on day 1. 84.2% EE was retained after 180 days, consistent with strong partitioning of the lipophilic active into the ethanol–phospholipid bilayer. FTIR confirmed preservation of the phospholipid bilayer and indicated non-covalent loading, with the resveratrol bands largely masked by the dominant lipid signals. Cryogenic Scanning Electron Microscopy (Cryo-SEM) confirmed near-spherical vesicles with narrow size distribution. In vitro release showed a sustained, controlled release profile relative to a 1.5% w/w resveratrol solution. Slower diffusion across the skin-mimicking Strat-M membrane was observed compared to cellulose acetate membrane. Conclusions: Optimized trans-resveratrol-loaded ethosomes represent a stable, efficient vesicular system enabling formulation stability and controlled topical release. The antioxidant and photoprotective efficacy of the loaded system was not assessed in this study and is identified as a topic for future work. Full article

A series of ten geranylated benzaldehydes (11–20) was designed, synthesized via Suzuki cross-coupling for the C–C series and S_N2 substitution for the C–O derivatives, and structurally characterized. The antifungal activity of all compounds against the phytopathogens Botrytis cinerea and Phytophthora cinnamomi, two important plant pathogens associated with substantial agricultural and economic losses worldwide, was evaluated in vitro using a mycelial growth inhibition assay. Dose–response treatment of the data indicates that (E)-2-((3,7-dimethylocta-2,6-dien-1-yl)oxy)-5-hydroxybenzaldehyde (19) is the most active compound exhibiting EC₅₀ values of 83 µg/mL and 7.34 µg/mL against B. cinerea and P. cinnamomi, respectively. To gain insight into the molecular basis of the observed antifungal activity, molecular docking studies were performed targeting the active site of succinate dehydrogenase (SDH, PDB ID: 2FBW), a key enzyme in the mitochondrial respiratory chain and a validated fungicide target. The calculated docking scores ranged from −6.0 to −7.5 kcal/mol, with compound 19 showing the highest binding affinity. Docking analysis reveals that compound 19 is stabilized within the SDH binding pocket through a network of hydrogen bonding and π–cation interactions involving the heme prosthetic group and key amino acid residues, providing a plausible structural rationale for its high antifungal activity, particularly against P. cinnamomi. Full article

4-Thiazolidinone derivatives, a group of compounds with a broad spectrum of activity and anticancer properties, are used in medicine as anti-inflammatory, antiviral, antibacterial, antidiabetic, and blood pressure-lowering drugs; some of them are now in phase II and III clinical trials as anticancer drugs. Here, we evaluated the anticancer potential of 4-thiazolidinones (2b, 12b, 14b) targeting tubulin and metastasis-related pathways in breast cancer models. Molecular docking revealed that compound 14b exhibited the strongest binding affinity to the paclitaxel-binding site of β-tubulin, outperforming 2b and 12b, though slightly weaker than Taxol. Biological assays confirmed significant tubulin inhibition, with 14b reducing β-tubulin levels up to eight-fold in MCF-7 cells and two-fold in MDA-MB-231 cells. All compounds promoted tubulin polymerization, showing paclitaxel-like activity, with comparable the maximum velocity (V_max) values. Cell cycle analysis demonstrated G2/M arrest in MCF-7 cells and S-phase accumulation in MDA-MB-231 cells. Overall, compound 14b demonstrated the most promising multitarget anticancer activity in vitro. Full article

Chronological age can be estimated from molecular profiles; however, predictive accuracy alone does not establish a biologically validated ageing clock. We therefore evaluated whether plasma protein intensities measured by data-independent acquisition mass spectrometry (DIA-MS) support chronological-age estimation in a cross-sectional cohort from Moscow, Russia, while explicitly examining acquisition-order and MS-batch confounding. Plasma samples from 350 adult participants aged 19.8 to 99.1 years were analyzed as single-shot, single-injection DIA-MS acquisitions on a Q Exactive HFX platform. The final matrix comprised 222 protein groups and was generated with DIA-NN version 1.8.1 using a two-pass predicted-library-assisted workflow, cross-run precursor-level normalization, normalized MaxLFQ-like protein–group quantification, and 1% precursor and protein–group false-discovery-rate thresholds. Descriptive associations were assessed using Spearman rank correlation with Bonferroni correction. Feature selection and missing-value imputation were confined to each training subset. Generalization was assessed primarily by holding out complete MS batches, with repeated, nested, and random five-fold analyses retained as internal comparators. Of the 222 proteins, 148 were associated with chronological age at the nominal threshold p < 0.05, and 98 remained significant after Bonferroni correction. The strongest descriptive associations involved fibrinogen beta chain (FGB; rs = 0.590), SERPINA3 (rs = 0.560), ITIH4 (rs = 0.542), complement C5 (rs = 0.538), and ceruloplasmin (rs = 0.518). In internal random-split analyses, a 50-feature Gradient Boosting strategy yielded MAE = 8.90 ± 1.06 years in repeated five-fold cross-validation and MAE = 9.10 ± 1.10 years in nested cross-validation. However, when complete MS batches were held out, aggregate MAE increased to 10.56 years (R² = 0.554) using a batch-stratified assignment and 11.87 years (R² = 0.461) using GroupKFold. These batch-held-out results constitute the primary estimate of generalization from the present dataset. To assess the trade-off between error and assay complexity, strategies using 5, 8, 10, 12, 15, 20, 30, and 50 proteins selected within each training fold were compared. The 8-feature strategy yielded MAE = 11.83 years in repeated random cross-validation, whereas the 50-feature strategy yielded MAE = 8.90 years. These estimates concern feature-number strategies, not fixed panels. The post hoc eight-protein list is reported only as an exploratory candidate set for future independent validation. Acquisition order was associated with chronological age (rs = 0.336, p = 1.03 × 10⁻¹⁰), and age and sex distributions differed strongly across 27 MS batches. Order alone predicted age with MAE = 3.98 years in a negative-control model, demonstrating that age information was encoded in the acquisition design. Accordingly, the present findings support only a proof-of-concept for plasma-proteomic prediction of chronological age within this dataset; they do not establish a batch-independent model, a clinical tool, or a biologically validated ageing clock. Full article

With the development of hydrogen pipelines, hydrogen embrittlement has become a critical issue affecting the safe service of pipeline steels. However, the critical hydrogen concentration for the hydrogen-induced ductile-to-brittle transition and its dependence on grain size remain unclear. Molecular dynamics simulations were performed to elucidate the effects of hydrogen concentration and grain size on the hydrogen-induced ductile-to-brittle transition by investigating hydrogen diffusion, dislocation emission, and fracture evolution in polycrystalline α-Fe. The results demonstrate that, with increasing hydrogen concentration, hydrogen atoms preferentially diffuse along grain boundaries and gradually reach segregation saturation, resulting in continuous degradation of mechanical properties. The initial fracture strain of both fine-grained and coarse-grained models decreases by more than 40%, while fracture energy decreases by more than 50%. Crack surface areas increase by factors of 2.48 and 1.86, respectively, indicating greater hydrogen sensitivity of the fine-grained model. At grain-boundary hydrogen concentrations of approximately 7–9%, suppressed grain-boundary dislocation emission triggers the transition from plastic deformation to brittle intergranular fracture, marking the onset of the hydrogen-induced ductile-to-brittle transition. A quantitative relationship between grain size and grain-boundary atom fraction was established to predict the critical hydrogen concentration for this transition. This study reveals the role of hydrogen concentration in regulating dislocation emission and intergranular fracture, providing insights for hydrogen embrittlement assessment and pipeline material design. Full article

Cephalotaxine (1) is a parent compound within the cephalotaxine alkaloids class mainly derived from Cephalotaxus plants. In this study, by coupling 1 with cinnamic acid, 17 novel cephalotaxine-cinnamic acid derivatives (S1–S17) were designed and synthesized to enhance their anti-tumor efficacy. Among them, S10 showed the strongest cytotoxic activity against Huh7 cells, with the IC₅₀ values of 9.3 and 5.9 μM after 24 h and 48 h, respectively, which were 21 and 32 times more potent than those of 1. In addition, compared with those against AML-12 cells, the proliferation inhibition rates of S10 against Huh7 cells were 5.0-fold lower, indicating a certain therapeutic window. Network pharmacology screening results indicate that S10 may exert regulatory effects closely related to cell migration and apoptosis through pathways such as PI3K/AKT. Molecular docking showed that S10 could effectively bind to the key targets PI3K and AKT. And the Western blot experiment results confirm that S10 could downregulate the expression of p-PI3K and p-AKT at the protein level while keeping total PI3K and AKT unchanged. Notably, S10 may regulate liver cancer cells by inhibiting the PI3K/AKT signaling pathway. Mechanistically, S10 induces S cycle arrest, reduces mitochondrial membrane potential, induces apoptosis, and inhibits migration and invasion. Overall, we reported S10 as a promising lead compound for the treatment of liver cancer. Full article

Mesoporous silicate nanoparticles are known for their pore size, pore volume, high surface area, and tunable surface properties and, as a result, have found application in medicine, healthcare, advanced materials, and devices. Furthermore, tailoring the silicate domain with certain metals has advanced the tissue engineering properties by moderating the cellular function at the molecular level for therapeutic response. However, limited efforts have been made to explore systemic synthesis protocols that could change structure or shape of mesoporous metal silicate nanostructures as the change in shape has inherent potential to tailor biological response. Here, we have focused on using Design of Experiments (DoE) to optimize reaction conditions for the synthesis of mesoporous strontium silicate nanostructures (MPSrSiO₂ NSs) (nanoparticles—NPs and nanorods—NRs) with different physicochemical properties. The conditions allowed a change in shape from NPs to NRs by tailoring the concentration of liquid ammonia (liq. NH₃, NH₄OH, 82.7 mM to 248.2 mM) during the pre-synthesis incubation state. The MPSrSiO₂ NPs had a significantly higher zeta potential compared to NPs (p = 0.0061). Also, NPs possessed significantly higher surface area (p = 0.0306), pore diameter (p = 0.0003), and pore volume (p = 0.0004) than NRs. In addition, the optimized reaction conditions allowed modulation of the physicochemical properties such as surface area, surface charge, amount of metal, pore diameter, pore volume, tailored degradation profile and release profile of loaded drug (gentamicin). Finally, the protocol has the advantage of allowing incorporation of other metals such as cerium, rhodium, and ruthenium independently and/or in combination. Full article

Moisture content is among the most routinely measured properties of foods, yet water quantity alone does not determine processing behavior, stability, texture, fluid release or sensory function. In heterogeneous food matrices, water occupies environments differing in molecular restriction, compartmentalization, exchange, connectivity and translational mobility. Time-domain nuclear magnetic resonance (TD-NMR) provides a rapid and non-destructive means of interrogating these properties through proton signal intensity, longitudinal and transverse relaxation, relaxation-time distributions, self-diffusion and multidimensional correlation measurements. This review develops a framework extending food-water analysis from quantity to molecular state, mobility, translational accessibility and function. Particular emphasis is placed on distinguishing local molecular environments reflected by relaxation from longer-range molecular displacement characterized by diffusion. Applications in meat, plant-based foods, dairy systems, cereals, gels, frozen and dried foods, and edible oils illustrate how TD-NMR descriptors can be connected with water holding, texture, juiciness, processing behavior, oxidation and shelf life. Integration with structural imaging, mechanical measurements, chemometrics and machine learning further positions TD-NMR as a molecular-state sensing platform for predictive food analysis, product design and intelligent manufacturing. Full article

The infrared spectral features of aero-engine wake serve as a crucial basis for infrared detection, tracking, and identification of aircraft. Their spectral line structure is regulated by the concentration and temperature of the exhaust gases, as well as atmospheric absorption effects. This study employs a high-precision numerical simulation model and conducts field experiments on infrared spectral detection of exhaust plumes to systematically investigate the influence mechanisms of three factors—fuel–air ratio (achieved by varying exhaust gas concentration), exhaust temperature, and atmospheric absorption effects—on key spectral features, including peak intensity, line broadening, shape, and position. Results indicate the following. The fuel–air ratio enhances peak intensity and broadens spectral line width by increasing CO₂ and H₂O concentrations within the fuel-lean operating regime (f = 0.025–0.031); exhaust temperature causes exponential spectral intensity growth and line broadening by elevating molecular energy level populations, while inducing H₂O spectral band redshifts and fine-structure evolution; selective absorption by atmospheric H₂O, CO₂, and O₃ causes severe spectral attenuation near bands at 1041 cm⁻¹, 1590 cm⁻¹, 2349 cm⁻¹, and 3756 cm⁻¹, with transmittance distribution modulated by geographical and seasonal factors. This study provides theoretical support for wake spectral feature extraction, infrared stealth design, and detection/tracking identification. Full article

Bromelain is a widely used as model for papain-like cysteine proteases and shares significant sequence homology with bacterial and viral counterparts, making it a suitable target for computational screening of potential modulators. In this study, we performed molecular docking and protein–ligand interaction profiling for eight synthetic derivatives containing 6-chloroquinolone (compounds 1–4), 1,3,5 triazine (compounds 5–7) or furopyrrole (8) scaffolds. In the quinoline series, the position of the methyl group on the piperidine ring appeared to influence efficacy (4 methyl > unsubstituted > 2 methyl). Molecular docking and PLIP interaction profiling revealed that the highest computed binding affinities (up to –12.4 kcal/mol for 5) did not directly correlate with experimental inhibition, but identified the residues predicted by docking and PLIP to contribute to ligand interactions: Lys18, Phe29, Ile163, Trp180, Tyr185, and Ile186. Ligands 6 and 7 formed H-bonds with catalytic residues His158 and Cys26, respectively. Sequence alignment revealed 42–49% identity between bromelain and bacterial cysteine proteases from Klebsiella pneumoniae and Acinetobacter baumannii, suggesting that bromelain may serve as a tentative model system for the preliminary study of pathogen cysteine proteases, although direct extrapolation would require experimental validation. To experimentally assess these predictions, we conducted a preliminary activity screen using an azocasein proteolytic assay. Compound 1 exhibited a moderate inhibitory effect, whereas compounds 2–8 produced only marginal changes, which lacked statistical significance after correction for multiple comparisons. These findings provide a structural basis for the rational design of new protease inhibitors and identify compound 1 as a preliminary screening hit and a possible starting point for further optimization. Full article

Harvest-window recognition of facility-grown Pleurotus ostreatus is challenged by clustered fruiting bodies, occlusion, and subtle differences between near-mature and mature stages. We developed a two-stage framework combining YOLO26s detection with a lightweight dual-view classifier, RepViT-RSG-BEHarvestNet. YOLO26s was selected from four candidate detectors using the validation subset of a 2946-image dataset. Matched detections produced 3547 paired target and context regions of interest. The classifier combined stage-guided expert routing with boundary soft labels and teacher distillation. On the independent test set, YOLO26s achieved a Precision of 0.9681, Recall of 0.9117, and mAP50 of 0.9787. Across ten paired runs on matched test regions, the final classifier achieved a Macro F1 of 0.8827 ± 0.0044, compared with 0.8589 ± 0.0054 for the dual-view baseline, while adding 0.071 M parameters. On the near-mature–mature subset, Macro F1 increased from 0.7994 ± 0.0115 to 0.8563 ± 0.0105. On all 296 test images containing 404 annotated targets, the complete pipeline achieved target-level Precision of 0.7770, Recall of 0.7941, a false harvest rate of 0.1007, and a missed harvest rate of 0.2059. Mean end-to-end latency was 94.7 ms per image. The results show improved boundary classification while identifying detection errors as a remaining constraint on complete-image harvest decisions. Full article

Theileria annulata causes tropical theileriosis in cattle and is endemic in Kazakhstan. Although molecular diagnostic methods for this pathogen exist, data on its molecular surveillance and genetic diversity in Kazakhstan remain limited. This study aimed to develop and experimentally validate a species-specific real-time PCR (qPCR) assay for the detection of Theileria annulata and to conduct molecular surveillance and phylogenetic analysis of circulating isolates. A total of 709 cattle blood samples from 10 regions of Kazakhstan were analysed. Species-specific primers and a probe were designed targeting the 18S rRNA gene, and diagnostic performance was evaluated against sequencing as the reference method. Theileria annulata infection was confirmed in 110 of 709 samples (15.51%), with positive samples identified in the Turkistan, West Kazakhstan, Kyzylorda, and Zhambyl regions. The developed assay showed high diagnostic sensitivity (99.09%), specificity (99.67%), and diagnostic efficiency (99.58%), with no cross-reactivity with Theileria orientalis, Theileria parva, Babesia bovis, Babesia bigemina, or Anaplasma marginale. Phylogenetic analysis of partial 28S rRNA sequences confirmed the species identity of the detected isolates and demonstrated their close relationship with previously reported Kazakhstani and Chinese isolates. The developed qPCR assay is suitable for the molecular diagnosis and surveillance of bovine tropical theileriosis in Kazakhstan. Full article

Background/Objectives: Rabies remains a fatal viral disease, and current conventional vaccine strategies face significant challenges regarding structural stability and large-scale manufacturing. This study aimed to design a novel messenger ribonucleic acid (mRNA) vaccine candidate targeting the rabies virus glycoprotein G (RABV-G) using an integrated immunoinformatic and structural modeling framework. Methods: The RABV-G sequence was systematically evaluated for evolutionary conservation and safety, followed by 3D structural modeling. Highly antigenic B-cell and T-cell epitopes were identified based on human leukocyte antigen (HLA) binding, toxicity, and glycosylation shielding analyses. Functional interactions were assessed via molecular docking with the Toll-like Receptor 4/Myeloid Differentiation factor 2 (TLR4-MD2) complex. Finally, a full-length mRNA construct was engineered and computationally evaluated for translational efficiency, structural stability, and immune simulation. Results: The RABV-G target exhibited high evolutionary conservation, with 53.82% of positions fully identical and an additional 43.70% highly conserved (70–99%) across 87 analyzed sequences. Structural validation confirmed a high-quality model, enabling the extraction of accessible, non-glycosylated epitopes. Molecular docking simulations revealed a highly favorable predicted structural interaction with the TLR4-MD2 receptor, suggesting a potential structural capacity to engage innate immune pathways, pending experimental validation. The codon-optimized mRNA construct exhibited a predicted thermodynamically stable secondary structure (MFE = −429.50 kcal/mol) with an accessible translation initiation site, pending experimental validation. Furthermore, in silico immune simulations predicted a robust and sustained activation of both humoral and cellular immunity, notably including memory B-cell expansion. Conclusions: The computationally designed mRNA vaccine candidate demonstrates highly favorable structural characteristics and immunogenic potential. While these in silico findings present a promising foundational framework for rabies prevention, subsequent experimental laboratory validation is strictly required to confirm its functional efficacy and translation. Full article

Controlling the hydrosilylation rate during the curing of polydimethylsiloxanes (PDMS) is essential for regulating processing parameters and the properties of silicone materials. This study explores the possibility of achieving such control through differences in the reactivity of terminal allylsilyl and vinylsilyl groups. Difunctional PDMS bearing terminal allyl, vinyl, or hydride groups, together with a narrowly dispersed monofunctional PDMS bearing a terminal hydride group, were synthesized for model experiments. The starting compounds and hydrosilylation products were characterized by ¹H and ²⁹Si NMR spectroscopy and gel permeation chromatography. When allylsilyl and vinylsilyl groups were present in the same reaction mixture, hydrosilylation preferentially involved vinylsilyl groups. Additional model experiments confirmed the higher relative reactivity of vinylsilyl groups and revealed competing isomerization of the allylic double bond, which likely contributes to the slower hydrosilylation of allylsilyl groups. These findings indicate that differences in functional group reactivity can be used to control the sequence of hydrosilylation reactions and guide the molecular design of silicone materials with tailored properties. Full article

Natural bioactive compounds, especially plant-derived phytoconstituents, have gained significant interest due to their structural diversity, multitarget pharmacological activities, and favourable safety profiles. Their pharmaceutical translation is often hindered by poor aqueous solubility, limited membrane permeability, chemical instability, extensive first-pass metabolism, and, therefore, low oral bioavailability. Phytosomes, which are molecular complexes of bioactive compounds with phospholipids, have emerged as a new, effective, lipid-based delivery platform that can overcome these biopharmaceutical limitations and improve solubility, membrane interactions, systemic exposure, and therapeutic efficacy. The present review critically analyses recent advancements in phytosomal drug delivery, from formulation development to clinical translation, focusing on molecular complexation mechanisms, formulation strategies, physicochemical characterisation, pharmacokinetic enhancement, therapeutic applications, and challenges in clinical translation. The current review combines pharmaceutical design principles with recent advances in quality-by-design (QbD), computational formulation optimisation, hybrid phytosomal systems, scalable manufacturing approaches, and targeted delivery strategies. In addition, prospects for the future extension of phospholipid complexation to bioactive compounds from marine organisms, fungi, microorganisms, and algae are discussed in relevance to the next-generation natural product therapeutics. The present review serves as an emerging link between the discovery of natural bioactive compounds and the development of clinically translatable phytosomal systems from a pharmaceutical perspective. Full article