Search Results (15,715)

Background and Objectives: Morning halitosis undermines social well-being, yet the combined influence of basal salivary flow and tongue coating in healthy adults is unclear. Methods: In a cross-sectional study of 92 university students (18–35 years), we measured unstimulated salivary flow rate (uSFR), tongue-coating index (TCI), total volatile sulfur compounds (VSCs; Halimeter^®), organoleptic score (0–5), and self-perceived halitosis (yes/no) under standardized early-morning conditions. Results: Thirty-seven participants (40.2%) reported morning halitosis and showed lower uSFR (0.2 ± 0.1 vs. 0.3 ± 0.1 mL·min⁻¹) and higher TCI (2.3 ± 0.5 vs. 1.9 ± 0.4), with higher organoleptic scores (3.4 ± 0.6 vs. 2.1 ± 0.7) and VSCs (272.9 ± 39.8 vs. 163.7 ± 45.9 ppb; all p < 0.001). VSCs correlated inversely with uSFR (ρ = −0.58) and positively with TCI (ρ = 0.44). In multivariable models, uSFR (β = −0.53) and TCI (β = 0.31) explained 54% of VSC variance; each 0.1 mL·min⁻¹ fall in uSFR increased the odds of self-perceived halitosis 1.9-fold (p = 0.001). Conclusions: Even among healthy young adults, lower basal saliva and heavier tongue coating are independent contributors to morning malodor. Hydration, daily tongue cleaning, and addressing mouth breathing are pragmatic, first-line strategies. Full article

Plastic pollution represents a persistent global issue, with catastrophic effects on ecosystems. Due to unique properties, these synthetic materials do not break down into biodegradable compounds when naturally dispersed, but degrade into smaller fragments, known as micro- (MPs) and nanoplastics (NPs), that easily enter the food chain. Among plastics, polypropylene (PP) is one of the most common, whose consumption has dramatically increased in recent years for single-use packaging and surgical masks. In this context, given the widespread detection of PP-MPs and NPs in various biological matrices, investigating their toxicity in living organisms is crucial. For these reasons, this study aims to assess how PP-MPs and NPs affect tissue regeneration following injury, proposing the freshwater leech Hirudo verbana as an established experimental model. Injured leeches were examined at different time points after plastic administration, and analyses were conducted using microscopy, immunofluorescence, and molecular biology techniques. The results demonstrate that plastic exposure induces fibrosis, disrupts tissue reorganization, delays wound repair, and activates the innate immune and oxidative stress responses. In summary, this project provides new insight into the adverse effects of PP particles on living organisms, highlighting for the first time their negative impact on proper tissue regeneration. Full article

To investigate the potential of metakaolin (MK) (5%, 10%, 15%, and 20% substitution of cement mass) and basalt fibre (volume contents of 0.1%, 0.2%, and 0.3%) in recycled aggregate concrete (RAC) products, RAC’s mechanical properties were first assessed with a singular incorporation of MK. The findings demonstrated that adding 15% MK optimised the compressive strength and flexural strength of RAC (at the recycled aggregate replacement levels of 30%, 45%, and 60% by weight). An orthogonal test was conducted to investigate the synergistic effect of MK and basalt fibre (BF), with the recycled coarse aggregate (RCA) replacement rate (mass ratio of RCA to natural coarse aggregates), MK content (cement mass substitution percentage), and BF content (volume dosage) identified as the influencing parameters. The variance analysis reveals that the influence of the replacement ratio of RCA on compressive strength surpasses that of MK content, which in turn exceeds that of BF content. Conversely, as for the flexural strength, BF is substantially more effective than that of MK. A model test of RAC curbs was performed based on the ideal mix ratio suggested by the single mixing of MK and MK and BF compound mixing inside the orthogonal test. The results demonstrate that the RAC curbs, with an RCA replacement rate of 30%, display optimal mechanical properties when 15% MK and 0.2% BF are incorporated. This surpasses the performance of 15% MK alone and illustrates that the mix incorporation of MK and BF is superior to that of MK alone. Full article

Some species of Cyperaceae are used in the treatment of gastrointestinal disorders by traditional communities in several countries, including Kenya, Nepal, Pakistan, and India. Although these ethnomedicinal uses are being confirmed through in vivo pharmacological trials, many plants in this family still lack scientific investigation. In this context, the present study aimed to review the pharmacological potential of Cyperaceae species in experimental models of gastrointestinal disorders and correlate it with the phenolic compounds and flavonoids present in these plants. The articles were retrieved from different databases, from the first report on the topic published in 1997 to August 2025. A total of 10 Cyperaceae species were identified that showed pharmacological potential against gastrointestinal disorders, including representatives of the genera Cyperus (6 spp.), Fimbristylis (2 spp.), Lagenocarpus (1 spp.), and Pycreus (1 spp.). The extracts of these plants demonstrated potential antiulcerogenic, gastroprotective, antidiarrheal, and intestinal anti-inflammatory effects in rodent models of ulcerative colitis, with particular attention on Cyperus rotundus L. A diverse array of bioactive compounds were identified in the Cyperaceae family, including luteolin, kaempferol, caffeic acid, quercetin, ferulic acid, rutin, myricetin, gallic acid, chlorogenic acid, apigenin, catechin, and orientin. These phytochemicals have been widely studied in experimental models of gastrointestinal disorders. It is likely that the flavonoids and phenolic compounds identified in Cyperaceae species are related to the pharmacological potential of these plants and can be used in the treatment of gastrointestinal disorders. Additional studies are needed to investigate the pharmacological potential of other Cyperaceae used empirically in traditional medicine for the treatment of diseases affecting the digestive system. Full article

(1) Objective: Volatile organic compounds (VOCs) monitoring in industrial parks is crucial for environmental regulation and public health protection. However, current techniques face challenges related to cost and real-time performance. This study aims to develop a dynamic calibration framework for accurate real-time conversion of VOCs volume fractions (nmol mol⁻¹) to mass concentrations (μg m⁻³) in industrial environments, addressing the limitations of conventional monitoring methods such as high costs and delayed response times. (2) Methods: By innovatively integrating photoionization detector (PID) with machine learning, we developed a robust conversion model utilizing PID signals, meteorological data, and a random forest’s (RF) algorithm. The system’s performance was rigorously evaluated against standard gas chromatography-flame ionization detectors (GC-FID) measurements. (3) Results: The proposed framework demonstrated superior performance, achieving a coefficient of determination (R²) of 0.81, root mean squared error (RMSE) of 48.23 μg m⁻³, symmetric mean absolute percentage error (SMAPE) of 62.47%, and a normalized RMSE (RMSE_norm) of 2.07%, outperforming conventional methods. This framework not only achieved minute-level response times but also reduced costs to just 10% of those associated with GC-FID methods. Additionally, the model exhibited strong cross-site robustness with R² values ranging from 0.68 to 0.69, although its accuracy was somewhat reduced for high-concentration samples (>1500 μg m⁻³), where the mean absolute percentage error (MAPE) was 17.8%. The inclusion of SMAPE and RMSE_norm provides a more nuanced understanding of the model’s performance, particularly in the context of skewed or heteroscedastic data distributions, thereby offering a more comprehensive assessment of the framework’s effectiveness. (4) Conclusions: The framework’s innovative combination of PID’s real-time capability and RF’s nonlinear modeling achieves accurate mass concentration conversion (R² = 0.81) while maintaining a 95% faster response and 90% cost reduction compared to GC-FID systems. Compared with traditional single-coefficient PID calibration, this framework significantly improves accuracy and adaptability under dynamic industrial conditions. Future work will apply transfer learning to improve high-concentration detection for pollution tracing and environmental governance in industrial parks. Full article

Phytophagous beetles, particularly those within the superfamilies Chrysomeloidea and Curculionoidea, constitute one of the most diverse and ecologically significant groups of insect herbivores. Within this group, the subfamily Bruchinae is especially notable for its close association with leguminous plant seeds. As most Bruchinae species do not feed during the adult stage, the timing and regulation of vitellogenesis remain unclear. Previous studies suggest that vitellogenesis may be triggered by volatile organic compounds emitted by host seeds, which promote juvenile hormone (JH) synthesis. This increase in JH is hypothesized to stimulate vitellogenesis, enhance female attractiveness, and ultimately facilitate fertilization and oviposition. To explore this hypothesis, we investigated the external cues regulating reproductive physiology in the capital breeder Zabrotes subfasciatus. Specifically, we examined the effects of host seeds and male presence on oviposition dynamics, fecundity, ovary activation, and the expression of vitellogenic genes (vg and vgR) throughout adult life. Our results show that females initiate vitellogenesis during the final phases of adult development, enabling oviposition to begin as early as the first day after emergence. Oviposition remains at basal levels throughout adult life unless both host seeds and males are present (p < 0.0001). This oviposition pattern is consistent with ovary activation dynamics, which reveal that vitellogenesis peaks early in the oviposition period and is prolonged by the presence of seeds and males (p < 0.05). Notably, vg and vgR gene expression respond differentially to these cues (p < 0.05). We integrate our findings with previous literature to propose a working model for the regulation of oviposition in the Bruchinae beetle Z. subfasciatus. Full article

Amiodarone (AMD) is an effective antiarrhythmic drug whose long-term use is limited by multi-organ toxicities linked to oxidative stress. This review synthesizes current evidence on how AMD induces reactive oxygen species (ROS) generation in vitro and in vivo, and the mechanistic pathways involved. AMD promotes ROS production through both direct and indirect mechanisms. Directly, AMD accumulates in mitochondria and impairs the electron transport chain, leading to electron leakage and superoxide formation. It also undergoes redox cycling, forming radical intermediates that trigger lipid peroxidation and deplete cellular antioxidants. AMD and its metabolites inhibit antioxidant enzymes (SOD, CAT, GPx) expression and/or activities and reduce glutathione level, compounding oxidative injury. Indirectly, AMD activates signaling pathways that exacerbate ROS generation. This compound can induce pro-inflammatory mediators such as TNF-α and modulate nuclear receptors such as AhR, PXR, CAR, and PPARs, altering the expression of metabolic enzymes and endogenous antioxidants. These processes are time- and dose-dependent: short exposures at low concentrations may transiently scavenge radicals, whereas chronic or higher-dose exposures consistently lead to net ROS accumulation. The oxidative effects of AMD vary by tissue and experimental models. In chronic models, organs such as the lung and liver show pronounced ROS-mediated injury, whereas acute or cell-based systems typically exhibit subtler changes. AMD-induced toxicity arises from multifactorial oxidative stress involving mitochondrial dysfunction, increased radical formation, depletion of antioxidant defenses, and activation of pro-oxidant signaling pathways. Recognizing these pathways suggests that antioxidant and mitochondria-targeted co-therapies could ameliorate the side effects of AMD. Full article

Modern dentistry depends on polymer composite materials for a wide range of applications. These materials, mainly composed of polymer resins and reinforced with inorganic fillers, offer mechanical strength, wear resistance, and durability for restorations and prosthetics. This study concentrated on the density and surface tension of monomers often used in dental resins and employed Quantitative Structure–Property Relationship (QSPR) modeling to investigate the influence of monomers’ structural features on these properties. Two main and two auxiliary models to predict both density and surface tension were built and validated. Additionally, two models based on CircuS descriptors were built and analyzed. Molecular descriptors from the models were interpreted and structural characteristics of dental monomers influencing their physicochemical properties were identified. It was found that the presence of heteroatoms increases both of the analyzed properties, while all of the other identified structural features exert an opposite influence on density and surface tension. Furthermore, the study showed that the density of dental monomers can be reliably predicted using the database containing regular organic compounds, but the surface tension requires the database containing specific monomers in order to perform satisfactorily. Full article

Xanthones from mangosteen pericarp (MP) are bioactive compounds with promising pharmaceutical and nutraceutical applications. However, their efficient and selective extraction using environmentally friendly solvents remains a challenge. This study aimed to evaluate tricaprylin (C8) and tricaprin (C10) as novel green co-extractants in supercritical carbon dioxide (scCO₂) extraction for the recovery of xanthones from MP, using a mass ratio of C8:C10 = 0.64:0.36, hereafter referred to as C8/C10, and to model extraction kinetics for process design and scale-up. Extraction performance was investigated using different C8/C10–MP mass ratios and scCO₂ conditions at temperatures of 60 °C and 70 °C and pressures of 250 bar, 350 bar, and 450 bar. A pseudo-first-order kinetic model was applied to describe the extraction profile, and the kinetic parameters were generalized using second-order polynomial functions of temperature and pressure. The highest xanthone yield (39.93 ± 0.37%) and total xanthone content (51.44 ± 2.22 mg/g) were obtained at a 40% C8/C10–MP ratio under 70 °C and 350 bar, where the C8/C10 mixture outperformed other tested co-extractants in both efficiency and selectivity, particularly for α-mangostin. The extraction profiles were well described by the pseudo-first-order kinetic model, and the generalized model predicted the extraction yield with an uncertainty of 2.3%. C8/C10 is a highly effective and scalable co-extractant for scCO₂ extraction of xanthones, offering a foundation for industrial applications in food, nutraceutical, and pharmaceutical sectors. Full article

Olive oil, a cornerstone of the Mediterranean diet, is increasingly recognized not only for its cardiovascular benefits but also for its potential role in cancer prevention and therapy. Among its bioactive constituents, several phenolic compounds—tyrosol, hydroxytyrosol, oleuropein, oleacein, and oleocanthal—have demonstrated promising anticancer activities in various experimental models. These compounds act synergistically through diverse mechanisms, including antioxidant, anti-inflammatory, and immunomodulatory effects, as well as modulation of cell proliferation, apoptosis, angiogenesis, and metastasis. Notably, oleocanthal selectively induces cancer cell death via lysosomal membrane permeabilization, while hydroxytyrosol and oleuropein exhibit potent radical-scavenging and anti-proliferative properties. This review synthesizes findings from in vitro, in vivo, and clinical studies on the anticancer potential of these polyphenols, with emphasis on their mechanisms of action and possible applications in cancer prevention and adjunctive therapy. Given the established link between obesity and cancer development, clinical studies examining the metabolic, anti-inflammatory, and immunomodulatory effects of olive polyphenols in populations with obesity or prediabetes provide valuable insights into their potential to influence cancer-related pathways indirectly. However, direct clinical evidence in cancer patients remains limited and preliminary, underscoring the need for focused, well-controlled trials with cancer-specific endpoints. Furthermore, it critically evaluates the translational relevance of these findings, highlighting gaps in clinical research and future directions. Literature was retrieved from Google Scholar, PubMed, and ScienceDirect using keywords such as cancer, immunomodulatory, anti-inflammatory, olive, tyrosol, hydroxytyrosol, oleuropein, oleacein, and oleocanthal. Given the rising global cancer burden and the favorable safety profiles of these natural molecules, elucidating their molecular actions may support the development of novel integrative therapeutic strategies. Full article

Artificial intelligence (AI) is emerging as a valuable complementary tool in small-molecule drug discovery, augmenting traditional methodologies rather than replacing them. This review examines the evolution of AI from early rule-based systems to advanced deep learning, generative models, diffusion models, and autonomous agentic AI systems, highlighting their applications in target identification, hit discovery, lead optimization, and safety prediction. We present both successes and failures to provide a balanced perspective. Notable achievements include baricitinib (BenevolentAI/Eli Lilly, an existing drug repurposed through AI-assisted analysis for COVID-19 and rheumatoid arthritis), halicin (MIT, preclinical antibiotic), DSP-1181 (Exscientia, discontinued after Phase I), and ISM001-055/rentosertib (Insilico Medicine, positive Phase IIa results). However, several AI-assisted compounds have also faced challenges in clinical development. DSP-1181 was discontinued after Phase I, despite a favorable safety profile, highlighting that the acceleration of discovery timelines by AI does not guarantee clinical success. Despite progress, challenges such as data quality, model interpretability, regulatory hurdles, and ethical concerns persist. We provide practical insights for integrating AI into drug discovery workflows, emphasizing hybrid human-AI approaches and the emergence of agentic AI systems that can autonomously navigate discovery pipelines. A critical evaluation of current limitations and future opportunities reveals that while AI offers significant potential as a complementary technology, realistic expectations and careful implementation are crucial for delivering innovative therapeutics. Full article

Background/Objectives: The static in vitro permeability assay based on cell monolayers has been widely used in the pharmaceutical industry and recognized by regulatory agencies as a surrogate method for BCS classification. However, the application of such an experiment to study the effects of formulations is limited by the oversensitivity to the excipient effect on drug permeability. In this article, we studied the effects of common excipients on the permeability of moderately and poorly absorbed model compounds across cell monolayers, using two approaches to control said oversensitivity. Methods: Drug permeability across MDCK-wt was assessed in the absence (control) or presence (treatment) of excipients, using minoxidil as a high-permeability marker. The effects of excipients were parameterized as a permeability ratio (PR = treatment/control) without or with normalization (nPR) by minoxidil permeability. Metrics were compared by either ANOVA (p < 0.01) or confidence intervals (CI90, as per bioequivalence metrics) to identify excipient effects. Results: Acyclovir and hydrochlorothiazide showed the highest and lowest number of interactions, respectively. The most impactful excipients were sodium lauryl sulfate, microcrystalline cellulose, and sodium starch glycolate. Unexpectedly, nPR increased the number of excipient effects across model drugs (19 vs. 21). Alternatively, the CI90 approach was more sensitive than ANOVA in identifying excipient effects (41 vs. 32). Conclusions: Minoxidil was not able to control the anticipated oversensitivity of cell-based permeability experiments. Meanwhile, ANOVA was overall able to reduce oversensitivity to excipient effects on drug permeability compared to CI90. Nonetheless, there might be a niche for CI90 analysis when comparing the performance of two formulations on the permeability of moderately and poorly absorbed drugs. Full article

Background/Objectives: Fungotherapy has long been recognized as a therapeutic approach for treating and preventing various diseases. As an important representative of the so-called functional mushrooms, Chaga plays a crucial role in this system. Since this species is of limited distribution in Bulgaria, we are interested in studying a related but different species, Inonotus nidus-pici Pilát, with potential benefits for human health. Methods: The phytochemical composition of phenolic compounds in the studied species was analyzed using spectrophotometric methods and high-performance liquid chromatography (HPLC). Additionally, antioxidant activity was assessed using various assays, and the gastroprotective effect was evaluated in experimental rat models with indomethacin-induced gastric damage. Results: The quantities of the main classes of phenolic compounds in the studied object were determined, and an enriched phenolic extract (EPE) was obtained. The amount of phenolic compounds, in decreasing order, is as follows: tannins (1.67 ± 0.02%), phenolic acids (1.50 ± 0.09%), and flavonoids (1.24 ± 0.04%). Quercetin was the most present flavonoid (15.95 ± 0.05 mg/g DWE), followed by (+)-catechin (9.86 ± 0.15 mg/g DWE) and kaempferol (1.67 ± 0.09 mg/g DWE) in the enriched phenolic extract. The quantity of other established compounds was significantly lower. Of all ten phenolic acids identified in the same extract, the highest concentration was found only for rosmarinic acid (6.41 ± 0.08 mg/g DWE) and somewhat for p-coumaric acid (2.13 ± 0.12 mg/g DWE). Among all the applied methods regarding antioxidant activity, the highest potential of the extract for reducing copper ions was the most pronounced (1506.93 μM TE/g DWE), and the ability of the extract to reduce iron ions was almost the same (1354.05 μM TE/g DWE). In the experimental indomethacin-induced gastric ulcer rat model, EPE (25 mg/kg and 10 mg/kg) demonstrated a dose-dependent gastroprotective effect. Conclusions: The results of the experiments confirm the potential of the wood fungus species as a source of valuable biologically active compounds with beneficial and pharmacological effects. However, further studies are needed to fully determine its chemical composition and the biological activities related to it. Full article

Voltage-gated Na⁺ channels (Nav) are the molecular determinants of action potential initiation and propagation. Among the nine voltage-gated Na⁺ channel isoforms (Nav1.1–Nav1.9), Nav1.2 and Nav1.6 are of particular interest because of their developmental expression profile throughout the central nervous system (CNS) and their association with channelopathies. Although the α-subunit coded by each of the nine isoforms can sufficiently confer transient Na⁺ currents (I_Na), in vivo these channels are modulated by auxiliary proteins like intracellular fibroblast growth factor (iFGFs) through protein–protein interaction (PPI), and probes developed from iFGF/Nav PPI complexes have been shown to precisely modulate Nav channels. Previous studies identified ZL0177, a peptidomimetic derived from a short peptide sequence at the FGF14/Nav1.6 PPI interface, as a functional modulator of Nav1.6-mediated I_Na⁺. However, the isoform specificity, binding sites, and putative physiological impact of ZL0177 on neuronal excitability remain unexplored. Here, we used automated planar patch-clamp electrophysiology to assess ZL0177’s functional activity in cells stably expressing Nav1.2 or Nav1.6. While ZL0177 was found to suppress I_Na in both Nav1.2- and Nav1.6-expressing cells, ZL0177 elicited functionally divergent effects on channel kinetics that were isoform-specific and supported by differential docking of the compound to AlphaFold structures of the two channel isoforms. Computational modeling predicts that ZL0177 modulates Nav1.2 and Nav1.6 in an isoform-specific manner, eliciting phenotypically divergent effects on action potential discharge. Taken together, these results highlight the potential of PPI derivatives for isoform-specific regulation of Nav channels and the development of therapeutics for channelopathies. Full article

Polygonum multiflorum (PM) residues represent an underutilized biomass resource, with pyrolysis offering a promising route for valorizing its biomass into valuable chemicals and biochar. This study elucidated how the intrinsic physicochemical properties of PM residue governed its pyrolysis kinetics, thermodynamics, mechanisms, and product distribution across varying thermal regimes (slow pyrolysis at 20 °C/min vs. fast pyrolysis). The primary devolatilization stage (174–680 °C) dominated the pyrolysis process. Applying three model-free kinetic approaches (FWO, KAS, Starink) over 0.1 < α < 0.7, this study observed a dramatic shift in apparent activation energy (219.7–354.7 kJ/mol). Major gaseous pyrolysis products identified included alcohols, aldehydes, ketones, acids, aromatic hydrocarbons, phenolics, CO, and CO₂. Ketones constituted the predominant fraction (23.80%), followed by acids (18.18%), phenolic derivatives (18.18%), N-containing compounds (14.28%), and furans (4.54%). The findings of this study contribute significant theoretical understanding and practical solutions for the effective pyrolysis and resource recovery from Polygonum multiflorum processing byproducts. Full article