Structure-based design and synthesis of novel highly potent and selective KRASG12C inhibitors.

Synthesis and biological evaluations of novel 18β-glycyrrhetinic acid derivatives as histone deacetylase 3 degraders with anti-inflammatory effects.

Mangrove-derived dissolved organic carbon and allochthonous refractory subsidies via submarine groundwater discharge at regional and global scales.

PEI-capped osmium nanoclusters (Os NCs) for dual-mode fluorescence and electrochemical detection of cyanide: A robust platform for environmental sensing.

Farnesyltransferase plays a critical role in the post-translational modification of mammalian proteins, including the Ras oncogene, which is strongly associated with cancer development. Essential oils from Syzygium cumini have demonstrated promising therapeutic effects, particularly in cancer treatment, potentially through the inhibition of farnesyltransferase activity. This study employed integrative computational approaches to investigate the anticancer potential of essential oils derived from S. cumini. Various compounds were screened for toxicity, biological activities, membrane permeability, gene expression profiles, and survival correlations were conducted to investigate cancer-associated properties. Molecular docking and molecular dynamics (MD) simulations were performed to evaluate the binding interactions and stability of ligand-protein complexes involving farnesyltransferase. α-Humulene epoxide II exhibited antineoplastic activity, functioned as an apoptosis agonist, and inhibited cancer-related targets such as HIF1A and MMP9. Bornyl acetate showed potential as a JAK2 inhibitor. Both compounds demonstrated favorable membrane permeability, indicating high bioavailability and effective cellular uptake. Analysis of the farnesyltransferase (FNTB) gene revealed significantly higher expression in cancerous tissues and a positive correlation with pro-tumor immune cell infiltration. Molecular docking identified Tipifarnib as the strongest binder, serving as a positive control, while α-humulene epoxide II and bornyl acetate showed moderate to weaker binding affinities. However, MD simulations confirmed that both essential oil compounds exhibit binding stability comparable to that of Tipifarnib. Finally, α-humulene epoxide II and bornyl acetate from S. cumini exhibit favorable drug-like properties, high predicted safety margins, and a lack of organ-specific toxicity, underscoring their suitability for further drug development.

The role of GPER-mediated AMPKα signal in the prevention effect of (-)-epicatechin on metabolic dysfunction-associated steatohepatitis.

Polyphenol-modified ovalbumin-lysozyme heteroprotein microcapsules: A complex coacervation approach for enhancing probiotic viability.

Interactions of microplastics, dissolved organic matter, and coexisting pollutants: Mechanisms, environmental implications, and knowledge gaps.

Discovery of highly selective and potent HPK1 inhibitors for cancer immunotherapy.

Photodegradation of PET plastics produces persistent compounds that accumulate in sediments.

A review of Allii macrostemonis Bulbus polysaccharides: Extraction, purification, structural characterization, and biological activity.

From roads to water organisms? - Sequential extraction indicates high bioavailability of Cd, Zn and Pb from tire and road wear particles from a highway tunnel and go-kart tracks.

Nano-selenium alleviates cadmium-induced ferroptosis in chicken liver by modulating the TRPM2 channel.

Integrated multi-omics unravels solanesol's multi-organ protection mechanisms against insulin resistance in type 2 diabetic mice.

Doxycycline (DC), a second-generation tetracycline antibiotic, is extensively used in human and veterinary medicine for its broad-spectrum activity, favorable pharmacokinetics, and high bioavailability. This review focuses on analytical methods for detecting and quantifying DC and its metabolites in pharmaceutical, biological, and environmental samples. Spectroscopic, chromatographic, and electroanalytical techniques have been explored, with high-performance liquid chromatography (HPLC) emerging as the most reliable due to its high sensitivity, selectivity, and reproducibility, particularly when coupled with fluorescence or mass spectrometric detectors. Although spectroscopic approaches are simple and economical, they often suffer from matrix interferences. Electroanalytical and voltammetric methods, by contrast, offer rapid and cost-effective alternatives suitable for field applications. Major analytical challenges include DC instability, complex sample matrices, and intricate preparation steps affecting quantification accuracy. Future research should focus on green, miniaturized, and automated analytical platforms that integrate nanomaterials, advanced separation techniques, and artificial intelligence to achieve rapid, accurate, and sustainable monitoring of DC and its metabolites in clinical and environmental settings.

This study investigates the adsorption/desorption behaviour of the widely used fungicide cymoxanil in twelve acidic agricultural soils, providing the first comprehensive assessment of its retention dynamics. Cymoxanil exhibited low adsorption, with Kd(ads) values ranging from 0.57 to 4.40 L kg−1 and adsorption percentages between 18.7 and 65.9% at the highest tested concentration, suggesting high mobility and bioavailability in soils and, consequently, a potential environmental and human health risk. Hysteresis was observed, with desorption percentages for the highest initial concentration ranging from 2.4% to 32.6%, indicating that part of the adsorbed compound remained relatively strongly retained. Adsorption was positively correlated with desorption parameters, reflecting a statistical association whereby soils with higher adsorption tended to exhibit lower desorption. Among soil physicochemical properties, pH appeared to play a key role in controlling cymoxanil retention, as higher pH was associated with greater adsorption and lower desorption in the studied soils. Organic matter, clay content, and exchangeable base cations also appeared to influence cymoxanil behaviour, although to a lesser extent than pH. In this regard, soils richer in organic matter and clay, and with higher effective cation exchange capacity (eCEC), tended to display greater retention. Overall, cymoxanil adsorption appears to be largely governed by physisorption mechanisms—electrostatic interactions, cation exchange, and hydrophobic partitioning—while the observed hysteresis suggests that specific interactions, such as hydrogen bonding and π-π interactions, may also contribute to retention without implying irreversible chemisorption.

Cannabidiol (CBD) is a non-psychoactive phyto-cannabinoid with numerous pharmacological potentials. CBD is a lipophilic drug with poor and varied bioavailability due to its low water solubility and extensive first-pass metabolism, and it is highly affected by the presence of food. A self-emulsifying drug delivery system (SEDDS) was developed to improve the aqueous solubility and oral bioavailability of CBD. The formulation strategy involved incorporating excipients that maintain drug solubility under both fasted and fed conditions, while potentially mitigating first-pass metabolism to enhance overall bioavailability and dose proportionality. Caproyl® 90, Tween® 20, and Transcutol® HP were selected as the oil phase, surfactant, and cosolvent, respectively, for formulation preparation and screening. CBD SEDDS formulations containing Caproyl® 90 ≤20% w/w and Tween® 20 above 40% w/w yield particles below 200 nm. CBD SEDDS with Tween® 20 65% w/w or higher showed in vitro release of more than 90%. After in vitro digestion, CTT1, CTT4, and CTT8 remained stable under gastrointestinal conditions and maintained CBD solubility of at least 50%. The most promising formulations, CTT4 and CTT8, were used for in vivo evaluations. Both formulations showed similar in vitro results; however, in vivo, CTT4 demonstrated 2.4-fold higher bioavailability than CTT8. Overall, optimizing the level of inhibitory surfactant appears to be a promising strategy for improving CBD bioavailability.

Sarcopenia is a global problem. It reduces a large number of people’s quality of life and health status, especially for the elderly. Protein is the core nutrient in muscles, and people need to eat enough protein, which helps keep muscle synthesis going. So sufficient protein intake plays an important role in preventing sarcopenia. Plantbased meat is a protein source and has many advantages. For example, it’s sustainable, thus helping reduce environmental pollution; it has high nutritional value with abundant protein and essential amino acids. It also has advantages like low fat content and no cholesterol. This makes it particularly suitable for older adults, who need a low-fat and low-cholesterol diet. The purpose of this study is to explore the application in sarcopenia with higher bioavailability. Through high-moisture extrusion, fermentation and sprouting methods, the impact of anti-nutritional factors can be reduced, and the soluble protein content can be increased, so the plant protein bioavailability will increase. And the review also discusses the mechanisms of plant-based meat in preventing sarcopenia. In view of the current preventing situation, this review sums up the advantages of plant-based meat, such as nutritional adaptability and various age-related diseases. There are also some challenges in taste improvement, consumer acceptance, production technology and marketing strategy. With the ongoing trend of population aging, the future development direction is also discussed. Plant-based meat offers theoretical frameworks to leverage it in enhancing elderly health, mitigating sarcopenia, ultimately enhancing their quality of life.

INTRODUCTION . Despite the decreasing acute hepatitis B (HBV) incidence due to active vaccine prophylaxis, HBV-specific post-exposure prophylaxis is still a relevant problem for both global and Russian healthcare. Advanced post-exposure prophylaxis, particularly intravenous specific immunoglobulin with its higher bioavailability and fast formation of protective titre, will better protect high-risk groups. Preparations of hepatitis B human immunoglobulins available in Russia are Antigep (Russia) for intravenous administration and Neohepatect (Germany). Enhancing vaccine prophylaxis of hepatitis B and import substitution requires development studies of the first hepatitis B immunoglobulin for intravenous administration produced in Russia. AIM . This study aimed to develop Russian human HBV immunoglobulin for intravenous administration and perform quality control, safety and pharmacokinetics study. MATERIALS AND METHODS . Human HBV immunoglobulin (Antigep-Neo) was obtained from the blood plasma of donors with high anti-HBV levels. Antigep-Neo was evaluated according to physico-chemical, biological, and molecular parameters, immunoglobulin A level, activity of the Fc function, and thrombogenic potential. Pharmacokinetic properties were studied in preclinical (rabbit) and clinical (healthy volunteers) studies. Neohepatect and Antigep immuno­globulin preparations were used as comparator drugs. RESULTS . Production of human antiglobulin is based on the standard Cohn fractionation followed by chromatographic purification and three virus removal and inactivation steps. Antihep-Neo is safe, it contains more than 95% of the human IgG, of them more than 99% are monomers and dimers. The product showed low anticomplementary activity (0.17±0.06 CH 50 /mg IgG) and low concentration of prekallikrein activator (7.45±2.11 IU/mL) and had no thrombogenic potential. Bioequivalence of Antigep-Neo and Neohepatect was confirmed in preclinical and clinical trials (differences in the pharmacokinetic profiles were not statistically significant). CONCLUSIONS . The developed human HBV immunoglobulin (Antigep-Neo) meets quality and safety regulatory requirements. Preclinical and clinical studies have confirmed similar pharmacokinetic profile of Antigep-Neo and Neohepatect (comparator).

A medicated lollipop is a kind of sugary treat that is typically made of hard candy and placed on a stick so that it may be licked or sucked on. There are many flavors and styles of lollipops available. Alternative names include sticky-pop, Lolly and sucker. There are various dosage forms available on the market; nevertheless, an additional dosage form that functions both locally and systematically may be required. The benefits of current research include longer dosage form retention in the oral hollow space, higher bioavailability, and a decrease in gastric inflammation through first metabolism. Lollipops are medicinal dose forms with flavors that are meant to be sucked and kept in the mouth or throat. The sweetened foundation of the lollipops typically contains one or more medications. The customary dosage for medications, tablets, and syrups.