Comprehensive studies of plasma pharmacokinetic and bone tissue distribution in rats to elucidate pharmacodynamic material basis of Psoraleae Fructus treating osteoporosis.

Broad-spectrum inhibitor of non-structural protein 2 protease shows therapeutic efficacy against Venezuelan equine encephalitis viral infection.

Surface modification of PET Fiber: Evaluation of the synergistic effect of a thermostable engineered cutinase with DBD plasma pretreatment.

Discovery and optimization of Menin-MLL inhibitors targeting acute myeloid leukemia.

Integrating renal transporter biomarkers into drug development: Discovery, clinical assessment, and precision medicine.

Plasma-facing components of future fusion systems will be expected to withstand years of operations in an extremely harsh environment. Long-term exposure to this environment will alter the material properties and therefore performance of the components. Using an integrated plasma-material interaction model that includes descriptions of the edge plasma, ion-surface interactions, and subsurface gas dynamics, we assess the evolution of 10 distinct spatial locations across the tungsten outer divertor target of the current ARC design during 10 pulses of deuterium-tritium (D-T) plasma exposure, for a total exposure time of 150 min, as well as a longer exposure of 4+ h. Our simulations show no erosion due to the extremely low ion energies in the detached plasma conditions, even with neon seeding of the plasma. The lowimpact energies also lead to a constant reflection coefficient, and therefore, the D-T content accumulation is primarily driven by particle flux, as more D-T is implanted. The content increases with each pulse. Gas diffusion is not affected by changes in substrate temperature that are caused by heat fluxes. When these simulations continue beyond the 10 initial pulses until D-T reaches the bulk boundary, the gases permeate through the backside of the W substrate at the same rate as they are implanted. Thus, the gas content accumulated in the material saturates, and the depth-resolved concentrations remain constant, at least within the ideal microstructure assumptions for the tungsten divertor. These results provide input for modeling the crystal plasticity evolution of the tungsten and the polycrystal evolution and grain growth dynamics under in-service conditions, from which critical stresses, temperatures, and doses can be extracted for use in device design optimization.

Serum neurofilament light chain (sNfL), a biomarker of axonal damage, has shown promise in clinical studies for monitoring paclitaxel-induced peripheral neurotoxicity (PIPN). The latter involves pathological changes in PIPN sites such as the dorsal root ganglia, peripheral nerves, and brain. However, the mechanistic link between paclitaxel and NfL concentrations in these tissues remains poorly understood, necessitating preclinical investigation. We developed a semi-mechanistic pharmacokinetic-pharmacodynamic model to characterize: (i) total and unbound paclitaxel concentrations in plasma, as well as in extracellular and intracellular compartments of PIPN sites; (ii) paclitaxel-tubulin complex formation; and (iii) NfL kinetics. The model was built using de novo-generated and previously reported data from rodents. Plasma pharmacokinetics of paclitaxel was captured using a two-compartment model, including Cremophor EL trapping and nonlinear tissue distribution. Paclitaxel pharmacokinetics in PIPN sites incorporated paclitaxel transport across the blood-to-PIPN sites barriers and paclitaxel-tubulin binding, described by capacity-limited kinetics with increased tubulin binding upon repeated plasma exposure. NfL kinetics in serum and cerebrospinal fluid were described using turnover models, with NfL leakage driven by paclitaxel-tubulin complex formation in PIPN sites. The model robustly predicted paclitaxel exposure across multiple doses and studies. While NfL predictions aligned with single-dose data, the model slightly underpredicted sNfL levels in an external validation dataset after repeated dosing of paclitaxel at 15mg/kg, suggesting additional mechanisms may be involved. Overall, the model successfully described the relationship between paclitaxel exposure and sNfL kinetics, offering a model-based framework for translational studies.

Non-thermal plasma (NTP) generates a complex mixture of reactive oxygen and nitrogen species (RONS) that can impose strong oxidative stress on eukaryotic cells. While the antimicrobial potential of NTP has been widely explored, much less is known about how eukaryotic cells respond to prolonged NTP-induced stress at the cellular and molecular level. Here, we investigated the cellular effects of extended NTP exposure using the fission yeast Schizosaccharomyces pombe as a non-pathogenic eukaryotic model. Our results indicate that extended exposure to NTP significantly reduces cell viability and is associated with increased oxidative stress, as evidenced by increased levels of intracellular RONS and mitochondrial superoxide. These oxidative changes were accompanied by pronounced cellular responses including tubulin depolymerisation, cell cycle arrest, and impaired cell division. In contrast, no significant changes were detected in the expression of genes involved in oxidative stress response and DNA repair. The observed effects are based on cellular, phenotypic, and transcriptomic analyses, while direct identification of oxidatively modified proteins remains to be addressed in future studies. KEY POINTS: • NTP increases intracellular RONS and mitochondrial superoxide levels • NTP causes tubulin depolymerisation, which is associated with cell cycle arrest • NTP alters the expression of genes involved in post-transcriptional regulation.

When water drops slide over a flat hydrophobic solid surface, negativecharges are spontaneously deposited at the rear of the drop, and the drops gain a positive charge. This phenomenon is known as slide electrification. Here, we demonstrate an alternative mechanism of spontaneous charge separation in sliding drops. Therefore, arrays of Janus micropillars were fabricated by photolithography. Each micropillar has a hydrophilic top created by reactive ion etching (RIE) and aminopropyltriethoxysilane (APTES) deposition, while the walls and substrate were hydrophobized by 1H,1H,2H,2H-perfluorooctyltrichlorosilane (PFOTS). Drops on these arrays show high apparent contact angles, remain in the Cassie state, and still contact the hydrophilic top faces. Sliding drops acquire charge, with polarity and magnitude governed by top-surface chemistry, including NH3 +/NH4 + formation and PFOTS removal after the RIE plasma exposure, and dense NH2 groups formation from thermally activated APTES vapor deposition. Unlike flat surfaces, high-speed reflection microscopy reveals tiny satellite droplets left on each pillar that evaporate within one second. Consequently, charge separation occurs within the liquid phase between the primary drop and deposited satellites, rather than directly at the contact line.

Abstract This study investigates the effects of non-thermal plasma exposure on the viability, stemness, paracrine expression, differentiation, and migration of rat adipose-derived stem cells (rADSCs). A self-fabricated plasma pad is employed to treat rADSCs under various conditions, including different exposure durations, electrode gaps, and treatment intervals. The results show that direct plasma treatment of adherent rADSCs enhances cell viability, with optimal proliferation observed after short-duration exposure (1 minute). In contrast, prolonged exposure or treatment of suspended cells significantly reduces viability. Repeated plasma treatments provide only limited benefits, while increasing the electrode distance diminishes the plasma effect. Surface marker analysis confirms that plasma-treated rADSCs retain mesenchymal stem cell characteristics, including sustained expression of CD29 and CD90 and absence of CD45. Gene expression analysis further indicates that plasma stimulation activates intracellular signaling pathways associated with proliferation. Moreover, plasma exposure does not impair the adipogenic differentiation potential or migration capacity of rADSCs. In summary, these findings demonstrate that carefully controlled plasma exposure can stimulate rADSC proliferation without compromising stem cell identity or function, thereby supporting its potential application in stem cell-based regenerative therapies.

Abstract Daraxonrasib (RMC-6236) is an innovative, first-in-class oral pan-RAS inhibitor leveraging a unique molecular glue mechanism to target all forms of RAS proteins. It is currently in phase III clinical trials and aims to treat solid tumors harboring RAS mutations, including NSCLC, PDAC and CRC. KRAS-mutant NSCLC develops brain metastases in 30% of patients. Effective therapies are urgently needed and the blood-brain barrier (BBB) poses an additional therapeutic hurdle. Pharmacokinetic studies of anticancer drugs serve as a foundation for designing effective dosing regimens, optimizing the formulation of a drug, assessing the bioavailability, identifying potential safety concerns and anticipating clinical drug–drug interactions of new therapies. Here, We assessed how drug efflux transporters expressed at the BBB (ABCB1, ABCG2), drug-metabolizing enzymes (CYP3A, CES1, CES2), and drug uptake transporters (OATP1A/1B) affect the plasma exposure and organ disposition of oral daraxonrasib in mice. In vitro, human ABCB1 transported daraxonrasib. The pharmacokinetics of orally administered daraxonrasib were studied in transporter- and enzyme-deficient mice, and in CYP3A4-humanized mice. Compared to wild-type controls, Abcb1a/b- and Oatp1a/1b-deficient mice had significantly increased plasma exposure of daraxonrasib, suggesting that these proteins transport daraxonrasib in vivo. Observed Abcb1a/b-mediated transport of daraxonrasib across the BBB was validated by oral co-administration of the ABCB1/ABCG2 inhibitor elacridar, resulting in 20-fold increased brain penetration in wild-type mice. In CYP3A4-humanized Cyp3a -/- mice, the plasma exposure of daraxonrasib was significantly (>3-fold) reduced. Hepatic metabolism was mildly reduced in Ces1-deficient mice, whereas Ces2 knockout mice showed unchanged daraxonrasib pharmacokinetics. Thus, daraxonrasib is a well-transported substrate of human ABCB1 in vitro and mouse Abcb1a in vivo, with pronounced effects on reducing plasma exposure and brain penetration of daraxonrasib. These phenomena might limit the efficacy of daraxonrasib against brain metastases. Elacridar co-administration represents a potential pharmacokinetic boosting strategy to target brain metastases during daraxonrasib treatment. Furthermore, Oatp1a/1b proteins appear to mediate hepatic uptake and clearance of daraxonrasib, and possibly the intestinal uptake is also facilitated. Finally, daraxonrasib clearance appears to be substantially mediated by human CYP3A4. Both the latter findings suggest that plasma levels of this oral drug could be sensitive to genetic polymorphisms and/or drug-drug or drug-food interactions affecting OATP and CYP3A activity. These findings may provide a mechanistic basis for optimizing daraxonrasib combination and boosting strategies in clinical settings. Citation Format: Davinia Arguedas, Viët Bui, Tjon Law, Jamie Rijmers, Renaud Tissier, M. Cristina Lebre, Jos H. Beijnen, Alfred H. Schinkel. Pharmacokinetics of daraxonrasib (RMC-6236): transporter and enzyme impact on a first-in-class pan-RAS molecular glue [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: RAS Oncogenesis and Therapeutics; 2026 Mar 5-8; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(5_Suppl_1):Abstract nr B008.

We investigated the effects of atmospheric-pressure plasma treatment on the growth of Saccharomyces cerevisiae by directly comparing plasma exposure and plasma-activated medium (PAM) under strictly identical discharge conditions. An atmospheric-pressure plasma jet operated with argon (Ar) or nitrogen (N2) was used. Yeast growth was analyzed using a phase-resolved kinetic framework that separately evaluated early growth behavior and exponential growth rate based on optical density measurements. Growth curves were normalized to same-day untreated controls to minimize day-to-day variability. Under N2 plasma conditions, both direct exposure and PAM treatment resulted in limited changes in growth kinetics (μrel = 0.67–0.97; trel ≈ 1.02–1.09). In contrast, Ar plasma treatment produced clear mode-dependent effects. Direct exposure delayed growth initiation (trel = 1.00–1.40) with a moderate reduction in μrel (0.63–0.84). PAM treatment strongly suppressed μrel (0.19–0.50), whereas trel varied across conditions without systematic prolongation (0.59–1.09). These findings demonstrate that treatment mode strongly influences which growth phase is predominantly affected, highlighting the importance of phase-resolved kinetic analysis for distinguishing plasma-induced biological effects beyond conventional endpoint measurements.

Calcitriol-mediated modulation of organic anion transporters: Insights from endogenous biomarkers and methotrexate pharmacokinetics.

Modification of chemical and mechanical properties of p-W-O coating after Magnum-PSI D2-N2 plasma exposure and its consequences for the analysis of LIBS spectra

Halogen-methyl hybridization unlocks orally bioavailable STING agonist for tumor immunotherapy.

Atmospheric cold plasma-induced secondary structure modifications of shrimp allergen arginine kinase.

Integrated pharmacokinetic properties, tissue distribution and metabolism of multiple active constituents in DBD for the treatment of GEM-induced myelosuppression.

Calycosin is an active compound of Danggui Buxue Decoction (DBD) with various pharmacological effects including anti-inflammatory and immunomodulatory activities. However, it remains unclear whether long-term administration and the multi component of DBD influence the disposition of calycosin. This study aimed to investigate the absorption, distribution, and metabolism of calycosin following long-term oral administration of DBD. SD rats were divided into six groups. Plasma was collected at 0.083-24 h after the last administration and separated for the determination of calycosin. For the tissue distribution study, rats were sacrificed 1 h after the last dose and tissues were collected. The concentrations of analytes were determined after sample preparation. Plasma collected within 1 h was used for metabolite identification of calycosin. Pharmacokinetic results indicated that the SH group exhibited the highest plasma exposure of calycosin. Calycosin accumulation was detected in the liver of six groups with levels ranking as MH > SH > ML > SL > MD > SD group. Metabolism studies revealed that the MD group had the highest number of calycosin metabolites. Both long-term administration and the complex composition influence the absorption, distribution, and metabolism of calycosin in rats after oral administration of DBD. Therefore, this study provides a theoretical basis for the rational clinical use of DBD and calycosin.

Evaluation of Drug-Drug Interaction Potential Between the Oral Antibiotic Zoliflodacin and the CYP3A4 Inhibitor Itraconazole: A Phase 1 Study in Healthy Participants.

Corona discharge plasma (CDP) is widely used for surface modification and sterilization; however, real-time, low-cost monitoring of plasma–gas interactions remains challenging. This study proposes an ultrasonic sensing approach to detect plasma-induced changes in gas acoustic properties inside a closed chamber. An Arduino Uno integrated with an HC-SR04 ultrasonic sensor was used to measure ultrasonic time-of-flight under controlled environmental conditions (28.3 °C, 59% relative humidity) before and during CDP operation. The apparent ultrasonic distance decreased from 12.08 ± 0.12 cm in ambient air to 11.13 ± 0.24 cm during plasma exposure, indicating altered sound propagation. Using standard gas-acoustic theory, this change was interpreted in terms of an effective acoustic molar mass (34.16 g/mol), reflecting plasma-induced modification of the gas medium rather than direct chemical composition. A simplified acoustic model suggests that heavier plasma-generated species, such as ozone and nitrogen oxides, play a qualitative role, while acknowledging that precise concentrations cannot be determined without independent diagnostics. The findings demonstrate an inexpensive approach by using ultrasonic sensing to monitor plasma-gas interactions. This work presents a novel, cost-effective method for monitoring plasma-induced reactive species using ultrasonic measurements and linking them to antibacterial effects in nonwoven textiles.