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What Is Known and Objective. Pyrotinib maleate, also known as pyrotinib, is an irreversible dual receptor tyrosine kinase inhibitor that primarily targets the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2). Cytochrome P450 3A4 (CYP3A4) enzyme mainly catalyzes pyrotinib, and its metabolism is influenced apparently by CYP3A4 strong inhibitor, but the effect of CYP3A4 moderate inhibitor is still unclear as a moderate inhibitor of CYP3A4 enzyme. This study evaluated the effect of fluconazole, a widespread antifungal medication, on the pharmacokinetics and safety tolerance of pyrotinib. Methods. This study was an open, single-dose, and self-controlled clinical trial. Eighteen healthy Chinese participants were enrolled in this study. All participants were administered fluconazole on days 6–18 and pyrotinib on days 1 and 9. The maximum plasma concentration (Cmax), time to Cmax (Tmax), area under the concentration–time curve from time 0 to the last measurable concentration (AUC0−t), area under the concentration–time curve from time 0 extrapolated to infinity (AUC0−∞), terminal elimination half-life (t1/2), apparent volume of distribution (Vz/F), and apparent clearance (CL/F) were calculated using WinNonlin software (version 8.1). Safety tolerance was assessed throughout the process. Results and Discussion. Compared with the single administration of pyrotinib, the exposure level was enhanced significantly after the coadministration of pyrotinib and fluconazole. The geometric mean ratios (pyrotinib + fluconazole/pyrotinib alone) of Cmax, AUC0−t, and AUC0−∞ were 2.16, 3.6, and 3.5, respectively. The parameter of t1/2 is 14.16 h and 24.03 h, and CL/F is 275.06 L/h and 78.42 L/h, for pyrotinib alone and with fluconazole. No serious adverse events were reported in this trial, and no participant withdrew from the trial because of adverse events. What Is New and Conclusion. The PK profile of pyrotinib, a CYP3A4 substrate, was significantly influenced by fluconazole, with increased exposure levels and prolonged t1/2. Dosage adjustment is suggested for the clinical application of pyrotinib when coadministered with fluconazole or other CYP3A4 inhibitors/inducers.

Supplementary Material 1

International audience; In this work, the relationship between the water flux through nanoporous two-dimensional hexagonal Boron Nitride (h-BN) and surface tension was investigated from equilibrium and pressure-driven molecular dynamics simulations by considering the most popular rigid water models. From the surface tension calculation, the contact angle was evaluated and compared with the experiment. We exhibit a correlation between the water flux through nanoporous h-BN predicted by the various water models and the surface tension as a result of the difference in the interfacial energy.

The separation of hydrocarbons by adsorption inside MOFs assisted by mechanical pressure was investigated employing molecular modelling. We focused on MIL-140B and ZIF-8 where explored several microscopical mechanisms of separation. We used a simulation technique called Hybrid Osmotic Monte Carlo simulation to modulate the gas pressure and mechanical pressure induced structure flexibility at the same time. With the use of external mechanical pressure, we were able to boost the selectivity for hexane isomers in MIL-140B by 80% and the linear hexane / mono-branched hexane isomer combination in ZIF-8 by 40%. We also investigated at the slow dynamics of butane/butene hydrocarbons inside the ZIF-8, wherein the simulation helped us to understand at an atomic level. Our results deliver a novel concept of adsorption/separation processes of MOFs., La séparation des hydrocarbures par adsorption utilisant les MOFs assistée par pression mécanique a été étudiée en utilisant la simulation moléculaire. Nous nous sommes concentrés sur MIL-140B et ZIF-8 où ont exploré plusieurs mécanismes microscopiques de séparation. Nous avons utilisé une technique de simulation intitulé Hybrid Osmotic Monte Carlo pour moduler la pression du gaz et la flexibilité de la structure induite par la pression mécanique externe en même temps. Avec l’application de la pression mécanique externe, nous avons pu augmenter de 80 % la sélectivité pour les isomères de l'hexane dans le MIL-140B et de 40 % pour le mélange binaire d’hexane linéaire / monobranché dans le ZIF-8. Nous avons également étudié la diffusion lente des hydrocarbures butane/butène dans ZIF-8, où la simulation dynamique moléculaire nous a aidés à avoir une vision de l’échelle atomistique. Nos résultats fournissent un nouveau concept de processus d'adsorption/séparation des MOF.

In this work, HfO2 thin films were deposited on Si (100) wafer by using reactive atomic layer deposition at different temperatures. By characterizing the Raman spectroscopy and XRD patterns, we find that with the substrate temperature increases, the structure of the film transforms continuously, and a substrate with sufficiently high temperature can generate enough energy to produce a film in the crystalline phase. UV–vis absorption spectrum shows that the anti-reflection effect of the deposited HfO2 thin films is effective. The characteristic reflective peak of the film exhibits a slightly blue shift with increasing the substrate temperature, indicating that the thickness of the film decreases as the substrate temperature increases. The refractive index of the visible to near infrared spectral range increases with the increase of temperature, and the film becomes more compact. The surface morphology of HfO2 films was measured by AFM, and the skewness, kurtosis and roughness of the films were also analysed. Increasing substrate temperature has led to improvement in the film uniformity and compactness. The above results indicate that the substrate temperature is a critical parameter in determining the film structure, morphology and optical properties.

supervisor Aziz Ghoufi (department of materials - nanosciences) and Guillaume Maurin (Montpellier), sous la direction de Aziz Ghoufi dans le département Matériaux-Nanosciences et Guillaume Maurin (Montpellier)

Localized magnetic fields (MFs) could easily penetrate the scalp, skull, and meninges, thus inducing an electrical current in both the central and peripheral nervous systems, which is primarily used in transcranial magnetic stimulation (TMS) for inducing specific effects on different regions or cells that play roles in various brain activities. Studies of repetitive transcranial magnetic stimulation (rTMS) have led to novel attractive therapeutic approaches. Neural stem cells (NSCs) in adult human brain are able to self-renew and possess multidifferential ability to maintain homeostasis and repair damage after acute central nervous system. In the present review, we summarized the electrical activity of NSCs and the fundamental mechanism of electromagnetic fields and their effects on regulating NSC proliferation, differentiation, migration, and maturation. Although it was authorized for the rTMS use in resistant depression patients by US FDA, there are still unveiling mechanism and limitations for rTMS in clinical applications of acute central nervous system injury, especially on NSC regulation as a rehabilitation strategy. More in-depth studies should be performed to provide detailed parameters and mechanisms of rTMS in further studies, making it a powerful tool to treat people who are surviving with acute central nervous system injuries.