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Tyrosine kinase inhibitors (TKIs) have emerged as the first-line small molecule drugs in many cancer therapies, exerting their effects by impeding aberrant cell growth and proliferation through the modulation of tyrosine kinase-mediated signaling pathways. However, there exists a substantial inter-individual variability in the concentrations of certain TKIs and their metabolites, which may render patients with compromised immune function susceptible to diverse infections despite receiving theoretically efficacious anticancer treatments, alongside other potential side effects or adverse reactions. Therefore, an urgent need exists for an up-to-date review concerning the biological matrices relevant to bioanalysis and the sampling methods, clinical pharmacokinetics, and therapeutic drug monitoring of different TKIs. This paper provides a comprehensive overview of the advancements in pretreatment methods, such as protein precipitation (PPT), liquid-liquid extraction (LLE), solid-phase extraction (SPE), micro-SPE (μ-SPE), magnetic SPE (MSPE), and vortex-assisted dispersive SPE (VA-DSPE) achieved since 2017. It also highlights the latest analysis techniques such as newly developed high performance liquid chromatography (HPLC) and high-resolution mass spectrometry (HRMS) methods, capillary electrophoresis (CE), gas chromatography (GC), supercritical fluid chromatography (SFC) procedures, surface plasmon resonance (SPR) assays as well as novel nanoprobes-based biosensing techniques. In addition, a comparison is made between the advantages and disadvantages of different approaches while presenting critical challenges and prospects in pharmacokinetic studies and therapeutic drug monitoring.

Benzodiazepines (BDZs) are used in clinics for anxiolysis, anticonvulsants, sedative hypnosis, and muscle relaxation. They have high consumptions worldwide because of their easy availability and potential addiction. They are often used for suicide or criminal practices such as abduction and drug-facilitated sexual assault. The pharmacological effects of using small doses of BDZs and their detections from complex biological matrices are challenging. Efficient pretreatment methods followed by accurate and sensitive detections are necessary. Herein, pretreatment methods for the extraction, enrichment, and preconcentration of BDZs as well as the strategies for their screening, identification, and quantitation developed in the past five years have been reviewed. Moreover, recent advances in various methods are summarized. Characteristics and advantages of each method are encompassed. Future directions of the pretreatment and detection methods for BDZs are also reviewed.

The ground motion intensity measure is a key parameter affecting the accuracy of probabilistic seismic demand analysis (PSDA). This paper uses the incremental dynamic analysis (IDA) results of 12 three-dimensional reinforced concrete (RC) high-rise structures to explore the efficiency and sufficiency of a spectral acceleration Sa(T) intensity measure (IM) in a continuous period T (0–8 s). Subsequently, the effects of higher modes and period softening on the results are investigated. Controlling periods – that is, the lower and upper bounds of periods – across the spectrum are also examined in order to propose an optimal IM Sa,GM that considers the effects of higher modes and nonlinear softening on the seismic responses of three-dimensional high-rise buildings. Finally, the proposed optimal IM Sa,GM is compared to the widely used IM of spectral acceleration at the first-mode period Sa(T1) of the structure and the improved IM Sa¯, which considers the first n modes in the field, based on the criteria of efficiency, practicality, sufficiency, proficiency, and scaling robustness. The results indicate that the efficiency and sufficiency of the IM Sa(T) fluctuate with increasing periods T and are affected by higher modes and period softening. Furthermore, the proposed optimal IM Sa,GM exhibits a significant decrease in dispersion with respect to the structural response (efficiency) and scores higher on sufficiency, practicality, proficiency, and effectivity robustness than the IMs Sa(T1) and Sa¯.

Frost damage to concrete can make concrete beams more vulnerable under seismic forces. However, research on the seismic performance of frost-damaged reinforced concrete (RC) beams is still in its infancy. In this paper, the effects of freeze–thaw cycles (FTCs) and concrete strength on the seismic performance of frost-damaged RC beams are studied using an artificial rapid freeze–thaw climate and pseudo–static test in sequence. The seismic resistance of frost-damaged RC beams is assessed in the following respects: general damage behavior and failure pattern, hysteresis response, displacement, strength, cumulative energy consumption, and shear component. It turns out that, with the increase in the number of FTCs (NFTCs), the load and displacement under different characteristic states, ductility ratio, and cumulative energy consumption decrease stage by stage, while the shear distortion and the contribution of shear displacement under the entire cyclic loading process are progressively enhanced. Simultaneously, the strength of the cracking point is more susceptible to FTC action than to yield and peak points, and the declining rate of strength under different characteristic points gradually increases. Based on the test results, a calculation formula for the skeleton curve of frost-damaged RC beam–column is established, taking the influences of the pristine concrete strength, NFTCs, and axial force ratio into account.

Endothelial-to-mesenchymal transition (EndMT), the process by which an endothelial cell (EC) undergoes a series of molecular events that result in a mesenchymal cell phenotype, plays an important role in atherosclerosis. 1-Palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC), derived from the oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphatidylcholine, is a proinflammatory lipid found in atherosclerotic lesions. Whether POVPC promotes EndMT and how simvastatin influences POVPC-mediated EndMT remains unclear. Here, we treated human umbilical vein ECs with POVPC, simvastatin, or both, and determined their effect on EC viability, morphology, tube formation, proliferation, and generation of NO and superoxide anion (O2•−). Expression of specific endothelial and mesenchymal markers was detected by immunofluorescence and immunoblotting. POVPC did not affect EC viability but altered cellular morphology from cobblestone-like ECs to a spindle-like mesenchymal cell morphology. POVPC increased O2− generation and expression of alpha-smooth muscle actin, vimentin, Snail-1, Twist-1, transforming growth factor-beta (TGF-β), TGF-β receptor II, p-Smad2/3, and Smad2/3. POVPC also decreased NO production and expression of CD31 and endothelial NO synthase. Simvastatin inhibited POVPC-mediated effects on cellular morphology, production of O2•− and NO, and expression of specific endothelial and mesenchymal markers. These data demonstrate that POVPC induces EndMT by increasing oxidative stress, which stimulates TGF-β/Smad signaling, leading to Snail-1 and Twist-1 activation. Simvastatin inhibited POVPC-induced EndMT by decreasing oxidative stress, suppressing TGF-β/Smad signaling, and inactivating Snail-1 and Twist-1. Our findings reveal a novel mechanism of atherosclerosis that can be inhibited by simvastatin.

By introducing the orbital angular momentum (OAM) eigenfunctions of the pulsed beam and two-frequency mutual coherence function in oceanic turbulence, we establish the received probability distribution of OAM modes of the ultrashort Laguerre-Gaussian pulsed beam propagating through oceanic turbulence. Our results show that the higher rate of dissipation of kinetic energy per unit mass of fluid, larger inner scale, smaller ratio of temperature and salinity contributions to the refractive index spectrum, or lower dissipation rate of the mean-squared temperature will cause the smaller pulse duration by its full-width half-maximum. The pulse duration has a weak dependence on the OAM quantum number. In addition, the smaller OAM quantum number and the larger transmission distance cause the smaller pulse delay. Our results will be useful for vortex pulsed beam in the optical ocean communication and remote sensing. Keywords: Vortex beams, Pulse, Oceanic turbulence, Orbital angular momentum, Optical communication