Demodulated method of optical fiber stokes temperature sensors

The optical fiber temperature sensoris one of the dis-tributed measurement apparatus applied to the smartstructures of civil and military engineering.In the dis-tributedfiber Ramantemperature sensor ,the anti-Stokesand Stokes scattering radiation is sensi…     

The Biological Fate of Pharmaceutical Excipient β-Cyclodextrin: Pharmacokinetics,Tissue Distribution,Excretion, and Metabolism of β-Cyclodextrin in Rats

β-cyclodextrin has a unique annular hollow ultrastructure that allows encapsulation of various poorly water-soluble drugs in the resulting cavity, thereby increasing drug stability. As a bioactive molecule, the metabolism of β-cyclodextrin is mainly completed by the flora in the colon, which can interact with API. In this study, understanding the in vivo fate of β-cyclodextrin, a LC-MS/MS method was developed to facilitate simultaneous quantitative analysis of pharmaceutical excipient β-cyclodextrin and API dextromethorphan hydrobromide. The established method had been effectively used to study the pharmacokinetics, tissue distribution, excretion, and metabolism of β-cyclodextrin after oral administration in rats. Results showed that β-cyclodextrin was almost wholly removed from rat plasma within 36 h, and high concentrations of β-cyclodextrin distributed hastily to organs with increased blood flow velocities such as the spleen, liver, and kidney after administration. The excretion of intact β-cyclodextrin to urine and feces was lower than the administration dose. It can be speculated that β-cyclodextrin metabolized to maltodextrin, which was further metabolized, absorbed, and eventually discharged in the form of CO₂ and H₂O. Results proved that β-cyclodextrin, with relative low accumulation in the body, had good safety. The results will assist further study of the design and safety evaluation of adjuvant β-cyclodextrin and promote its clinical development.     

Newly Emerging Strategies in Antiviral Drug Discovery: Dedicated to Prof. Dr. Erik De Clercq on Occasion of His 80th Anniversary

Viral infections pose a persistent threat to human health. The relentless epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global health problem, with millions of infections and fatalities so far. Traditional approaches such as random screening and optimization of lead compounds by organic synthesis have become extremely resource- and time-consuming. Various modern innovative methods or integrated paradigms are now being applied to drug discovery for significant resistance in order to simplify the drug process. This review provides an overview of newly emerging antiviral strategies, including proteolysis targeting chimera (PROTAC), ribonuclease targeting chimera (RIBOTAC), targeted covalent inhibitors, topology-matching design and antiviral drug delivery system. This article is dedicated to Prof. Dr. Erik De Clercq, an internationally renowned expert in the antiviral drug research field, on the occasion of his 80th anniversary.     

The System Profile of Renal Drug Transporters in Tubulointerstitial Fibrosis Model and Consequent Effect on Pharmacokinetics

With the widespread clinical use of drug combinations, the incidence of drug–drug interactions (DDI) has significantly increased, accompanied by a variety of adverse reactions. Drug transporters play an important role in the development of DDI by affecting the elimination process of drugs in vivo, especially in the pathological state. Tubulointerstitial fibrosis (TIF) is an inevitable pathway in the progression of chronic kidney disease (CKD) to end-stage renal disease. Here, the dynamic expression changes of eleven drug transporters in TIF kidney have been systematically investigated. Among them, the mRNA expressions of Oat1, Oat2, Oct1, Oct2, Oatp4C1 and Mate1 were down-regulated, while Oat3, Mrp2, Mrp4, Mdr1-α, Bcrp were up-regulated. Pearson correlation analysis was used to analyze the correlation between transporters and Creatinine (Cr), OCT2 and MATE1 showed a strong negative correlation with Cr. In contrast, Mdr1-α exhibited a strong positive correlation with Cr. In addition, the pharmacokinetics of cimetidine, ganciclovir, and digoxin, which were the classical substrates for OCT2, MATE1 and P-glycoprotein (P-gp), respectively, have been studied. These results reveal that changes in serum creatinine can indicate changes in drug transporters in the kidney, and thus affect the pharmacokinetics of its substrates, providing useful information for clinical use.     

Discovery of Novel Non-Oxime Reactivators Showing In Vivo Antidotal Efficiency for Sarin Poisoned Mice

A family of novel efficient non-oxime compounds exhibited promising reactivation efficacy for VX and sarin inhibited human acetylcholinesterase was discovered. It was found that aromatic groups coupled to Mannich phenols and the introduction of imidazole to the ortho position of phenols would dramatically enhance reactivation efficiency. Moreover, the in vivo experiment was conducted, and the results demonstrated that Mannich phenol L10R1 (30 mg/kg, ip) could afford 100% 48 h survival for mice of 2*LD₅₀ sarin exposure, which is promising for the development of non-oxime reactivators with central efficiency.     

Resolving Deep Sub-Wavelength Scattering of Nanoscale Sidewalls Using Parametric Microscopy

The quantitative optical measurement of deep sub-wavelength features with sub-nanometer sensitivity addresses the measurement challenge in the semiconductor fabrication process. Optical scatterings from the sidewalls of patterned devices reveal abundant structural and material information. We demonstrated a parametric indirect microscopic imaging (PIMI) technique that enables recovery of the profile of wavelength-scale objects with deep sub-wavelength resolution, based on measuring and filtering the variations of far-field scattering intensities when the illumination was modulated. The finite-difference time-domain (FDTD) numerical simulation was performed, and the experimental results were compared with atomic force microscopic (AFM) images to verify the resolution improvement achieved with PIMI. This work may provide a new approach to exploring the detailed structure and material properties of sidewalls and edges in semiconductor-patterned devices with enhanced contrast and resolution, compared with using the conventional optical microscopy, while retaining its advantage of a wide field of view and relatively low cost.     

Fracture Prediction for an Advanced High-Strength Steel Sheet Using the Fully Coupled Elastoplastic Damage Model with Stress-State Dependence

In this study,the numerical simulations of sheet metal forming processes are performed based on a fully coupled elastoplastic damage model.The effects of stress...     

Peridynamic modeling and simulation of coupled thermomechanical removal of ice from frozen structures

Meccanica - In this work, a bond-based peridynamic de-icing model has been developed to simulate the thermo-mechanical ice removal process of frozen structures. In the proposed numerical method,...     

A Study of the Role of Microfractures in Counter-Current Spontaneous Imbibition by Lattice Boltzmann Simulation

Transport in Porous Media - During waterflooding, spontaneous imbibition is a fundamental recovery mechanism in fractured reservoirs. A large number of numerical and experimental studies have been...