The Critical Role of Passive Permeability in Designing Successful Drugs

Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients.     

基于DSP的多元数据同步采集与存储系统的设计与实现

从硬件和软件两个角度出发,介绍基于DSP的多元数据同步采集与存储系统的组成、工作模式以及功能的测试。系统主要由上位机和数字采集与存储单元组成,其中数字采集与存储单元的硬件部分包括电源模块,值班电路模块,数据采集模块,数据存储模块,时钟同步模块。系统采用DSP作为中央处理芯片,利用经过同步后的秒脉冲作为触发信号,实现同步数据采集。以CF卡作为存储介质,实现数据自容式存储。软件部分实现自检、同步、数据采集存储功能。经过测试,系统工作稳定,功能正常,同步精度在100ns以内。     

Impact of an Engineered Copper-Titanium Dioxide Nanocomposite and Parent Substrates on the Bacteria Viability,Antioxidant Enzymes and Fatty Acid Profiling

Due to the systematic increase in the production of nanomaterials (NMs) and their applications in many areas of life, issues associated with their toxicity are inevitable. In particular, the performance of heterogeneous NMs, such as nanocomposites (NCs), is unpredictable as they may inherit the properties of their individual components. Therefore, the purpose of this work was to assess the biological activity of newly synthesized Cu/TiO₂-NC and the parent nanoparticle substrates Cu-NPs and TiO₂-NPs on the bacterial viability, antioxidant potential and fatty acid composition of the reference Escherichia coli and Bacillus subtilis strains. Based on the toxicological parameters, it was found that B. subtilis was more sensitive to NMs than E. coli. Furthermore, Cu/TiO₂-NC and Cu-NPs had an opposite effect on both strains, while TiO₂-NPs had a comparable mode of action. Simultaneously, the tested strains exhibited varied responses of the antioxidant enzymes after exposure to the NMs, with Cu-NPs having the strongest impact on their activity. The most considerable alternations in the fatty acid profiles were found after the bacteria were exposed to Cu/TiO₂-NC and Cu-NPs. Microscopic images indicated distinct interactions of the NMs with the bacterial outer layers, especially in regard to B. subtilis. Cu/TiO₂-NC generally proved to have less distinctive antimicrobial properties on B. subtilis than E. coli compared to its parent components. Presumably, the biocidal effects of the tested NMs can be attributed to the induction of oxidative stress, the release of metal ions and specific electrochemical interactions with the bacterial cells.     

A Simple and Effective Mass Spectrometric Approach to Identify the Adulteration of the Mediterranean Diet Component Extra-Virgin Olive Oil with Corn Oil

Extra virgin olive oil (EVOO) with its nutraceutical characteristics substantially contributes as a major nutrient to the health benefit of the Mediterranean diet. Unfortunately, the adulteration of EVOO with less expensive oils (e.g., peanut and corn oils), has become one of the biggest source of agricultural fraud in the European Union, with important health implications for consumers, mainly due to the introduction of seed oil-derived allergens causing, especially in children, severe food allergy phenomena. In this regard, revealing adulterations of EVOO is of fundamental importance for health care and prevention reasons, especially in children. To this aim, effective analytical methods to assess EVOO purity are necessary. Here, we propose a simple, rapid, robust and very sensitive method for non-specialized mass spectrometric laboratory, based on the matrix-assisted laser desorption/ionization mass spectrometry (MALDI-TOF MS) coupled to unsupervised hierarchical clustering (UHC), principal component (PCA) and Pearson’s correlation analyses, to reveal corn oil (CO) adulterations in EVOO at very low levels (down to 0.5%).     

粉煤灰砖抗折强度测量结果不确定度的评定

通过对粉煤灰砖抗折强度测量结果不确定度的评定,分析出影响试验结果的各种因素,为提高检测水平和精确度提供指导。     

The influence of sonication time on the biogenic amines formation as a critical point in uncured dry-fermented beef manufacturing

In this study, the influence of sonication time on the biogenic amines formation as a critical point in uncured dry-fermented beef manufacturing was studied. Samples of musculus semimembranosus were sonicated at different times (5 and 10 min) using ultrasound cold bath (4 °C) in acid whey (US 40 kHz and acoustic power 480 W). The effect of sonication on biogenic amine (BA) formation was investigated during 93 days of ripening period. Other parameters (pH value, water activity, microbial counts) that might provide further information on the product under study were also determined. The use of ultrasound during beef marinating in acid whey has a positive effect on retarding histamine (HIS), cadaverine (CAD), tyramine (TYR) and putrescine (PUT) formation. Moreover, the sonication treatment did not inhibit the growth of lactic acid bacteria (LAB) in dry-fermented beef during the whole ripening period. The pathogen bacteria (Staphylococcus aureus, Clostridium sp., Listeria monocytogenes) were not detected in all samples neither after 31 nor after 93 days of ripening period.     

Discovery of Affinity-Based Probes for Btk Occupancy Assays

Bruton's tyrosine kinase (Btk) is an attractive target for the treatment of a wide array of B-cell malignancies and autoimmune diseases. Small-molecule covalent irreversible Btk inhibitors targeting Cys481 have been developed for the treatment of such diseases. In clinical trials, probe molecules are required in occupancy studies to measure the level of engagement of the protein by these covalent irreversible inhibitors. The result of this pharmacodynamic (PD) activity provides guidance for appropriate dosage selection to optimize inhibition of the drug target and correlation of target inhibition with disease treatment efficacy. This information is crucial for successful evaluation of drug candidates in clinical trials. Based on the pyridine carboxamide scaffold of a novel solvent-accessible pocket (SAP) series of covalent irreversible Btk inhibitors, we successfully developed a potent and selective affinity-based biotinylated probe 12 (2-[(4-{4-[5-(1-{5-[(3aS,4S,6aR)-2-oxo-hexahydro-1H-thieno[3,4-d]imidazol-4-yl]pentanamido}-3,6,9,12-tetraoxapentadecan-15-amido)pentanoyl]piperazine-1-carbonyl}phenyl)amino]-6-[1-(prop-2-enoyl)piperidin-4-yl]pyridine-3-carboxamide). Compound 12 has been used in Btk occupancy assays for preclinical studies to determine the therapeutic efficacy of Btk inhibition in two mouse lupus models driven by TLR7 activation and type I interferon.     

激光脉冲编码抗有源干扰效果研究

激光脉冲编码是激光制导武器的抗干扰措施之一。角度欺骗式干扰和高重频干扰是目前半主动激光制导武器的主要有源干扰来源。为研究不同激光脉冲编码方式对激光半主动制导武器抗这两种干扰性能的影响,本文针对敌方激光告警机的识别算法与我方导引头的解码过程,提出自相关函数与归一化互相关函数评价方法,并对目前主要编码方式进行仿真,仿真结果表明:激光脉冲编码的抗角度欺骗式干扰能力受编码序列周期性与脉冲间隔随机性的影响；抗高重频激光干扰能力受编码序列脉冲间隔随机性的影响；LFSR状态码的抗角度欺骗式干扰与抗高重频干扰效果均优于其他编码方式。     

Synthesis of amino-cosubstituted polyorganophosphazenes and fabrication of their nanoparticles for anticancer drug delivery

The development of safe drug carriers is cardinal in cancer therapy, which can target the cancer cells and release the loaded drug on-demand without damaging the healthy cells of the body. In our work, we synthesized three different biodegradable polymers, poly[(ethyl aminobezoate) (ethyl glycinato) phosphazenes] (PABGPs), in different mole ratio of side groups. The successful synthesis of these PABGPs was confirmed by ¹H NMR, ³¹P NMR, FT-IR, and gel permeation chromatography. These PABGPs were fabricated into drug (camptothecin, CPT, a hydrophobic anticancer drug) loaded nanoparticles. These drug-loaded nanoparticles showed good drug release behaviors under normal physiological conditions (pH 7.4 and temperature 37°C). These PABGPs-based nanoparticles may find their application as effective drug carriers for cancer therapy.     

Monolithically-integrated BiVO4/p+-n GaAs1-xPx tandem photoanodes capable of unassisted solar water splitting

Monolithically-integrated tandem photoanodes were fabricated on substrates consisting of epitaxial n-GaAs_1-xP_x (x ? 0.32) grown on n⁺-GaAs wafers. A p⁺-n junction photovoltaic (PV) cell was first formed by zinc diffusion into the n-GaAs_0.68P_0.32 from a deposited ZnO coating. After diffusion the ZnO serves as a transparent electrical contact to the resulting p⁺-GaAs_0.68P_0.32 surface layer. Transparent, conducting SnO₂:F provides chemical and mechanical protection for the ZnO and the underlying PV cell, and it electrically connects this cell to a top BiVO₄ photocatalyst layer. In some photoanodes, a WO₃ thin film was interposed between the SnO₂:F and BiVO₄. All oxide coatings were produced by ultrasonic spray pyrolysis except WO₃, which was spin coated. Unassisted (unbiased) solar water splitting was achieved, with a solar-to-hydrogen efficiency approaching 2%, without addition of any co-catalyst to the BiVO₄ surface. This work can provide insights to other researchers regarding scalable, low cost approaches for the planar monolithic integration of oxide photoanode materials with PV cells to create new tandem devices.