Enzyme‐Induced Matrix Softening Regulates Hepatocarcinoma Cancer Cell Phenotypes

The progression of cancer is often accompanied by changes in the mechanical properties of an extracellular matrix. However, limited efforts have been made to reproduce these biological events in vitro. To this end, this study demonstrates that matrix remodeling caused by matrix metalloproteinase (MMP)‐1 regulates phenotypic activities and modulates radiosensitivity of cancer cells exclusively in a 3D matrix. In this study, hepatocarcinoma cells are cultured in a collagen‐based gel tailored to present an elastic modulus of ≈4.0 kPa. The subsequent exposure of the gel to MMP‐1 decreases the elastic modulus from 4.0 to 0.5 kPa. In response to MMP‐1, liver cancer cells undergo active proliferation, downregulation of E‐cadherin, and the loss of detoxification capacity. The resulting spheroids are more sensitive to radiation than the spheroids cultured in the stiffer gel not exposed to MMP‐1. Overall, this study serves to better understand and control the effects of MMP‐induced matrix remodeling.     

Quantitative determination of sodium stearyl fumarate in a tablet formulation from continuous manufacturing using a high-pH reversed-phase HPLC method

This study demonstrates the first use of a reversed-phase (RP) high-performance liquid chromatography method with a high-pH buffer for the analysis of sodium stearyl fumarate (SSF) from a tablet formulation. After examining the retention time and peak shape using various buffer concentrations, buffer pH, and RP stationary phases, an optimized method was established using the XBridge® BEH C18 at high pH. This column was further evaluated for method specificity, accuracy, precision, linearity, stability, and sensitivity. Finally, the method was successfully used as a convenient and robust analytical procedure to accurately quantitate SSF in stratified tablets from a continuous manufacturing process to confirm the excipient uniformity throughout the process.     

pH对毛细管电泳分离多肽的影响

设计了一个针对高年级本科生的毛细管电泳分离实验，用以研究pH对生物小分子多肽分离的影响。5种多肽包括Bradykinin、[Hyp3]-bradykinin、Angiotensin I、Leucine Enkephalin和[Met5]-Enkaphalin，被用于毛细管电泳的分离实验。研究了毛细管电泳生物分析实验中最重要的2个因素即电渗流和样品吸附随pH的变化以及对于分离的影响。在pH=10的条件下，酸性多肽几乎没有吸附，少量的碱性多肽有吸附。在pH=6的条件下，碱性多肽具有非常强的吸附从而导致非常差的分离效果，在pH=2.3的条件下，5种多肽都能被很好地分离，由于多肽此时都带有正电荷因此几乎没有吸附。而在此pH，电渗流消失。对具有一定分析化学基础理论知识的学生而言，这是一个非常好的生物分析实验，有助于学生充分理解相关环境因素对仪器分析的重要影响。     

Measurement of fiber propagation constants using a prism-fiber coupler

We report on the use of a prism-fiber coupler to determine the propagation constants for the scalar modes in an optical fiber by measuring, respectively, the incident angle, θ_i, and the position of the m-lines coupled out of the fiber by the prism coupler. The position is related to the value of the corresponding propagation constant. The degeneracy of the modes is shown on the m-line photographs. Good agreement is obtained between measured and calculated values of the propagation constants.     

Deep insights into the hydrolysis of N,N‐dialkylaminoethyl methacrylates in aqueous solution with 1H NMR spectroscopy

N,N‐dialkylaminoethyl methacrylate (DAEA) monomers are extensively used to prepare multi‐responsive polymers. However, these monomers face high risk of hydrolysis in their ester groups when being polymerized in water‐containing medias. Here, NMR spectroscopy was employed to continuously track the hydrolysis and solubility of four widely used DAEA monomers [CH₂CH₂R₁COO(CH₂)₂N(R₂)₂; R₁ = H or CH₃; R₂ = CH₃, CH₂CH₃ or CH(CH₃)₂] under typical polymerization conditions. With this technique, the hydrolysis reactivity and absolute hydrolysis amount of these monomers are separately examined, and then their kinetic correlations with solubility, molecular structure, pH, and temperature are established, so that the hydrolysis of DAEA monomers and even other esters with similar cyclic structure can be predicted. The present efforts are expected to provide a general understanding for the hydrolysis of all the DAEA monomers, benefitting to the optimization of polymerization toward well‐defined DAEA copolymers, as well as the design of smart soft matter for specific applications. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2018 , 56, 914–923     

pH reversible micelle transition of a tertiary amine-based gemini surfactant in aqueous solution

In this work, we prepared a tertiary amide-based gemini surfactant (DSTAPA), which contained two pH-sensitive tertiary amide head groups. Then the molecule state distribution and self-assembly transition of the surfactant in aqueous solution were investigated under different pH conditions. The DSTAPA molecules were on the states of double cationic (DSTAPAH²⁺), single cationic (DSTAPAH⁺), and double tertiary amine groups (DSTAPA) under acidic, neutral, and basic conditions, respectively. With the variation of the molecule states, the sample was water-like below pH of 6.8 and immediately transformed to gel-like fluid between pH of 6.8 and 7.8, then changed to white precipitate with the further increase of pH value. Furthermore, the microstructure and regulation mechanism were investigated by rheological measurements, dynamic light scattering, and cryogenic transmission electron microscopy. The appearance and micelle transitions of the DSTAPA aqueous solution are actually owing to the spherical–worm-like micelle transition, leading to dramatic viscosity increase and hydrogel formation. This transition was completely reversible and repeated for at least three cycles. Finally, a reasonable mechanism of the transition was proposed based on the viewpoints of the molecular states and micelle structures. The DSTAPA aqueous system with pH-reversible property has a great potential application in oil and gas production.     

UPLC-MS-Based Metabolomic Study of Streptomyces Strain HCCB10043 Under Different pH Conditions Reveals Important Pathways Affecting the Biosynthesis of A21978C Compounds

The A21978C family of compounds includes precursors of daptomycin, an important antibiotic for the treatment of diseases infected by Gram-positive resistant bacteria. Focusing on these valuable compounds, the differences in metabolites obtained with or without pH control in their producing strain Streptomyces parvus HCCB10043 were investigated by comparative metabolomics analysis based on UPLC-TOF-MS technology. According to principal component analysis, there were fourteen biomarker compounds selected under the two pH culture conditions. The ten known compounds were divided into two types: a glycoside family participating in the primary metabolism (daidzein, glycitein, genistein, and soyasaponin Bb) and a peptide family of secondary metabolites (valistatin, bestatin, 3-amino-2-hydroxy-4-phenylbutanoylvalylisoleucine, and arylomycins A2, A4, and A5). Through orthogonal partial least squares-discriminant analysis, three compounds, soyasaponin Bb and arylomycins A2 and A4 were identified as the most relevant compounds to A21978C1-3 production, the glycolytic pathway, and the NRPS synthesis pathway. The competitive relationship between arylomycin and A21978C was verified. These results have demonstrated the usefulness of the metabolomic strategy based on UPLC-MS in studying significant metabolic changes in actinomycetes. Moreover, this metabolomic strategy can provide new ideas and guidance for the regulation and improvement of secondary metabolites production.