Highlights d Endothelial loss of pfkfb3 impairs ischemic muscle revascularization and regeneration d EC-derived lactate instructs MCT1-dependent macrophage functional polarization d Lactate-polarized macrophages promote muscle revascularization and regeneration d Restoring lactate levels improves macrophage polarization and recovery from ischemia

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The chemical profiles of propolis vary greatly due to the botanic sources and geographic origins, which limit its standardization for modern usages. Here, we proposed a reliable 1H NMR-based metabolomic approach, to discriminate the function and quality of Chinese propolis. A total 63 Chinese propolis samples from different temperate regions were collected and extracted for NMR analysis. Twenty-one compositions in ethanol extracts were assigned based on characteristic chemical shifts and previous literature reports. Significant geographic indicators were identified after the PCA and orthogonal partial least squares discriminant analysis (OPLS-DA) analysis of the obtained 1H NMR data. It was found that the composition discriminations arose from long-term acclimation of the different climates of botanic origin and caused the differences in the biological activities. This study provides us a reasonable instruction for the quality control of Chinese propolis.

The principles of quality by design (QbD) have been applied in cell culture manufacturing process development and characterization in the biotech industry. Here we share our approach and practice in developing and characterizing a cell culture manufacturing process using QbD principles for establishing a process control strategy. Process development and characterization start with critical quality attribute identification, followed by process parameter and incoming raw material risk assessment, design of experiment, and process parameter classification, and conclude with a design space construction. Finally, a rational process control strategy is established and documented.

A new stigmasterone 7α,15α-dihydroxystigmast-4-en-3-one (1), along with fifteen known compounds was isolated from the EtOAc and n-BuOH fractions of the EtOH extract of Agathis macrophylla. The structure of these compounds 1-16 were established mainly by spectroscopic analysis and by comparison of the spectroscopic data with those reported for structurally related compounds. The isolated compounds 1-8 were screened for cytotoxicity in A549 tumor cell line using RSB assay. Compounds 1 and 2 displayed moderate cytotoxicity against A549 tumor cell line with IC50 value of 36.5 and 16.0 μmol/L, respectively.

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We developed a J-compensated QHSQC NMR method for the quantitative measurement of enantiopurity and concentration of levofloxacin in a complex drug matrix. The pulse sequence can achieve uniform signal responses by the suppression of the heteronuclear coupling modulation and alleviation of the homonuclear coupling evolution. Furthermore, we discuss the influence of relaxation on peak intensities and propose the selection conditions of reference signals to achieve accurate quantifications. The evaluation of the methodology shows that the results obtained by selected peaks are in accordance with theoretical analysis with good reliability and linearity. The enantiomeric separation and quantification of levofloxacin in creams are achieved by using a chiral solvating agent, a reference compound, and the J-compensated QHSQC pulse sequence. To our knowledge, this is the first example of QHSQC methodology to quantify enantiomers in the complex matrix.