Metabolomic profiling of single enlarged lysosomes.

Lysosomes are critical for cellular metabolism and are heterogeneously involved in various cellular processes. The ability to measure lysosomal metabolic heterogeneity is essential for understanding their physiological roles. We therefore built a single-lysosome mass spectrometry (SLMS) platform integrating lysosomal patch-clamp recording and induced nano-electrospray ionization (nanoESI)/mass spectrometry (MS) that enables concurrent metabolic and electrophysiological profiling of individual enlarged lysosomes. The accuracy and reliability of this technique were validated by supporting previous findings, such as the transportability of lysosomal cationic amino acids transporters such as PQLC2 and the lysosomal trapping of lysosomotropic, hydrophobic weak base drugs such as lidocaine. We derived metabolites from single lysosomes in various cell types and classified lysosomes into five major subpopulations based on their chemical and biological divergence. Senescence and carcinoma altered metabolic profiles of lysosomes in a type-specific manner. Thus, SLMS can open more avenues for investigating heterogeneous lysosomal metabolic changes during physiological and pathological processes.

Differences between phytophagous and predatory species in Pentatomidae based on the mitochondrial genome.

Pentatomidae includes many species of significant economic value as plant pests and biological control agents. The feeding habits of Pentatomidae are closely related to their energy metabolism and ecological adaptations. In this study, we sequenced the mitochondrial genomes of 12 Asopinae species using the next-generation sequencing to explore the effect of dietary changes on mitochondrial genome evolution. Notably, all sequences were double-stranded circular DNA molecules containing 37 genes and one control region. We then compared and analyzed the mitochondrial genome characteristics of phytophagous and predatory bugs. Notably, no significant difference was observed in the length of the mitochondrial genomes between the predatory and phytophagous bugs. However, the AT content was higher in the mitochondrial genomes of phytophagous bugs than that of predatory bugs. Moreover, phytophagous bugs prefer codon usage patterns ending in A/T compared with predatory bugs. The evolution rate of predatory bugs was lower than that of phytophagous bugs. The phylogenetic relationships across phytophagous bugs' lineages were largely consistent at depth nodes based on different datasets and tree-reconstructing methods, and strongly supported the monophyly of predatory bugs. Additionally, the estimated divergence times indicated that Pentatomidae explosively radiated in the Early Cretaceous. Subsequently, the subfamily Asopinae and the genus Menida diverged in the Late Cretaceous. Our research results provide data supporting for the evolutionary patterns and classification of Pentatomidae.

Phylogenetic and divergence analysis of Pentatomidae, with a comparison of the mitochondrial genomes of two related species (Hemiptera, Pentatomidae).

Pentatomidae, the most diverse family of Pentatomoidea, is found worldwide. Currently, the phylogenetic relationships among Pentatomidae tribes remain unstable, and subfamily divergence has not been estimated. Here, we sequenced and analyzed the complete mitochondrial genomes of two species of Lelia, and studied the phylogenetic relationships among Pentatominae tribes. We also selected three available fossil as the calibration points in the family, and preliminarily discussed the divergence time of Pentatomidae. Trees of Pentatomidae were reconstructed using the Bayesian inference method. Divergence times of Pentatominae were estimated based on the nucleotide sequences of protein-coding genes with a relaxed clock log-normal model in BEASTv.1.8.2. The results showed that the gene arrangements, nucleotide composition, and codon preferences were highly conserved in Lelia. Further, a phylogenetic analysis recovered Eysarcorini, Strachiini, Phyllocephalini, and Menidini as monophyletic with strong support, however, the monophyly of Antestiini, Nezarini, Carpocorini, Pentatomini and Cappaeini were rejected. Moreover, Pentatominae diverged from Pentatomidae soon after the origin of the Cretaceous Period, at approximately 110.38 Ma. This study enriches the mitochondrial genome database of Pentatomidae and provides a reference for further phylogenetic studies, and provides a more accurate estimate of divergence time.

Synthesis and Biological Activity of Embelin and its Derivatives: An Overview.

Embelin is a naturally occurring para-benzoquinone isolated from Embelia ribes (Burm. f.) of the Myrsinaceae family, and contains two carbonyl groups, a methine group and two hydroxyl groups. With embelin as the lead compound, more than one hundred derivatives have been reported. Embelin is well known for its ability to antagonize the X-linked inhibitor of apoptosis protein (XIAP) with an IC50 value of 4.1 µM. The potential of embelin and its derivatives in the treatment of various cancers has been extensively studied. In addition, these compounds display a variety of other biological effects: antimicrobial, antioxidant, analgesic, anti-inflammatory, anxiolytic and antifertility activity. This paper reviews the recent progress in the synthesis and biological activity of embelin and its derivatives. Their cellular mechanisms of action and prospects in the research and development of new drugs are also discussed.

Design, synthesis and evaluation of cinnamic acid ester derivatives as mushroom tyrosinase inhibitors.

Tyrosinase is a key enzyme in melanin biosynthesis, and is also involved in the enzymatic browning of plant-derived foods. Tyrosinase inhibitors are very important in medicine, cosmetics and agriculture. In order to develop more active and safer tyrosinase inhibitors, an efficient approach is to modify natural product scaffolds. In this work, two series of novel tyrosinase inhibitors were designed and synthesized by the esterification of cinnamic acid derivatives with paeonol or thymol. Their inhibitory effects on mushroom tyrosinase were evaluated. Most of these compounds (IC50: 2.0 to 163.8 µM) are found to be better inhibitors than their parent compounds (IC50: 121.4 to 5925.0 µM). Among them, (E)-2-acetyl-5-methoxyphenyl-3-(4-hydroxyphenyl)acrylate (5a), (E)-2-acetyl-5-methoxyphenyl-3-(4-methoxyphenyl)acrylate (5g) and (E)-2-isopropyl-5-methylphenyl-3-(4-hydroxyphenyl)acrylate (6a) showed strong inhibitory activities; the IC50 values were 2.0 µM, 8.3 µM and 10.6 µM, respectively, compared to the positive control, kojic acid (IC50: 32.2 µM). Analysis of the inhibition mechanism of 5a, 5g and 6a demonstrated that their inhibitory effects on tyrosinase are reversible. The inhibition kinetics, analyzed by Lineweaver-Burk plots, revealed that 5a acts as a non-competitive inhibitor while 5g and 6a are mixed-type inhibitors. Furthermore, docking experiments were carried out to study the interactions between 6a and mushroom tyrosinase.

Correction: design, synthesis and evaluation of cinnamic acid ester derivatives as mushroom tyrosinase inhibitors.

[This corrects the article DOI: 10.1039/C8MD00099A.].