Edmondsonfog4291

DNA gyrase, a type II topoisomerase found predominantly in bacteria, is the target for a variety of 'poisons', namely natural product toxins (e.g. albicidin, microcin B17) and clinically important synthetic molecules (e.g. fluoroquinolones). THZ531 supplier Resistance to both groups can be mediated by pentapeptide repeat proteins (PRPs). Despite long-term studies, the mechanism of action of these protective PRPs is not known. We show that a PRP, QnrB1 provides specific protection against fluoroquinolones, which strictly requires ATP hydrolysis by gyrase. QnrB1 binds to the GyrB protein and stimulates ATPase activity of the isolated N-terminal ATPase domain of GyrB (GyrB43). We probed the QnrB1 binding site using site-specific incorporation of a photoreactive amino acid and mapped the crosslinks to the GyrB43 protein. We propose a model in which QnrB1 binding allosterically promotes dissociation of the fluoroquinolone molecule from the cleavage complex.Enhancers play important roles in controlling gene expression in a choreographed spatial and temporal manner during development. However, it is unclear how these regulatory regions are established during differentiation. Here we investigated the genome-wide binding profile of the forkhead transcription factor FOXK2 in human embryonic stem cells (ESCs) and downstream cell types. This transcription factor is bound to thousands of regulatory regions in human ESCs, and binding at many sites is maintained as cells differentiate to mesendodermal and neural precursor cell (NPC) types, alongside the emergence of new binding regions. FOXK2 binding is generally associated with active histone marks in any given cell type. Furthermore newly acquired, or retained FOXK2 binding regions show elevated levels of activating histone marks following differentiation to NPCs. In keeping with this association with activating marks, we demonstrate a role for FOXK transcription factors in gene activation during NPC differentiation. FOXK2 occupancy in ESCs is therefore an early mark for delineating the regulatory regions, which become activated in later lineages.Increasing the fluorescence quantum yield of fluorophores is of great interest for in vitro and in vivo biomedical imaging applications. At the same time, photobleaching and photodegradation resulting from continuous exposure to light are major considerations in the translation of fluorophores from research applications to industrial or healthcare applications. A number of tetrapyrrolic compounds, such as heme and its derivatives, are known to provide fluorescence contrast. In this work, we found that biliverdin (BV), a naturally-occurring tetrapyrrolic fluorophore, exhibits an increase in fluorescence quantum yield, without exhibiting photobleaching or degradation, in response to continuous ultraviolet (UV) irradiation. We attribute this increased fluorescence quantum yield to photoisomerization and conformational changes in BV in response to UV irradiation. This enhanced fluorescence can be further altered by chelating BV with metals. UV irradiation of BV led to an approximately 10-fold increase in its 365 nm fluorescence quantum yield, and the most favorable combination of UV irradiation and metal chelation led to an approximately 18.5-fold increase in its 365 nm fluorescence quantum yield. We also evaluated these stimuli-responsive behaviors in biliverdin nanoparticles (BVNPs) at the bulk-state and single-particle level. We determined that UV irradiation led to an approximately 2.4-fold increase in BVNP 365 nm quantum yield, and the combination of UV irradiation and metal chelation led to up to a 6.75-fold increase in BVNP 365 nm quantum yield. Altogether, these findings suggest that UV irradiation and metal chelation can be utilized alone or in combination to tailor the fluorescence behavior of imaging probes such as BV and BVNPs at selected wavelengths.Since obesity occurs when energy intake is higher than energy expenditure, increasing energy expenditure is an effective strategy to prevent or treat obesity. Brown adipose tissue (BAT) is a classic energy-consuming organ whose thermogenesis function can be activated by dietary components. Gentisic acid (2,5-dihydroxybenzoic acid, (DHB)) is widely found in food and exhibits many physiological functions, which include anti-inflammatory, antimicrobial, antioxidant, and hepatoprotective properties. However, its anti-obesity effect and mechanism have yet to be examined. This study investigated the effect and mechanism of DHB in preventing diet-induced obesity in mice from the perspective of energy metabolism. The C57BL/6 mice were fed a normal diet (ND), a high-fat and high-fructose diet (HFFD) or HFFD plus 2 mg mL-1 DHB (DHB + HFFD) for 12 weeks. Measuring obesity, lipid metabolism, energy metabolism and BAT related indicators. Moreover, the C3H10T1/2 cells were used to assess the effect of DHB on brown adipocytes in vitro. The results proved that, at the end of the experiment, the body weight of the mice in the DHB + HFFD group was 14.97% lower than in the HFFD group. DHB reduced the weight of the major organs, improved insulin sensitivity, and decreased systemic lipid accumulation. Moreover, DHB administration significantly increased energy metabolism, which was (partly) due to the activation of BAT thermogenesis. Furthermore, DHB supplementation enhanced the expression of the fatty acid oxidation related proteins in BAT and the brown adipocytes, indicating that DHB augmented the utilization of fatty acids by BAT, which is the primary substance of thermogenesis. This study reveals that DHB administration prevents HFFD induced obesity in mice by (at least partly) accelerating the oxidation of fatty acids and stimulating the thermogenesis of BAT.Tumor cells can be selectively killed by heat application based on the different tolerances of normal cells and tumor cells to temperature. However, the limited clinical application of photothermal therapy (PTT) is mainly due to various practical implementation difficulties, of which the most important is how to fully heat the tumor. The combination of PTT and chemotherapy can synergistically enhance cell membrane permeability and reduce the dose of chemotherapy drugs to not only effectively kill the tumor but also reduce the damage to normal tissues. It is of great significance to develop materials that can be simultaneously used for tumor PTT and chemotherapy. Therefore, in this study, a functionalized tellurium (Te) nanosystem (DOX/PEI@TeNPs) was prepared to achieve chemo-photothermal cancer combination therapy. Our research showed that the DOX/PEI@TeNP morphology was controllable, and it had good photothermal conversion efficiency and light stability. Moreover, DOX/PEI@TeNPs containing doxorubicin (DOX) showed almost no drug release in normal tissues and neutral-pH environments, while in tumor cells and tissues, it massively released DOX to kill cancer cells.