ment of each isomeric structure.Bleomycin has a long-studied mechanism of action through the formation of a complex with metals, such as iron. The bleomycin-iron complex was recently shown to induce membrane damage by free radical reactivity. Because the use of Fe nanoparticles is spreading for drug delivery strategies, molecular mechanisms of cell damage must include different compartments in order to observe the progression of the cell reactivity. In this study, human embryonic kidney (HEK-293) cells were exposed for 24 h to bleomycin and polymeric iron oxide nanoparticles (Fe-NPs), alone or in combination. The fatty acid-based membrane lipidomic analysis evidenced the fatty acid remodeling in response to the treatments. Bleomycin alone caused the increase of saturated fatty acid (SFA) moieties in cell membrane glycerophospholipids with concomitant diminution of monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acid levels. Under Fe-NPs treatment, omega-6 PUFA decreased and trans fatty acid isomers increased. Under coadministration bleomycin and Fe-NPs, all membrane remodeling changes disappeared compared to those of the controls, with only an increase of omega-6 PUFA that elevates peroxidation index remaining. Our results highlight the important role of fatty-acid-based membrane lipidome monitoring to follow up the fatty acid reorganization induced by the drug, to be considered as a side effect of the pharmacological activity, suggesting the need of an integrated approach for the investigation of drug and carrier molecular mechanisms.HMG-CoA reductase inhibitors (known as statins) are commonly prescribed worldwide for the management of coronary heart disease and the underlying dyslipidemia. This class of drugs has been shown to infer a significant decrease in the risk of cardiovascular morbidity and mortality. Only recently though have the beneficial effects of statins in other diseases such as non-alcoholic steatohepatitis been highlighted. Importantly, also, multiple studies have revealed that statin use was associated with lower cancer-associated mortality across multiple types of cancers. This work aims to review those studies with a particular focus on liver cancer. We also provide a review of the proposed mechanisms of action describing how statins can induce chemo-preventive and antitumor effects.A high-nuclear Mn 72 W 48 cluster has been successfully synthesized by employing acetate coordinated Mn12 and Na2WO4 as starting materials. To investigate the synthesis mechanism, a series of synthesis experiments and high-resolution ESI-MS tests were designed and conducted. These experimental results demonstrate that inorganic tungstates exhibit better coordination capacity and variability than organic acetates in Mn 12 . Furthermore, a series of low nuclearity Mn clusters and Mn-W species were successfully detected and a possible synthesis mechanism of Mn 72 W 48 was proposed. These results show that inorganic tungstate ligands have a great potential to construct high-nuclear transition-metal-oxo clusters by forming various intermediates.Glycosylation is a major protein post-translational modification whose dysregulation has been associated with many diseases. Herein, an on-tissue chemical derivatization strategy based on positively charged hydrazine reagent (Girard’s reagent P) coupled with matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was developed for analysis of N-glycans from FFPE treated tissue sections. The performance of the proposed approach was evaluated by analysis of monosaccharides, oligosaccharides, N-glycans released from glycoproteins, as well as MS imaging of N-glycans from human cancer tissue sections. The results demonstrated that the signal-to-noise ratios for target saccharides were notably improved after chemical derivatization, in which signals were enhanced by 230-fold for glucose and over 28-fold for maltooctaose. Improved glycome coverage was obtained for N-glycans derived from glycoproteins and tissue samples after chemical derivatization. Furthermore, on-tissue derivatization was applied for MALDI-MSI of N-glycans from human laryngeal cancer and ovarian cancer tissues. Differentially expressed N-glycans among the tumor region, adjacent normal tissue region, and tumor proximal collagen stroma region were imaged, revealing that high-mannose type N-glycans were predominantly expressed in the tumor region. Overall, our results indicate that the on-tissue labeling strategy coupled with MALDI-MSI shows great potential to spatially characterize N-glycan expression within heterogeneous tissue samples with enhanced sensitivity. This study provides a promising approach to better understand the pathogenesis of cancer related aberrant glycosylation, which is beneficial to the design of improved clinical diagnosis and therapeutic strategies.Practical applications of lithium-sulfur (Li-S) batteries have been severely hindered by their low capacity, poor rate performance, and fast capacity degradation, which mainly originate from the notorious polysulfide shuttle effect. Herein, with density functional theory calculations, we show that the alloying of Fe into carbon-coated Co not only provides moderate binding interactions with the polysulfides to hinder their diffusion but also serves as an active catalyst in the spontaneous and successive lithiation of S8 to Li2S. Based on the fast migration of Li ions and the spontaneous lithiation of Li2S2 on the carbon-coated Fe-Co alloy, the entrapping-conversion processes of polysulfides are both thermodynamically and kinetically promoted in redox cycling. Experimentally, rationally designed Co7Fe3@porous graphite carbon-carbon nanotubes (Co7Fe3@PGC-CNT) electrocatalysts are introduced into Li-S batteries through separator functionalization. Consistent with theoretical predictions, Li-S batteries with Co7Fe3@PGC-CNT modified separators exhibit a dramatically enhanced rate capacity (788 and 631 mAh g-1 at 10 and 15 C rates, respectively) and cycling stability (a slow capacity decay of 0.05% per cycle over 1000 cycles at 2.0 C), which are superior to those of most reported Li-S batteries coupled with state-of-the-art separators. Furthermore, it is shown that the excellent hindering of the shuttle effects enables a high areal capacity of 4.7 mAh cm-2 after 90 cycles at a high sulfur loading of 6.7 mg cm-2. Our work provides a feasible method for developing high-energy and long-life Li-S batteries, which might drive the commercialization of Li-S batteries.The capping reagent plays an essential role in the functional properties of gold nanoparticles (AuNPs). Multiple stimuli-responsive materials are generated via diverse surface modification. The ability of the organic ligand shell on a gold surface to create a porous shell capable of binding small molecules is demonstrated as an approach to detect molecules, such as methane, that would be otherwise difficult to sense. Thiols are the most studied capping ligands of AuNPs used in chemiresistors. Phosphine capping groups are usually seen as stabilizers in synthesis and catalysis. However, by virtue of the pyramidal shape of triarylphosphines, they are natural candidates to create intrinsic voids within the ligand shell of AuNPs. In this work, surface-functionalized (capped) AuNPs with chelating phosphine ligands are synthesized via two synthetic routes, enabling chemiresistive methane gas detection at sub-100 ppm levels. These AuNPs are compared to thiol-capped AuNPs, and studies were undertaken to evaluate structure-property relationships for their performance in the detection of hydrocarbons. Polymer overcoatings applied to the conductive networks of the functionalized AuNP arrays were shown to reduce resistivity by promoting the formation of conduction pathways with decreased core-core distance between nanoparticles. Observations made in the context of developing methane sensors provide insight relevant to applications of phosphine or phosphine-containing surface groups in functional AuNP materials.A solid understanding of the mechanisms governing ligand binding is crucial for rational design of therapeutics targeting the dopamine D2 receptor (D2R). Here, we use G protein-coupled inward rectifier potassium (GIRK) channel activation in Xenopus oocytes to measure the kinetics of D2R antagonism by a series of aripiprazole analogues, as well as the recovery of dopamine (DA) responsivity upon washout. The aripiprazole analogues comprise an orthosteric and a secondary pharmacophore and differ by the length of the saturated carbon linker joining these two pharmacophores. Two compounds containing 3- and 5-carbon linkers allowed for a similar extent of recovery from antagonism in the presence of 1 or 100 μM DA (>25 and >90% of control, respectively), whereas recovery was less prominent (∼20%) upon washout of the 4-carbon linker compound, SV-III-130, both with 1 and 100 μM DA. Prolonging the coincubation time with SV-III-130 further diminished recovery. Curve-shift experiments were consistent with competition between SV-III-130 and DA. Two mutations in the secondary binding pocket (V91A and E95A) of D2R decreased antagonistic potency and increased recovery from SV-III-130 antagonism, whereas a third mutation (L94A) only increased recovery. Our results suggest that the secondary binding pocket influences recovery from inhibition by the studied aripiprazole analogues. We propose a mechanism, supported by in silico modeling, whereby SV-III-130 initially binds reversibly to the D2R, after which the drug-receptor complex undergoes a slow transition to a second ligand-bound state, which is dependent on secondary binding pocket integrity and irreversible during the time frame of our experiments.The chemosensory system of any animal relies on a vast array of detectors tuned to distinct chemical cues. Odorant receptors and the ion channels of the TRP family are all uniquely expressed in olfactory tissues in a species-specific manner. Great effort has been made to characterize the molecular and pharmacological properties of these proteins. Nevertheless, most of the natural ligands are highly hydrophobic molecules that are not amenable to controlled delivery. We sought to develop photoreleasable, biologically inactive odorants that could be delivered to the target receptor or ion channel and effectively activated by a short light pulse. Chemically distinct ligands eugenol, benzaldehyde, 2-phenethylamine, ethanethiol, butane-1-thiol, and 2,2-dimethylethane-1-thiol were modified by covalently attaching the photoremovable protecting group (8-cyano-7-hydroxyquinolin-2-yl)methyl (CyHQ). The CyHQ derivatives were shown to release the active odorant upon illumination with 365 and 405 nm light. We characterized their bioactivity by measuring activation of recombinant TRPV1 and TRPA1 ion channels expressed in HEK 293 cells and the electroolfactogram (EOG) response from intact mouse olfactory epithelium (OE). Illumination with 405 nm light was sufficient to robustly activate TRP channels within milliseconds of the light pulse. Photoactivation of channels was superior to activation by conventional bath application of the ligands. Photolysis of the CyHQ-protected odorants efficiently activated an EOG response in a dose-dependent manner with kinetics similar to that evoked by the vaporized odorant amyl acetate (AAc). We conclude that CyHQ-based, photoreleasable odorants can be successfully implemented in chemosensory research.