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Identification of catalytic active sites is pivotal in the design of highly effective heterogeneous metal catalysts, especially for structure-sensitive reactions. Downsizing the dimension of the metal species on the catalyst increases the dispersion, which is maximized when the metal exists as single atoms, namely, single-atom catalysts (SACs). SACs have been reported to be efficient for various catalytic reactions. We show here that the Pt SACs, although with the highest metal atom utilization efficiency, are totally inactive in the cyclohexane (C6H12) dehydrogenation reaction, an important reaction that could enable efficient hydrogen transportation. Instead, catalysts enriched with fully exposed few-atom Pt ensembles, with a Pt-Pt coordination number of around 2, achieve the optimal catalytic performance. The superior performance of a fully exposed few-atom ensemble catalyst is attributed to its high d-band center, multiple neighboring metal sites, and weak binding of the product.In frozen density embedding (FDE), the properties of a target molecule are computed in the presence of an effective embedding potential, which accounts for the attractive and repulsive contributions of the environment. The formally exact embedding potential, however, is in practice calculated using explicit kinetic-energy functionals for which the resulting potentials are in many cases not repulsive enough to account fully for Pauli repulsion by the electrons of the environment and to compensate thereby the strong electron-nuclear attraction. For the excited states on the target molecule, this leads to charge spill-out when diffuse basis functions are included, which allow that valence electrons are excited to those regions of the environment where the strong nuclear attraction is not sufficiently compensated by repulsive contributions. To reduce this insufficiency, we propose in the present work the inclusion of atomic all-electron pseudopotentials for all environment atoms on top of the conventional embedding potential. In the current work, the pseudopotentials are applied for computing vertical excitation energies of local excited states in complex systems employing the second-order algebraic diagrammatic construction (ADC(2)) scheme. The proposed approach leads to significantly reduced charge spill-out and an improved agreement of FDE and supermolecular calculations in the frozen solvent approximation. In particular, when diffuse functions are employed, the mean absolute deviation (MAD) is reduced from 0.27 to 0.05 eV for the investigated cases.The biocatalytic toolbox has recently been expanded to include enzyme-catalyzed carbene transfer reactions not occurring in Nature. Herein, we report the development of a biocatalytic strategy for the synthesis of enantioenriched α-trifluoromethyl amines through an asymmetric N-H carbene insertion reaction catalyzed by engineered variants of cytochrome c552 from Hydrogenobacter thermophilus. Using a combination of protein and substrate engineering, this metalloprotein scaffold was redesigned to enable the synthesis of chiral α-trifluoromethyl amino esters with up to >99% yield and 955 er using benzyl 2-diazotrifluoropropanoate as the carbene donor. When the diazo reagent was varied, the enantioselectivity of the enzyme could be inverted to produce the opposite enantiomers of these products with up to 99.50.5 er. This methodology is applicable to a broad range of aryl amine substrates, and it can be leveraged to obtain chemoenzymatic access to enantioenriched β-trifluoromethyl-β-amino alcohols and halides. Computational analyses provide insights into the interplay of protein- and reagent-mediated control on the enantioselectivity of this reaction. This work introduces the first example of a biocatalytic N-H carbenoid insertion with an acceptor-acceptor carbene donor, and it offers a biocatalytic solution for the enantioselective synthesis of α-trifluoromethylated amines as valuable synthons for medicinal chemistry and the synthesis of bioactive molecules.Herein, we report on the experimental measurements for estimated relative mobility shifts caused by changes in mass distribution from isotopic substitutions in isotopologues and isotopomers with high-resolution cyclic ion mobility separations. By utilizing unlabeled and fully labeled isotopologues with the same isotopic substitutions (i.e., 2H or 13C), we created a highly precise mobility scale for each set analyzed to determine the magnitude of such mass distribution shifts and thus calculate estimated deviations from expected, theoretical reduced mass contributions. We observed relative mobility shifts in various isotopologues (e.g., hexadecyltrimethylammonium, sucrose, and palmitic acid species) that deviated from reduced mass theory, according to the Mason-Schamp relationship, ranging in estimated magnitude from ∼0.007% up to ∼0.1% in relative mobility. More interestingly, it was found that two deuterated palmitic acid isotopomers also differed by ∼0.03% from one another in their respective relative mobility shifts. Our results are the first report of isotopologue and isotopomer separations on a commercially available cyclic ion mobility spectrometry-mass spectrometry platform. We envision that our presented mobility scale methodology will have broad applicability in studying the effect of mass distribution changes from isotopic substitutions in other biomolecules and help pave the way for the improvement of ion mobility theory and collision cross section calculators.Improving signal-to-noise and, thereby, image contrast is one of the key challenges needed to expand the useful applications of mass spectrometry imaging (MSI). Both instrumental and data analysis approaches are of importance. Univariate denoising techniques have been used to improve contrast in MSI images with varying levels of success. Additionally, various multivariate analysis (MVA) methods have proven to be effective for improving image contrast. However, the distribution of important but low intensity ions can be obscured in the MVA analysis, leading to a loss of chemically specific information. In this work we propose inverse maximum signal factors (MSF) denoising as an alternative approach to both denoising and multivariate analysis for MSI imaging. This approach differs from the standard MVA techniques in that the output is denoised images for each original mass peak rather than the frequently difficult to interpret scores and loadings. Five tests have been developed to optimize and validate the resucessing techniques available for studying mass spectrometry images.Macrophages are white blood cells with diverse functions contributing to a healthy immune response as well as the pathogenesis of cancer, osteoarthritis, atherosclerosis, and obesity. Due to their pleiotropic and dynamic nature, tools for imaging and tracking these cells at scales spanning the whole body down to microns could help to understand their role in disease states. Here we report fluorescent and radioisotopic quantum dots (QDs) for multimodal imaging of macrophage cells in vivo, ex vivo, and in situ. Macrophage specificity is imparted by click-conjugation to dextran, a biocompatible polysaccharide that natively targets these cell types. The emission spectral band of the crystalline semiconductor core was tuned to the near-infrared for optical imaging deep in tissue, and probes were covalently conjugated to radioactive iodine for nuclear imaging. The performance of these probes was compared with all-organic dextran probe analogues in terms of their capacity to target macrophages in visceral adipose tissue using in vivo positron emission tomography/computed tomography (PET/CT) imaging, in vivo fluorescence imaging, ex vivo fluorescence, post-mortem isotopic analyses, and optical microscopy. All probe classes exhibited equivalent physicochemical characteristics in aqueous solution and similar in vivo targeting specificity. However, dextran-mimetic QDs provided enhanced signal-to-noise ratio for improved optical quantification, long-term photostability, and resistance to chemical fixation. In addition, the vascular circulation time for the QD-based probes was extended 9-fold compared with dextran, likely due to differences in conformational flexibility. The enhanced photophysical and photochemical properties of dextran-mimetic QDs may accelerate applications in macrophage targeting, tracking, and imaging across broad resolution scales, particularly advancing capabilities in single-cell and single-molecule imaging and quantification.Teicoplanin is a glycopeptide antibiotic deployed to combat Gram-positive bacterial infection and has recently been associated with development of adverse drug reactions, particularly following previous exposure to vancomycin. In this study, we generated teicoplanin-specific monoclonal T-cell populations from healthy volunteers expressing HLA-A*3201 and defined pathways of T-cell activation and HLA allele restriction. Teicoplanin-responsive T-cells were CD8+, HLA class I-restricted, and cross-reacted with the lipoglycopeptide daptomycin in proliferation and cytokine/cytolytic molecule (granzyme B, Perforin, and FasL) release assays. These data show that teicoplanin activates T-cells, which may play a role in the pathogenesis of teicoplanin-induced adverse events, in HLA-A*3201 positive donors.Oyster hemocytes are the primary vehicles transporting and detoxifying metals and are regarded as important cells for the occurrence of colored oysters due to copper (Cu) contamination. However, its heterogeneous responses under Cu exposure have not been studied. Single-cell transcriptome profiling (scRNA-seq) provides high-resolution visual insights into tissue dynamics and environmental responses. Here, we used scRNA-seq to study the responses of different cell populations of hemocytes under Cu exposure in an estuarine oyster Crassostrea hongkongensis. The 1900 population-specific Cu-responsive genes were identified in 12 clusters of hemocytes, which provided a more sensitive technique for examining Cu exposure. The granulocyte, semigranulocyte, and hyalinocyte had specific responses, while the granulocyte was the most important responsive cell type and displayed heterogeneity responses of its two subtypes. In one subtype, Cu was transported with metal transporters and chelated with Cu chaperons in the cytoplasm. Excess Cu disturbed oxidative phosphorylation and induced reactive oxygen species production. EG-011 in vivo However, in the other subtype, endocytosis was mainly responsible for Cu internalization, which was sequestered in membrane-bound granules. Collectively, our results provided the first mRNA expression profile of hemocytes in oysters and revealed the heterogeneity responses under Cu exposure.Neuropathic pain is a challenging clinical problem and remains difficult to treat. Altered gene expression in peripheral sensory nerves and neurons due to nerve injury is well documented and contributes critically to the synaptic plasticity in the spinal cord and the initiation and maintenance of chronic pain. However, our understanding of the epigenetic mechanisms regulating the transcription of pro-nociceptive (e.g., NMDA receptors and α2δ-1) and antinociceptive (e.g., potassium channels and opioid and cannabinoid receptors) genes are still limited. In this review, we summarize recent studies determining the roles of histone modifications (including methylation, acetylation, and ubiquitination), DNA methylation, and noncoding RNAs in neuropathic pain development. We review the epigenetic writer, reader, and eraser proteins that participate in the transcriptional control of the expression of key ion channels and neurotransmitter receptors in the dorsal root ganglion after traumatic nerve injury, which is commonly used as a preclinical model of neuropathic pain.