Arnoldford9527

Narrow-spectrum antimicrobials specifically eradicate the target pathogens but suffer from significantly lagging development. Photodynamic therapy eliminates cells with reactive oxygen species (ROS) generated upon light irradiation but is intrinsically a wide-spectrum modality. We herein converted photodynamic therapy into a narrow-spectrum modality by taking advantage of a previously unnoticed physics recognition pathway. We found that negatively charged nanospheres undergo selective entropy gain-driven adsorption onto spherical bacteria, but not onto rod-like bacteria. This bacterial morphology-targeting selectivity, combined with the extremely limited effective radii of action of ROS, enabled photodynamic nanospheres to kill >99% of inoculated spherical bacteria upon light irradiation and less then 1% of rod-like bacteria under comparable conditions, indicative of narrow-spectrum activity against spherical bacteria. This work unveils the bacterial morphology selectivity in the adsorption of negatively charged nanospheres and suggests a new approach for treating infections characterized by overthriving spherical bacteria in niches naturally dominated by rod-like bacteria.The activation energy (EA) spectra of the potential energy landscape (PEL) provide a convenient perspective for interpreting complex phenomena in amorphous materials; however, the link between the EA spectra and other physical properties in metallic glasses is still mysterious. By systematically probing the EA spectra for numerous metallic glass samples with distinct local geometric ordering, which correspond to broad processing histories, we found that the shear moduli of the samples are strongly correlated with the arithmetic mean of the EA spectra rather than with the local geometrical ordering. Furthermore, we studied the correlation of the obtained EA spectra and various well-established physical parameters. The outcome of our research clearly demonstrates that the soft-mode parameter Ψ and the EA spectrum are correlated; therefore, this could be a good indicator of metallic glass properties and sheds important light on the structure-property relationship in metallic glass through the medium of the PEL.The binding site and energy is an invaluable descriptor in high-throughput screening of catalysts, as it is accessible and correlates with the activity and selectivity. Recently, comprehensive binding energy prediction machine-learning models have been demonstrated and promise to accelerate the catalyst screening. Here, we present a simple and versatile representation, applicable to any deep-learning models, to further accelerate such process. Our approach involves labeling the binding site atoms of the unrelaxed bare surface geometry, hence, for the model application, DFT calculations can be completely removed if the optimized bulk structure is available as is the case when using the Materials Project database. In addition, we present ensemble learning, where a set of predictions are used together to form a predictive distribution which reduces the model bias. We apply the labeled site approach and ensemble to crystal graph convolutional neural network and the ~40,000 data set of alloy catalysts for CO2 reduction. The proposed model applied to the latter data set of unrelaxed structures shows 0.116 and 0.085 eV mean absolute error respectively for CO and H binding energy, better than the best method (0.13 and 0.13 eV) in the literature that requires costly geometry relaxations. The analysis of the model parameters demonstrates that the model can effectively learn the chemical information related to the binding site.In the present work, the synthesis of acetylated salicins, which occur naturally in many Salicaceae species, is reported. The preparation of 2-O-acetylsalicin, 2-O-acetylchlorosalicin, and 2-O-acetylethylsalicin from peracetylated bromosalicin with selective acid-catalyzed deacetylation and one-pot nucleophilic substitution of bromine as the key steps is described. The base-catalyzed O-2 → O-6 acetyl migration afforded 6-O-acetylsalicin derivatives in good yields. Thus, the first synthesis of 6-O-acetylsalicin (fragilin) using acetyl group migration is reported as well as the synthesis of 6-O-acetylchlorosalicin and 6-O-acetylethylsalicin. The NaOMe-catalyzed deacetylation of acetylated glycosides gave salicin, chlorosalicin, and ethylsalicin recently reported from Alangium chinense.Oleanolic acid (OA) is a natural, biologically active pentacyclic triterpenoid found in Cornus officinalis. Although C. officinalis and OA have antiproliferative actions, the effects and mechanisms of OA in benign prostatic hyperplasia (BPH) are unclear. We examined the effect of OA in an animal model of testosterone-induced BPH. Male rats were injected with testosterone propionate with or without OA. The inhibitory effect of OA on BPH-1 cells was determined in vitro. Rats with BPH exhibited outstanding BPH symptoms, including prostatic enlargement, upregulated dihydrotestosterone and 5α-reductase 2 levels, and histological changes. Compared with the BPH group, the OA group showed fewer pathological alterations and regular androgen events. OA inhibited prostate cell proliferation by downregulating the expression of proliferating cell nuclear antigen (PCNA) and cell cycle markers in BPH-induced animals. see more This indicated that OA has superior therapeutic effect in the BPH animal model than finasteride. In vitro studies demonstrated upregulation of PCNA and cell cycle proteins, whereas OA clearly reduced this upregulation. Thus, OA may inhibit the development of BPH by targeting cell cycle progression markers. These suggest that OA is a potential agent for BPH treatment.Metadynamics is an enhanced sampling method of great popularity, based on the on-the-fly construction of a bias potential that is a function of a selected number of collective variables. We propose here a change in perspective that shifts the focus from the bias to the probability distribution reconstruction while retaining some of the key characteristics of metadynamics, such as flexible on-the-fly adjustments to the free energy estimate. The result is an enhanced sampling method that presents a drastic improvement in convergence speed, especially when dealing with suboptimal and/or multidimensional sets of collective variables. The method is especially robust and easy to use and in fact requires only a few simple parameters to be set, and it has a straightforward reweighting scheme to recover the statistics of the unbiased ensemble. Furthermore, it gives more control of the desired exploration of the phase space since the deposited bias is not allowed to grow indefinitely and it does not push the simulation to uninteresting high free energy regions. We demonstrate the performance of the method in a number of representative examples.Mn2+ doping of lead halide perovskites has garnered recent interest because it produces stable orange luminescence in tandem with perovskite emission. Here, we observe enhanced Mn2+ luminescence at the edges of Mn2+-doped CsPbCl3 perovskite microplates and suggest an explanation for its origin using the high spatiotemporal resolution of time-resolved cathodoluminescence (TRCL) imaging. We reveal two luminescent decay components that we attribute to two different Mn2+ populations. While each component appears to be present both near the surface and in the bulk, the origin of the intensity variation stems from a higher proportion of the longer lifetime component near the perovskite surface. We suggest that this higher emission is caused by an increased probability of electron-hole recombination on Mn2+ near the perovskite surface due to an increased trap concentration there. This observation suggests that such surface features have yet untapped potential to enhance emissive properties via control of surface-to-volume ratio.Three new alkanoyl imidazoles, designated bulbimidazoles A-C (1-3), were found from the culture extract of the gammaproteobacterium Microbulbifer sp. DC3-6 isolated from a stony coral of the genus Tubastraea. The absolute configuration of the anteiso-methyl substitution in 1 was established to be a mixture of (R)- and (S)-configurations in a ratio of 991 by applying the Ohrui-Akasaka method. Compounds 1-3 displayed unique broad-spectrum antimicrobial activity against Gram-positive and -negative bacteria and fungi with MICs ranging from 0.78 to 12.5 μg/mL. They also exhibited cytotoxicity toward P388 murine leukemia cells with IC50 in the micromolar range.Two new diterpenoids with tetrasubstituted 3-oxodihydrofuran substituents, named higginsianins D (1) and E (2), were isolated from the mycelium of the fungus Colletotrichum higginsianum grown in liquid culture. They were characterized as methyl 2-[6-hydroxy-5,8a-dimethyl-2-methylene-5-(4-methylpent-3-enyl)-decahydronaphthalen-1-ylmethyl]-4,5-dimethyl-3-oxo-2,3-dihydrofuran-2-carboxylate and its 21-epimer by using NMR, HRESIMS, and chemical methods. The relative configurations of higginsianins D and E, which did not afford crystals suitable for X-ray analysis, were determined by NOESY experiments and by comparison with NMR data of higginsianin B. The absolute configuration was established by comparison of experimental and calculated electronic circular dichroism data. The evaluation of 1 and 2 for antiproliferative activity against human A431 cells derived from epidermoid carcinoma and H1299 non-small-cell lung carcinoma cells revealed that 2 exhibited higher cytotoxic activity than 1, with an IC50 value of 1.0 μM against A431 cells. Remarkably, both 1 and 2 were almost ineffective against immortalized keratinocytes, used as a preneoplastic cell line model.A retrosynthetic disconnection-reconnection analysis of epoxypolyenes-substrates that can undergo cyclization to podocarpane-type tricycles-reveals relay-actuated Δ6,7-functionalized monoterpenoid alcohols for ruthenium benzylidene catalyzed olefin cross-metathesis with homoprenyl benzenes. Successful implementation of this approach provided several epoxypolyenes as expected (E/Z, ca. 2-31). The method is further generalized for the cross-metathesis of pre-existing trisubstituted olefins in other relay-actuated Δ6,7-functionalized monoterpenoid alcohols with various other trisubstituted alkenes to form new trisubstituted olefins. Epoxypolyene cyclization of an enantiomerically pure, but geometrically impure, epoxypolyene substrate provides an enantiomerically pure, trans-fused, podocarpane-type tricycle (from the E-geometrical isomer).Overexpression of phosphopantetheinyl transferase (PPtase)-encoding genes sfp and svp in the marine-derived Verrucosispora sp. SCSIO 40062 led to the production of two new aminofuran monomers, proximicin F (1) and proximicin G (3) and a new dimer diproximicin A (2), along with two known compounds, proximicins B (4) and C (5). Their structures were unambiguously elucidated on the basis of detailed NMR spectroscopic analysis and high-resolution electrospray ionization mass spectrometry (HRESIMS) data. Proximicin B (4) showed moderate antibacterial activities against Staphylococcus aureus, methicillin-resistant S. aureus, and Bacillus subtilis.