Label-free nanoscopy of cell metabolism by ultrasensitive reweighted visible stimulated Raman scattering.

Super-resolution imaging of cell metabolism is hindered by the incompatibility of small metabolites with fluorescent dyes and the limited resolution of imaging mass spectrometry. We present ultrasensitive reweighted visible stimulated Raman scattering (URV-SRS), a label-free vibrational imaging technique for multiplexed nanoscopy of intracellular metabolites. We developed a visible SRS microscope with extensive pulse chirping to improve the detection limit to ~4,000 molecules and introduced a self-supervised multi-agent denoiser to suppress non-independent noise in SRS by over 7.

Glabridin Hypnosis in Zebrafish Larvae Is Associated With Effects on Multiple Anesthetic Target Receptors.

Background: R-Glabridin is a major flavonoid of licorice (Glycyrrhiza glabra) root and known to modulate GABAA receptors, which are targets of many clinical hypnotics. However, R-glabridin hypnotic activity has not been reported in animals.

Methods: Inverted photomotor responses (IPMRs) were used to assess the hypnotic effects of natural R-glabridin and synthetic R/S-glabridin in wild-type zebrafish larvae and transgenic larvae lacking functional GABAA receptor β3 subunits (β30/0).

Identification of Rocaglate Acyl Sulfamides as Selective Inhibitors of Glioblastoma Stem Cells.

Glioblastoma (GBM) is the most aggressive and frequently occurring type of malignant brain tumor in adults. The initiation, progression, and recurrence of malignant tumors are known to be driven by a small subpopulation of cells known as tumor-initiating cells or cancer stem cells (CSCs). GBM CSCs play a pivotal role in orchestrating drug resistance and tumor relapse.

Evolution of a Strategy for the Unified, Asymmetric Total Syntheses of DMOA-Derived Spiromeroterpenoids.

DMOA-derived spiromeroterpenoids are a group of natural products with complex structures and varied biological activities. Recently, we reported the first enantioselective total synthesis of five spiromeroterpenoids based on a fragment coupling strategy. This full account describes details of a strategy evolution that culminated in successful syntheses of the targeted natural products.

Amidino-rocaglates (ADRs), a class of synthetic rocaglates, are potent inhibitors of SARS-CoV-2 replication through inhibition of viral protein synthesis.

Coronaviruses are highly transmissible respiratory viruses that cause symptoms ranging from mild congestion to severe respiratory distress. The recent outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has underscored the need for new antivirals with broad-acting mechanisms to combat increasing emergence of new variants. Currently, there are only a few antivirals approved for treatment of SARS-CoV-2.