A phytochemical investigation of an extract of the leaves of Piper betle, guided by a synergistic antibacterial screen, led to the isolation and structural elucidation of 10 new neolignans, Pibeneolignan A-J (1-10), together with 11 known compounds. The structures and absolute configurations of the new compounds were elucidated on the basis of spectroscopic data, single-crystal X-ray diffraction analysis, and experimental and calculated ECD investigations. Compounds 1 and 2 are new naturally occurring neolignan skeletons, based on the cyclohept-2-ene-1,4-dione framework. We propose that these natural products are biosynthetically formed from bicyclic [3.2.1] neolignans by oxidative cleavage and ring opening at C-1' and C-2'. selleck chemicals llc Among these compounds, 9, 13, 15, and 16, in combination with norfloxacin against an effluxing S. aureus strain (SA1199B), exhibited significant synergistic activity with fractional inhibitory concentration indices (FICIs) of 0.078, 0.156, 0.125, and 0.25, respectively. Bacterial growth curves, ethidium bromide (EtBr) efflux, and qRt-PCR were further employed to verify their synergistic antibacterial mechanism. Furthermore, computational molecular modeling suggested the binding of compounds 14-17 and 19 to the active site of the modeled structure of the NorA efflux pump, which is the main efflux pump in SA1199B.G-protein coupled receptors (GPCRs) exist in an equilibrium of multiple conformational states, including different active states, which depend on the nature of the bound ligand. In consequence, different conformational states can initiate specific signal transduction pathways. The study identified compound 7e, which acts as a potent 5-hydroxytryptamine type 6 receptor (5-HT6R) neutral antagonist at Gs and does not impact neurite growth (process controlled by Cdk5). MD simulations highlighted receptor conformational changes for 7e and inverse agonist PZ-1444. In cell-based assays, neutral antagonists of the 5-HT6R (7e and CPPQ), but not inverse agonists (SB-258585, intepirdine, PZ-1444), displayed glioprotective properties against 6-hydroxydopamine-induced and doxorubicin-induced cytotoxicity. These suggest that targeting the activated conformational state of the 5-HT6R with neutral antagonists implicates the protecting properties of astrocytes. Additionally, 7e prevented scopolamine-induced learning deficits in the novel object recognition test in rats. We propose 7e as a probe for further understanding of the functional outcomes of different states of the 5-HT6R.Total syntheses of the sesquiterpenes (+)-sootepdienone, (-)-jambolanin C, (-)-jambolanin I, and (-)-gibberodione have been accomplished in 10 steps each from R-(+)-pulegone, allowing assignment of the absolute configuration of the natural products. A key step in the synthetic pathways involves the one-carbon ring expansion of a cyclic allylic phosphonate to a substituted cycloheptenone by a tandem oxidative cleavage/intramolecular Horner-Wadsworth-Emmons reaction.Minimally invasive methods for temperature sensing and thermal modulation in living tissues have extensive applications in biological research and clinical care. As alternatives to bioelectronic devices for this purpose, functional nanomaterials that self-assemble into optically active microstructures offer important features in remote sensing, injectability, and compact size. This paper introduces a transient, or bioresorbable, system based on injectable slurries of well-defined microparticles that serve as photopumped lasers with temperature-sensitive emission wavelengths (>4-300 nm °C-1). The resulting platforms can act as tissue-embedded thermal sensors and, simultaneously, as distributed vehicles for thermal modulation. Each particle consists of a spherical resonator formed by self-organized cholesteric liquid crystal molecules doped with fluorophores as gain media, encapsulated in thin shells of soft hydrogels that offer adjustable rates of bioresorption through chemical modification. Detailed studies highlight fundamental aspects of these systems including particle sensitivity, lasing threshold, and size. Additional experiments explore functionality as photothermal agents with active temperature feedback (ΔT = 1 °C) and potential routes in remote evaluation of thermal transport properties. Cytotoxicity evaluations support their biocompatibility, and ex vivo demonstrations in Casper fish illustrate their ability to measure temperature within biological tissues with resolution of 0.01 °C. This collective set of results demonstrates a range of multifunctional capabilities in thermal sensing and modulation.Self-healing polymer electrolytes are reported with light-switchable conductivity based on dynamic N-donor ligand-containing diarylethene (DAE) and multivalent Ni2+ metal-ion coordination. Specifically, a polystyrene polymer grafted with poly(ethylene glycol-r-DAE)acrylate copolymer side chains was effectively cross-linked with nickel(II) bis(trifluoromethanesulfonimide) (Ni(TFSI)2) salts to form a dynamic network capable of self-healing with fast exchange kinetics under mild conditions. Furthermore, as a photoswitching compound, the DAE undergoes a reversible structural and electronic rearrangement that changes the binding strength of the DAE-Ni2+ complex under irradiation. This can be observed in the DAE-containing polymer electrolyte where irradiation with UV light triggers an increase in the resistance of solid films, which can be recovered with subsequent visible light irradiation. The increase in resistance under UV light irradiation indicates a decrease in ion mobility after photoswitching, which is consistent with the stronger binding strength of ring-closed DAE isomers with Ni2+. 1H-15N heteronuclear multiple-bond correlation nuclear magnetic resonance (HMBC NMR) spectroscopy, continuous wave electron paramagnetic resonance (cw EPR) spectroscopy, and density functional theory (DFT) calculations confirm the increase in binding strength between ring-closed DAE with metals. Rheological and in situ ion conductivity measurements show that these polymer electrolytes efficiently heal to recover their mechanical properties and ion conductivity after damage, illustrating potential applications in smart electronics.