Notes

One on one D(sp3)-H allylation involving 2-alkylpyridines using Morita-Baylis-Hillman carbonates via a tandem nucleophilic substitution/aza-Cope rearrangement.
Additionally, combining UDCA with the proteasome inhibitor bortezomib (BTZ) achieved a synergistic effect through enhancing the PERK/ATF4/CHOP pathway and protracting ER stress. UDCA inhibited GBM progression, and the combination with BTZ achieved a synergistic effect via protracted ER stress. Thus, UDCA, alone or with combination of BTZ, shows promise as a possible therapeutic agent for the treatment of GBM.Clostridioides difficile (C. difficile) infection (CDI) is the primary cause of nosocomial antibiotic-associated diarrhea, with high recurrence rates following initial antibiotic treatment regimens. Restoration of the host gut microbiome through probiotic therapy is under investigation to reduce recurrence. Current in vitro methods to assess C. difficile deactivation by probiotic microorganisms are based on C. difficile growth inhibition, but the cumbersome and time-consuming nature of the assay limits the number of assessed permutations. Phenotypic alterations to the C. difficile cellular structure upon interaction with probiotics can potentially enable rapid assessment of the inhibition without the need for extended culture. Because supernatants from cultures of commensal microbiota reflect the complex metabolite milieu that deactivates C. difficile, we explore coculture of C. difficile with an optimal dose of supernatants from probiotic culture to speed growth inhibition assays and enable correlation with alterations to its prolate ellipsoidal structure. Based on sensitivity of electrical polarizability to C. difficile cell shape and subcellular structure, we show that the inhibitory effect of Lactobacillus spp. supernatants on C. difficile can be determined based on the positive dielectrophoresis level within just 1 h of culture using a highly toxigenic strain and a clinical isolate, whereas optical and growth inhibition measurements require far greater culture time. We envision application of this in vitro coculture model, in conjunction with dielectrophoresis, to rapidly screen for potential probiotic combinations for the treatment of recurrent CDI.Arylsulfatase A (ARSA) plays a crucial role in the reproduction of mammals due to its involvement in the specific gamete interaction preceding sperm and egg fusion leading to fertilization. Recently, it has been shown that zona pellucida (ZP) sperm binding and in vivo fertilization in mice are markedly hampered by using a specific anti-ARSA antibody. Herein, the design and discovery of the first ARSA small molecule inhibitor based on a coumarin-containing polycycle are presented. Through a structure-based approach applied on our in-house library, compound 1r was identified as an ARSA reversible inhibitor (ARSAi); then its activity was validated through both surface plasmon resonance and biochemical inhibition experiments, the first providing a KD value of 21 μM and the latter an IC50 value of 13.2 μM. Further investigations highlighted that compound 1r induced 20% sperm death at 25 μM and also impaired sperm motility; nevertheless both the effects were mediated by ROS production, since they were rescued by the cotreatment of 1r and N-acetyl cysteine (NAC). Interestingly, while 1r was not able to hamper the ZP/sperm binding, it markedly decreased the in vitro oocyte fertilization by mouse sperm up to 60%. Notably, this effect was not hampered by 1r/NAC coadministration, hence allowing the ruling out of an ROS-dependent mechanism. In conclusion, herein is reported the first ever hit of ARSAi as a chemical tool that will enable better exploration of ARSA's biological role in fertilization as well as provide a starting point for developing 1r structure optimization aimed at increasing enzyme inhibition potency but also providing a deeper understanding of the involvement of ARSA in the fertilization pathway mechanism.Solar-driven interfacial evaporation with heat localization is an efficient method for large-scale water purification. However, due to the high latent heat of water evaporation and dilute solar flux (1 kW m-2), the solar steam productivity is low. Here, the latent heat of water evaporation was reduced because of the capillary water state in wood channels. We constructed a wood-based 3D solar evaporator via regulating the hydrophilicity of a surface of burnt wood and adjusting the height of the wood above a water surface. Capillary water was formed in the light absorption layer, resulting in the latent heat decrease from 2444 to 1769 J g-1. A high evaporation rate of 1.93 kg m-2 h-1 under one sun irradiation (1 kW m-2) was achieved. Together with the environmental energy-harvesting ability, the evaporation rate reached 3.91 kg m-2 h-1 (per occupied area), which is among the best values ever reported. More importantly, the 3D solar evaporator works efficiently in a water collection device, yielding 2.2 times more water than that of a common interfacial evaporator.Boiling heat transfer through a porous medium offers an attractive combination of enormous liquid-vapor interfacial area and high bubble nucleation site density. In this work, we characterize the boiling performances of porous media by employing the well-ordered and highly interconnected architecture of inverse opals (IOs). see more The boiling characterization identifies hydrodynamic mechanisms through which structural characteristics affect the boiling performance of metallic microporous architecture by validating empirical measurements. The boiling performances can be optimized through the rational design of both the structural thicknesses and pore diameters of IOs, which demonstrate up to 336% enhancement in boiling heat-transfer coefficient (HTC) over smooth surfaces. The optimal HTC and critical heat flux occur at approximately 3-4 μm in porous structure thickness, which is manifested through the balance of liquid-vapor occupation within the spatial confinement of the IO structure. The optimization of boiling performances with varying pore diameters (0.3-1.0 μm) can be attributed to the hydraulic competitions between permeability and viscous resistance to liquid-vapor transport. This study unveils thermophysical understandings to enhance multiphase heat transfer in microporous media for ultrahigh heat flux thermal management.
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