Somatic frameshift mutation inside PIK3CA brings about CLOVES syndrome through invoking PI3KAKTmTOR path

We describe herein the first access to 12-membered cyclic[7,0]ortho,meta-diarylheptanoids. The key features of the synthesis include both a Suzuki-Miyaura coupling and a ring closing metathesis. Actinidione, a promising natural product, along with a bioactive tetracyclic derivative were obtained in 14 steps for the first time from cheap commercially available substrates with an overall yield of 18-21%. Our modus operandi complies with the principles of the synthesis ideality by using notably strategic reactions.Directional motion in response to specific signals is critically important for micro/nanomotors in precise cargo transport, obstacle avoidance, collective control, and complex maneuvers. In this work, a kind of isotropic light-driven micromotor that is made of hedgehog-shaped TiO2 and functional multiwall carbon nanotubes (Hs-TiO2@FCNTs) has been developed. The FCNTs are closely entangled with Hs-TiO2 and form a close-knit matrix on the surface of Hs-TiO2, which facilitates the transfer of electrons from Hs-TiO2 to FCNTs. Due to the high redox potential of Hs-TiO2, excellent electron-hole separation efficiency by the addition of FCNTs, and isotropic morphology of the micromotor, these Hs-TiO2@FCNT micromotors show phototactic and fuel-free propulsion under unidirectional irradiation of UV light. It is the first time to demonstrate isotropic micromotors that are propelled by self-electrophoresis. The isotropy of Hs-TiO2@FCNT micromotors makes them immune to the rotational Brownian diffusion and local flows, exhibiting superior directionality. The motion direction of our micromotors can be precisely tuned by light and a velocity of 8.9 μm/s is achieved under 160 mW/cm2 UV light illumination. Photodegradation of methylene blue and active transportation of polystyrene beads are demonstrated for a proof-of-concept application of our micromotors. The isotropic design of the Hs-TiO2@FCNT micromotors with enhanced photocatalytic properties unfolds a new paradigm for addressing the limitations of directionality control and chemical fuels in the current asymmetric light-driven micromotors.Lewis acid catalysts have been shown to promote carbonyl-olefin metathesis through a critical four-membered-ring oxetane intermediate. Recently, Brønsted-acid catalysis of related substrates was similarly proposed to result in a transient oxetane, which fragments within a single elementary step via a postulated oxygen-atom transfer mechanism. Herein, careful quantum chemical investigations show that Brønsted acid (triflic acid, TfOH) instead invokes a mechanistic switch to a carbonyl-ene reaction, and oxygen-atom transfer is uncompetitive. TfOH's conjugate base is also found to rearrange H atoms and allow isomerization of the carbocations that appear after the carbonyl-ene reaction. The mechanism explains available experimental information, including the skipped diene species that appear transiently before product formation. ML792 clinical trial The present study clarifies the mechanism for activation of intramolecular carbonyl-olefin substrates by Brønsted acids and provides important insights that will help develop this exciting class of catalysts.In this work, we show that polarization rotation enhances the piezoresponse in a high-performance lead-free piezoelectric material, Na1/2Bi1/2V1-xTi x O3, a solid solution between tetragonal Na1/2Bi1/2VO3 and rhombohedral Na1/2Bi1/2TiO3, obtained by high-pressure synthesis. The system forms a pure perovskite structure with a favorable morphotropic phase boundary (MPB) located around x = 0.90, which separates the tetragonal and rhombohedral phases. In addition, a distinct monoclinic phase with polarization rotation as functions of composition and temperature is observed. XRD measurements revealed the moderately high Curie temperature of 523 K at x = 0.95 in the MPB. The piezoelectric coefficient d33 of the monoclinic x = 0.95 sample, 42 pC/N, is higher than those of the tetragonal and rhombohedral phases. Even though the present lead-free Na1/2Bi1/2V1-xTi x O3 ceramics feature smaller d33 values compared to many currently available lead-free piezoelectric materials as a result of insufficient poling and low density, we expect our findings open up opportunities for exploring promising lead-free piezoelectric materials in Na1/2Bi1/2VO3-based perovskites.We have proposed a new constant-pH (CpH) hybrid Monte Carlo (MC) method with a configuration-selection (CS) scheme, called the CS-CpH method, to obtain pH-dependent physical properties within a framework of atomistic molecular simulation. The CS-CpH method consists of carrying out a short equilibrium molecular dynamics (MD) and a searching MD coupled with thermostats and barostats to generate physically plausible configurations with changed protonation states (PSs) that are subsequently accepted or rejected according to the Metropolis MC procedure. As an example, we have applied it to glutamic acid in aqueous solution and have demonstrated that it can work to generate reasonably the pH-dependent microscopic configuration ensemble compatible with the experimental pKa value and also to show interestingly the molecular diffusivity correlated with pH-dependent solvation shell. In conclusion, we believe that the present CS-CpH method becomes a quite useful tool to study the microscopic origin of various pH-dependent phenomena, interpreting them in the atomistic chemical processes.We report the development of in situ (online) EPR and coupled EPR/NMR methods to study redox flow batteries, which are applied here to investigate the redox-active electrolyte, 2,6-dihydroxyanthraquinone (DHAQ). The radical anion, DHAQ3-•, formed as a reaction intermediate during the reduction of DHAQ2-, was detected and its concentration quantified during electrochemical cycling. The fraction of the radical anions was found to be concentration-dependent, the fraction decreasing as the total concentration of DHAQ increases, which we interpret in terms of a competing dimer formation mechanism. Coupling the two techniques-EPR and NMR-enables the rate constant for the electron transfer between DHAQ3-• and DHAQ4- anions to be determined. We quantify the concentration changes of DHAQ during the "high-voltage" hold by NMR spectroscopy and correlate it quantitatively to the capacity fade of the battery. The decomposition products, 2,6-dihydroxyanthrone and 2,6-dihydroxyanthranol, were identified during this hold; they were shown to undergo subsequent irreversible electrochemical oxidation reaction at 0.