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Stomach Microbiota along with Atherosclerosis-Focusing about the Plaque Stability.
The decay of the fluid velocity within the aggregate is quantified via the concept of penetration depth (δ). Analysis shows that the dimensionless penetration depth (δ* = δ/Rg) approaches asymptotic constancy with respect to cluster size in contrast to a weak dependency of the form δ* ∼ (Rg/a)-(df - 1)/2, predicted by the mean-field theory (a being the monomer radius). Furthermore, the penetration depth is found to decrease rapidly, in an exponential manner, with increasing β. This establishes a quantitative relationship between the resistance experienced by the cluster and the degree of penetration of fluid into it. The implications of these results are further discussed.Agonists of stimulators of interferon genes (STING) are a promising class of immunotherapeutics that trigger potent innate immunity. However, the therapeutic efficacy of conventional STING agonists, such as 2',3'-cyclic guanosine monophosphate-adenosine monophosphate (cGAMP), is severely restricted to poor cytosolic delivery and lacks the capacity to promote the recognition of tumor-specific antigens. Here, we tackle these challenges through a nanovaccine platform based on Fenton-reactive and STING-activating nanoparticles, synergistically contributing to the generation of tumor-cell-derived apoptotic bodies (ABs). ABs loaded with exogenous cGAMP are readily phagocytosed by antigen-presenting cells (APCs), as a Trojan horse for rendering tumor cells with high immunogenicity instead of a noninflammatory response. This leads to enhanced STING activation and an improved tumor-specific antigen presentation ability, boosting the adaptive immunity in collaboration with innate immune. The strategy of exploiting a metal-based nanovaccine platform possesses great potential to be clinically translated into a trinitarian system of diagnosis, treatment, and prognosis.An atom-economical direct synthesis of carbazoles having aryl and aryl ketone groups has been achieved through Pd(II)-catalyzed cascade reactions between 1-(indol-2-yl)but-3-yn-1-ols and aldehydes. The reaction proceeds through alkyne-carbonyl metathesis, an uncommon pathway using palladium catalysts, and constitutes a fast intermolecular assembly through four carbon-carbon bond formations in one pot. Absence of the aldehyde substrate resulted in the formation of C4-aryl-substituted carbazoles. The reaction is amenable to the synthesis of biscarbazole derivatives.Optoelectronic synapses have been utilized as neuromorphic vision sensors for image preprocessing in artificial visual systems. Self-powered optoelectronic synapses, which can directly convert optical power into electrical power, are promising for practical applications. The Schottky junction tends to be a promising candidate as the energy source for electrical operations. However, fully utilizing the potential of Schottky barriers is still challenging. Herein, organic self-powered optoelectronic synapses with planar diode architecture are fabricated, which can simultaneously sense and process ultraviolet (UV) signals. The photovoltaic operations are facilitated by the built-in potential originating from the molecular-layer-defined asymmetric Schottky contacts. Diverse synaptic behaviors under UV light stimulation without external power supplies are facilitated by the interfacial carrier-capturing layer, which emulates the membranes of synapses. Furthermore, retina-inspired image preprocessing functions are demonstrated on the basis of synaptic plasticity. Therefore, our devices provide the potential for the development of power-efficient and advanced artificial visual systems.Unlike traditional fungicides targeting fungi, plant elicitors usually lack direct fungicidal activity but improve the plant immune system to resist fungi infection, which has gained increasing attention for better fungi resistance management and environment protection. (E)-methyl-2-(2-((((Z)-(amino-(3,4-dichloroisothiazol-5-yl)methylene)amino)oxy)methyl)phenyl)-2-(methoxyimino)acetate (CL-15C) was found to be a fungicide candidate with a broad spectrum. Here, we studied its immune-inducing ability and mechanism to strengthen the resistance of Arabidopsis thaliana against Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) and Oryza sativa L. against Magnaporthe oryzae. CL-15C promoted a 2.20- and 1.47-fold increase in phenylalanine ammonia-lyase (PAL) activity in A. thaliana and O. sativa, respectively. It also facilitated a 1.89- and 1.32-fold increase in accumulation of salicylic acid (SA) in A. thaliana and O. sativa, respectively. Differential genes were clustered in the SA signaling pathway at 24 h after a CL-15C treatment in A. thaliana. Because PAL is a rate-limiting enzyme in the phenylalanine metabolic pathway, after a CL-15C treatment, a pal1(PAL 1) mutant was more susceptible to Pst DC3000 when compared with the wild type. MEDICA16 price Bacterial counts in leaves after a CL-15C treatment showed a 1.11-fold reduction in the pal1 mutant and a 1.54-fold reduction in the wild type. The effect of CL-15C on the PAL enzyme activity and SA content was attenuated in the pal1 mutant. Present experimental data implied that the immune-inducing activity of CL-15C was dependent on PAL gene-mediated synthesis of SA.Drug resistance caused by epidermal growth factor receptor (EGFR) mutation has largely limited the clinical use of EGFR tyrosine kinase inhibitors (EGFR-TKIs) for the treatment of non-small-cell lung cancer (NSCLC). Herein, to overcome the intractable problem of drug resistance, proteolysis targeting chimeras (PROTACs) targeting EGFR mutants were developed by optimizing covalent EGFR ligands. Covalent or reversible covalent pyrimidine- or purine-containing PROTACs were designed, synthesized, and evaluated. As a consequence, covalent PROTAC CP17, with a novel purine-containing EGFR ligand, was discovered as a highly potent degrader against EGFRL858R/T790M and EGFRdel19, reaching the lowest DC50 values among all reported EGFR-targeting PROTACs. Furthermore, CP17 exhibited excellent cellular activity against the H1975 and HCC827 cell lines with high selectivity. Mechanism investigation indicated that the lysosome was involved in the degradation process. Importantly, the covalent binding strategy was proven to be an effective approach for the design of PROTACs targeting EGFRL858R/T790M, which laid the practical foundation for further development of potent EGFR-targeting PROTACs.Copper bismuth oxide (CBO) is an emerging photocathode in photoelectrochemical (PEC) water splitting but exhibits limited performance due to the severe recombination of photogenerated charges at the semiconductor-liquid junction (SCLJ). For the first time, a set of operational spectroelectrochemical experiments including electrochemical impedance spectroscopy (EIS), transient photocurrent spectroscopy (TPS), and intensity-modulated photocurrent/voltage spectroscopy (IMVS, IMPS) are designed to investigate the charge dynamics at the SCLJ. It is indicated that there are dense surface states above the valence band of CBO, inducing the "Fermi level pinning" (FLP) effect at the SCLJ. The kinetic parameters speculated by IMVS and IMPS indicate the charge transfer efficiency of below 10% with even a bias of ∼0.7 V applied. TPS confirms the sluggish dynamics because of the charging behavior of the surface states. It is expected that this work would provide new connotations of charge dynamics at the SCLJ for the further optimization of CBO-based PEC systems.Ligands that enable the delocalization of excitons beyond the physical boundary of the inorganic core of semiconductor quantum dots (QDs), called "exciton-delocalizing ligands (EDLs)", offer the opportunity to design QD-based environmental sensors with dynamically responsive optical spectra, because the degree of exciton delocalization depends on the electronic structure of the EDL. This paper demonstrates dynamic, reversible tuning of the optical bandgap of a dispersion of CdSe QDs through the redox states of their 1,3-dimesitylnaphthoquinimidazolylidene N-heterocyclic carbene (nqNHC) ligands. Upon binding of the nqNHC ligands to the QD, the optical bandgap bathochromically shifts by up to 102 meV. Electrochemical reduction of the QD-bound nqNHC ligands shifts the bandgap further by up to 25 meV, a shift that is reversible upon reoxidation.Constructing artificial dynamic architectures inside cells to rationally interfere with organelles is emerging as an efficient strategy to regulate the behaviors and fate of cells, thus providing new routes for therapeutics. Herein, we develop an intracellular K+-mediating dynamic assembly of DNA tetrahedrons inside cells, which realizes efficient mitochondrial interference and consequent regulation on the energy metabolism of living cells. In the designer DNA tetrahedron, one vertex was modified with triphenylphosphine (TPP) for mitochondrial targeting, and the other three vertexes were tethered with guanine-rich sequences that could realize K+-mediating formation of intermolecular G-quadruplexes, which consequently led to the assembly of DNA tetrahedrons to form aggregates in the cytoplasm. The DNA aggregates specially targeted mitochondria and served as a polyanionic barrier for substance communication, thus generating a significant inhibition effect on the aerobic respiration function of mitochondria and the associated glycolysis process, which consequently reduced the production of intracellular adenosine triphosphate (ATP). The lack of ATP impeded the formation of lamellipodium that was essential for the movement of cells, consequently resulting in a significant inhibitory effect on cell migration. Remarkably, the migration capacity was suppressed by as high as 50% for cancer cells. This work provides a new strategy for the manipulation of organelles via the endogenous molecule-mediating dynamic assembly of exogenous artificial architectures inside living cells, which is envisioned to have great potential in precise biomedicine.Here, a new three-dimensional (3D) porous h-BC2N was designed via the assembly of prismane C8 and boron nitride chains as the candidates for alkali metal ion battery anodes. By systematic calculations, it is found that h-BC2N is both thermally and mechanically stable, even at a temperature as high as 1000 K. Li ions can migrate with multiple diffusion directions in h-BC2N, and the minimum diffusion barrier is only 0.10 eV lower than that of graphite. The theoretical specific capacity of the h-BC2N anode for Li is 549 mAh/g, which is higher than that reported for graphite. h-BC2N is also a promising anode for sodium (NIBs) and potassium ion batteries (KIBs) whose specific capacities are also large (549 mAh/g), and the energy barriers are 0.35 and 0.19 eV, respectively. Additionally, LIBs, NIBs, and KIBs exhibit voltage stability upon charging/discharging and good cycling stability. This theoretical exploration may open a new frontier in the search for more practical 3D porous structures as LIBs, NIBs, and KIBs anodes.In the present work, we have calculated several density functional theory (DFT) reactivity descriptors for the aminopolycarboxylate (APC) acids at the B3LYP/6311++G (d,p) levels of theory, aiming to analyze their reactivity. Reactivity descriptors such as ionization energy, molecular hardness, electrophilicity, and condensed Fukui function local indices have been determined to predict the reactivity of APCs. The influence of the solvent was taken into account by employing the CPCM model. The results indicate that the solvation slightly modifies the tendency of the reactivity of the APCs studied. On the other hand, we applied a global and local charge-transfer partitioning model, which introduces two charge-transfer channels [one for accepting electrons (electrophilic) and another for donating one (nucleophilic)] to the complexation reaction of a set of APC acids with transition metals (Mn, Co, and Ni targets enlarged by Fe, Cu, and Zn). The correlation between the charges obtained for the interaction between APC acids and transition metal stability constants provides support for their interpretation as measures of the electrophilicity and nucleophilicity of a chemical species and, at the same time, allows one to describe the donation and back-donation processes in terms of the DFT of chemical reactivity.
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