In Vitro and In Vivo Antibacterial Activity,Toxicity and Resistance Analysis of Pleuromutilin Derivative Z33 against Methicillin-Resistant Staphylococcus aureus

The novel pleuromutilin derivative, which showed excellent in vitro antibacterial activity against MRSA, 22-(2-(2-(4-((4-(4-nitrophenyl)piperazin-1-yl)methyl)-1H-1,2,3-triazol-1-yl)acetamido)phenyl)thioacety-l-yl-22-deoxypleuromutilin (Z33), was synthesized and characterized in our previous work. In this study, the preliminary pharmacodynamics and safety of Z33 were further evaluated. In in vitro antibacterial activity assays, Z33 was found to be a potent bactericidal antibiotic against MRSA that induced dose-dependent growth inhibition and long-term post-antibiotic effect (PAE). The drug-resistance test demonstrated that Z33 possessed a narrow mutant selection window and lower propensities to select resistance than that of tiamulin. Cytochrome P450 (CYP450) inhibition assay determined that the inhibitory effect of Z33 was similar to that of tiamulin against the activity of CYP3A4, and was lower than that of tiamulin on the activity of CYP2E1. Toxicity determination showed that both Z33 and tiamulin displayed low cytotoxicity of RAW264.7 cells. Furthermore, Z33 was found to be a high-security compound with a 50% lethal dose (LD₅₀) above 5000 mg/kg in the acute oral toxicity test in mice. In an in vivo antibacterial activity test, Z33 displayed better therapeutic effectiveness than tiamulin in the neutropenic mouse thigh infection model. In summary, Z33 was worthy of further development as a highly effective and safe antibiotic agent against MRSA infection.     

Phenothiazine-based covalent organic frameworks with low exciton binding energies for photocatalysis

Designing delocalized excitons with low binding energy (E_b) in organic semiconductors is urgently required for efficient photochemistry because the excitons in most organic materials are localized with a high E_b of >300 meV. In this work, we report the achievement of a low E_b of ∼50 meV by constructing phenothiazine-based covalent organic frameworks (COFs) with inherent crystallinity, porosity, chemical robustness, and feasibility of bandgap engineering. The low E_b facilitates effective exciton dissociation and thus promotes photocatalysis by using these COFs. As a demonstration, we subject these COFs to photocatalytic polymerization to synthesize polymers with remarkably high molecular weight without any requirement of the metal catalyst. Our results can facilitate the rational design of porous materials with low E_b for efficient photocatalysis.

We report the construction of phenothiazine-based covalent organic frameworks, which exhibited diverse structures, the feasibility of bandgap engineering, and unprecedented ultralow exciton binding energy of ∼50 meV for photocatalytic polymerization.     

Mesoporous sodium four-coordinate aluminosilicate nanoparticles modulate dendritic cell pyroptosis and activate innate and adaptive immunity

Pyroptosis is a programmed cell death widely studied in cancer cells for tumour inhibition, but rarely in dendritic cell (DC) activation for vaccine development. Here, we report the synthesis of sodium stabilized mesoporous aluminosilicate nanoparticles as DC pyroptosis modulators and antigen carriers. By surface modification of sodium-stabilized four-coordinate aluminium species on dendritic mesoporous silica nanoparticles, the resultant Na-^IVAl-DMSN significantly activated DC through caspase-1 dependent pyroptosis via pH responsive intracellular ion exchange. The released proinflammatory cellular contents further mediated DC hyperactivation with prolonged cytokine release. In vivo studies showed that Na-^IVAl-DMSN induced enhanced cellular immunity mediated by natural killer (NK) cells, cytotoxic T cells, and memory T cells as well as humoral immune response. Our results provide a new principle for the design of next-generation nanoadjuvants for vaccine applications.

Na-^IVAl-DMSN acts as both antigen carriers and modulators to “hyperactivate” dendritic cells (DCs) via potassium (K⁺) efflux dependent pyroptosis, eventually leading to enhanced adaptive and innate immunity.     

Large-scale synthesis of ultrafine Si nanoparticles by ball milling

Si nanoparticles have been synthesized by ball-milling of graphite and SiO₂ powders. The solid-phase reaction, C(graphite)+SiO₂→Si+CO₂, was found to be a novel technique for fabrication of ultrafine Si particles. The reduced Si in the powder assembled as nanoparticles with a wide range of diameters. Multiple-peak structures were observed in the photoluminescence spectra of the Si nanoparticles at room temperature. The peak energies were found to coincide with the PL peak pinning energies previously reported in porous Si. Thus, the fine structures of luminescence spectra could be attributed to the size quantization of the Si nanoparticles formed via solid-phase reaction during ball-milling.     

Focused ion beam fabrication and magneto-electrical transport properties of La0.67Ca0.33MnO3 nanobridge

La_0.67Ca_0.33MnO₃ particle films with an average particle size of ~150 nm were grown on single-crystal silicon substrate using pulsed electron deposition technique and then focused ion beam was introduced to fabricate nanobridge in size of 300 × 900 nm on the particle film. The magneto-transport properties of both samples were studied. For the film, there is only one resistance peak at 182 K in temperature-dependent resistance (R–T) curves, which is far lower than ferromagnetic–paramagnetic transition temperature (T _C) of 250 K. When compared to the film, double peaks were observed in both R–T curves and magnetoresistance dependent on temperature (MR–T) curves of the nanobridge, one peak is at 186 K, which is very close to metal–insulator transition temperature (T _P) of film, the other one is at 250 K, which is close to the T _C of film, and these two peaks caused separately by grain and grain boundary (GB), which demonstrated that the electrical transport behavior of grain was separated from that of GB.     

Sudden Change of Quantum Discord in Qutrit-Qutrit System Under Depolarising Noise

The effects of decoherence on quantum discord of two-qutrit system under the influence of multilocal, collective and global depolarising noises are investigated. Sudden change of quantum discord with the decoherence parameter and the initial state parameter occurs for the qutrits being coupled to multilocal or global depolarising noises. On the other hand, decoherence cannot induce sudden change of quantum discord when the system is collectively coupled to the depolarising noise. In addition, the local unitary transformation can alter the region in which the phenomenon of sudden change exists.     

The evolution of polarization inside ultrathin PbTiO3 films: a theoretical study

How to control the material properties by manipulating the unitcell thickness is crucial for applications of ferroelectric ultrathin films. To understand the polarization behaviour of ultrathin PbTiO₃ (PTO) films grown on SrTiO₃ (STO) substrate, we have systematically explored the strength and direction of polarization in each unitcell layer, using density functional theory combined with Born effective charge method. Strikingly, we find that the polar state of ultrathin PTO films is a composite result depending not only on thickness but also on boundary condition, initial polarization direction, etc. Besides, we also studied the surface effect on the polarization in the thicker PTO films for comparison with the ultrathin ones, which suggests that the surface effect is basically confined in a small range (3–5 unitcells thick at surface region) no matter what kinds of surface terminations and polarization directions.     

SINGLE MACHINE SCHEDULING WITH CONTROLLABLE PROCESSING TIMES AND COMPRESSION COSTS （Part Ⅱ Heuristics for the General Case）

A single machine scheduling problem with controllable processing times and compression costs is considered. The objective is to find an optimal sequence to minimize the cost ofcompletion times and the cost of compression. The complexity of this problem is still unknown.In Part Ⅱ of this paper,the authors have considered a special case where the compression timesand the compression costs are equal among all jobs. Such a problem appears polynomiafiy solvable by developing an O(n^2) algorithm. In this part(Part Ⅱ ),a general case where the controllable processing times and the compression costs are not equal is discussed. Authors proposehere two heuristics with the first based on some previous work and the second based on the algorithm developed in Part Ⅱ . Computational results are presented to show the efficiency and therobustness of these heuristics.