Established Liposome-Coated IMB16-4 Polymeric Nanoparticles (LNPs) for Increasing Cellular Uptake and Anti-Fibrotic Effects In Vitro

As a global health problem, liver fibrosis still does not have approved treatment. It was proved that N-(3,4,5-trichlorophenyl)-2(3-nitrobenzenesulfonamide) benzamide (IMB16-4) has anti-hepatic fibrosis activity. However, IMB16-4 displays poor water solubility and poor bioavailability. We are devoted to developing biodegraded liposome-coated polymeric nanoparticles (LNPs) as IMB16-4 delivery systems for improving aqueous solubility, cellular uptake, and anti-fibrotic effects. The physical states of IMB16-4−LNPs were analyzed using a transmission electron microscope (TEM), high-performance liquid chromatography (HPLC), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD) and differential scanning calorimeter (DSC). The results show that IMB16-4−LNPs increased the drug loading compared to liposomes and enhanced cellular uptake behavior compared with IMB16-4−NPs. In addition, IMB16-4−LNPs could repress the expression of hepatic fibrogenesis-associated proteins, indicating that IMB16-4−LNPs exhibited evident anti-fibrotic effects.     

Covalent labeling of a chromatin reader domain using proximity-reactive cyclic peptides

Chemical probes for chromatin reader proteins are valuable tools for investigating epigenetic regulatory mechanisms and evaluating whether the target of interest holds therapeutic potential. Developing potent inhibitors for the plant homeodomain (PHD) family of methylation readers remains a difficult task due to the charged, shallow and extended nature of the histone binding site that precludes effective engagement of conventional small molecules. Herein, we describe the development of novel proximity-reactive cyclopeptide inhibitors for PHD3—a trimethyllysine reader domain of histone demethylase KDM5A. Guided by the PHD3–histone co-crystal structure, we designed a sidechain-to-sidechain linking strategy to improve peptide proteolytic stability whilst maintaining binding affinity. We have developed an operationally simple solid-phase macrocyclization pathway, capitalizing on the inherent reactivity of the dimethyllysine ε-amino group to generate scaffolds bearing charged tetraalkylammonium functionalities that effectively engage the shallow aromatic ‘groove’ of PHD3. Leveraging a surface-exposed lysine residue on PHD3 adjacent to the ligand binding site, cyclic peptides were rendered covalent through installation of an arylsulfonyl fluoride warhead. The resulting lysine-reactive cyclic peptides demonstrated rapid and efficient labeling of the PHD3 domain in HEK293T lysates, showcasing the feasibility of employing proximity-induced reactivity for covalent labeling of this challenging family of reader domains.

We describe the development of covalent cyclic peptide ligands which target a chromatin methylation reader domain using a proximity-reactive sulfonyl fluoride moiety.     

Dynamic Variation of Amino Acid Contents and Identification of Sterols in Xinyang Mao Jian Green Tea

As important biomolecules in Camellia sinensis L., amino acids (AAs) are considered to contribute to the overall green tea sensory quality and undergo dynamic changes during growth. However, limited by analytical capacity, detailed AAs composition in different growth stages remains unclear. To address this question, we analyzed the dynamic changes of 23 AAs during leaf growth in Xinyang Mao Jian (XYMJ) green tea. Using amino acid analyzer, we demonstrated that most AAs are abundant on Pure Brightness Day and Grain Rain Day. After Grain Rain, 23 AAs decreased significantly. Further analysis shows that theanine has a high level on the day before Spring Equinox and Grain Rain, accounting for 44–61% of the total free AAs content in tea leaves. Glu, Pro, and Asp are the second most abundant AAs. Additionally, spinasterol and 22,23-dihydrospinasterol are first purified and identified in ethanol extract of XYMJ by silica gel column chromatography method. This study reveals the relationship between plucking days and the dynamic changes of AAs during the growth stage and proves the rationality of the traditional plucking days of XYMJ green tea.     

气相生长氮化铝单晶的新方法

通过在钨坩埚盖开小孔的方法改变氮化铝结晶衬底上的温度场分布,在开孔处形成局部低温区;由于孔的几何尺寸的限制和氮化铝晶体生长的各向异性,开孔处的氮化铝晶体单晶化;随后,开孔处的单晶起籽晶的作用,逐渐长成较大尺寸、较高质量的氮化铝单晶.目前用该方法已经制备出直径大于2mm的氮化铝单晶体.     

CFD-DEM-VDGM method for simulation of particle fluidization behavior in multi-ring inclined-hole spouted fluidized bed

The simulation of particle fluidization behavior in a complex geometry with a large number of particles is challenging owing to the complexity of unstructured c...     

Fumigant Activity of Bacterial Volatile Organic Compounds against the Nematodes Caenorhabditis elegans and Meloidogyne incognita

Plant-parasitic nematodes infect a diversity of crops, resulting in severe economic losses in agriculture. Microbial volatile organic compounds (VOCs) are potential agents to control plant-parasitic nematodes and other pests. In this study, VOCs emitted by a dozen bacterial strains were analyzed using solid-phase microextraction followed by gas chromatography–mass spectrometry. Fumigant toxicity of selected VOCs, including dimethyl disulfide (DMDS), 2-butanone, 2-pentanone, 2-nonanone, 2-undecanone, anisole, 2,5-dimethylfuran, glyoxylic acid, and S-methyl thioacetate (MTA) was then tested against Caenorhabditis elegans. DMDS and MTA exhibited much stronger fumigant toxicity than the others. Probit analysis suggested that the values of LC₅₀ were 8.57 and 1.43 μg/cm³ air for DMDS and MTA, respectively. MTA also showed stronger fumigant toxicity than DMDS against the root-knot nematode Meloidogyne incognita, suggesting the application potential of MTA.     

Quantum Circuit Optimization for Solving Discrete Logarithm of Binary Elliptic Curves Obeying the Nearest-Neighbor Constrained

In this paper, we consider the optimization of the quantum circuit for discrete logarithm of binary elliptic curves under a constrained connectivity, focusing on the resource expenditure and the optimal design for quantum operations such as the addition, binary shift, multiplication, squaring, inversion, and division included in the point addition on binary elliptic curves. Based on the space-efficient quantum Karatsuba multiplication, the number of CNOTs in the circuits of inversion and division has been reduced with the help of the Steiner tree problem reduction. The optimized size of the CNOTs is related to the minimum degree of the connected graph.     

Numerical Study on Entropy Generation of the Multi-Stage Centrifugal Pump

The energy loss of the multi-stage centrifugal pump was investigated by numerical analysis using the entropy generation method with the RNG k-ε turbulence model. Entropy generation due to time-averaged motion and velocity fluctuation was mainly considered. It was found that the entropy generation of guide vanes and impellers account for 71.2% and 23.3% of the total entropy generation under the designed flow condition. The guide vanes are the main hydraulic loss domains and their entropy generation is about 9 W/K, followed by impellers. There are vortices at the tongue of the guide vane inlet as well as flow separations in the impellers, which lead to entropy generation. The fluid impacts the outer surface of the guide vanes, resulting in the increase in entropy generation. There are refluxes near the guide vane tongues which also increase the entropy generation of this part. The entropy generation distribution of the guide vanes and impellers was investigated, which found that the positive guide vane has more entropy generation compared with the reverse guide. The entropy generation of the blade suction surface is higher compared with the pressure surface. This study indicated that the entropy generation method has distinct advantages in the assessment of hydraulic loss.     

Cloning,Expression, Purification,and Characterization of β-Galactosidase from Bifidobacterium longum and Bifidobacterium pseudocatenulatum

Expression and purification of β-galactosidases derived from Bifidobacterium provide a new resource for efficient lactose hydrolysis and lactose intolerance alleviation. Here, we cloned and expressed two β-galactosidases derived from Bifidobacterium. The optimal pH for BLGLB1 was 5.5, and the optimal temperature was 45 °C, at which the enzyme activity of BLGLB1 was higher than that of commercial enzyme E (300 ± 3.6 U/mg) under its optimal conditions, reaching 2200 ± 15 U/mg. The optimal pH and temperature for BPGLB1 were 6.0 and 45 °C, respectively, and the enzyme activity (0.58 ± 0.03 U/mg) under optimum conditions was significantly lower than that of BLGLB1. The structures of the two β-galactosidase were similar, with all known key sites conserved. When o-nitrophenyl-β-D-galactoside (oNPG) was used as an enzyme reaction substrate, the maximum reaction velocity (V_max) for BLGLB1 and BPGLB1 was 3700 ± 100 U/mg and 1.1 ± 0.1 U/mg, respectively. The kinetic constant (K_m) of BLGLB1 and BPGLB1 was 1.9 ± 0.1 and 1.3 ± 0.3 mmol/L, respectively. The respective catalytic constant (k_cat) of BLGLB1 and BPGLB1 was 1700 ± 40 s⁻¹ and 0.5 ± 0.02 s⁻¹, respectively; the respective k_cat/K_m value of BLGLB1 and BPGLB1 was 870 L/(mmol∙s) and 0.36 L/(mmol∙s), respectively. The K_m, k_cat and V_max values of BLGLB1 were superior to those of earlier reported β-galactosidase derived from Bifidobacterium. Overall, BLGLB1 has potential application in the food industry.     

Computational fluid dynamic-discrete element method coupling analysis of particle transport in branched networks

An understanding of the particle transport characteristics in a branched network helps to predict the particle distribution and prevent undesired plugging in various engineering systems.Quantitative analysis of particle flow characteristics is challenging in that experiments are expensive and particle flow is difficult to detect without disturbing the flow.To overcome this difficulty,man-made fractal tree-like branched networks were built,and a coupled computational fluid dynamic and discrete element method model was applied.A series of numerical simulations was carried out to analyze the influence of fractal structure parameters of networks on the particle flow characteristics.The joint influence of inertial,shunt capacity and superposition from upstream branches on particle flow was investigated.The injection position at the inlet determined the particle velocity and its future flow path.The particle density ratio,particle size and bifurcation angle had a greater influence on the shunting of K2 branches than that in the K1 level and N_k22/N_k21 reached a maximum at 60°.Compared with a network with an even number of branches,there was a preferential branch when the branch number was odd.The preferential branch effect or asymmetry degree of the level(K2)branches had a more significant impact on particle shunting than that from the upstream branches(K1).