Identification of the main flavonoids of Abelmoschus manihot (L.) medik and their metabolites in the treatment of diabetic nephropathy

Introduction: Huangkui capsule (HKC) is made from the ethanol extract of Abelmoschus manihot (L.) Medik [Malvaceae; abelmoschi corolla] and received approval from the China Food and Drug Administration (Z19990040) in 1999. Currently, HKC is used for treatment of the patients with diabetic nephropathy (DN) in China. The bioactive chemical constituents in HKC are total flavonoids of A. manihot (L.) Medik (TFA). The present study aims to identify the primary flavonoid metabolites in HKC and TFA and their metabolism fates in db/db mice, the animal model for the study of type 2 diabetes and DN.Methods: HKC (0.84 g/kg/d) and TFA (0.076 g/kg/d) or vehicle were respectively administered daily via oral gavage in db/db mice for 4 weeks. The metabolism fate of the main metabolites of HKC in serum, liver, kidney, heart, jejunum, colon, jejunal contents, colonic contents, and urine of db/db mice were analyzed with a comprehensive metabolite identification strategy.Results and Discussion: In db/db mice administered with HKC and TFA, 7 flavonoid prototypes and 38 metabolites were identified. The related metabolic pathways at Phases I and II reactions included dehydroxylation, deglycosylation, hydrogenation, methylation, glucuronidation, sulphation, and corresponding recombined reactions. Quercetin, isorhamnetin, quercetin sulphate, quercetin monoglucuronide, and isorhamnetin monoglucuronide presented a high exposure in the serum and kidney of db/db mice. Thereby, the present study provides a pharmacodynamic substance basis for better understanding the mechanism of A. manihot (L.) Medik for medication of DN

Electron acceleration and X-ray generation from near-critical-density carbon nanotube foams driven by moderately relativistic lasers

Direct laser acceleration of electrons in near-critical-density (NCD) carbon nanotube foams (CNFs) has its advantages in the high-efficiency generation of relativistic electrons and broadband X-rays. Here, we report the first simultaneous measurement on the spectra of laser-driven electrons and X-rays from CNFs at moderately relativistic intensities of around 5\times{10}^{19}\ W/cm^2.\ The density and thickness of the CNFs were scanned in the experiments, indicating the optimized electrons temperature of 5.5 MeV and X-ray critical energy of 5 keV. Two-dimensional (2D) particle-in-cell (PIC) simulations confirm that the electrons, with a temperature significantly higher than the pondermotive scale, are directly accelerated by the laser along the NCD plasma channel, while the bright X-rays are emitted by these electrons through betatron radiation or Thomson backscattering inside the channel. The simultaneously generated electrons and X-rays, automatically synchronized with the femtosecond laser driver, are suitable for applications such as bi-modal radiography.Comment: arXiv admin note: text overlap with arXiv:2010.0570

Synchronous post-acceleration of laser-driven protons in helical coil targets by controlling the current dispersion

Post-acceleration of protons in helical coil targets driven by intense, ultrashort laser pulses can enhance ion energy by utilizing the transient current from the targets’ self-discharge. The acceleration length of protons can exceed a few millimeters, and the acceleration gradient is of the order of GeV/m. How to ensure the synchronization between the accelerating electric field and the protons is a crucial problem for efficient post-acceleration. In this paper, we study how the electric field mismatch induced by current dispersion affects the synchronous acceleration of protons. We propose a scheme using a two-stage helical coil to control the current dispersion. With optimized parameters, the energy gain of protons is increased by four times. Proton energy is expected to reach 45 MeV using a hundreds-of-terawatts laser, or more than 100 MeV using a petawatt laser, by controlling the current dispersion

Poly lactic-co-glycolic acid controlled delivery of Disulfiram to target liver cancer stem-like cells

Disulfiram (DS), an anti-alcoholism drug, shows very strong cytotoxicity in many cancer types. However its clinical application in cancer treatment is limited by the very short half-life in the bloodstream. In this study, we developed a poly lactic-co-glycolic acid (PLGA)-encapsulated DS protecting DS from the degradation in the bloodstream. The newly developed DS-PLGA was characterized. The DS-PLGA has very satisfactory encapsulation efficiency, drug-loading content and controlled release rate in vitro. PLGA encapsulation extended the half-life of DS from shorter than 2 minutes to 7 hours in serum. In combination with copper, DS-PLGA significantly inhibited the liver cancer stem cell population. CI-isobologram showed a remarkable synergistic cytotoxicity between DS-PLGA and 5-FU or Sorafenib. It also demonstrated very promising anticancer efficacy and antimetastatic effect in liver cancer mouse model. Both DS and PLGA are FDA approved products for clinical application. Our study may lead to repositioning of DS into liver cancer treatment

Application of Approximate Pattern Matching in Two Dimensional Spaces to Grid Layout for Biochemical Network Maps

Background For visualizing large-scale biochemical network maps, it is important to calculate the coordinates of molecular nodes quickly and to enhance the understanding or traceability of them. The grid layout is effective in drawing compact, orderly, balanced network maps with node label spaces, but existing grid layout algorithms often require a high computational cost because they have to consider complicated positional constraints through the entire optimization process. Results We propose a hybrid grid layout algorithm that consists of a non-grid, fast layout (preprocessor) algorithm and an approximate pattern matching algorithm that distributes the resultant preprocessed nodes on square grid points. To demonstrate the feasibility of the hybrid layout algorithm, it is characterized in terms of the calculation time, numbers of edge-edge and node-edge crossings, relative edge lengths, and F-measures. The proposed algorithm achieves outstanding performances compared with other existing grid layouts. Conclusions Use of an approximate pattern matching algorithm quickly redistributes the laid-out nodes by fast, non-grid algorithms on the square grid points, while preserving the topological relationships among the nodes. The proposed algorithm is a novel use of the pattern matching, thereby providing a breakthrough for grid layout. This application program can be freely downloaded from http://www.cadlive.jp/hybridlayout/hybridlayout.html

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Gearing Urban Metabolism toward the Carbon Neutrality Target: A Case Study of Hebei Province, China

Urban metabolism has emerged over the past decades as an important new paradigm of regional and urban sustainability governance towards a Chinese national scheme of ‘carbon neutrality’ by 2060. Hebei province in China faces twin pressures related to its supply of water and energy resources, which has brought humans and nature into conflict. Overcoming this tension in the human-land relationship in Hebei and determining a suitable development path for the future has become a core issue for the achievement of coordinated development within the Beijing–Tianjin–Hebei region. This paper constructs a system to simulate the metabolism of water, energy, and human relationships, and uses this model to carry out simulations for Hebei province. The model establishes five scenarios: a natural development scenario, economic growth scenario, water conservation development scenario, energy conservation development scenario, and low carbon scenario. The simulation results show that, without intervention, the natural development scenario results in greater pressure on supply gaps and a greater demand for water and energy, with more production of industrial waste gas and domestic wastewater discharges. The economic growth, water conservation development, and energy conservation development scenarios focus on single economic, water conservation, and energy conservation measures by looking at core economic, water, and energy elements within the metabolic system; however, solving issues with individual elements merely leads to other, remaining problems. Under the low carbon scenario, issues with multiple elements in Hebei’s metabolic system are considered more comprehensively, so the simulation results are better than those in the other scenarios, and it better fits the future orientation of sustainable development of Hebei province

Research on the Technology Innovation Efficiency of China’s Listed New Energy Vehicle Enterprises

As a new industry, the healthy development of new energy vehicle industry is of great significance for effectively solving environmental problems and energy crises. The purpose of this study was to analyze the technological innovation process of China’s new energy vehicle enterprises and construct the evaluation index system of technology innovation efficiency of China’s new energy vehicle enterprises and SBM model-based network DEA model from the two aspects of technology research and development stage and achievement transformation stage. The overall technological innovation efficiency and staged efficiency of 16 listed new energy vehicle enterprises in China were measured and combined with the Malmquist Index Model. The technical change and efficiency change of 16 listed new energy vehicle enterprises in China, spanning from 2012 to 2018, were analyzed. The results show that the average overall efficiency of technological innovation of 16 new energy automobile companies is 0.5515, and the standard deviation is 0.2341. It reflects the low overall efficiency of technological innovation of Chinese new energy vehicle enterprises and the uneven development and the huge gap between different enterprises. From 2012 to 2018, the M index is less than 1, and the technical level change (TC) has a greater negative impact on the M index