Elucidating Charge Separation Dynamics in a Hybrid Metal–Organic Framework Photocatalyst for Light-Driven H\u3csub\u3e2\u3c/sub\u3e Evolution

Metal–organic frameworks (MOFs) have emerged as novel scaffolds for artificial photosynthesis due to their unique capability in incorporating homogeneous photosensitizer and catalyst to their robust heterogeneous matrix. In this work, we report the charge separation dynamics between molecular Ru-photosensitizer and Pt-catalyst, both of which were successfully incorporated into a Zr-MOF that demonstrates excellent activity and stability for light-driven H2 generation from water. Using optical transient absorption (OTA) spectroscopy, we show that charge separation in this hybrid MOF occurs via electron transfer (ET) from Ru-photosensitizer to Pt-catalyst. Using Pt L3-edge X-ray transient absorption (XTA) spectroscopy, we observed the intermediate reduced Pt site, directly confirming the formation of charge separated state due to ET from Ru-photosensitizer and unraveling their key roles in photocatalysis

Common Reservoirs for Penicillium marneffei Infection in Humans and Rodents, China

Human penicilliosis marneffei is an emerging infectious disease caused by the fungus Penicillium marneffei. High prevalence of infection among bamboo rats of the genera Rhizomys and Cannomys suggest that these rodents are a key facet of the P. marneffei life cycle. We trapped bamboo rats during June 2004–July 2005 across Guangxi Province, China, and demonstrated 100% prevalence of infection. Multilocus genotypes show that P. marneffei isolates from humans are similar to those infecting rats and are in some cases identical. Comparison of our dataset with genotypes recovered from sites across Southeast Asia shows that the overriding component of genetic structure in P. marneffei is spatial, with humans containing a greater diversity of genotypes than rodents. Humans and bamboo rats are sampling an as-yet undiscovered common reservoir of infection, or bamboo rats are a vector for human infections by acting as amplifiers of infectious dispersal stages

An integrated software for virus community sequencing data analysis

BACKGROUND: A virus community is the spectrum of viral strains populating an infected host, which plays a key role in pathogenesis and therapy response in viral infectious diseases. However automatic and dedicated pipeline for interpreting virus community sequencing data has not been developed yet.RESULTS: We developed Quasispecies Analysis Package (QAP), an integrated software platform to address the problems associated with making biological interpretations from massive viral population sequencing data. QAP provides quantitative insight into virus ecology by first introducing the definition "virus OTU" and supports a wide range of viral community analyses and results visualizations. Various forms of QAP were developed in consideration of broader users, including a command line, a graphical user interface and a web server. Utilities of QAP were thoroughly evaluated with high-throughput sequencing data from hepatitis B virus, hepatitis C virus, influenza virus and human immunodeficiency virus, and the results showed highly accurate viral quasispecies characteristics related to biological phenotypes.CONCLUSIONS: QAP provides a complete solution for virus community high throughput sequencing data analysis, and it would facilitate the easy analysis of virus quasispecies in clinical applications.</p

Multiobjective optimization algorithm for accurate MADYMO reconstruction of vehicle-pedestrian accidents

In vehicle–pedestrian accidents, the preimpact conditions of pedestrians and vehicles are frequently uncertain. The incident data for a crash, such as vehicle deformation, injury of the victim, distance of initial position and rest position of accident participants, are useful for verification in MAthematical DYnamic MOdels (MADYMO) simulations. The purpose of this study is to explore the use of an improved optimization algorithm combined with MADYMO multibody simulations and crash data to conduct accurate reconstructions of vehicle–pedestrian accidents. The objective function of the optimization problem was defined as the Euclidean distance between the known vehicle, human and ground contact points, and multiobjective optimization algorithms were employed to obtain the local minima of the objective function. Three common multiobjective optimization algorithms—nondominated sorting genetic algorithm-II (NSGA-II), neighbourhood cultivation genetic algorithm (NCGA), and multiobjective particle swarm optimization (MOPSO)—were compared. The effect of the number of objective functions, the choice of different objective functions and the optimal number of iterations were also considered. The final reconstructed results were compared with the process of a real accident. Based on the results of the reconstruction of a real-world accident, the present study indicated that NSGA-II had better convergence and generated more noninferior solutions and better final solutions than NCGA and MOPSO. In addition, when all vehicle-pedestrian-ground contacts were considered, the results showed a better match in terms of kinematic response. NSGA-II converged within 100 generations. This study indicated that multibody simulations coupled with optimization algorithms can be used to accurately reconstruct vehicle-pedestrian collisions

Icariin Prevents IL-1 β

Purpose. To explore the effect and possible mechanism of icariin, a prenylated flavonol glycoside derived from the Chinese herb Epimedium sagittatum that was applied to IL-1β pretreated human nucleus pulposus (NP) cells. Methods. Human NP cells were isolated from intervertebral discs of patients with scoliosis and lumbar spondylolisthesis. The cells were divided into five groups: A (blank control); B (20 ng/ml IL-1β); C (20 ng/ml IL-1β + 20 μM icariin); D (20 μM icariin + 20 ng/ml IL-1β + 25 μM LY294002); E (20 ng/ml IL-1β + 25 μM LY294002). For each of the five groups, the CCK8, apoptosis rates, ROS rates, and JC-1 rates were determined and an electron micrograph was performed. Different expression levels of apoptosis proteins and proteins in the PI3K/AKT pathway were detected via western blot. Results. We found that the damage effects on human nucleus pulposus cells from 20 ng/ml of IL-1β exposure were attenuated by icariin. When the PI3K/AKT pathway was blocked by LY294002, a specific inhibitor of this pathway, the protective effect of icariin was impaired. In summary, icariin might be a protective traditional Chinese medicine, which prevents inflammation-induced degeneration of intervertebral discs partly through the PI3K/AKT pathway

Characterization of gene expression profiles in HBV-related liver fibrosis patients and identification of ITGBL1 as a key regulator of fibrogenesis

Although hepatitis B virus (HBV) infection is the leading cause of liver fibrosis (LF), the mechanisms underlying liver fibrotic progression remain unclear. Here, we investigated the gene expression profiles of HBV-related LF patients. Whole genome expression arrays were used to detect gene expression in liver biopsy samples from chronically HBV infected patients. Through integrative data analysis, we identified several pathways and key genes involved in the initiation and exacerbation of liver fibrosis. Weight gene co-expression analysis revealed that integrin subunit β-like 1 (ITGBL1) was a key regulator of fibrogenesis. Functional experiments demonstrated that ITGBL1 was an upstream regulator of LF via interactions with transforming growth factor β1. In summary, we investigated the gene expression profiles of HBV-related LF patients and identified a key regulator ITGBL1. Our findings provide a foundation for future studies of gene functions and promote the development of novel antifibrotic therapies

Therapeutic effects of the novel subtype-selective histone deacetylase inhibitor chidamide on myeloma-associated bone disease

Histone deacetylases are promising therapeutic targets in hematological malignancies. In the work herein, we investigated the effect of chidamide, a new subtype-selective histone deacetylase inhibitor that was independently produced in China, on multiple myeloma and its associated bone diseases using different models. The cytotoxicity of chidamide toward myeloma is due to its induction of cell apoptosis and cell cycle arrest by increasing the levels of caspase family proteins p21 and p27, among others. Furthermore, chidamide exhibited significant cytotoxicity against myeloma cells co-cultured with bone mesenchymal stromal cells and chidamide-pretreated osteoclasts. Importantly, chidamide suppressed osteoclast differentiation and resorption in vitro by dephosphorylating p-ERK, p-p38, p-AKT and p-JNK and inhibiting the expression of Cathepsin K, NFATc1 and c-fos. Finally, chidamide not only prevented tumor-associated bone loss in a disseminated murine model by partially decreasing the tumor burden but also prevented rapid receptor activator of nuclear factor κ-β ligand (RANKL)-induced bone loss in a non-tumor-bearing mouse model. Based on our results, chidamide exerted dual anti-myeloma and bone-protective effects in vitro and in vivo. These findings strongly support the potential clinical use of this drug as a treatment for multiple myeloma in the near future

Docetaxel-Loaded Pluronic P123 Polymeric Micelles: in Vitro and in Vivo Evaluation

In this work, novel docetaxel (DTX) -loaded Tween 80-free Pluronic P123 (P123) micelles with improved therapeutic effect were developed. The freeze-dried DTX-loaded P123 micelles (DTX-micelles) were analyzed by HPLC, TEM and DLS to determine the DTX loading, micelle morphology, size, respectively. The in vitro cytotoxic activity of DTX-micelles in HepG2, A549 and malignant melanoma B16 cells were evaluated by MTT assay. The corresponding in vivo antitumor efficacy was assessed in Kunming mice bearing B16 tumor after intravenous administration. The DTX-loading and efficiency into the micelles were 2.12 ± 0.09% and 86.34 ± 3.32%, respectively. The DTX-micelles were spherical with a mean particle size of 50.7 nm and size distribution from 22 to 84 nm, which suggested that they should be able to selectively accumulate in solid tumors by means of EPR effect, with a zeta potential of −12.45 ± 3.24 mV. The in vitro release behavior of DTX from DTX-micelles followed the Weibull equation. Compared with Duopafei®, DTX-micelles showed higher cytotoxicity against HepG2 (P < 0.01), A549 (P < 0.05) and B16 (P < 0.01) cells. In addition, DTX-micelles exhibited remarkable antitumor activity and reduced toxicity on B16 tumor in vivo. The tumor inhibition rates (TIR) of DTX-micelles was 91.6% versus 76.3% of Duopafei® (P < 0.01). These results suggested that P123 micelles might be considered as an effective DTX delivery system

Simulation Studies for the First Pathfinder of the CATCH Space Mission

The Chasing All Transients Constellation Hunters (CATCH) space mission is an intelligent constellation consisting of 126 micro-satellites in three types (A, B, and C), designed for X-ray observation with the objective of studying the dynamic universe. Currently, we are actively developing the first Pathfinder (CATCH-1) for the CATCH mission, specifically for type-A satellites. CATCH-1 is equipped with Micro Pore Optics (MPO) and a 4-pixel Silicon Drift Detector (SDD) array. To assess its scientific performance, including the effective area of the optical system, on-orbit background, and telescope sensitivity, we employ the Monte Carlo software Geant4 for simulation in this study. The MPO optics exhibit an effective area of $41$ cm$^2$ at the focal spot for 1 keV X-rays, while the entire telescope system achieves an effective area of $29$ cm$^2$ at 1 keV when taking into account the SDD detector's detection efficiency. The primary contribution to the background is found to be from the Cosmic X-ray Background. Assuming a 625 km orbit with an inclination of $29^\circ$, the total background for CATCH-1 is estimated to be $8.13\times10^{-2}$ counts s$^{-1}$ in the energy range of 0.5--4 keV. Based on the background within the central detector and assuming a Crab-like source spectrum, the estimated ideal sensitivity could achieve $1.9\times10^{-12}$ erg cm$^{-2}$ s$^{-1}$ for an exposure of 10$^4$ s in the energy band of 0.5--4 keV. Furthermore, after simulating the background caused by low-energy charged particles near the geomagnetic equator, we have determined that there is no need to install a magnetic deflector