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PDE1 has been demonstrated to be a potential drug target for a variety of diseases, such as Alzheimer's disease and cardiovascular disease. In the past decades, numerous PDE1 inhibitors with structural diversities have been developed and patented by pharmaceutical companies, providing drug candidates for exploring novel disease indications of PDE1.This review aims to provide an overview of PDE1 inhibitors reported in patents from 2008 to present.Among current PDE1 inhibitors, only a few of them showed high selectivity over other PDEs, which might cause severe side effects in the clinic. The development of highly selective PDE1 inhibitors is still the 'top priority' in the following research. The selective recognition mechanism of PDE1 with inhibitors should be further elucidated by X-ray crystallography in order to provide evidence for the rational design of selective PDE1 inhibitors. In addition, PDE1 inhibitors should be applied to different clinical indications beyond CNS diseases.

Flame stabilization in a kerosene-fueled scramjet combustor was investigated experimentally through Schlieren, flame luminosity, and wall pressure measurement, aiming to obtain better insight into combustion characteristics. Experiments were conducted in a direct-connected supersonic combustion facility with inflow conditions of Mach number 2.0, stagnation pressure 0.82 MPa, and temperature 950 K, simulating the flight condition of Mach number 4.0. Results revealed that kerosene was able to be ignited when the equivalence ratio of pilot hydrogen reached 0.080, but was unsuccessful when the equivalence ratio was 0.040. Once ignited, the intense combustion induced high back pressure forcing the flame to spread into the isolator. The pilot flame invariably appeared in the cavity shear layer and attached to the cavity ramp under different equivalence ratios of pilot hydrogen. With the mass flux of pilot hydrogen increased, the kerosene flame located near the cavity ramp was asymmetrical and unstable since it propagated upstream repeatedly. Therefore, the kerosene could be ignited by a suitable equivalence ratio of continuous pilot hydrogen, potentially accompanied with unstable combustion.

This paper presents a discrete element model for simulations of the compaction process of hot mixed asphalt (HMA). The model is anchored by the concept of a fine aggregate matrix (FAM), whi...

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and devastating lung disease lacking effective therapy. To identify whether phosphodiesterase-1 (PDE1) inhibition could act as a novel target for the treatment of IPF, hit-to-lead structural optimizations were performed on the PDE9/PDE1 dual inhibitor (R)-C33, leading to compound 3m with an IC50 of 2.9 nM against PDE1C, excellent selectivity across PDE subfamilies, reasonable drug-like properties, and remarkable pharmacodynamic effects as an anti-IPF agent. Oral administration of compound 3m (10 mg/kg) exerted more significant anti-pulmonary fibrosis effects than pirfenidone (150 mg/kg) in a bleomycin-induced IPF rat model and prevented transforming growth factor-β-induced fibroblast-to-myofibroblast conversion in vitro, indicating that PDE1 inhibition could serve as a novel target for the efficient treatment of IPF.

Phosphodiesterase-9 (PDE9) is a promising target for the treatment of Alzheimer’s disease (AD). To discover efficient PDE9 inhibitors with good metabolic stability and solubility, a series of novel pyrazolopyrimidinone derivatives have been designed with the assistance of molecular docking and dynamics simulations. All the fourteen synthesized compounds gave excellent inhibition ratio against PDE9 at 10 nM. Compound 1k with the IC50 of 2.0 nM against PDE9, showed good metabolic stability (t1/2 of 57 min) in the RLM as well as good solubility (195 mg/L). The analysis on binding modes of targeted compounds may provide insight for further structural modification.

We employ TiO 2 single-crystal films as a substrate and use a photochemical deposition method to prepare Ag-doped and Ag/N co-doped TiO 2 single-crystal films. We also investigate the optical and magnetic properties of the samples using various measurements. No diffraction peaks related to silver oxide appear in the X-ray diffraction (XRD) spectra, which implies the existence of Ag atoms in Ag-doped TiO 2 single-crystal films. X-ray photoelectron spectroscopy (XPS) spectra indicate the existence of Ti 4+ and Ag° in Ag/N co-doped TiO 2 single-crystal films. It is found that Ag is deposited on a TiO 2 single-crystal film surface in the form of Ag particles. Meanwhile, Ag particles can slightly enhance ferromagnetism in Ag-doped TiO 2 single-crystal films compared with the TiO 2 single-crystal film sample. Oxygen vacancies and Ag particle synergy influence ferromagnetism in Ag/N co-doped TiO 2 single-crystal films.

In this work, the TiO2 nanorod arrays (TNAs), TNAs/Cu2O-10CYC, and TNAs/Cu2O-30CYC composites photo-catalysts for solar water splitting anode was successfully prepared via cyclic impregnation growth method. The structure, surface morphology and element chemical states have been investigated and discussed in detail. The UV–vis and PL results confirm that interaction has been formed between TNAs and Cu2O in the composite photo-catalysts and the TNAs/Cu2O composites exhibit broad spectrum absorption. Three factors affecting on the enhancement of solar light hydrogen production efficiency, e.g. enhanced UV-light absorption in solar spectrum, massive charge carrier generation and improved surface-interface reaction due to the absorbing visible light by the narrow band gap Cu2O and the injecting electrons into TiO2 conduction band, are proposed based on the experimental results. The TNAs/Cu2O-10CYC composite samples exhibit highest enhanced photocatalytic activities in the hydrogen production, which H2 evolution efficiency is about 4-fold higher than that of pure TNAs. It indicates that the efficient photo generated electron-hole transformation and separation in TNAs/Cu2O-10CYC composite sample leads to the improvement of photocatalytic performance. The present study provides a new light to prepare TNAs/Cu2O of novel configuration with promising potential applications.

The multi-target-directed-ligand (MTDL) strategy has been widely applied in the discovery of novel drugs for the treatment of Alzheimer’s disease (AD) because of the multifactorial pathological mechanisms of AD. Phosphodiesterase-2 (PDE2) has been identified to be a novel and promising target for AD. However, MTDL combining with the inhibitory activity against PDE2A and other anti-AD factors such as antioxidants has not been developed yet. Herein, a novel series of PDE2 inhibitors with antioxidant capacities were designed, synthesized, and evaluated. Most compounds showed remarkable inhibitory activities against PDE2A as well as antioxidant activities. Compound 6d was selected, which showed good IC50 of 6.1 nM against PDE2A, good antioxidant activity (ORAC (Trolox) = 8.4 eq.) and no cytotoxicity to SH-SY5Y cells. Molecular docking and dynamics simulations were applied for the rational design and explanation of structure–activity relationship (SAR) of lead compounds.

A new model is proposed for the optimal scheduling of gas-electric integrated energy systems, considering the incentive demand response (IBDR) to provide the reserve ancillary service. By incorporating the IBDR, one hand, the system can give full play to the complementary functions of different energy sources to enhance the efficiency of the system; on the other hand, more flexibility can be utilized to cope with the uncertainty of wind power with IBDR providing reserves with conventional units simultaneously. We establish the IBDR model with segmental price-quantity curves, and the transient gas flow and steady state power flow are combined to formulate the operation model of gas-electric integrated systems. A 6-node power network and a 12-node natural gas network were selected to construct a gas-electric integrated energy system. The simulation results show that the IBDR can improve the flexibility of the system and decrease the total operation cost of the gas-electric integrated energy system.

Demand response is becoming a rational option to guarantee system reliability and reduce the investment. To tackle the possible overload caused by wind power uncertainty and N-1 contingency, a stochastic mixed integer linear programming model is proposed first. In addition, extreme scenario method is utilized to guarantee the robustness of planning scheme. The proposed method is validated in the modified Garver 6-bus system with practical scenario input. The simulation results demonstrate that the demand response helps to relieve the power flow overload and reducing transmission line investment.

We propose an optical fiber sensor combined with a polymer fiber Fizeau interferometer and an airgap hollow core fiber Fabry-Perot interferometer to simultaneously measure relative humidity (RH) and temperature (T) with good sensitivity.

Nitrogen-doped titanium dioxide (TiO2) nanotube arrays were synthesized by anodization in ethylene glycol electrolyte and annealing in ammonia at 500 °C. Detailed analysis showed that the nitrogen-doped titania nanotubes were pure anatase of ordered structure, with a crystallite size of 8.5 nm. The doping nitrogen atoms were induced on the interstitial sites and substitutional sites and the ratio of oxygen vacancies increased to 27.15 %, resulting in an add-on peak in the absorption spectrum and extended the absorption from 387 to 618 nm. The photocatalytic activity of the nitrogen-doped TiO2 nanotubes was evaluated by photocatalytic degradation of methyl blue under visible light irradiation. Significant improvement of photocatalytic activity under visible light irradiation was observed. We assumed the nitrogen doping induced the effect produced by nitrogen atoms, Ti3+ cations and oxygen vacancies and the size effect of the TiO2 crystallite should be responsible for the effective photocatalytic activity.

According to the color development reaction between starch/iodine reagent and products which obtained by fumigating melamine with chlorine, a method for determination of melamine in milk was put forward. The conditions of method were researched. The best conditions are as follows. Volume ratio of milk and extraction agent is 1:1. 5, dissolved with ultrasonic washer for 5 minutes, centrifugal separation 4000r/min for 5 minutes, extracted by C008 cation exchange resin column. The results are as follows: detection limit is 10mg/L, the linear range is 25-250 mg/L, related coefficient r is 0.994, coefficient of recovery is 94%-110%, and relatively standard deviation is 0.9%. This method is easy handling, cheap equipment, good practicability and recovery, can be used as low cost detection method.