Chronic hepatitis B virus (HBV) infection is a serious public health burden, and current therapies cannot achieve satisfactory cure rate. There are high unmet medical needs of novel therapeutic agents with differentiated mechanism of action (MOA) from the current standard of care. RG7834, a compound from the dihydroquinolizinone (DHQ) chemical series, is a first-in-class highly selective and orally bioavailable HBV inhibitor which can reduce both viral antigens and viral DNA with a novel mechanism of action. Here we report the discovery of RG7834 from a phenotypic screening and the structure–activity relationship (SAR) of the DHQ chemical series. RG7834 can selectively inhibit HBV but not other DNA or RNA viruses in a virus panel screening. Both in vitro and in vivo profiles of RG7834 are described herein, and the data support further development of this compound as a chronic HBV therapy.

Activity-tracking applications and location-based services using short-range communication (SRC) techniques have been abruptly demanded in the COVID-19 pandemic, especially for automated contact tracing. The attention from both public and policy keeps raising on related practical problems, including 1) how to protect data security and location privacy? 2) how to efficiently and dynamically deploy SRC Internet of Thing (IoT) witnesses to monitor large areas? To answer these questions, in this paper, we propose a decentralized and permissionless blockchain protocol, named Bychain. Specifically, 1) a privacy-preserving SRC protocol for activity-tracking and corresponding generalized block structure is developed, by connecting an interactive zeroknowledge proof protocol and the key escrow mechanism. As a result, connections between personal identity and the ownership of on-chain location information are decoupled. Meanwhile, the owner of the on-chain location data can still claim its ownership without revealing the private key to anyone else. 2) An artificial potential field-based incentive allocation mechanism is proposed to incentivize IoT witnesses to pursue the maximum monitoring coverage deployment. We implemented and evaluated the proposed blockchain protocol in the real-world using the Bluetooth 5.0. The storage, CPU utilization, power consumption, time delay, and security of each procedure and performance of activities are analyzed. The experiment and security analysis is shown to provide a real-world performance evaluation.

The purpose of this study was to conduct a pilot study in order to obtain reliable results for further planning of a well-designed pivotal trial comparing the bioequivalence (BE) of two paroxetine tablet formulations in healthy Chinese subjects. Before conducting the pivotal trial, the pilot trial enrolled 14 subjects to help in study design, establishing the recruitment period, determining pharmacokinetics (PK) time points and sample size, and assessing BE of the two formulations. The single-center, randomized, open-label, single-dose, two period crossover study with a 7-day washout interval was conducted after obtaining information from the fasted pilot trial in 72 healthy volunteers for a pivotal study under fed and fasted conditions, respectively. There were 19 PK sample collection time points employed in both the pilot and pivotal trials. A sensitive and specific liquid chromatography- tandem mass spectrometry (LC-MS/ MS) method was developed and validated for determining paroxetine in human plasma. BE between two articles was determined by calculating 90% confidence intervals (CIs) for the ratio of Cmax 91.38 - 110.39% for the pilot trial, 99.81 - 114.08% for pivotal trial under fasted condition, and 94.06 - 110.41% for pivotal trial under fed condition, AUC(0-t) 96.06 - 110.52% for pilot study, 100.88 - 113.05% for the pivotal trial under fasted condition, and 97.08 - 106.06% for pivotal study under fed condition, and AUC(0-∞) 96.17 - 110.42% for the pilot study, 100.85 - 112.81% for the pivotal trial under fasted condition and 97.22 - 106.14% for the pivotal study under fed condition, respectively. These values for the test and reference products are within the 80 - 125% interval proposed by FDA and EMEA. It was concluded that the proposed method was successfully applied to a PK study in healthy Chinese volunteers, and results showed from both the pilot and pivotal studies that the two paroxetine formulations are bioequivalent in their rates and extent of absorption.

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In the paper, the homomorphic filter is improved , and a new filter is made , which is based on the low-pass frequency filter and high-pass filter. The performance of the new filter is analysised through comparing to other classical filter. The new filter is experimented, and its application was discussed.