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ABSTRACT: Duck hepatitis A virus type 3 (DHAV-3) is an infectious virus that is highly fatal to ducklings and causes significant economic losses in the duck industry worldwide. Biosecurity and vaccination are required to control the pathogen. In the present study, we attenuated a lowly pathogenic DHAV-3 clinical isolate, named as HB, by serial passaging in duck embryos, and followed by several adaptive proliferations in specific-pathogen-free (SPF) chicken embryos. The virulence of DHAV-3 at different passages was assessed by infecting 3-day-old ducklings. We found that the HB strain lost pathogenicity to ducklings from the 55th passage onwards. The 80th passage strain (HB80), which achieved good growth capacity in duck embryos with a viral titer of 108.17 50% egg lethal dose per milliliter (ELD50/mL), was selected as a live attenuated vaccine candidate. The HB80 strain did not induce clinical symptoms or pathological lesions in 3-day-old ducklings and showed no virulence reversion after 5 rounds of in vivo back-passage. The minimum effective dose of HB80 was determined to be 104.5 ELD50 by hypodermic inoculation of the neck. Importantly, a single dose of HB80 elicited good immune responses and provided complete protection against challenge with the lethal DHAV-3 strain. Compared with the genomic sequence of the parental HB strain, HB80 had 7 amino acid substitutions, two of them are in the hypervariable region of the VP1 and polymerase-encoding 3D regions, which may play a role in virulence attenuation. Our data suggest that the attenuated HB80 strain is a promising vaccine candidate for the prevention of DHAV-3 infections in China. HB80 has been registered as a New Veterinary Drug Registration Certificate by the Chinese Ministry of Agriculture and Rural Affairs (MARA), and is the first live attenuated DHAV-3 vaccine strain to be officially licensed in China.

Summary: Drug repurposing is a promising approach to find new therapeutic indications for approved drugs. Many computational approaches have been proposed to prioritize candidate anticancer drugs by gene or pathway level. However, these methods neglect the changes in gene interactions at the edge level. To address the limitation, we develop a computational drug repurposing method (iEdgePathDDA) based on edge information and pathway topology. First, we identify drug-induced and disease-related edges (the changes in gene interactions) within pathways by using the Pearson correlation coefficient. Next, we calculate the inhibition score between drug-induced edges and disease-related edges. Finally, we prioritize drug candidates according to the inhibition score on all disease-related edges. Case studies show that our approach successfully identifies new drug-disease pairs based on CTD database. Compared to the state-of-the-art approaches, the results demonstrate our method has the superior performance in terms of five metrics across colorectal, breast, and lung cancer datasets.

Ribonucleotide reductase M2 (RRM2) is a small subunit in ribonucleotide reductases, which participate in nucleotide metabolism and catalyze the conversion of nucleotides to deoxynucleotides, maintaining the dNTP pools for DNA biosynthesis, repair, and replication. RRM2 performs a critical role in the malignant biological behaviors of cancers. The structure, regulation, and function of RRM2 and its inhibitors were discussed. RRM2 gene can produce two transcripts encoding the same ORF. RRM2 expression is regulated at multiple levels during the processes from transcription to translation. Moreover, this gene is associated with resistance, regulated cell death, and tumor immunity. In order to develop and design inhibitors of RRM2, appropriate strategies can be adopted based on different mechanisms. Thus, a greater appreciation of the characteristics of RRM2 is a benefit for understanding tumorigenesis, resistance in cancer, and tumor microenvironment. Moreover, RRM2-targeted therapy will be more attention in future therapeutic approaches for enhancement of treatment effects and amelioration of the dismal prognosis.

Abstract System disturbances, such as the change of required service durations, the failure of resources, and temporary tasks during the scheduling process of data relay satellite network (DRSN), are difficult to be predicted, which may lead to unsuccessful scheduling of tasks. A high-efficiency and robust DRSN calls for smarter and more flexible disturbances elimination strategies. Here, we unify the above three system disturbances as temporary task arrival and extend the static scheduling model of DRSN. Specifically, we derive and define a scheduling model that unifies the static scheduling and dynamic scheduling processes. Meanwhile, we propose a k-step dynamic scheduling algorithm considering breakpoint transmission (k-steps-BT) to solve the above model. Based on the principle of backtracking algorithm and search tree, k-steps-BT can eliminate disturbances quickly by rescheduling tasks and can determine the rescheduling scheme when temporary tasks arrive. Finally, extensive experiments are carried out to verify the proposed model and algorithm. The results show that the proposed model and algorithm can significantly improve the task completion rate of dynamic scheduling without drastic adjustments to the static scheduling scheme.

Polysaccharide is one of the principal bioactive components found in medicinal mushrooms and has been proven to enhance host immunity. However, the possible mechanism of immunomodulatory activity of Cordyceps militaris polysaccharide is not fully understood. Hot water extraction and alcohol precipitation, DEAE-Sephadex A-25 chromatography, and Sephadex G-100 chromatography were used to isolate polysaccharide from C. militaris. A high-molecular-weight polysaccharide isolated from C. militaris was designated as HCMP, which had an Mw of 6.18 × 105 Da and was composed of arabinose, galactose, glucose, mannose, and xylose in a mole ratio of 2.00:8.01:72.54:15.98:1.02. The polysaccharide content of HCMP was 91.2% ± 0.16. The test in vitro showed that HCMP activated mouse macrophage RAW 264.7 cells by enhancing phagocytosis and NO production, and by regulating mRNA expressions of inflammation-related molecules in RAW 264.7 cells. Western blotting revealed that HCMP induced the phosphorylation of mitogen-activated protein kinases (MAPKs). Moreover, using inhibitors of MAPKs decreased the mRNA levels of inflammation-related molecules induced by HCMP. These data evidenced that the immunomodulatory effect of HCMP on RAW 264.7 macrophages was mediated via the MAPK signaling pathway. These findings suggested that HCMP could be developed as a potent immunomodulatory agent for use in functional foods and dietary supplements.

A numerical research is conducted to clarify the unsteady airflow and pressure characteristics in the full-scale underground highway station to ensure the passenger safety and energy saving in Heating, ventilation and air-conditioning design. Results show pressure characteristics in the tunnel change greatly due to the propagations of compression and expansion waves. The propagations of compression and expansion waves determine the local pressures together. For the first two locations X = −900 m and X = −800 m, the pressure climbs to the peak when the head of the train reaches. However, for the other locations, the pressure is not the maximum when the train reaches, due to the effect of Initial Expansion Wave (IEW). With the raising of train speeds, the positive maximum velocities are increased by 32.60% and 47.58%, respectively. It should be noted that there are two peak values of horizontal velocities successively, with the train speed of 250 km/h and 300 km/h.

China’s grain production has been on a pathway paralleled with urbanization in recent 40 years, from lower efficiency and productivity to the higher ones, and has met complex impact factors and contradiction between sustainable development of farming and urbanization. Spatial-temporal pattern of grain production in China, by total and per capita output, was analyzed through Local Moran’I from 1985 to 2019. Until 2019, the high-output countries were mainly aggregated in the main plains and basins on the third step of China’s terrain and the low-output areas increased in the southeastern coastal regions; the countries with high per capita output almost disappeared and the low areas increased a lot in the central and southern regions Then the impact factors, by total output in the whole country and in grain surplus-shortage regions, were detected and found out through Geodetector. In the whole country, cultivated land areas, agricultural machinery, total meat output and value-added of primary industry not only played important role independently, but also had mutual coupling effect in grain total output. And in the grain surplus regions, major factors were cultivated land areas and value-added of primary industry, while in the grain shortage regions, were labors and market as well as economic factors. Thirdly, factor mechanism of China’s grain production for four types of development orientations, i.e., orientation on production scale, production efficiency and benefit, product quality and economic coordination, were concluded, and the way of grain production in different regions with unique suitability and advantage were expounded.

In less than eight months, the COVID-19 (coronavirus disease 2019) caused by the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus has resulted in over 20,000,000 confirmed cases and over 700,000 deaths around the world. With the increasing worldwide spreading of this disease, the lack of effective drugs against SARS-CoV-2 infection makes the situation even more dangerous and unpredictable. Although many forces are speeding up to develop prevention and treatment therapeutics, it is unlikely that any de novo drugs will be available in months. Drug repurposing holds the promise to significantly save the time for drug development, since it could use existing clinic drugs to treat new diseases. Based on the “steric-clashes alleviating receptor (SCAR)” strategy developed in our lab recently, we screened the library of clinic and investigational drugs, and identified nine drugs that might be repurposed as covalent inhibitors of the priming proteases (cathepsin B, cathepsin L, and TMPRSS2) of the spike protein of SARS-CoV-2. Among these hits, five are known covalent inhibitors, and one is an anti-virus drug. Therefore, we hope our work would provide rational and timely help for developing anti-SARS-CoV-2 drugs.

A practical structural health monitoring (SHM) system based on Lamb wave for high-speed train car-body structures is presented. The system can detect the occurrence and report the location and probabilistic size of structural damage in real-time. Based on the theory of Lamb wave, a piezoelectric transducer array network is implemented to generate and acquire the detection signal by mounting on the surface of the structure to be monitored. An algorithm, that can locate, quantify and image the damage based on the damage index that indicates the differential between baseline signal and current acquired signal, is proposed to develop the system. Furthermore, a system framework of three-layer architecture and a diagnosis strategy are designed to build the SHM system. Finally, the system is implemented on China's latest high-speed train (CRH380A) operated along the Chengdu-Chongqing High-Speed Railway after well tuning then demonstrates the feasibility and reliable in practical application.

Condition-based maintenance is a more advanced maintenance strategy, owing to reducing inspection and maintenance costs and improving the reliability of targeted assets. The maintenance strategies in the Chinese Railway industry are transforming from plan-based to condition-based, which has heightened the need for the completion of relevant research. This study proposes an experience-based health status evaluation method for train wheels, which considers factors in the wheel manufacturing process, operational process and maintenance process. The manufacturing factors are indicated by material properties and press-fitting influence factor, while operational and maintenance factors are indicated by wheel diameter and damages. Based on the health evaluation values, a decision-making function is constructed to divide wheels into four categories: fine, attention, pre-alarm and scrapped. Finally, the PHM + Wheel system is developed based on the proposed health evaluation method to provide support for maintenance strategy. The PHM+Wheel system has been practically applied to the Chinese Railway industry with adequate feedback received.

Personized treatment of breast cancer is still a challenge, and more treatment options for breast cancer are warranted. Combination therapies have been a highly appreciated strategy for breast cancer treatment in recent years, and the development of new combination therapies could improve patient outcomes. Adenosine and polyamines are both endogenous metabolites with indispensable biological functions. Adenosine binds with the A1 adenosine receptor (A1AR) to downregulate cAMP concentration, and both low cAMP content and high polyamine levels stimulate the growth and proliferation of cancer cells. In this work, we initially used a polyamine synthesis inhibitor, DFMO (α-difluoromethylornithine), and an A1AR inhibitor, DPCPX (8-cyclopentyl-1,3-dipropylxanthine) to investigate if simultaneously inhibiting A1AR and polyamine synthesis has synergistical antitumor effects. Next, we investigated a dual inhibitor (ODC-MPI-2) of A1AR and ODC (ornithine decarboxylase 1), the rate-limiting enzyme in polyamine biosynthesis. We investigated if ODC-MPI-2 could inhibit the proliferation and growth of breast cancer cells. Our data showed that DFMO and DPCPX synergistically inhibit the growth and proliferation of MCF-7 cells. We also demonstrated that ODC-MPI-2 reduces cellular polyamine levels and elevates cAMP concentration. We further showed that ODC-MPI-2 inhibits the growth, proliferation, and migration/invasion of MCF-7 cells. Finally, ODC-MPI-2 showed a preference for inhibiting triple-negative breast cancer cells. The dual inhibition of ODC and A1AR is a new combination therapy strategy for treating breast cancer, and dual inhibitors of ODC and A1AR may be effective future drugs for treating breast cancer.

Earth observation satellite (EOS) systems often encounter emergency observation tasks oriented to sudden disasters (e.g., earthquake, tsunami, and mud-rock flow). However, EOS systems may not be able to provide feasible coverage time windows for emergencies, which requires that an appropriately selected satellite transfers its orbit for better observation. In this context, we investigate the orbit maneuver optimization problem. First, by analyzing the orbit coverage and dynamics, we construct three models for describing the orbit maneuver optimization problem. These models, respectively, consider the response time, ground resolution, and fuel consumption as optimization objectives to satisfy diverse user requirements. Second, we employ an adaptive differential evolution (DE) integrating ant colony optimization (ACO) to solve the optimization models, which is named ACODE. In ACODE, key components (i.e., genetic operations and control parameters) of DE are formed into a directed acyclic graph and an ACO is appropriately embedded into an algorithm framework to find reasonable combinations of the components from the graph. Third, we conduct extensive experimental studies to show the superiority of ACODE. Compared with three existing algorithms (i.e., EPSDE, CSO, and SLPSO), ACODE can achieve the best performances in terms of response time, ground resolution, and fuel consumption, respectively.

Airship-based Earth observation is of great significance in many fields such as disaster rescue and environment monitoring. To facilitate efficient observation of high-altitude airships (HAA), a high-quality observation scheduling approach is crucial. This paper considers the scheduling of the imaging sensor and proposes a hierarchical observation scheduling approach based on task clustering (SA-TC). The original observation scheduling problem of HAA is transformed into three sub-problems (i.e., task clustering, sensor scheduling, and cruise path planning) and these sub-problems are respectively solved by three stages of the proposed SA-TC. Specifically, a novel heuristic algorithm integrating an improved ant colony optimization and the backtracking strategy is proposed to address the task clustering problem. The 2-opt local search is embedded into a heuristic algorithm to solve the sensor scheduling problem and the improved ant colony optimization is also implemented to solve the cruise path planning problem. Finally, extensive simulation experiments are conducted to verify the superiority of the proposed approach. Besides, the performance of the three algorithms for solving the three sub-problems are further analyzed on instances with different scales.

Ganoderma lucidum is an interesting shelf fungus that is also of medical importance in East Asian countries such as China, Japan and Korea. The fruit bodies of different Ganoderma species have similar colors and shapes, but are different regarding their medicinal properties. In order to provide molecular evidence for the genuine origin of G. lucidum, G. sinense and G. tsuga, fungal immunomodulatory protein (FIP) genes were cloned using genomic walker technology and their sequences were then determined. Based on the sequences of cloned FIP genes, we designed three pairs of species-specific primers for amplification and sequencing of FIP genes. These new primers allowed an effective amplification and sequencing of FIP genes from representative species of G. lucidum, G. sinense and G. tsuga. Phylogenetic relationships were resolved quite efficiently by the FIP gene sequences, which proved to be more useful than other genetic marker techniques in phylogenetic reconstruction of G. lucidum, G. sinense and G. tsuga.