Synergistic effect of combination chemotherapy with praziquantel and DW-3-15 for Schistosoma japonicum in vitro and in vivo.

BACKGROUND: Schistosomiasis is a debilitating and neglected tropical disease for which praziquantel (PZQ) remains the first-choice drug for treatment and control of the disease. In our previous studies, we found that the patented compound DW-3-15 (patent no. ZL201110142538.2) displayed significant and stabilized antiparasitic activity through a mechanism that might be distinct from PZQ. Here, we investigated the antischistosomal efficacy of PZQ combined with DW-3-15 against schistosomula and adult worms of Schistosoma japonicum in vitro and in vivo, to verify whether there was a synergistic effect of the two compounds. METHODS: The antischistosomal efficacy of PZQ combined with DW-3-15 in comparison with an untreated control and monotherapy group against schistosomula and adult worms was assessed both in vitro and in vivo. Parasitological studies, scanning electron microscopy, combination index, and histopathological analysis were used for the assessment. RESULTS: The results showed significantly reduced viability of schistosomes, achieving 100% viability reduction for juveniles and males by combination chemotherapy using PZQ together with DW-3-15 in vitro. The combination index was 0.28, 0.27, and 0.53 at the higher concentration of PZQ combined with DW-3-15 against juveniles, males, and females, respectively, indicating that the two compounds display strong synergism. Scanning electron microscopy observations also demonstrated that the compound combination induced more severe and extensive alterations to the tegument and subtegument of S. japonicum than those with each compound alone. In vivo, compared with the single-compound-treated group, the group treated with the higher-dose combination demonstrated the best schistosomicidal efficacy, with significantly reduced worm burden, egg burden, and granuloma count and area, which was evident against schistosomula and adult worms. CONCLUSIONS: Our study provides a potential novel chemotherapy for schistosomiasis caused by S. japonicum. It would improve the antischistosomal effect on schistosomula and adult worms of S. japonicum, and decrease individual dosages.

MiR-130a-3p Alleviates Liver Fibrosis by Suppressing HSCs Activation and Skewing Macrophage to Ly6Clo Phenotype.

Emerging evidences have highlighted the crucial role of microRNAs (miRNAs) in the liver cirrhosis, but the relationship between miR-130a-3p and liver cirrhosis is not entirely clear. As we all know, schistosomiasis, as one of the zoonoses, can lead to liver cirrhosis when it advances. In this study, we investigated the biological functions of miR-130a-3p on the liver fibrosis of schistosomiasis in vivo and in vitro. The mice infected with Schistosoma japonicum (S. japonicum) were treated with lentivirus vector (LV)-miR-130a-3p by hydrodynamic injection through the tail vein. Our findings showed significantly decreased expression of miR-130a-3p both in the serum of patients with cirrhosis and in the liver of mice infected with S. japonicum. The results showed that LV-miR-130a-3p could effectively enter into the liver and alleviate liver granulomatous inflammation and collagen deposition. Simultaneously, LV-miR-130a-3p-promoted macrophages presented the Ly6Clo phenotype, concomitant with the decreased expression of the tissue inhibitor of metalloproteinases (TIMP) 1, and increased the expression of matrix metalloproteinase (MMP) 2, which contributed to the dissolution of collagen. Furthermore, overexpression of miR-130a-3p not only inhibited the activation and proliferation of hepatic stellate cells (HSCs) but also induced the apoptosis of HSCs. In addition, we also confirmed that miR-130a-3p enables to bind with mitogen-activated protein kinase (MAPK) 1 and transforming growth factor-beta receptors (TGFBR) 1 and TGFBR2 genes and inhibit the expressions of these genes. Our findings suggested that miR-130a-3p might represent as the potential candidate biomarker and therapeutic target for the prognosis identification and treatment of schistosomiasis liver fibrosis.

Determinants of Tourism Stocks During the COVID-19: Evidence From the Deep Learning Models.

This paper examines the determinants of tourism stock returns in China from October 25, 2018, to October 21, 2020, including the COVID-19 era. We propose four deep learning prediction models based on the Back Propagation Neural Network (BPNN): Quantum Swarm Intelligence Algorithms (QSIA), Quantum Step Fruit-Fly Optimization Algorithm (QSFOA), Quantum Particle Swarm Optimization Algorithm (QPSO) and Quantum Genetic Algorithm (QGA). Firstly, the rough dataset is used to reduce the dimension of the indices. Secondly, the number of neurons in the multilayer of BPNN is optimized by QSIA, QSFOA, QPSO, and QGA, respectively. Finally, the deep learning models are then used to establish prediction models with the best number of neurons under these three algorithms for the non-linear real stock returns. The results indicate that the QSFOA-BPNN model has the highest prediction accuracy among all models, and it is defined as the most effective feasible method. This evidence is robust to different sub-periods.

Seasonal variations and public search interests in Toxoplasma: a 16-year retrospective analysis of big data on Google Trends.

BACKGROUND: This study aims to understand whether there is a seasonal change in the internet search interest for Toxoplasma by using the data derived from Google Trends (GT). METHODS: The present study searched for the relative search volume (RSV) for the search term 'Toxoplasma' in GT within six major English-speaking countries (Australia, New Zealand [Southern Hemisphere] and Canada, Ireland, the UK and the USA [Northern Hemisphere] from 1 January 2004 to 31 December 2019, utilizing the category of 'health'. Data regarding the RSV of Toxoplasma was obtained and further statistical analysis was performed in R software using the 'season' package. RESULTS: There were significantly seasonal patterns for the RSV of the search term 'Toxoplasma' in five countries (all p<0.05), except for the UK. A peak in December-March and a trough in July-September (Canada, Ireland, the UK and the USA) were observed, while a peak in June/August and a trough in December/February (Australia, New Zealand) were also found. Moreover, the presence of seasonal patterns regarding RSV for 'Toxoplasma' between the Southern and Northern Hemispheres was also found (both p<0.05), with a reversed meteorological month. CONCLUSIONS: Overall, our study revealed the seasonal variation for Toxoplasma in using internet search data from GT, providing additional evidence on seasonal patterns in Toxoplasma.

Coevolution with pollinating resin midges led to resin-filled nurseries in the androecia, gynoecia and tepals of Kadsura (Schisandraceae).

Background and Aims: Resin is a defence against herbivores and a floral reward in a few African and South American species whose bee pollinators collect it for nest construction. Here we describe a new role for floral resin from the Asian genus Kadsura (Schisandraceae). Kadsura tepals tightly cover a globe formed by carpels (in females) or near-fused stamens with fleshy connectives (in male flowers of most, but not all species). Methods: We carried out field observations at four sites in China and used pollinator behavioural assays, chemical analyses and time-calibrated insect and plant phylogenies to investigate the specificity of the interactions and their relationship to floral structure. Key Results: Nocturnal resin midges ( Resseliella , Cecidomyiidae) walk around on the flowers' sexual organs to oviposit, thereby transferring pollen and wounding tissues. The larvae then develop in resin-filled chambers. Male and female floral scents are dominated by α-pinene, while the resinous exudate is dominated by caryophyllene. As revealed by barcoding of multiple midge larvae per flower species, the mutualisms are species specific and appear to have evolved over the past 6-9 million years. Conclusions: Resin feeding, not pollen or ovule feeding, by midge larvae explains the abundant Kadsura exudates, highlighting the poorly known world of nocturnal flower-fly interactions.