Intranasal immunisation with recombinant Toxoplasma gondii uridine phosphorylase confers resistance against acute toxoplasmosis in mice.

Toxoplasmosis is caused by Toxoplasma gondii, which infects all warm-blooded animals, including humans. Currently, control measures for T. gondii infection are insufficient due to the lack of effective medications or vaccines. In this paper, recombinant T. gondii uridine phosphorylase (rTgUPase) was expressed in Escherichia coli and purified via Ni2+-NTA agarose. rTgUPase was inoculated intranasally into BALB/c mice, and the induced immune responses were evaluated by mucosal and humoral antibody and cytokine assays and lymphoproliferative measurements. Moreover, the protective effect against the T. gondii RH strain infection was assessed by calculating the burdens of tachyzoites in the liver and brain and by recording the survival rate and time. Our results revealed that mice immunised with 30 µg rTgUPase produced significantly higher levels of secretory IgA (sIgA) in nasal, intestinal, vaginal and vesical washes and synthesised higher levels of total IgG, IgG1 and, in particular, IgG2a in their blood sera. rTgUPase immunisation increased the production of IFN-gamma, interleukin IL-2 and IL-4, but not IL-10 from isolated mouse spleen cells and enhanced splenocyte proliferation in vitro. rTgUPase-inoculated mice were effectively protected against infection with the T. gondii RH strain, showing considerable reduction of tachyzoite burdens in liver and brain tissues after 30 days of infection, and a 44.29% increase in survival rate during an acute challenge. The above findings show that intranasal inoculation with rTgUPase provoked mucosal, humoral and cellular immune responses and indicate that rTgUPase might serve as a promising vaccine candidate for protecting against toxoplasmosis.

Title: L'immunisation intranasale avec l'uridine phosphorylase recombinante de Toxoplasma gondii confère une résistance contre la toxoplasmose aiguë chez la souris. Abstract: La toxoplasmose est causée par Toxoplasma gondii, qui infecte tous les animaux à sang chaud, y compris les humains. Actuellement, les mesures de contrôle de l'infection à T. gondii sont insuffisantes en raison du manque de médicaments ou de vaccins efficaces. Dans cet article, l'uridine phosphorylase recombinante de T. gondii (rTgUPase) a été exprimée dans Escherichia coli et purifiée via de l'agarose Ni2+-NTA. La rTgUPase a été inoculée par voie intranasale à des souris BALB/c et les réponses immunitaires induites ont été évaluées par des dosages d'anticorps et de cytokines muqueuses et humorales et par des mesures de lymphoprolifération. De plus, l'effet protecteur contre l'infection par la souche RH de T. gondii a été évalué en calculant la charge de tachyzoïtes dans le foie et le cerveau et en enregistrant le taux et la durée de survie. Nos résultats ont révélé que les souris immunisées avec 30 µg de rTgUPase produisaient des taux significativement plus élevés d'IgA sécrétoires (sIgA) dans les lavages nasaux, intestinaux, vaginaux et vésicaux et synthétisaient des taux plus élevés d'IgG totales, d'IgG1 et, en particulier, d'IgG2a dans leur sérum sanguin. L'immunisation par la rTgUPase a augmenté la production d'IFN-gamma, d'interleukine IL-2 et IL-4, mais pas d'IL-10 à partir de cellules de rate de souris isolées et a amélioré la prolifération des splénocytes in vitro. Les souris inoculées par la rTgUPase ont été efficacement protégées contre l'infection par la souche RH de T. gondii, montrant une réduction considérable de la charge de tachyzoïtes dans les tissus hépatiques et cérébraux après 30 jours d'infection et une augmentation de 44,29 % du taux de survie lors d'une épreuve aiguë. Les résultats ci-dessus montrent que l'inoculation intranasale de rTgUPase provoque des réponses immunitaires muqueuses, humorales et cellulaires et indiquent que la rTgUPase pourrait servir de candidat vaccin prometteur pour la protection contre la toxoplasmose.

Discovering hematoma-stimulated circuits for secondary brain injury after intraventricular hemorrhage by spatial transcriptome analysis.

Introduction: Central nervous system (CNS) diseases, such as neurodegenerative disorders and brain diseases caused by acute injuries, are important, yet challenging to study due to disease lesion locations and other complexities. Methods: Utilizing the powerful method of spatial transcriptome analysis together with novel algorithms we developed for the study, we report here for the first time a 3D trajectory map of gene expression changes in the brain following acute neural injury using a mouse model of intraventricular hemorrhage (IVH). IVH is a common and representative complication after various acute brain injuries with severe mortality and mobility implications. Results: Our data identified three main 3D global pseudospace-time trajectory bundles that represent the main neural circuits from the lateral ventricle to the hippocampus and primary cortex affected by experimental IVH stimulation. Further analysis indicated a rapid response in the primary cortex, as well as a direct and integrated effect on the hippocampus after IVH stimulation. Discussion: These results are informative for understanding the pathophysiological changes, including the spatial and temporal patterns of gene expression changes, in IVH patients after acute brain injury, strategizing more effective clinical management regimens, and developing novel bioinformatics strategies for the study of other CNS diseases. The algorithm strategies used in this study are searchable via a web service (www.combio-lezhang.online/3dstivh/home).

Spatiotemporal Transformer Neural Network for Time-Series Forecasting.

Predicting high-dimensional short-term time-series is a difficult task due to the lack of sufficient information and the curse of dimensionality. To overcome these problems, this study proposes a novel spatiotemporal transformer neural network (STNN) for efficient prediction of short-term time-series with three major features. Firstly, the STNN can accurately and robustly predict a high-dimensional short-term time-series in a multi-step-ahead manner by exploiting high-dimensional/spatial information based on the spatiotemporal information (STI) transformation equation. Secondly, the continuous attention mechanism makes the prediction results more accurate than those of previous studies. Thirdly, we developed continuous spatial self-attention, temporal self-attention, and transformation attention mechanisms to create a bridge between effective spatial information and future temporal evolution information. Fourthly, we show that the STNN model can reconstruct the phase space of the dynamical system, which is explored in the time-series prediction. The experimental results demonstrate that the STNN significantly outperforms the existing methods on various benchmarks and real-world systems in the multi-step-ahead prediction of a short-term time-series.

ANKRD49 promotes the invasion and metastasis of lung adenocarcinoma via a P38/ATF-2 signalling pathway.

Lung adenocarcinoma (LUAD) is the most challenging neoplasm to treat in clinical practice. Ankyrin repeat domain 49 protein (ANKRD49) is highly expressed in several carcinomas; however, its pattern of expression and role in LUAD are not known. Tissue microarrays, immunohistochemistry, χ2 test, Spearman correlation analysis, Kaplan-Meier, log-rank test, and Cox's proportional hazard model were used to analyse the clinical cases. The effect of ANKRD49 on the LUAD was investigated using CCK-8, clonal formation, would healing, transwell assays, and nude mice experiment. Expressions of ANKRD49 and its associated downstream protein molecules were verified by real-time PCR, Western blot, immunohistochemistry, and/or immunofluorescence analyses. ANKRD49 expression was highly elevated in LUAD. The survival rate and Cox's modelling analysis indicated that there may be an independent prognostic indicator for LUAD patients. We also found that ANKRD49 promoted the invasion and migration in both in in vitro and in vivo assays, through upregulating matrix metalloproteinase (MMP)-2 and MMP-9 activities via the P38/ATF-2 signalling pathway Our findings suggest that ANKRD49 is a latent biomarker for evaluating LUAD prognosis and promotes the metastasis of A549 cells via upregulation of MMP-2 and MMP-9 in a P38/ATF-2 pathway-dependent manner.

Artificial intelligence in cancer target identification and drug discovery.

Artificial intelligence is an advanced method to identify novel anticancer targets and discover novel drugs from biology networks because the networks can effectively preserve and quantify the interaction between components of cell systems underlying human diseases such as cancer. Here, we review and discuss how to employ artificial intelligence approaches to identify novel anticancer targets and discover drugs. First, we describe the scope of artificial intelligence biology analysis for novel anticancer target investigations. Second, we review and discuss the basic principles and theory of commonly used network-based and machine learning-based artificial intelligence algorithms. Finally, we showcase the applications of artificial intelligence approaches in cancer target identification and drug discovery. Taken together, the artificial intelligence models have provided us with a quantitative framework to study the relationship between network characteristics and cancer, thereby leading to the identification of potential anticancer targets and the discovery of novel drug candidates.

Green synthesis of manganese-cobalt-tungsten composite oxides for degradation of doxycycline via efficient activation of peroxymonosulfate.

The advanced oxidation process of peroxymonosulfate activated by solid catalyst is one of the main technologies to solve the pollution of antibiotics in water environment.In this work, a series of composites (MCW) containing Mn, Co, and W were synthesized using green ball milling, which does not produce the three wastes (waste gas, waste water and industrial residue). It shows a unique and high catalytic activity for peroxymonosulfate-based degradation of doxycycline (DC) under the pH condition between 4 and 9, and it can be reused five times. MCW composites remove DC using singlet oxygen and superoxide free radicals, as well as a large number of oxygen vacancies for electron storage. The formation rate of free radicals is determined by the conversion rates of Mn3+/Mn2+ and Co3+/Co2+. In addition, there are three ways to degrade DC to form 18 kinds of intermediates, and the toxicity of all the intermediates were predicted by ECOSAR program. The highly active catalysts obtained using a green synthetic route for the activation of peroxymonosulfate show a great potential for decontamination of antibiotics wastewater.

Developing an Embedding, Koopman and Autoencoder Technologies-Based Multi-Omics Time Series Predictive Model (EKATP) for Systems Biology research.

It is very important for systems biologists to predict the state of the multi-omics time series for disease occurrence and health detection. However, it is difficult to make the prediction due to the high-dimensional, nonlinear and noisy characteristics of the multi-omics time series data. For this reason, this study innovatively proposes an Embedding, Koopman and Autoencoder technologies-based multi-omics time series predictive model (EKATP) to predict the future state of a high-dimensional nonlinear multi-omics time series. We evaluate this EKATP by using a genomics time series with chaotic behavior, a proteomics time series with oscillating behavior and a metabolomics time series with flow behavior. The computational experiments demonstrate that our proposed EKATP can substantially improve the accuracy, robustness and generalizability to predict the future state of a time series for multi-omics data.

Developing the novel bioinformatics algorithms to systematically investigate the connections among survival time, key genes and proteins for Glioblastoma multiforme.

BACKGROUND: Glioblastoma multiforme (GBM) is one of the most common malignant brain tumors and its average survival time is less than 1 year after diagnosis. RESULTS: Firstly, this study aims to develop the novel survival analysis algorithms to explore the key genes and proteins related to GBM. Then, we explore the significant correlation between AEBP1 upregulation and increased EGFR expression in primary glioma, and employ a glioma cell line LN229 to identify relevant proteins and molecular pathways through protein network analysis. Finally, we identify that AEBP1 exerts its tumor-promoting effects by mainly activating mTOR pathway in Glioma. CONCLUSIONS: We summarize the whole process of the experiment and discuss how to expand our experiment in the future.

Effects of forest regeneration practices on the flux of soil CO2 after clear-cutting in subtropical China.

Reforestation after clear-cutting is used to facilitate rapid establishment of new stands. However, reforestation may cause additional soil disturbance by affecting soil temperature and moisture, thus potentially influencing soil respiration. Our aim was to compare the effects of different reforestation methods on soil CO2 flux after clear-cutting in a Chinese fir plantation in subtropical China: uncut (UC), clear-cut followed by coppicing regeneration without soil preparation (CC), clear-cut followed by coppicing regeneration and reforestation with soil preparation, tending in pits and replanting (CCRP), and clear-cut followed by coppicing regeneration and reforestation with overall soil preparation, tending and replanting (CCRO). Clear-cutting significantly increased the mean soil temperature and decreased the mean soil moisture. Compared to UC, CO2 fluxes were 19.19, 37.49 and 55.93 mg m-2 h-1 higher in CC, CCRP and CCRO, respectively (P < 0.05). Differences in CO2 fluxes were mainly attributed to changes in soil temperature, litter mass and the mixing of organic matter with mineral soil. The results suggest that, when compared to coppicing regeneration, reforestation practices result in additional CO2 released, and that regarding the CO2 emissions, soil preparation and tending in pits is a better choice than overall soil preparation and tending.