Time-aware neural ordinary differential equations for incomplete time series modeling.

Internet of Things realizes the ubiquitous connection of all things, generating countless time-tagged data called time series. However, real-world time series are often plagued with missing values on account of noise or malfunctioning sensors. Existing methods for modeling such incomplete time series typically involve preprocessing steps, such as deletion or missing data imputation using statistical learning or machine learning methods. Unfortunately, these methods unavoidable destroy time information and bring error accumulation to the subsequent model. To this end, this paper introduces a novel continuous neural network architecture, named Time-aware Neural-Ordinary Differential Equations (TN-ODE), for incomplete time data modeling. The proposed method not only supports imputation missing values at arbitrary time points, but also enables multi-step prediction at desired time points. Specifically, TN-ODE employs a time-aware Long Short-Term Memory as an encoder, which effectively learns the posterior distribution from partial observed data. Additionally, the derivative of latent states is parameterized with a fully connected network, thereby enabling continuous-time latent dynamics generation. The proposed TN-ODE model is evaluated on both real-world and synthetic incomplete time-series datasets by conducting data interpolation and extrapolation tasks as well as classification task. Extensive experiments show the TN-ODE model outperforms baseline methods in terms of Mean Square Error for imputation and prediction tasks, as well as accuracy in downstream classification task.

Functional analysis of the nonstructural protein NSs of tomato zonate spot virus.

Tomato zonate spot virus (TZSV), a member of the genus orthotospovirus, causes severe damage to vegetables and ornamental crops in southwest China. The NSs protein is an RNA silencing suppressor in various orthotospovirus like TZSV, but its mechanism and role in virus infection are poorly understood. Here, we observed that an NSs-GFP fusion protein was transiently expressed on the plasma membrane and Golgi bodies in Nicotiana benthamiana plants. The TZSV NSs gene was silenced and infiltrated into N. benthamiana and N. tabacum cv. K326. RT-qPCR and Indirect enzyme-linked immunosorbent assay (ID-ELISA) showed that the transcription and the protein expression of the NSs gene were inhibited by more than 90.00%, and the symptoms on silenced plants were alleviated. We also found that the expression of the Zingipain-2-like gene significantly decreased when the NSs gene was silenced, resulting in co-localization of the NSs-GFP and the Zingipain-2-like-mCherry fusion protein. The findings of this study provide new insights into the mechanism of silencing suppression by NSs, as well as its effect on systemic virus infection, and also support the theory of disease resistance breeding and control and prevention of TZSV in the field.

Anti-tumor effects of Solanum nigrum L. extraction on C6 high-grade glioma.

ETHNOPHARMACOLOGICAL RELEVANCE: Solanum nigrum L. (SN) is a traditional Chinese medicine with anti-tumor effects, has been used in cancer for centuries, but the role on high-grade gliomas (HGG) is not clear. AIM OF THE STUDY: This work was to investigate the anti-tumor effects of SN extract on rat C6 glioma in vitro and in vivo, providing a new medium for the treatment of HGG. MATERIALS AND METHODS: After identification and quality inspection of SN medicinal materials by HPLC-MS/MS and HPLC, CCK8 and colony formation assay were conducted to study the effects of SN on vitality and proliferation of C6 cells. Cell morphology was evaluated by HE staining, and flow cytometry was used for apoptosis analysis. The effects on cell migration and invasion were determined by transwell and wound healing assay. Western blot was used to further investigate the influence of SN on migration, invasion and apoptosis of tumor cells. In addition, the rat intracranial transplanted tumor model was used to evaluate the effects of SN on growth and infiltration of tumor and proliferation of transplanted tumor cells. RESULTS: SN extract suppressed the viability of C6 cells in a dose-dependent manner. The extract attenuated cell cloning, migration and invasion, and induced cell Annexin V+ PI+ late-stage apoptosis. Besides, SN induced the expression of apoptotic proteins including Bax and Cleaved Caspase-3, downregulated anti-apoptotic protein Bcl-2, and decreased the level of migratory proteins MMP-2 and MMP-9. Moreover, SN reduced the growth and infiltration of C6 glioma tissue and suppressed the proliferation of tumor cells in rat brain. CONCLUSIONS: SN extract has significant inhibitory activity on the growth and invasion of C6 HGG in vivo and in vitro.

Streptochlorin analogues as potential antifungal agents: Design, synthesis, antifungal activity and molecular docking study.

Streptochlorin is a small molecule of indole alkaloid isolated from marine Streptomyces sp., it is a promising lead compound due to its potent bioactivity in preventing many phytopathogens in our previous study, but further structural modifications are required to improve its antifungal activity. Our work in this paper focused on the replacement of oxazole ring in streptochlorin with the imidazole ring, to discover novel analogues. Based on this design strategy, three series of streptochlorin analogues were efficiently synthesized through sequential Vilsmeier-Haack reaction, Van Leusen imidazole synthesis and halogenation reaction. Some of the analogues displayed excellent activity in the primary assays, and this is highlighted by compounds 4g and 4i, the growth inhibition against Alternaria Leaf Spot and Rhizoctorzia solani under 50 µg/mL are 97.5% and 90.3%, respectively, even more active than those of streptochlorin, pimprinine and Osthole. Molecular docking models indicated that streptochlorin binds with Thermus thermophiles Leucyl-tRNA Synthetase in a similar mode to AN2690, offering a perspective on the mode of action study for antifungal activities of streptochlorin derivatives. Further study is still ongoing with the aim of discovering synthetic analogues, with improved antifungal activity and clear mode of action.

Small-Molecule Fms-like Tyrosine Kinase 3 Inhibitors: An Attractive and Efficient Method for the Treatment of Acute Myeloid Leukemia.

Fms-like tyrosine kinase 3 (FLT3) is an important member of the class III receptor tyrosine kinase (RTK) family, which is involved in the proliferation of hematopoietic cells and lymphocytes. In recent years, increasing evidence have demonstrated that the activation and mutation of FLT3 is closely implicated in the occurrence and development of acute myeloid leukemia (AML). The exploration of small-molecule inhibitors targeting FLT3 has aroused wide interest of pharmaceutical chemists and is expected to bring new hope for AML therapy. In this review, we specifically highlighted FLT3 mediated JAK/STAT, RAS/MAPK, and PI3K/AKT/mTOR signaling. The structural properties and biological activities of representative FLT3 inhibitors reported from 2014 to the present were also summarized. In addition, the major challenges in the current advance of novel FLT3 inhibitors were further analyzed, with the aim to guide future drug discovery.

[Construction of recipient strain of expression-secretion system in filamentous fungi].

Glucoamylase overproducing A. niger T21 was mutated by UV mutagensis. An extracellular acid protease-deficient mutant, A. niger T21-201, which produced only 0.76% extracellular acid protease activity of the parent strain, was screened by casein-degradating plate and determination of protease activity. Moreover, the growth properties and the ability to secrete glucoamylase of A. niger T21-201 are identical to these of starting strain T21. The comparison of expression-secretion levels of heterologous gene in A. niger T21-201 and T21 was carried out with bacterial vhb as reporter, the level of expression-secretion of VHb in A. niger T21-201 was 6-7 times higher than that in T21, but the transcriptional levels of vhb gene in both strains were similar revealed by Northern blot. Therefore, it was demonstrated that the deficiency of acid protease of recipient T21-201 has significant effect on the protection of heterologous protein.