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Protein kinases C (PKCs) are a family of serine/threonine kinases involved in various cellular processes, including proliferation, differentiation, cell survival, and apoptosis. Here, we report the identification, structure-activity relationship (SAR), and 3D-QSAR studies of 69 natural indolocarbazoles, including 15 new compounds, from marine streptomyces strains. Interestingly, we found that the chair conformational isomer of 7-oxo-staurosporine (compound 15) inhibited PKCθ more potently than the corresponding boat isomer. An evaluation of kinase selectivity and antitumor efficacy revealed that 15 was a potent dual PKCθ/δ inhibitor and that it could efficiently inhibit tumor growth in pancreatic cancer (PC) by inducing cellular apoptosis and suppressing the NF-κB/p-P65 pathway. In addition, we demonstrated that overexpression of p-PKCδ and p-P65 was associated with poor survival rates in patients with PC, and p-PKCθ expression also showed significant positive correlations with p-PKCδ and p-P65 levels. Finally, the PC patient-derived xenograft model further confirmed the potential anti-PC efficacy of 15.

Three new indolocarbazoles alkaloids together with nine known compounds were isolated from the rice solid fermentation of the marine-derived Streptomyces sp. A65. Their structures were elucidated by interpretation of spectroscopic and spectrometric data (1D and 2D NMR, IR, and HRESIMS). The absolute configurations of compounds 1 and 2 were determined by single-crystal X-ray crystallographic analysis, and 3 was assigned on the basis of experimental and calculated electronic circular dichroism spectra. All of these compounds were evaluated for cytotoxic activity assay. Compounds 6 and 10 exhibited significant cytotoxicity against PC3 cell lines with IC50 values of 1.96 and 2.92 μM, respectively; Compounds 2 and 3 showed moderate cytotoxic activity with IC50 values of 9.67 and 6.79 μM, respectively. Additionally, compounds 1–4 also were also tested for enzyme inhibition activities of Protein kinase C and Brution tyrosine kinase. They showed moderate activity with IC50 values ranging from 0.25 μM to 1.91 μM except for compound 1, which has no inhibition activity for protein kinase C.

Three new indolocabazole analogues (1-3), one eudesmane-type derivative (4), one bisphenol A propyl ether analogue (5), were purified from the fermentation of the marine- derived Streptomyces sp. A68 and its Rifampicin-resistant mutant strain R-M1. The structures were established through the interpretation of spectroscopic data combined with literature data review. The absolute stereochemistry of 1 was further confirmed by X-ray crystallography analysis. Bioactivity test showed that compounds 1-3 had evident cytotoxic activity towards PC-3 cell lines. Furthermore, 1-3 and 5 also exhibited potent kinase inhibitory activity against PKCα, ROCK II and BTK with IC50 of values ranging from 0.17 to 3.24 μM.

As chemical industry is a fundamental strategic sector as well as one pillar industry of our national economy, chemical industrial parks of various scales has been built in many places to facilitate the production of chemical enterprises. However, considering the inflammability, explosibility and toxicity of the raw materials and products of such enterprises, accidents are very likely during the production, transportation and storage, forming major threats to human lives, the environment and property. By making use of key technologies of the Internet of Things such as sensing, accessing and networking, massive information storage, analyzing and processing capabilities of big data technology and the data computing methods of cloud computing technology, this paper designs a safety production information management platform for the daily supervision and emergency rescue of chemical industrial parks, proposes the system communication network framework based on the Internet of Things and the three-layer platform technical framework based on cloud computing, describes the technical structure and function of the sensing layer, the transmission layer, the infrastructure layer, the platform layer and the application layer of the platform, and elaborates key technologies including the design thought of uniform big data analyzing platform, regional collaborative emergency management operating mechanism, the combination of RFID technology and sensor network technology and model design of expert decision-making. The platform can realize logistics management of dangerous articles and key environment parameter monitoring of dangerous chemical enterprises, help enterprises in the safety compliance management to the whole production process, allow red light early warning and start responding early warning mechanism and rescue plan automatically, so as to effectively avoid the occurrence of potential accidents and safeguard and improve the economic and social benefits of enterprises.

Four new analogues of brefeldin A named 7, 7-dimethoxybrefeldin C (3), 6β-hydroxybrefeldin C (4), 4-epi-15-epi-brefeldin A (5), 4-epi-8α-hydroxy-15-epi-brefeldin C (6), together with four known analogues (1, 7-9) were isolated from a fermentation of the sediment-derived fungus Penicillium sp. DT-F29. The structures of these compounds were elucidated on the basis of extensive spectroscopic and chemical methods. In the bioactivity assays, only compounds 1 and 8 showed significant inhibitory activities against human lung adenocarcinoma cell. In addition, compound 1 was first reported for the potent ability to reactivate latent HIV with EC50 value of 0.03 μM.

National College English Test (CET) is a nationwide examination that Ministry of Education is in charge of, with over 20 million examinees sitting CET every year. In recent years, on the basis of conventional written test, there are another three kinds of tests available, namely Internet-Based CET, Comparative CET and Predictive CET, which utilizes as many as five different sets of software, with no direct data sharing layer, for management. Therefore, the author succeeded in development of CET management information system based on multi-system data integration technology. This thesis puts forward corresponding solutions to problems, like incomplete functions and unfriendly data interface, occurring in the use of original multiple system, focuses on introducing the methods for centralized integration of basic data at the data sharing layer, realization of algorithm for intelligent arrangement of examination supervision and that for sampling of student qualification for Comparative CET, and realization of functions like standardized processing of scores in above-mentioned three tests, and elaborates the thinking clews for CET management in some university by combining with the said system. The said system has been put into service successfully, with good value for popularization.

Vineomycin A1 (1) and B2 (2) were isolated from the culture broth of marine actinomycete Streptomyces sp. A6H. Five hydrolysis products were obtained by rational hydrolysis and methanolysis of the fermentation extract. Their structures were characterised as aquayamycin (3), vineomycinone B2 (4), 9-C-D-olivosyltetrangulol (5), 7-O-methylgaltamycinone (6) and vineomycinone B2 methyl ester (7). In addition to these compounds, two ester derivatives, vineolactone A (8) and vineomycinone B2 benzyl ester (9) of compound 4 were generated semisynthetically. Compound 6 is a new analogue of galtamycinone, while compounds 8 and 9 are new members of vineomycins. Cytotoxic activities and antimicrobial activities were determined for all compounds. The results indicate that only compound 1 showed significant activities with IC50 value of 0.34 μM against H1975 and MIC value of 4 μg/mL against Staphylococcus aureus.