MicroRNA-33b inhibits liver cancer cell proliferation, migration and invasion via down-regulation of Fli-1 and MMP-2 protein expressions

Purpose: To study the influence of microRNA-33b (miR-33b) on liver cancer cell proliferation, migration and invasiveness, and the mechanism involved. Methods: MicroRNA-33b or Fli-1 overexpression plasmid was transfected into liver cancer (SMMC7721) cells. Cell proliferation, migration, and invasiveness were determined using cell counting kit 8 (CCK-8), scratch test, and Transwell invasion assay, respectively. The amounts of miR-33b and Fli-1 in liver cancer tissues,  paracancerous normal tissues, and miR-33b overexpression and control groups were measured using qRT-PCR, while protein concentration of matrix metalloproteinase 2 (MMP-2) was assayed using Western blotting. Results: Fli-1 protein was markedly upregulated in liver cancerous cells, relative to paracancerous normal tissues (p < 0.05). MicroRNA-33b protein expression was also significantly upregulated in miR33b overexpression group, but the corresponding Fli-1 expression was downregulated in miR-33b overexpression group, relative to control (p < 0.05). MicroRNA-33b overexpression significantly and time-dependently inhibited SMMC7721 cell proliferation and migration, but it reduced the degree of apoptosis (p < 0.05). Liver cancer (SMMC7721) cells in miR-33b overexpression group were less invasive than the control group (p < 0.05). Similarly, miR-33b overexpression significantly downregulated MMP-2 protein expression in SMMC7721cells (p < 0.05). Conclusion: Overexpression of miR-33b suppresses the proliferation, migratory and invasive potential of hepatic cancer cells via down-regulation of Fli-1 and MMP-2 protein expression. This finding may be useful in the identification of new liver cancer drugs

Building microbial factories for the production of aromatic amino acid pathway derivatives: From commodity chemicals to plant-sourced natural products

The aromatic amino acid biosynthesis pathway, together with its downstream branches, represents one of the most commercially valuable biosynthetic pathways, producing a diverse range of complex molecules with many useful bioactive properties. Aromatic compounds are crucial components for major commercial segments, from polymers to foods, nutraceuticals, and pharmaceuticals, and the demand for such products has been projected to continue to increase at national and global levels. Compared to direct plant extraction and chemical synthesis, microbial production holds promise not only for much shorter cultivation periods and robustly higher yields, but also for enabling further derivatization to improve compound efficacy by tailoring new enzymatic steps. This review summarizes the biosynthetic pathways for a large repertoire of commercially valuable products that are derived from the aromatic amino acid biosynthesis pathway, and it highlights both generic strategies and specific solutions to overcome certain unique problems to enhance the productivities of microbial hosts

Macrolactonization catalyzed by the terminal thioesterase domain of the nonribosomal peptide synthetase responsible for lichenysin biosynthesis

The excised terminal thioesterase of the lichenysin nonribosomal peptide synthetase was found to be a highly efficient and versatile enzyme. Its activity strictly requires the R configuration of the beta-hydroxy fatty acid and the side chains of aspartate-5 and isoleucine-7, but tolerates changes in five other residues of the substrate. Characterization of this enzyme facilitates future effort to engineer the lichenysin synthetase for biotechnological applications. (c) 2005 Elsevier Ltd. All rights reserved

Joint Cancer Segmentation and PI-RADS Classification on Multiparametric MRI Using MiniSegCaps Network

MRI is the primary imaging approach for diagnosing prostate cancer. Prostate Imaging Reporting and Data System (PI-RADS) on multiparametric MRI (mpMRI) provides fundamental MRI interpretation guidelines but suffers from inter-reader variability. Deep learning networks show great promise in automatic lesion segmentation and classification, which help to ease the burden on radiologists and reduce inter-reader variability. In this study, we proposed a novel multi-branch network, MiniSegCaps, for prostate cancer segmentation and PI-RADS classification on mpMRI. MiniSeg branch outputted the segmentation in conjunction with PI-RADS prediction, guided by the attention map from the CapsuleNet. CapsuleNet branch exploited the relative spatial information of prostate cancer to anatomical structures, such as the zonal location of the lesion, which also reduced the sample size requirement in training due to its equivariance properties. In addition, a gated recurrent unit (GRU) is adopted to exploit spatial knowledge across slices, improving through-plane consistency. Based on the clinical reports, we established a prostate mpMRI database from 462 patients paired with radiologically estimated annotations. MiniSegCaps was trained and evaluated with fivefold cross-validation. On 93 testing cases, our model achieved a 0.712 dice coefficient on lesion segmentation, 89.18% accuracy, and 92.52% sensitivity on PI-RADS classification (PI-RADS ≥ 4) in patient-level evaluation, significantly outperforming existing methods. In addition, a graphical user interface (GUI) integrated into the clinical workflow can automatically produce diagnosis reports based on the results from MiniSegCaps

Building microbial factories for the production of aromatic amino acid pathway derivatives: From commodity chemicals to plant-sourced natural products

The aromatic amino acid biosynthesis pathway, together with its downstream branches, represents one of the most commercially valuable biosynthetic pathways, producing a diverse range of complex molecules with many useful bioactive properties. Aromatic compounds are crucial components for major commercial segments, from polymers to foods, nutraceuticals, and pharmaceuticals, and the demand for such products has been projected to continue to increase at national and global levels. Compared to direct plant extraction and chemical synthesis, microbial production holds promise not only for much shorter cultivation periods and robustly higher yields, but also for enabling further derivatization to improve compound efficacy by tailoring new enzymatic steps. This review summarizes the biosynthetic pathways for a large repertoire of commercially valuable products that are derived from the aromatic amino acid biosynthesis pathway, and it highlights both generic strategies and specific solutions to overcome certain unique problems to enhance the productivities of microbial hosts.This is a manuscript of an article published as Cao, Mingfeng, Meirong Gao, Miguel Suastegui, Yanzhen Mei, and Zengyi Shao. "Building microbial factories for the production of aromatic amino acid pathway derivatives: From commodity chemicals to plant-sourced natural products." Metabolic Engineering (2019). DOI: 10.1016/j.ymben.2019.08.008. </p

Geochemical Characteristics and Paleoenvironmental Signi cance of the Ordovician Paleokarst Reservoir in the Maigaiti Slope of Tarim Basin

The Ordovician carbonatites of the Maigaiti slope have formed the conditions for the development of large oil and gas fields with karst reservoirs. This study systematically analyzed the isotopic characteristics of carbon, oxygen, and strontium and enrichment trace elements regularity to examine the geochemical features of the paleo-karstification products, various periods of paleo-karstification, and paleoenvironmental conditions of the Ordovician. Affected by terrigenous clasts, the Lianglitage Formation is composed of limestone with a relatively high 87Sr/86Sr value and a frequently fluctuating sea level, which exhibits an overall increasing-to-decreasing trend variation. Of all samples affected by the atmospheric freshwater leaching effect, δ18O values were negative, and δ13C values varied greatly toward both ends. The fissure/cave infills were rich in Fe and Mn but poor in Sr, and the Sr/Ba value was considerably less than 1, which confirms the existence of ancient weathered crust and the development of an atmospheric freshwater karst environment. Four different paleo-karstification periods were identified according to the carbon and oxygen isotopic characteristics of calcite. Combined with the trace element characteristics of the infills, the paleo-karstification in the Yingshan Formation was subdivided based on three hydrological environment conditions. Erosion modification of buried acid compaction-released water from late-period corrosion pores, caves, and fissures formed by syndiagenetic paleo-karstification and weathered crust bare paleo-karstification due to atmospheric freshwater leaching can significantly improve the reserving and permeability characteristics of the karst reservoir to develop a large paleokarst reservoir