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Cascaded H-bridge power electronic transformers (CHB-PET) play a pivotal role in distribution grids and their efficient operation. The input series and output parallel (ISOP) configurations result in a huge number of power switching devices, high-frequency transformers (HFT), and capacitors in high-voltage, high-capacity CHB-PET, leading to the need for high hardware costs and huge-sized CHB-PET, which further poses a significant challenge to the engineering feasibility and marketability of the CHB-PET. To address these issues, a CHB-PET topology is proposed in this paper. The novel topology exploits the concept of multi-frequency modulation to achieve power decoupling and power unit multiplexing through reasonable LC resonant frequency selection, which optimizes the ISOP structure and ultimately reduces the hardware cost and size of the CHB-PET. In this study, the effectiveness of reducing the number of power switching devices and HFT is firstly analyzed, and after describing its working principle, the control strategy of each power conversion link of PET is discussed before the correctness and effectiveness of the CHB-PET topology and control strategy proposed in this paper are verified via simulation. [ABSTRACT FROM AUTHOR]

Lincomycin is one of the most important antibiotics in clinical practice. To further understand the regulatory mechanism on lincomycin biosynthesis, we investigated a pleiotropic transcriptional regulator AdpAlin in the lincomycin producer Streptomyces lincolnensis NRRL 2936. Deletion of adpA lin (which generated Δ adpA lin ) interrupted lincomycin biosynthesis and impaired the morphological differentiation. We also found that putative AdpA binding sites were unusually scattered in the promoters of all the 8 putative operons in the lincomycin biosynthetic gene cluster (BGC). In Δ adpA lin , transcript levels of structural genes in 8 putative operons were decreased with varying degrees, and electrophoretic mobility shift assays (EMSAs) confirmed that AdpAlin activated the overall putative operons via directly binding to their promoter regions. Thus, we speculated that the entire lincomycin biosynthesis is under the control of AdpAlin. Besides, AdpAlin participated in lincomycin biosynthesis by binding to the promoter of lmbU which encoded a cluster sited regulator (CSR) LmbU of lincomycin biosynthesis. Results of qRT-PCR and catechol dioxygenase activity assay showed that AdpAlin activated the transcription of lmbU. In addition, AdpAlin activated the transcription of the bldA by binding to its promoter, suggesting that AdpAlin indirectly participated in lincomycin biosynthesis and morphological differentiation. Uncommon but understandable, AdpAlin auto-activated its own transcription via binding to its own promoter region. In conclusion, we provided a molecular mechanism around the effect of AdpAlin on lincomycin biosynthesis in S. lincolnensis , and revealed a cascade regulation of lincomycin biosynthesis by AdpAlin, LmbU, and BldA. [ABSTRACT FROM AUTHOR]

Lincomycin is one of the most important antibiotics in clinical practice. To further understand the regulatory mechanism on lincomycin biosynthesis, we investigated a pleiotropic transcriptional regulator AdpA lin in the lincomycin producer Streptomyces lincolnensis NRRL 2936. Deletion of adpA lin (which generated Δ adpA lin ) interrupted lincomycin biosynthesis and impaired the morphological differentiation. We also found that putative AdpA binding sites were unusually scattered in the promoters of all the 8 putative operons in the lincomycin biosynthetic gene cluster (BGC). In Δ adpA lin , transcript levels of structural genes in 8 putative operons were decreased with varying degrees, and electrophoretic mobility shift assays (EMSAs) confirmed that AdpA lin activated the overall putative operons via directly binding to their promoter regions. Thus, we speculated that the entire lincomycin biosynthesis is under the control of AdpA lin . Besides, AdpA lin participated in lincomycin biosynthesis by binding to the promoter of lmbU which encoded a cluster sited regulator (CSR) LmbU of lincomycin biosynthesis. Results of qRT-PCR and catechol dioxygenase activity assay showed that AdpA lin activated the transcription of lmbU . In addition, AdpA lin activated the transcription of the bldA by binding to its promoter, suggesting that AdpA lin indirectly participated in lincomycin biosynthesis and morphological differentiation. Uncommon but understandable, AdpA lin auto-activated its own transcription via binding to its own promoter region. In conclusion, we provided a molecular mechanism around the effect of AdpA lin on lincomycin biosynthesis in S. lincolnensis , and revealed a cascade regulation of lincomycin biosynthesis by AdpA lin , LmbU, and BldA., (Copyright © 2019 Kang, Wang, Hou, Wang, Ye, Zhu, Wu and Zhang.)

Objective: To investigate the clinical significance of serum let-7a-5p and miR-21-5p in the diagnosis of breast cancer., Methods: We examined 32 healthy people and 30 patients with benign breast lesions as controls and 90 breast cancer patients as study subjects. The expression of let-7a-5p and miR-21-5p were detected in all subjects' samples, and Cel-miR-39-3p was used as a spike-in reference. Serum miRNAs were extracted by the TRIzol method, and reverse transcription was performed with specific primers for let-7a-5p, miR-21-5p and Cel-miR-39-3p, and 2-μL reverse transcription products were used as PCR templates. A SLAN-96P fluorescent quantitative PCR instrument was used for quantitative PCR detection., Results: (1) The serum levels of carcinoembryonic antigen (CEA)and carbohydrate antigen 15-3 (CA15-3) in the breast cancer group were higher than those in the healthy controls and patients with benign breast lesions; (2) The expression level of let-7a-5p in the serum of the breast cancer group was lower than that in the healthy control group ( P <0.05), but there was no significant difference compared to the breast benign lesion group ( P >0.05); (3) The serum expression level of miR-21-5p in the breast cancer group was lower than that in the healthy control group ( P <0.05) but was not significantly different from that in the patients with benign breast lesions ( P >0.05)., Conclusion: Reduced expression of Let-7a-5p and miR-21-5p levels is of little value for early diagnosis of breast cancer; however reduced expression of Let-7a-5p and miRNA-21-5p may serve as non-invasive biomarkers for the diagnosis of breast cancer metastasis, and combination of these markers with CEA and CA15-3 can help to distinguish benign breast lesions from breast cancer., (© 2019 by the Association of Clinical Scientists, Inc.)

Lincomycin A is a clinically important antimicrobial agent produced by Streptomyces lincolnensis In this study, a new regulator designated LmbU (GenBank accession no. ABX00623.1) was identified and characterized to regulate lincomycin biosynthesis in S. lincolnensis wild-type strain NRRL 2936. Both inactivation and overexpression of lmbU resulted in significant influences on lincomycin production. Transcriptional analysis and in vivo neomycin resistance (Neo r ) reporter assays demonstrated that LmbU activates expression of the lmbA , lmbC , lmbJ , and lmbW genes and represses expression of the lmbK and lmbU genes. Electrophoretic mobility shift assays (EMSAs) demonstrated that LmbU can bind to the regions upstream of the lmbA and lmbW genes through the consensus and palindromic sequence 5'-CGCCGGCG-3'. However, LmbU cannot bind to the regions upstream of the lmbC , lmbJ , lmbK , and lmbU genes as they lack this motif. These data indicate a complex transcriptional regulatory mechanism of LmbU. LmbU homologues are present in the biosynthetic gene clusters of secondary metabolites of many other actinomycetes. Furthermore, the LmbU homologue from Saccharopolyspora erythraea (GenBank accession no. WP&#95;009944629.1) also binds to the regions upstream of lmbA and lmbW , which suggests widespread activity for this regulator. LmbU homologues have no significant structural similarities to other known cluster-situated regulators (CSRs), which indicates that they belong to a new family of regulatory proteins. In conclusion, the present report identifies LmbU as a novel transcriptional regulator and provides new insights into regulation of lincomycin biosynthesis in S. lincolnensis IMPORTANCE Although lincomycin biosynthesis has been extensively studied, its regulatory mechanism remains elusive. Here, a novel regulator, LmbU, which regulates transcription of its target genes in the lincomycin biosynthetic gene cluster ( lmb gene cluster) and therefore promotes lincomycin biosynthesis, was identified in S. lincolnensis strain NRRL 2936. Importantly, we show that this new regulatory element is relatively widespread across diverse actinomycetes species. In addition, our findings provide a new strategy for improvement of yield of lincomycin through manipulation of LmbU, and this approach could also be evaluated in other secondary metabolite gene clusters containing this regulatory protein., (Copyright © 2017 American Society for Microbiology.)