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Insect group h chitinase is a promising target for designing non-target safe pesticides in that it is exclusively distributed in lepidopteran insects, over 80% of which are agricultural pests. In this work, lynamicin B was discovered to be an inhibitor of OfChi-h, the group h chitinase from the lepidopteran pest Ostrinia furnacalis. Lynamicin B was revealed to competitively inhibit OfChi-h with a Ki value of 8.76 μM and does not significantly inhibit other chitinases. The co-crystal structure of lynamicin B and OfChi-h revealed that the dichloroindolyl group of lynamicin B occupies an unexplored pocket below subsites +1 and +2 of the substrate-binding cleft, which is vital for its selectivity. Feeding experiments demonstrated that lynamicin B exhibited high insecticidal activities against other lepidopteran pests Mythimna separata and Spodoptera frugiperda besides O. furnacalis. Moreover, lynamicin B did not affect Trichogramma ostriniae, a natural enemy of O. furnacalis. This study provides a natural-derived potent pesticide for the control of lepidopteran pests, leaving its natural enemy unaffected.

Although great progress has been made in the early diagnosis and targeted therapy of lung adenocarcinoma (LUAD), the survival of patients with LUAD remains unsatisfactory. There is an urgent requirement for new biomarkers to guide the diagnosis, prognosis and treatment of LUAD. Following an initial bioinformatics screen, the present study focused on cyclin B1 (CCNB1) in LUAD. A total of 94 patients with LUAD from a single hospital were included in the study. CCNB1 protein expression was detected and scored in 94 LUAD samples and 30 normal tissue samples by immunohistochemistry. The associations between CCNB1 expression and the clinicopathological features of the patients with LUAD were analyzed. Furthermore, the relationship between prognosis and the CCNB1 expression level was analyzed using Cox regression and survival analyses. Weighted gene co-expression network analysis and RNA-sequencing were also applied to identify the potential molecular mechanisms of CCNB1 in LUAD. CCNB1 was highly expressed in patients with LUAD and was associated with poor prognosis. It may affect the expression of CPLX1, PPIF, SRPK2, KRT8, SLC20A1 and CBX2 genes and function via different pathways. CCNB1 has the potential to become a novel prognostic target for LUAD.

Tumor acidic microenvironment is the main feature of many solid tumors. As a part of the tumor microenvironment, it has a profound impact on the occurrence and development of tumors. However, the research on how tumor cells sense the changes of the external microenvironment and how the intracellular subcellular structures transmit the signals from extracellular to intracellular is unclear. In this study, we identify that the acidic microenvironment enhances cancer cell motility, and the expression of membrane-anchored membrane type 1-matrix metalloproteinase is also associated with cell motility, which indicates more degradation of the ECM under the acidic microenvironment. Moreover, the expression of cofilin is low in the acidic microenvironment, and the F-actin filaments are distributed more along the cells. The cytoskeletal F-actin changes are consistent with the potential of a high-invasive phenotype. Further study reveals the upstream control of the signal transductions from extracellular to intracellular, that is, the integrin β1 functions to trigger the biological responses under the acidic microenvironment. Our results demonstrate that the acidic microenvironment enhances cancer cell motility through the integrin β1/cofilin/F-actin signal axis. This study clearly shows the scheme of the signal transmissions from extracellular to intracellular and further reveals the cytoskeletal roles for the contributions of cancer cell motility under acidic microenvironment, which provides new targets for cancer intervention from the biochemical and biophysical perspectives.

Esophageal squamous cell carcinoma (ESCC) is a kind of malignant tumor with high incidence and mortality in the digestive system. The aim of this study is to explore the function of lnc-ABCA12-3 in the development of ESCC and its unique mechanisms. RT-PCR was applied to detect gene transcription levels in tissues or cell lines like TE-1, EC9706, and HEEC cells. Western blot was conducted to identify protein expression levels of mitochondrial apoptosis and toll-like receptor 4 (TLR4)/nuclear factor kappa-B (NF-κB) signaling pathway. CCK-8 and EdU assays were carried out to measure cell proliferation, and cell apoptosis was examined by flow cytometry. ELISA was used for checking the changes in glycolysis-related indicators. Lnc-ABCA12-3 was highly expressed in ESCC tissues and cells, which preferred it to be a candidate target. The TE-1 and EC9706 cells proliferation and glycolysis were obviously inhibited with the downregulation of lnc-ABCA12-3, while apoptosis was promoted. TLR4 activator could largely reverse the apoptosis acceleration and relieved the proliferation and glycolysis suppression caused by lnc-ABCA12-3 downregulation. Moreover, the effect of lnc-ABCA12-3 on ESCC cells was actualized by activating the TLR4/NF-κB signaling pathway under the mediation of exosome. Taken together, the lnc-ABCA12-3 could promote the proliferation and glycolysis of ESCC, while repressing its apoptosis probably by regulating the TLR4/NF-κB signaling pathway under the mediation of exosome.

Lung adenocarcinoma (LUAD), a malignant respiratory tumor with an extremely poor prognosis, has troubled the medical community all over the world. According to recent studies, fatty acid metabolism (FAM) and long non-coding RNAs (lncRNAs) regulation have shown exciting results in tumor therapy. In this study, the original LUAD patient data was obtained from the TCGA database, and 12 FAM-related lncRNAs (AL390755.1, AC105020.6, TMPO-AS1, AC016737.2, AC127070.2, LINC01281, AL589986.2, GAS6-DT, AC078993.1, LINC02198, AC007032.1, and AL021026.1) that were highly related to the progression of LUAD were finally identified through bioinformatics analysis, and a risk score model for clinical reference was constructed. The window explores the immunology and molecular mechanism of LUAD, aiming to shed the hoping light on LUAD treatment.

Marine-derived fungi are emerging as attractive producers of structurally novel secondary metabolites with diverse bioactivities. However, the lack of efficient genetic tools limits the discovery of novel compounds and the elucidation of biosynthesis mechanisms. Here, we firstly established an effective PEG-mediated chemical transformation system for protoplasts in two marine-derived fungi, Spiromastix sp. SCSIO F190 and Aspergillus sp. SCSIO SX7S7. Next, we developed a simple and versatile CRISPR-Cas9-based gene disruption strategy by transforming a target fungus with a single plasmid. We found that the transformation with a circular plasmid encoding cas9, a single-guide RNA (sgRNA), and a selectable marker resulted in a high frequency of targeted and insertional gene mutations in both marine-derived fungal strains. In addition, the histone deacetylase gene rpd3 was mutated using the established CRISPR-Cas9 system, thereby activating novel secondary metabolites that were not produced in the wild-type strain. Taken together, a versatile CRISPR-Cas9-based gene disruption method was established, which will promote the discovery of novel natural products and further biological studies.

A genome-directed discovery strategy to identify new tetrahydroisoquinolines (THIQs) was applied to deep-sea derived Streptomyces niveus SCSIO 3406; 11 THIQs were found representing three THIQ clas...

Teratoma is a common type of mediastinal tumor, often located in the anterior mediastinum. Mediastinal teratomas often occur in young and middle-aged people, and account for 5–21.5% of mediastinal tumors. Mature cystic teratoma is a common type of mediastinal teratoma, its onset is slow, and most patients are asymptomatic. In a few patients, the tissue around the mediastinum is invaded or there is malignant transformation, which results in chest pain, chest tightness, a cough, and other symptoms. In this case, the patient had a giant teratoma, compressing large blood vessels and nerves, complicated by pleural and pericardial effusion. The 21-year-old female patient was misdiagnosed with tuberculous disease because of chronic cough and expectoration. Her initial symptoms improved after anti-tuberculosis treatment; however, an imaging examination showed that the lesion had enlarged some 9 months later. Surgery was performed at our hospital, as the tumor was squeezing blood vessels, and the trachea was seriously adhering to the surrounding tissue. To avoid damage to the peripheral blood vessels and nerves, many residual tissues were retained after the operation. The post-operative pathology results confirmed that the patient had a mature mediastinal cystic teratoma. One year after the operation, there was no recurrence, the peripheral blood vessels had basically returned, and the patient did not have any nerve injury. Effusion caused by mediastinal teratoma should be carefully differentiated from tuberculous diseases to avoid unnecessary damage to patients during treatment. Separation can be difficult in benign mediastinal tumors with severe adhesion. To avoid the trauma caused by the excessive separation of a tumor, it is our view that part of the residual tissue should be retained and left to be absorbed naturally.

Marine-derived fungi are emerging as attractive producers of structurally novel secondary metabolites with diverse bioactivities. However, the lack of efficient genetic tools limits the discovery of novel compounds and the elucidation of biosynthesis mechanisms. Here, we firstly established an effective PEG-mediated chemical transformation system for protoplasts in two marine-derived fungi

Two new chlorinated bis-indole alkaloids, dionemycin (1) and 6-OMe-7',7″-dichorochromopyrrolic acid (2), along with seven known analogs 3-9, were isolated from the deep-sea derived Streptomyces sp. SCSIO 11791. Their structures were elucidated by extensive HRESIMS, and 1D and 2D NMR data analysis. In vitro antibacterial and cytotoxic assays revealed that, compound 1, shows anti-staphylococcal activity with an MIC range of 1-2 μg/mL against six clinic strains of methicillin-resistant Staphylococcus aureus (MRSA) isolated from human and pig. Additionally, compound 1 displayed cytotoxic activity against human cancer cell lines NCI-H460, MDA-MB-231, HCT-116, HepG2, and noncancerous MCF10A with an IC50 range of 3.1-11.2 μM. Analysis of the structure-activity relationship reveals that the chlorine atom at C-6″ could be pivotal for conferring their bioactivities, thus providing hints on chemical modifications on bis-indole alkaloid scaffold in drug design.

Baeyer–Villiger monooxygenases (BVMOs) play important roles in the biosynthesis of natural products. We describe here in vivo gene inactivation/complementation studies as well as in vitro enzyme as...

Background Preoperative mediastinal staging is crucial for the optimal management of clinical stage I non-small cell lung cancer (NSCLC). Purpose To develop a deep learning signature for N2 metastasis prediction and prognosis stratification in clinical stage I NSCLC. Materials and Methods In this retrospective study conducted from May 2020 to October 2020 in a population with clinical stage I NSCLC, an internal cohort was adopted to establish a deep learning signature. Subsequently, the predictive efficacy and biologic basis of the proposed signature were investigated in an external cohort. A multicenter diagnostic trial (registration number: ChiCTR2000041310) was also performed to evaluate its clinical utility. Finally, on the basis of the N2 risk scores, the instructive significance of the signature in prognostic stratification was explored. The diagnostic efficiency was quantified with the area under the receiver operating characteristic curve (AUC), and the survival outcomes were assessed using the Cox proportional hazards model. Results A total of 3096 patients (mean age ± standard deviation, 60 years ± 9; 1703 men) were included in the study. The proposed signature achieved AUCs of 0.82, 0.81, and 0.81 in an internal test set (

It has been reported that tumor-associated macrophages (TAMs) participate in modulating the progression of cancer in the tumor microenvironment. However, the crosstalk between TAMs and non-small cell lung cancer (NSCLC) is still unclear.We investigated whether NSCLC-derived exosomes could affect TAMs, which feedback modulated progression of NSCLC.MiR-181b expression was measured by RT-PCR. Human THP-1 monocyte was differentiated into macrophages with phorbol myristate acetate, which were further identified by transmission electron microscopy and western blot. Macrophage M1 and M2 polarizations were detected by flow cytometry, RT-PCR and western blot. Proliferation, migration, and invasion of NSCLC cells treated with conditioned mediums were detected by EdU and Transwell assays.We demonstrated that miR-181b was up-regulated in exosomes derived from NSCLC patients' serum and NSCLC cells. MiR-181b could be transferred to macrophages via exosomes in the co-culture system of macrophages and NSCLC cells, which promoted macrophage M2 polarization. Further examinations revealed that exosomes derived from NSCLC cells could enhanced macrophage M2 polarizations by regulating miR-181b/JAK2/STAT3 axis, and silencing miR-181b in NSCLC cells and JAK2 inhibitor used in macrophages could reverse the effects. Importantly, the conditioned medium of macrophages treated with NSCLC cell-derived exosomes could promote NSCLC cell proliferation, migration, and invasion. Silencing miR-181b in NSCLC cells and JAK2 inhibitor used in macrophages could block the effects.All of these results indicated that exosomal miR-181b participated in the crosstalk between NSCLC cells and TAMs, providing potential therapeutic targets for NSCLC.

PurposeTo investigate the surgical prognosis and efficacy of adjuvant therapy in non-small cell lung cancer (NSCLC) with occult lymph node metastasis (ONM) defined by positron emission tomography-computed tomography (PET-CT).MethodsA total of 3537 NSCLC patients receiving surgical resection were included in this study. The prognosis between patients with ONM and evident nodal metastasis, ONM patients with and without adjuvant therapy were compared, respectively.ResultsONM was associated with significantly better prognosis than evident nodal metastasis whether for patients with N1 (5-year OS: 56.8% versus 52.3%, adjusted p value=0.267; 5-year RFS: 44.7% versus 33.2%, adjusted p value=0.031) or N2 metastasis (5-year OS: 42.8% versus 32.3%, adjusted p value=0.010; 5-year RFS: 31.3% versus 21.6%, adjusted p value=0.025). In ONM population, patients receiving adjuvant therapy yielded better prognosis comparing to those without adjuvant therapy (5-year OS: 50.1% versus 33.5%, adjusted p value

Macrophages are a heterogeneous group of phagocytes that play critical roles in inflammation, infection and tumor growth. Macrophages respond to different environmental factors and are thereby polarized into specialized functional subsets. Although hypoxia is an important environmental factor, its impact on human macrophage polarization and subsequent modification of the inflammatory microenvironment have not been fully established. The present study aimed to elucidate the effect of hypoxia exposure on the ability of human macrophages to polarize into the classically activated (pro-inflammatory) M1, and the alternatively activated (anti-inflammatory) M2 phenotypes. The effect on the inflammatory microenvironment and the subsequent modification of A549 lung carcinoma cells was also investigated. The presented data show that hypoxia promoted macrophage polarization towards the M2 phenotype, and modified the inflammatory microenvironment by decreasing the release of proinflammatory cytokines. Modification of the microenvironment by proinflammatory M1 macrophages under hypoxia reversed the inhibition of malignant behaviors within the proinflammatory microenvironment. Furthermore, it was identified p38 signaling (a major contributor to the response to reactive oxygen species generated by hypoxic stress), but not hypoxia-induced factor, as a key regulator of macrophages under hypoxia. Taken together, the data suggest that hypoxia affects the inflammatory microenvironment by modifying the polarization of macrophages, and thus, reversing the inhibitory effects of a proinflammatory microenvironment on the malignant behaviors of several types of cancer cell.

The Institute of Plasma Physics, Chinese Academy of Sciences (ASIPP), is in charge of the manufacturing and testing of the 60 high-temperature superconducting current lead series to be completed at the end of 2020 for the International Thermonuclear Experimental Reactor (ITER). This paper first summarizes the testing items and testing results of the ITER lead prototypes in 2015/2016, then, based on the prototypes experiences, discuss the final test piping and instrument diagram for the ITER lead series production testing. A new 5-K test platform to expedite the series testing is also introduced, and a new feature, the 30-kV high-voltage (HV) class insulation for the cryogenic temperature and voltage measurements to allow in situ HV testing, is introduced. The detailed test procedures and test items for the series are discussed finally.

Tumor‑associated macrophages (TAMs) are critical components of the tumor microenvironment that are tightly associated with malignancies in human cancers, including lung cancer. LGK‑974, a small molecular inhibitor of Wnt secretion, was reported to block Wnt/β‑catenin signaling and exert anti‑inflammatory effects by suppressing pro‑inflammatory gene expression in cancer cells. Although it was reported that Wnt/β‑catenin was critical in regulating TAMs, it is still largely unknown whether LGK‑974 regulates tumor malignancies by regulating TAMs. The present study firstly verified that the polarization of TAMs was regulated by LGK‑974. LGK‑974 increased M1 macrophage functional markers and decreased M2 macrophage functional markers. The addition of Wnt3a and Wnt5a, two canonical Wnt signaling inducers, reversed the decrease in M1 macrophage functional markers, including mannose receptor, IL‑10 and Arg1, by activating Wnt/β‑catenin signaling. Conditioned medium from LGK‑974‑modified TAMs inhibited the malignant behaviors in A549 and H1299 cells, including proliferation, colony formation and invasion, by blocking Wnt/β‑catenin signaling. LGK‑974‑modified TAMs blocked the cell cycle at the G1/G0 phase, which was reversed by the addition of Wnt3a/5a, indicating that LGK‑974 regulates the microenvironment by blocking Wnt/β‑catenin signaling. Taken together, the results indicate that LGK‑974 indirectly inhibited the malignant behaviors of A549 and H1299 cells by regulating the inflammatory microenvironment by inhibiting Wnt/β‑catenin signaling in TAMs.

A genome-directed discovery strategy to identify new tetrahydroisoquinolines (THIQs) was applied to deep-sea derived

Background Micropapillary/solid (MP/S) growth patterns of lung adenocarcinoma are vital for making clinical decisions regarding surgical intervention. This study aimed to predict the presence of a MP/S component in lung adenocarcinoma using radiomics analysis. Methods Between January 2011 and December 2013, patients undergoing curative invasive lung adenocarcinoma resection were included. Using the "PyRadiomics" package, we extracted 90 radiomics features from the preoperative computed tomography (CT) images. Subsequently, four prediction models were built by utilizing conventional machine learning approaches fitting into radiomics analysis: a generalized linear model (GLM), Naive Bayes, support vector machine (SVM), and random forest classifiers. The models' accuracy was assessed using a receiver operating curve (ROC) analysis, and the models' stability was validated both internally and externally. Results A total of 268 patients were included as a primary cohort, and 36.6% (98/268) of them had lung adenocarcinoma with an MP/S component. Patients with an MP/S component had a higher rate of lymph node metastasis (18.4% versus 5.3%) and worse recurrence-free and overall survival. Five radiomics features were selected for model building, and in the internal validation, the four models achieved comparable performance of MP/S prediction in terms of area under the curve (AUC): GLM, 0.74 [95% confidence interval (CI): 0.65-0.83]; Naive Bayes, 0.75 (95% CI: 0.65-0.85); SVM, 0.73 (95% CI: 0.61-0.83); and random forest, 0.72 (95% CI: 0.63-0.81). External validation was performed using a test cohort with 193 patients, and the AUC values were 0.70, 0.72, 0.73, and 0.69 for Naive Bayes, SVM, random forest, and GLM, respectively. Conclusions Radiomics-based machine learning approach is a very strong tool for preoperatively predicting the presence of MP/S growth patterns in lung adenocarcinoma, and can help customize treatment and surveillance strategies.

A 26-year-old female was admitted to the emergency department of thoracic surgery complaining of chest tightness, shortness of breath, and a history of bilateral tuberculosis. A chest Computed Tomography (CT) scan showed bilateral pleural effusion. After that, the patient was implanted with bilateral intercostal drainage tubes. Further analysis of the pleural effusion was conducted to confirm the diagnosis of bilateral chylothorax. We initiated conservative treatment consisting of fasting and total parenteral nutrition. After the failure of conservative treatment, the patient underwent ligation of the thoracic duct by right-sided thoracotomy combined with talc slurry. On the first day postoperatively, the right pleural effusion had decreased significantly, while the left pleural effusion had not. Subsequently, talc slurry was injected into the left thoracic drainage tube of the patient. Bilateral pleural effusion was significantly reduced. Re-examination chest X-ray showed the disappearance of pleural effusion, and the patient was discharged good healthy. Chest X-rays were reexamined one month postoperatively, and the patient's lung was well dilated, with no recurrence of pleural effusion. In this case, it was shown that conservative treatment is the first choice for chylothorax. However, if this proves to be ineffective, early surgical treatment should be considered. Early diagnosis and timely surgical intervention are the key factors to improve the prognosis of patients.

Background Mitochondrial fission regulator 2 (MTFR2) was involved in the progression and development of various cancers. However, the relationship between MTFR2 with lung adenocarcinoma (LUAD) had not been reported. Herein, this study analyzed the clinical significance and potential mechanisms of MTFR2 in LUAD via bioinformatics tools. Results We found that the level of MTFR2 was increased, and correlated with sex, age, smoking history, neoplasm staging, histological subtype and TP53 mutation status in LUAD patients. Kaplan-Meier survival analysis showed LUAD patients with increased MTFR2 had a poor prognosis. In addition, univariate COX regression analysis showed neoplasm staging, T stage, distant metastasis and MTFR2 level were risk factors for the prognosis of LUAD. A total of 1127 genes were coexpressed with MTFR2, including 840 positive and 208 negative related genes. KEGG and GSEA found that MTFR2 participated in the progression of LUAD by affecting cell cycle, DNA replication, homologous recombination, p53 signaling pathway and other mechanisms. The top 10 coexpressed genes, namely CDK1, CDC20, CCNB1, PLK1, CCNA2, AURKB, CCNB2, BUB1B, MAD2L1 and BUB1 were highly expressed, and were associated with poor prognosis in LUAD. Conclusions Consequently, we elucidated MTFR2 was a biomarker for diagnosis and poor prognosis in LUAD, and might participate in the progression of LUAD via affecting cell cycle, DNA replication, homologous recombination and p53 signaling pathway.

Thoracic endometriosis is characterized by the presence of normal functioning endometrial tissues in normal pleural, diaphragm, or lung parenchyma, and main clinical symptoms include pneumothorax, menstrual hemothorax, menstrual hemoptysis, and pulmonary nodules. Chest X-ray (CXR), computed tomography (CT), magnetic resonance imaging (MRI), bronchoscopy, and surgical biopsy could be applied to the diagnosis of TE. Both drug therapy and surgical treatment were widely used to treat this disease, but no theory was used to guide the choice of treatment options. This paper introduces a case of menstrual hemoptysis due to endometriosis, and the final surgical treatment was chosen. The patient recovered well postoperatively and reported no hemoptysis during 2 months of follow-up. Reexamination of the chest through CT showed no ground-glass lesions or pulmonary exudative lesions. We make the following recommendations for patient selection when considering a surgical approach to the treatment of TE. Patients for whom surgery should be considered are those who (I) do not respond to drug therapy or relapse once drug therapy is withdrawn, (II) cannot tolerate drug therapy or who may wish to get pregnant in the near future (III) have limited lesions which are able to be completely removed during surgery. Patients in whom surgery is not recommended include those who have extensive lesions which cannot be surgically removed, including those with diaphragm or pleural involvement as the diseased tissues must be completely removed to avoid recurrence, and those who are unfit for surgery.

Streptomyces sp. SCSIO ZS0520 is a deep-sea hydrothermal vent-derived actinomycete. Our previous metabolism investigation showed that Streptomyces sp. SCSIO ZS0520 is a producer of cytotoxic actinopyrones. Here, another four types of secondary metabolites were identified, including six salinomycin isomers (2–7), the macrolide elaiophylin (8), the triterpene N-acetyl-aminobacteriohopanetriol (9), and the pyrone minipyrone (10). Among them, compounds 2–6 and 10 are new compounds. To understand the biosynthetic pathway of these compounds, a bioinformatic analysis of the whole genome was carried out, which identified 34 secondary metabolite biosynthetic gene clusters. Next, the biosynthetic pathways responsive to four types of products were deduced on the basis of gene function predictions and structure information. Taken together, these findings prove the metabolite potential of ZS0520 and lay the foundations to solve the remaining biosynthetic issues in four types of marine natural products.

Background Spindle and kinetochore associated complex subunit 1/2/3 (SKA1/2/3), which stabilized spindle microtubules attaching to kinetochore (KT) in the middle stage of mitosis, were dysregulated, and closely related to prognosis in several malignant tumors. Nevertheless, the potential clinical value of SKA1/2/3, especially in terms of prognosis and development of NSCLC, had not been fully elucidated. Methods ONCOMINE, GEPIA, UALCAN, TCGA, STRING and other databases were used to analyze the expression of SKA1/2/3 in patients with lung adenocarcinoma (LUAD) and its clinical value, and to explore the possible regulatory mechanism of SKA in the occurrence and development of LUAD. Results In patients with LUAD, SKA1/2/3 mRNA expression level was significantly up-regulated, and AUC was 0.9558, 0.7034 and 0.9775, respectively. Increased SKA 1/2/3 expression was associated with smoking, tissue typing, and poor prognosis in LUAD patients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) showed that SKA1/2/3 was mainly enriched in DNA replication, cell cycle, homologous recombination, p53 signaling pathway, etc. Hub genes in protein-protein interactions are CDK1, BUB1, CCNA2, CDC20, CCNB2, CCNB1, BUB1B, AURKB, TOP2A and MAD2L1. Hub gene expression in LUAD is increased, and its increased expression is related to poor prognosis of LUAD patients. Finally, the expression of SKA1/2/3 and its correlation with clinicopathological features were verified in 30 clinical LUAD samples. Conclusions SKA1/2/3 may serve as a potential prognostic biomarker and target for LUAD. In addition, SKA 1/2/3 may affect the prognosis of LUAD through DNA replication, cell cycle, homologous recombination and p53 signaling pathway.

Background Upregulation of the six-transmembrane epithelial antigen of prostate-1 (STEAP1) is closely associated with prognosis of numerous malignant cancers. However, its role in lung adenocarcinoma (LUAD), the most common type of lung cancer, remains unknown. This study aimed to investigate the role of STEAP1 in the occurrence and progression of LUAD and the potential mechanisms underlying its regulatory effects. Methods STEAP1 mRNA and protein expression were analyzed in 40 LUAD patients via real-time PCR and western blotting, respectively. We accessed the clinical data of 522 LUAD patients from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) to investigate the expression and prognostic role of STEAP1 in LUAD. Further, we performed gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, and gene set enrichment analysis (GSEA) to elucidate the potential mechanism underlying the role of STEAP1 in LUAD. The protein-protein interaction (PPI) network of STEAP1 was analyzed using the Search Tool for the Retrieval of Interacting Genes (STRING) database, and hub genes with significant positive and negative associations with STEAP1 were identified and their role in LUAD prognosis was predicted. Results STEAP1 was significantly upregulated in LUAD patients and associated with LUAD prognosis. Further, TCGA data indicated that STEAP1 upregulation is correlated with the clinical prognosis of LUAD. GO and KEGG analysis revealed that the genes co-expressed with STEAP1 were primarily involved in cell division, DNA replication, cell cycle, apoptosis, cytokine signaling, NF-kB signaling, and TNF signaling. GSEA revealed that homologous recombination, p53 signaling pathway, cell cycle, DNA replication, apoptosis, and toll-like receptor signaling were highly enriched upon STEAP1 upregulation. Gene Expression Profiling Interactive Analysis (GEPIA) analysis revealed that the top 10 hub genes associated with STEAP1 expression were also associated with the LUAD prognosis. Conclusion STEAP1 upregulation potentially influences the occurrence and progression of LUAD and its co-expressed genes via regulation of homologous recombination, p53 signaling, cell cycle, DNA replication, and apoptosis. STEAP1 is a potential prognostic biomarker for LUAD.

Streptomyces niveus SCSIO 3406 was isolated from a sediment sample collected from South China Sea at a depth of 3536 m. Four new sesquiterpenoid naphthoquinones, marfuraquinocins A-D, and two new geranylated phenazines, i. e. phenaziterpenes A and B, were isolated from the fermentation broth of the strain. Here, we present its genome sequence, which contains 7,990,492 bp with a G+C content of 70.46% and harbors 7088 protein-encoding genes. The genome sequence analysis revealed the presence of a 28,787 bp gene cluster encoding for 24 open reading frames including 1,3,6,8-tetrahydroxynaphthalene synthase and monooxygenase, seven phenazine biosynthesis proteins, two prenyltransferases and a squalene-hopene cyclase. These genes are known to be necessary for the biosynthesis of both marfuraquinocins and phenaziterpenes. Outside the gene cluster (and scattered around the genome), there are seven genes belonging to the methylerythritol phosphate pathway for the biosynthesis of the essential primary metabolite, isopentenyl diphosphate, as well as six geranyl diphosphate/farnesyl diphosphate synthase genes. The strain S. niveus SCSIO 3406 showed type I PKS, type III PKS and nonribosomal peptide synthetase cluster. The sequence will provide the genetic basis for better understanding of biosynthesis mechanism of the above mentioned six compounds and for the construction of improved strain for the industrial production of antimicrobial agents.

In order to meet the heating requirement of EAST tokamak, ion cyclotron range of frequency (ICRF) heating is utilized as one of the main auxiliary heating methods, which plays an important role in coupling radio frequency (RF) power into the plasma. As a member of plasma facing components, ICRF antenna suffers the plasma radiation as well which is one of the causes of the thermal load on the antenna. Plasma radiation and RF thermal load during the operation of ICRF and thermal load caused by HALO current during vertical displacement event will contribute together to a huge thermal load on the surface of the antenna and consequently the structural stability and reliability of ICRF antenna will be affected. Therefore, cooling channels is needed to remove heat on the ICRF antenna. In this paper, cooling channels for straps of ICRF antenna are designed based on the thermal load on the antenna, and thermal-structural analysis of straps with cooling channels is also carried out by the finite-element method.

Background and objective Mediastinal infection is a serious infection of mediastinal connective tissue, with more complications and higher mortality. Application of broad-spectrum antibiotics and nutritional support, early sufficient drainage is the key to successful treatment. In the mode of drainage, this paper discusses the application of continuous negative pressure drainage technique to treat acute anterior mediastinal infection of severe mouth pharynx source, and the good results are summarized and shared. Methods In January to December in 2017, a total of 17 cases treated acute mediastinal infection is derived from the throat, has formed a mediastinal abscess, surgery adopts retrosternal counterpart negative pressure drainage way, namely the sternum nest and free sternum xiphoid process under the incision on the first mediastinal clearance, make breakthrough and placed drainage device, suture closed wound, continuous negative pressure drainage, negative pressure using 3 cm-5 cm water column. Results Among the 17 patients, 14 patients were relieved by continuous negative pressure drainage, and then the drainage tube was removed. In 2 cases, the infection broke into the right thoracic cavity, and the closed drainage caused the negative pressure to disappear, and the negative pressure drainage was replaced by the conventional drainage, and the drainage tube was removed after the drainage tube was clear. One patient had formed a mediastinal abscess incision drainage time later, complicated with septic shock and sepsis, resulting in the death of multiple organ failure. Conclusion The traditional treatment of severe acute mediastinal infection is sternal incision and drainage. Continuous negative pressure drainage adequate drainage of mediastinal can relieve patients' pain, effusion, and avoid the dressing out repeatedly. It is an effective method. However, there are limitations in this method, which need to be further optimized.

Background The deep-sea-derived microbe Streptomyces koyangensis SCSIO 5802 produces neoabyssomicins A–B (1–2) and abyssomicins 2 (3) and 4 (4). Neoabyssomicin A (1) augments human immunodeficiency virus-1 (HIV-1) replication whereas abyssomicin 2 (3) selectively reactivates latent HIV and is also active against Gram-positive pathogens including methicillin-resistant Staphylococcus aureus (MRSA). Structurally, neoabyssomicins A–B constitute a new subtype within the abyssomicin family and feature unique structural traits characteristic of extremely interesting biosynthetic transformations. Results In this work, the biosynthetic gene cluster (BGC) for the neoabyssomicins and abyssomicins, composed of 28 opening reading frames, was identified in S. koyangensis SCSIO 5802, and its role in neoabyssomicin/abyssomicin biosynthesis was confirmed via gene inactivation and heterologous expression experiments. Bioinformatics and genomics analyses enabled us to propose a biosynthetic pathway for neoabyssomicin/abyssomicin biosynthesis. Similarly, a protective export system by which both types of compounds are secreted from the S. koyangensis producer was identified, as was a four-component ABC transporter-based import system central to neoabyssomicin/abyssomicin biosynthesis. Furthermore, two regulatory genes, abmI and abmH, were unambiguously shown to be positive regulators of neoabyssomicin/abyssomicin biosynthesis. Consistent with their roles as positive regulatory genes, the overexpression of abmI and abmH (independent of each other) was shown to improve neoabyssomicin/abyssomicin titers. Conclusions These studies provide new insight into the biosynthesis of the abyssomicin class of natural products, and highlight important exploitable features of its BGC for future efforts. Elucidation of the neoabyssomicin/abyssomicin BGC now enables combinatorial biosynthetic initiatives aimed at improving both the titers and pharmaceutical properties of these important natural products-based drug leads. Electronic supplementary material The online version of this article (10.1186/s12934-018-0875-1) contains supplementary material, which is available to authorized users.

Neoabyssomicin A (1) possessing a caged 6/6/6 ring system fused with two additional 6/9 lactone rings, neoabyssomicin B (2) featuring a 12-membered macrolactone ring and its seco-form, neoabyssomicin C (3), along with the known abyssomicin 2 (4) and 4 (5), were discovered from the deep-sea derived Streptomyces koyangensis SCSIO 5802. The structures of 1–3 were elucidated on the basis of MS, NMR spectroscopic and X-ray diffraction data analyses. A plausible biogenetic relationship of 1–5 is proposed. Additionally, compound 4 shows antibacterial activities against a panel of Gram-positive pathogens, including clinical MRSA strains, with MICs of 3–15 μg/mL; compounds 1 and 3 also were found to augment HIV-1 virus replication in a human lymphocyte model.

Significance l -galactofuranose ( l -Gal f ), the furanose form of l -galactose, is rare in nature yet plays a central role in secondary metabolite structures with medicinal potential. Importantly, the biosynthetic enzymes and mechanisms driving l -Gal f biosynthesis have eluded characterization. We report here a previously unknown mutase, MtdL, that generates GDP- l -Gal f from its galactopyranose analog GDP- l -Gal p using unique chemistry. MtdL mediates the pyranose–furanose conversion solely by the presence of bivalent cation. The ubiquitous nature of this Gal p → Gal f chemistry is suggested by numerous mutase homologs that are phylogenetically widespread in various phyla of Bacteria, Eukaryota, and Archaea. Thus, a genetic marker for l -Gal f -containing natural products and their producers has been discovered. Additionally, mutase homologs may constitute targets for antimicrobial drugs.

Biosynthetic pathways containing multiple core enzymes have potential to produce structurally complex natural products. Here we mined a fungal gene cluster that contains two predicted terpene cyclases (TCs) and a nonribosomal peptide synthetase (NRPS). We showed the flv pathway produces flavunoidine 1, an alkaloidal terpenoid. The core of 1 is a tetracyclic, cage-like, and oxygenated sesquiterpene that is connected to dimethylcadaverine via a C-N bond and is acylated with 5,5-dimethyl-l-pipecolate. The roles of all flv enzymes are established on the basis of metabolite analysis from heterologous expression.

A new butenolide derivative (

Pulmonary arteriovenous fistulas (PAVFs) are uncommon vascular malformations (1). Dyspnea and fatigue are the most common symptoms, with spontaneous hemothorax being a rare complication. Herein, we present a case with spontaneous hemothorax caused by the intrapleural rupture of the PAVF.

The antimicrobial nucleoside antibiotic A201A is produced by the deep-sea derived Marinactinospora thermotolerans SCSIO 00652. Bioinformatics analysis revealed that mtdV, downstream within the A201A biosynthetic gene cluster, encodes a protein with low homology to a group of chorismate pyruvate-lyases. To explore the role of mtdV in A201A biosynthesis, mtdV was inactivated and HPLC analysis revealed that the resulting ΔmtdV mutant failed to produce A201A; production was partially restored by adding exogenous 4-hydroxybenzoic acid (4HB) to the fermentation. In vitro biochemical assays showed that MtdV catalyzes the conversion of chorismate into 4HB, thereby firmly demonstrating that MtdV is a chorismate lyase involved in A201A biosynthesis. In addition, supplementation of the ΔmtdV mutant with various 4HB analogs enabled production of seven new A201A analogs. Antimicrobial assays showed that the purified A201A analogs 3'-F-A201A and 3'-Cl-A201A were just as active as A201A against the test strains with MIC values of 1-8 μg mL-1.

A new butenolide derivative (1) featuring octyl substitution at γ-position, together with four known analogues (2–5) were isolated from marine-derived Streptomyces koyangensis SCSIO 5802. The structure of 1 was elucidated by HR-MS and NMR spectroscopic data analyses. The absolute configuration of the stereo centre in lactone ring of 1 was determined by comparison of CD spectrum with those of known compounds. Compound 1 exhibited mild antiviral activity against herpes simplex virus with EC50 value of 25.4 µM.

Desotamides A, a cyclohexapeptide produced by the deep-sea-derived Streptomyces scopuliridis SCSIO ZJ46, displays notable antibacterial activities against strains of Streptococcus pnuemoniae, Staphylococcus aureus, and methicillin-resistant Staphylococcus epidermidis (MRSE). In this study, to further explore its antibacterial potential and reveal the antibacterial structure-activity relationship of desotamides, 13 cyclopeptides including 10 new synthetic desotamide A analogues and wollamides B/B1/B2 were synthesized and evaluated for their antibacterial activities against a panel of Gram-positive and -negative pathogens. The bioactivity data reveal that residues at position II and VI greatly impact antibacterial activity. The most potent antibacterial analogues are desotamide A4 (13) and A6 (15) where l-allo-Ile at position II was substituted with l-Ile and Gly at position VI was simultaneously replaced by d-Lys or d-Arg; desotamides A4 (13) and A6 (15) showed a 2–4-fold increase of antibacterial activities against a series of Gram-positive pathogens including the prevalent clinical drug-resistant pathogen methicillin-resistant Staphylococcus aureus (MRSA) with MIC values of 8–32 μg/mL compared to the original desotamide A. The enhanced antibacterial activity, broad antibacterial spectrum of desotamides A4 and A6 highlighted their potential as new antibiotic leads for further development.

Fusion Tokamaks are complex machines which require special conditions for their operation, in particular, high vacuum inside the vessel and high temperature of the vessel walls. During plasma phases, the first wall components are highly stressed and a control is necessary in case of doubt about their condition. To be able to make safely such an inspection in a short period of time is a great advantage. The Articulated Inspection Arm (AIA) developed by the CEA provides the capability for fast inspections of the first wall overall surface keeping the vacuum and temperature conditions of the vessel. The robot prototype was validated in Tore Supra in 2008. In the frame of a joint laboratory, CEA/IRFM and ASIPP have decided to upgrade the existing AIA prototype to use it routinely in the EAST and WEST tokamaks. The robot has followed an important upgrade program in 2013 and 2014. The document presents the various upgrades made on the mechanics, the sensors, the electronics, the control station and the integration adaptation for the operation on EAST. From the AIA experience, thoughts for future inspection robots are given.

Three new abyssomicin monomers designated neoabyssomicins D (1), E (2), and A2 (3) and the two dimeric neoabyssomicins F (4) and G (5) were discovered from the marine-derived Streptomyces koyangensis SCSIO 5802, and their structures rigorously elucidated. Neoabyssomicin D (1) possesses an unprecedented 8/5/5/7 ring skeleton, the biosynthesis of which (as well as 2) is proposed herein. Additionally, dimeric agents 4 and 5 were found to be active against methicillin-resistant Staphylococcus aureus and vesicular stomatitis virus, respectively.

Eukaryotic translation initiation factor 5A2 (EIF5A2) has been demonstrated to be upregulated in numerous types of human cancer and is associated with cancer progression. However, the expression and role of EIF5A2 in non-small cell lung cancer (NSCLC) remains unclear. In the present study, the role of EIF5A2 in NSCLC was investigated, in addition to the underlying molecular mechanisms by which EIF5A2 acts. Relative EIF5A2 expression levels were determined in NSCLC cells and compared with levels in non-cancerous lung tissues. Short interfering (si)RNA targeted against EIF5A2 was used to knock down EIF5A2 levels in NSCLC cells. Cell proliferation, apoptosis rate, migration ability and invasion ability were determined in untreated and siRNA-treated NSCLC cells, in addition to the relative protein expression levels of various tumorigenic proteins and E-cadherin. EIF5A2 expression was significantly higher in NSCLC tissues compared with adjacent normal tissues. Knockdown of EIF5A2 in the NSCLC cells significantly inhibited cell proliferation and induced apoptosis. Furthermore, EIF5A2 silencing suppressed cell migratory and invasive capacities in vitro. Silencing of EIF5A2 in the NSCLC cells resulted in the downregulation of the tumorigenic proteins, apoptosis regulator Bcl-2 and myc proto-oncogene protein, and upregulation of E-cadherin, suggesting that EIF5A2 promotes proliferation and metastasis through these proteins. EIF5A2 may therefore serve as a novel therapeutic target for the treatment of NSCLC.

Additional file 1: Table S1. Bacteria used in this study. Table S2. Plasmids used in this study. Table S3. Primers used in this study. Figure S1. Chemical structures of tetronate-containing natural products and the unique set of five highly conserved genes responsible for tetronate biosynthesis. Figure S2. HPLC analyses of fermentation extracts of the inactivated mutants of boundary genes. Figure S3. Alignments of seven KS domains of AbmB1–B3. Figure S4. Alignments of five KR domains of AbmB1–B2. Figure S5. Alignments of five DH domains of AbmB1–B2. Figure S6. Alignments of five AT domains of AbmB1–B2. Figure S7. Alignments of AbmT with the typical type II TEs. Figure S8. The 14 transmembrane helices of AbmD. Figure S9. Alignments of AbmI with previously characterized SARP regulators. Figure S10. Alignments of AbmH with previously characterized LuxR-regulators. Figure S11. The quantitative HPLC standard curve for abyssomicin 2. Figures S12–S30. Disruption of 19 abm-related genes in wild-type S. koyangensis SCSIO 5802 via PCR-targeting.

Joints are essential components of poloidal field coil in fusion device, serving as an electric and coolant transfer between adjacent superconductors. The design of full size joint sample has been carried out by ASIPP. In the future, this sample will be tested in the Sultan facility at Villigen. The test contents include joint total resistance at 4.2 K and 55 kA with 2 T external field, and AC losses at 4.2 K and 45 kA with an external field varying from 0 to 2 T in 1 s. This paper mainly describes the design and analysis of full size joint sample. This sample is composed of two single conductor legs, a praying-hand joint to be placed in the high field, and two terminals to be connected to the transformer of the test facility. The temperature sensors and voltage taps are used for measuring and calculating the DC resistance and AC loss. In order to support the design, the electromagnetic and mechanical analyses are performed. According to the electromagnetic and mechanical analyses, the results show that this design is feasible.