Accumulating evidence suggests that M2-polarized tumor-associated macrophages (TAMs) play an important role in cancer progression and metastasis, making M2 polarization of TAMs an ever more appealing ...target for therapeutic intervention. Astragaloside IV (AS-IV), a saponin component isolated from Astragali radix, has been reported to inhibit the invasion and metastasis of lung cancer, but its effects on TAMs during lung cancer progression have not been investigated.
Human THP-1 monocytes were induced to differentiate into M2 macrophages through treatments with IL-4, IL-13, and phorbol myristate acetate (PMA). We used the lung cancer cell lines A549 and H1299 cultured in conditioned medium from M2 macrophages (M2-CM) to investigate the effects of AS-IV on tumor growth, invasion, migration, and angiogenesis of lung cancer cells. Macrophage subset distribution, M1 and M2 macrophage-associated markers, and mRNA expression were analyzed by flow cytometry and quantitative PCR. The activation of adenosine monophosphate-activated protein kinase (AMPK) signaling pathways that mediate M2-CM-promoted tumor migration was detected using western blotting.
Here we found that AS-IV significantly inhibited IL-13 and IL-4-induced M2 polarization of macrophages, as illustrated by reduced expression of CD206 and M2-associated genes, and that AS-IV suppressed the M2-CM-induced invasion, migration, and angiogenesis of A549 and H1299 cells. In vivo experiments demonstrated that AS-IV greatly inhibited tumor growth and reduced the number of metastases of Lewis lung cancer. The percentage of M2 macrophages was decreased in tumor tissue after AS-IV treatment. Furthermore, AS-IV inhibited AMPKα activation in M2 macrophages, and silencing of AMPKα partially abrogated the inhibitory effect of AS-IV.
AS-IV reduced the growth, invasion, migration, and angiogenesis of lung cancer by blocking the M2 polarization of macrophages partially through the AMPK signaling pathway, which appears to play an important role in AS-IV's ability to inhibit the metastasis of lung cancer.
Human infections with zoonotic coronaviruses (CoVs), including severe acute respiratory syndrome (SARS)-CoV and Middle East respiratory syndrome (MERS)-CoV, have raised great public health concern ...globally. Here, we report a novel bat-origin CoV causing severe and fatal pneumonia in humans.
We collected clinical data and bronchoalveolar lavage (BAL) specimens from five patients with severe pneumonia from Wuhan Jinyintan Hospital, Hubei province, China. Nucleic acids of the BAL were extracted and subjected to next-generation sequencing. Virus isolation was carried out, and maximum-likelihood phylogenetic trees were constructed.
Five patients hospitalized from December 18 to December 29, 2019 presented with fever, cough, and dyspnea accompanied by complications of acute respiratory distress syndrome. Chest radiography revealed diffuse opacities and consolidation. One of these patients died. Sequence results revealed the presence of a previously unknown β-CoV strain in all five patients, with 99.8% to 99.9% nucleotide identities among the isolates. These isolates showed 79.0% nucleotide identity with the sequence of SARS-CoV (GenBank NC_004718) and 51.8% identity with the sequence of MERS-CoV (GenBank NC_019843). The virus is phylogenetically closest to a bat SARS-like CoV (SL-ZC45, GenBank MG772933) with 87.6% to 87.7% nucleotide identity, but is in a separate clade. Moreover, these viruses have a single intact open reading frame gene 8, as a further indicator of bat-origin CoVs. However, the amino acid sequence of the tentative receptor-binding domain resembles that of SARS-CoV, indicating that these viruses might use the same receptor.
A novel bat-borne CoV was identified that is associated with severe and fatal respiratory disease in humans.
Multi-Orientation Scene Text Detection with Adaptive Clustering Yin, Xu-Cheng; Pei, Wei-Yi; Zhang, Jun ...
IEEE transactions on pattern analysis and machine intelligence,
2015-Sept.-1, 2015-Sep, 2015-9-1, 20150901, Letnik:
37, Številka:
9
Journal Article
Recenzirano
Text detection in natural scene images is an important prerequisite for many content-based image analysis tasks, while most current research efforts only focus on horizontal or near horizontal scene ...text. In this paper, first we present a unified distance metric learning framework for adaptive hierarchical clustering, which can simultaneously learn similarity weights (to adaptively combine different feature similarities) and the clustering threshold (to automatically determine the number of clusters). Then, we propose an effective multi-orientation scene text detection system, which constructs text candidates by grouping characters based on this adaptive clustering. Our text candidates construction method consists of several sequential coarse-to-fine grouping steps: morphology-based grouping via single-link clustering, orientation-based grouping via divisive hierarchical clustering, and projection-based grouping also via divisive clustering. The effectiveness of our proposed system is evaluated on several public scene text databases, e.g., ICDAR Robust Reading Competition data sets (2011 and 2013), MSRA-TD500 and NEOCR. Specifically, on the multi-orientation text data set MSRA-TD500, the <inline-formula><tex-math>f</tex-math> <inline-graphic xlink:type="simple" xlink:href="yin-ieq1-2388210.gif"/> </inline-formula> measure of our system is <inline-formula><tex-math>71</tex-math> <inline-graphic xlink:type="simple" xlink:href="yin-ieq2-2388210.gif"/> </inline-formula> percent, much better than the state-of-the-art performance. We also construct and release a practical challenging multi-orientation scene text data set (USTB-SV1K), which is available at http://prir.ustb.edu.cn/TexStar/MOMV-text-detection/.
Small cell lung cancer (SCLC) is a recalcitrant, aggressive neuroendocrine-type cancer for which little change to first-line standard-of-care treatment has occurred within the last few decades. ...Unlike nonsmall cell lung cancer (NSCLC), SCLC harbors few actionable mutations for therapeutic intervention. Lysine-specific histone demethylase 1A (LSD1 also known as KDM1A) inhibitors were previously shown to have selective activity in SCLC models, but the underlying mechanism was elusive. Here, we found that exposure to the selective LSD1 inhibitor ORY-1001 activated the NOTCH pathway, resulting in the suppression of the transcription factor ASCL1 and the repression of SCLC tumorigenesis. Our analyses revealed that LSD1 bound to the
locus, thereby suppressing NOTCH1 expression and downstream signaling. Reactivation of NOTCH signaling with the LSD1 inhibitor reduced the expression of ASCL1 and neuroendocrine cell lineage genes. Knockdown studies confirmed the pharmacological inhibitor-based results. In vivo, sensitivity to LSD1 inhibition in SCLC patient-derived xenograft (PDX) models correlated with the extent of consequential NOTCH pathway activation and repression of a neuroendocrine phenotype. Complete and durable tumor regression occurred with ORY-1001-induced NOTCH activation in a chemoresistant PDX model. Our findings reveal how LSD1 inhibitors function in this tumor and support their potential as a new and targeted therapy for SCLC.
Type 2 diabetes (T2D) is a heterogeneous complex disease affecting more than 29 million Americans alone with a rising prevalence trending toward steady increases in the coming decades. Thus, there is ...a pressing clinical need to improve early prevention and clinical management of T2D and its complications. Clinicians have understood that patients who carry the T2D diagnosis have a variety of phenotypes and susceptibilities to diabetes-related complications. We used a precision medicine approach to characterize the complexity of T2D patient populations based on high-dimensional electronic medical records (EMRs) and genotype data from 11,210 individuals. We successfully identified three distinct subgroups of T2D from topology-based patient-patient networks. Subtype 1 was characterized by T2D complications diabetic nephropathy and diabetic retinopathy; subtype 2 was enriched for cancer malignancy and cardiovascular diseases; and subtype 3 was associated most strongly with cardiovascular diseases, neurological diseases, allergies, and HIV infections. We performed a genetic association analysis of the emergent T2D subtypes to identify subtype-specific genetic markers and identified 1279, 1227, and 1338 single-nucleotide polymorphisms (SNPs) that mapped to 425, 322, and 437 unique genes specific to subtypes 1, 2, and 3, respectively. By assessing the human disease-SNP association for each subtype, the enriched phenotypes and biological functions at the gene level for each subtype matched with the disease comorbidities and clinical differences that we identified through EMRs. Our approach demonstrates the utility of applying the precision medicine paradigm in T2D and the promise of extending the approach to the study of other complex, multifactorial diseases.
An unprecedented hydroalkylation of racemic allylic alcohols and racemic ketimine esters enabled by Cu/Ru relay catalysis has been developed via merging the ruthenium‐catalyzed asymmetric ...borrowing‐hydrogen reaction with a copper‐catalyzed asymmetric Michael addition in a one‐pot procedure. The current method enables the efficient preparation of highly functionalized δ‐hydroxyesters bearing 1,4‐nonadjacent stereocenters in good yields with high levels of diastereoselectivity and excellent enantioselectivity under mild reaction conditions. The full complement of the four stereoisomers of hydroalkylation products could be readily accessed by orthogonal permutations of two chiral metal catalysts. The current work highlights the power of relay catalysis for the stereodivergent construction of 1,4‐nonadjacent stereocenters that were otherwise inaccessible.
An unprecedented stereodivergent hydroalkylation of racemic allylic alcohols and racemic ketimine esters enabled by dual Cu/Ru relay catalysis has been developed. Merging the ruthenium‐catalyzed asymmetric borrowing‐hydrogen reaction with a copper‐catalyzed asymmetric Michael addition into a one‐pot procedure provided a route to highly functionalized δ‐hydroxyesters bearing 1,4‐nonadjacent stereocenters in good yields with excellent stereoselectivity under mild reaction conditions.
The adsorption and electrooxidation of CO molecules at well‐defined Pt(hkl) single‐crystal electrode surfaces is a key step towards addressing catalyst poisoning mechanisms in fuel cells. Herein, we ...employed in situ electrochemical shell‐isolated nanoparticle‐enhanced Raman spectroscopy (SHINERS) coupled with theoretical calculation to investigate CO electrooxidation on Pt(hkl) surfaces in acidic solution. We obtained the Raman signal of top‐ and bridge‐site adsorbed CO* molecules on Pt(111) and Pt(100). In contrast, on Pt(110) surfaces only top‐site adsorbed CO* was detected during the entire electrooxidation process. Direct spectroscopic evidence for OH* and COOH* species forming on Pt(100) and Pt(111) surfaces was afforded and confirmed subsequently via isotope substitution experiments and DFT calculations. In summary, the formation and adsorption of OH* and COOH* species plays a vital role in expediting the electrooxidation process, which relates with the pre‐oxidation peak of CO electrooxidation. This work deepens knowledge of the CO electrooxidation process and provides new perspectives for the design of anti‐poisoning and highly effective catalysts.
CO electrooxidation on Pt(hkl) surfaces in acidic solution has been investigated using in situ shell‐isolated nanoparticle‐enhanced Raman spectroscopy (SHINERS). Direct spectroscopic evidence for OH* and COOH* species was observed and further confirmed by deuterium isotopic experiments and DFT calculations.
Intratumoural hypoxia induces HIF-1α and promotes tumour progression, metastasis and treatment resistance. HIF-1α stability is regulated by VHL-E3 ligase-mediated ubiquitin-dependent degradation; ...however, the hypoxia-regulated deubiquitinase that stabilizes HIF-1α has not been identified. Here we report that HAUSP (USP7) deubiquitinase deubiquitinates HIF-1α to increase its stability, induce epithelial-mesenchymal transition and promote metastasis. Hypoxia induces K63-linked polyubiquitinated HAUSP at lysine 443 to enhance its functions. Knockdown of HAUSP decreases acetylation of histone 3 lysine 56 (H3K56Ac). K63-polyubiquitinated HAUSP interacts with a ubiquitin receptor CBP to specifically mediate H3K56 acetylation. ChIP-seq analysis of HAUSP and HIF-1α binding reveals two motifs responsive to hypoxia. HectH9 is the E3 ligase for HAUSP and a prognostic marker together with HIF-1α. This report demonstrates that hypoxia-induced K63-polyubiquitinated HAUSP deubiquitinates HIF-1α and causes CBP-mediated H3K56 acetylation on HIF-1α target gene promoters to promote EMT/metastasis, further defining HAUSP as a therapeutic target in hypoxia-induced tumour progression.
Cement production is the main source of industrial process-related CO2 emissions, taking up approximately half of total industrial process-related CO2 emissions. However, limited research has ...investigated the process-related CO2 emissions from global cement production, in particular, has not taken into account the impacts of dynamic socio-economic development context. This study aims to explore the trajectory of industrial process-related CO2 emissions in the cement industry under different Shared Socioeconomic Pathways (SSPs), to provide more evidence for the existing climate change integrated assessment analysis. By investigating the relationship between per capita GDP and per capita cement production process-related CO2 emissions drawing on the historical data during 1950–2014 in 31 developed countries, the cement production process-related CO2 emissions from 175 countries in 12 regions in the world during 2015–2100 under five SSP scenarios are given here. The results show that the largest amount of global cumulative cement process-related CO2 emissions would be 45.45 billion tons under SSP3 scenario. The countries that contribute the most to the global cumulative cement production process-related CO2 emissions from 2015 to 2100 are India, China, Nigeria, United States of America and Pakistan.
•The industrial process-related CO2 emissions from cement production is targeted.•Project global process-related CO2 emissions under five Shared Socioeconomic Pathways.•Cement process-related CO2 emissions from 175 countries in 2015–2100 are given.•The global cumulative process-related CO2 emissions under SSP3 are the highest.•The process-related CO2 emissions are quite different in 12 regions under SSP1-SSP5.
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