Benmelstobart, anlotinib and chemotherapy in extensive-stage small-cell lung cancer: a randomized phase 3 trial.

Immunochemotherapy is the first-line standard for extensive-stage small-cell lung cancer (ES-SCLC). Combining the regimen with anti-angiogenesis may improve efficacy. ETER701 was a multicenter, double-blind, randomized, placebo-controlled phase 3 trial that investigated the efficacy and safety of benmelstobart (a novel programmed death-ligand 1 (PD-L1) inhibitor) with anlotinib (a multi-target anti-angiogenic small molecule) and standard chemotherapy in treatment-naive ES-SCLC. The ETER701 trial assessed two primary endpoints: Independent Review Committee-assessed progression-free survival per RECIST 1.1 and overall survival (OS). Here the prespecified final progression-free survival and interim OS analysis is reported. Patients randomly received benmelstobart and anlotinib plus etoposide/carboplatin (EC; n = 246), placebo and anlotinib plus EC (n = 245) or double placebo plus EC ('EC alone'; n = 247), followed by matching maintenance therapy. Compared with EC alone, median OS was prolonged with benmelstobart and anlotinib plus EC (19.3 versus 11.9 months; hazard ratio 0.61; P = 0.0002), while improvement of OS was not statistically significant with anlotinib plus EC (13.3 versus 11.9 months; hazard ratio 0.86; P = 0.1723). The incidence of grade 3 or higher treatment-related adverse events was 93.1%, 94.3% and 87.0% in the benmelstobart and anlotinib plus EC, anlotinib plus EC, and EC alone groups, respectively. This study of immunochemotherapy plus multi-target anti-angiogenesis as first-line treatment achieved a median OS greater than recorded in prior randomized studies in patients with ES-SCLC. The safety profile was assessed as tolerable and manageable. Our findings suggest that the addition of anti-angiogenesis therapy to immunochemotherapy may represent an efficacious and safe approach to the management of ES-SCLC. ClinicalTrials.gov identifier: NCT04234607 .

E3 ligase TRIM28 promotes anti-PD-1 resistance in non-small cell lung cancer by enhancing the recruitment of myeloid-derived suppressor cells.

BACKGROUND: Alterations in several tripartite motif-containing (TRIM) family proteins have been implicated in the pathogenesis of lung cancer. TRIM28, a member of the TRIM E3 ligase family, has been associated with tumorigenesis, cell proliferation, and inflammation. However, little is known about TRIM28 expression and its role in the immune microenvironment of non-small cell lung cancer (NSCLC). METHODS: We assessed the clinical significance of TRIM28 in tissue microarrays and TCGA cohorts. We investigated the function of TRIM28 in syngeneic mouse tumor models, the KrasLSL-G12D/+; Tp53fl/fl (KP) mouse model, and humanized mice. Immune cell composition was analyzed using flow cytometry and immunohistochemistry. RESULTS: Our findings revealed a positive correlation between TRIM28 expression and the infiltration of suppressive myeloid-derived suppressor cells (MDSCs) in NSCLC. Moreover, silencing TRIM28 enhanced the efficacy of anti-PD-1 immunotherapy by reshaping the inflamed tumor microenvironment. Mechanistically, we demonstrated that TRIM28 could physically interact with receptor-interacting protein kinase 1 (RIPK1) and promote K63-linked ubiquitination of RIPK1, which is crucial for sustaining activation of the NF-κB pathway. Mutagenesis of the E3 ligase domain corroborated the essential role of E3 ligase activity in TRIM28-mediated NF-κB activation. Further experiments revealed that TRIM28 could upregulate the expression of CXCL1 by activating NF-κB signaling. CXCL1 could bind to CXCR2 on MDSCs and promote their migration to the tumor microenvironment. TRIM28 knockdown increased responsiveness to anti-PD-1 therapy in immunocompetent mice, characterized by increased CD8+T tumor-infiltrating lymphocytes and decreased MDSCs. CONCLUSION: The present study identified TRIM28 as a promoter of chemokine-driven recruitment of MDSCs through RIPK1-mediated NF-κB activation, leading to the suppression of infiltrating activated CD8+T cells and the development of anti-PD-1 resistance. Understanding the regulation of MDSC recruitment and function by TRIM28 provides crucial insights into the association between TRIM28 signaling and the development of an immunosuppressive tumor microenvironment. These insights may inform the development of combination therapies to enhance the effectiveness of immune checkpoint blockade therapy in NSCLC.

Large scale transparency-adjustable mini-LED display with recoverable color gamut by a highly transparent electrochromic shutter.

In this work, a 25 inch (400 × 500 mm) transparency-adjustable mini-LED (TA-MLED) display is constructed of a transparent mini-LED (T-MLED) screen and an electrochromic (EC) shutter. The shutter shows a high transmittance of 86.5% with imperceptible color shift, enabling a perfect vision experience for see-through application. Furthermore, the response speed of the shutter is accelerated by optimal designs in splicing and driving. The coloring time is 55 s, and bleaching time is 36 s. Transmittance of the TA-MLED could be modulated from 3% to 60%. The transparency-adjustable property extends availability of the see-through display screens under strong light irradiations. The T-MLED's color gamut in CIE 1976 shrinks from 145.1% sRGB to 3.6% sRGB with 5161 cd/m2 of backside illumination, and is significantly enhanced to 83.5% sRGB with the active EC shutter.

E3 ligase TRIM15 facilitates non-small cell lung cancer progression through mediating Keap1-Nrf2 signaling pathway.

BACKGROUND: Recent studies have indicated that some members of the tripartite motif (TRIM) proteins function as important regulators for non-small cell lung cancer (NSCLC), However, the regulatory mechanism underpinning aberrant expression of TRIM in NSCLC remains unclear. Here we report that TRIM15 plays important roles in NSCLC progression through modulating Keap1-Nrf2 signaling pathway. METHODS: TRIM15 expression was evaluated by western blot analysis, tissue microarray-based immunohistochemistry analysis. The interactions between TRIM15 and Keap1 were analyzed by co-immunoprecipitation (Co-IP) and immunofluorescence co-localization assay. The correlation between TRIM15 and Keap1 was measured by Co-IP and ubiquitination analysis in vitro. Gain- and lost-of-function experiments were used to detect TRIM15 promotes proliferation and invasion of NSCLC cells both in vitro and vivo. RESULTS: Here, we revealed that TRIM15 was frequently upregulated in NSCLC samples and associated with poor prognosis. Functionally, TRIM15 knockdown resulted in decreased cancer cell proliferation and metastasis, whereas ectopic TRIM15 expression facilitated tumor cancer cell proliferation and metastasis in vitro and in vivo. Moreover, TRIM15 promoted cell proliferation and metastasis depends on its E3 ubiquitin ligase. Mechanistically, TRIM15 directly targeted Keap1 by ubiquitination and degradation, the principal regulator of Nrf2 degradation, leading to Nrf2 escaping from Keap1-mediated degradation, subsequently promoting antioxidant response and tumor progression. CONCLUSIONS: Therefore, our study characterizes the pivotal roles of TRIM15 promotes NSCLC progression via Nrf2 stability mediated by promoting Keap1 ubiquitination and degradation and could be a valuable prognostic biomarker and a potential therapeutic target in NSCLC. Video Abstract.

Ectodermal­neural cortex 1 affects the biological function of lung cancer through the MAPK pathway.

Ectodermal­neural cortex 1 (ENC1), a highly expressed protein in lung cancer tissues, was identified from the Cancer Genome Atlas (TCGA) database. The objective of the present study was to examine the effects of ENC1 on the biological functions of lung cancer cells. For this purpose, the expression of ENC1 was examined by RT­qPCR to compare mRNA expression levels between 28 lung cancer tissue samples and para­cancerous tissue samples. The association between ENC1 expression and clinicopathological features was evaluated between the 2 tissue types. Using RT­qPCR and western blot analysis, the expression of ENC1 was investigated in a normal lung cell line (16HBE) and 2 lung cancer cell lines (A549 and H1299). The effect of siRNA targeting ENC1 (si­ENC1) on the proliferation of A549 and H1299 cells was detected by CCK­8 assay at the indicated time points. Transwell assay was used to measure the migration and invasion of A549 and H1299 cells following transfection with siRNA targeting ENC1 (si­ENC1). The expression levels of several proteins related to migration and invasion were examined by western blot analysis. A mouse model of subcutaneous tumor xenotransplantation was established in nude mice to examine the effects of ENC1 downregulation on cancer cells. The results revealed that the expression of ENC1 in lung cancer tissues and lung cancer cells was significantly higher than that in para­cancerous tissues and non­cancer lung cells, respectively. The knockdown of ENC1 in the A549 and H1299 cells using si­ENC1 significantly decreased cell proliferation, migration and invasion compared with the untransfected cells. The knockdown of ENC1 significantly downregulated the levels of matrix metalloproteinase (MMP)2, MMP9, N­cadherin, p­c­Jun N­terminal kinase (JNK), p­extracellular signal­regulated kinase (ERK) and p­p38. The levels of E­cadherin were upregulated. In the mouse lung tumor model, reduced levels of ENC1 inhibited the growth of lung tumors. On the whole, the present study demonstrates that ENC1 is involved in the proliferation, migration and invasion of lung cancer cells, and may thus be an effective diagnostic target for certain cancers. The inhibition or reduction of ENC1 activity may represent a breakthrough in the treatment of lung cancer.

Expression and Bioinformatics-Based Functional Analysis of UAP1 in Lung Adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LAD) is the most prevalent type of lung cancer. The abnormal expression of UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1) has been reported to be involved in many biological processes of cancer cells, but the expression of UAP1 in LAD is unclear. METHODS: Bioinformatics was used to analyse the LAD gene expression data and related clinical data in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. DAVID6.8 was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) signal pathway enrichment analyses of UAP1 expression-related genes. The STRING database was used to analyse protein-protein interaction (PPI) networks. RNA isolation and reverse transcription-quantitative polymerase chain reaction (RT­qPCR) assay were used to detect the expression of UAP1 in tissues and blood samples. RESULTS: We found that UAP1 was upregulated in LAD tissues and correlated with poor clinical outcome. GO analysis showed that these genes were enriched in biological processes and functions including intracellular transport, cellular protein catabolic process, and mitochondria (P<0.05). The KEGG pathway analysis showed that these genes were mainly involved in the signalling pathways of amino sugar and nucleotide sugar metabolism, the aminoacyl-tRNA biosynthesis signalling pathway, and protein export (P<0.05). The PPI analysis showed that EPRS, COPB1, CCT3, ALDH18A1 and ARF1 genes had marked or potential interaction with UAP1 (P<0.01). In addition, UAP1 expression was upregulated in LAD tissues compared to normal tissues. High levels of UAP1 expression were associated with larger tumour sizes and later TNM stages. RT­qPCR detection in serum further showed that UAP1 expression was upregulated in the plasma of LAD patients compared to that of healthy volunteers. High expression of UAP1 in serum suggests a poor prognosis for LAD patients. CONCLUSION: UAP1 could be a novel diagnostic biomarker and a promising therapeutic target for LAD.

Cancer-derived exosomal TRIM59 regulates macrophage NLRP3 inflammasome activation to promote lung cancer progression.

BACKGROUND: Exosomes are emerging as important mediators of the cross-talk between tumor cells and the microenvironment. The communication between tumor-derived exosomes and macrophages has a critical role in facilitating tumor progression. However, the mechanisms by which exosomes modulate tumor development in lung cancer are not fully understood. METHODS: Short hairpin RNA mediated knockdown or exogenous expression of TRIM59 combined with in vitro and in vivo assays were performed to prove the functional significance of TRIM59. Western blotting, real-time PCR, co-immunoprecipitation, immunofluorescence (IF) staining assays, proximity ligation assay (PLA), ubiquitination assays, lactate secretion and lipid droplets content measurement, and rescue experiments were used to evaluate the mechanism. Lewis lung carcinoma (LLC) cells were injected via subcutaneously or tail vein into C57BL/6 wild-type (WT) and transgenic mice to assess the role of TRIM59 in vivo. RESULTS: We demonstrated that tripartite motif-containing 59 (TRIM59) was expressed in lung cancer cells-derived exosomes, and can be transferred to macrophages through the exosomes. Activated macrophages by TRIM59 promote lung cancer progression in vitro and in vivo. Mechanistic investigations revealed that TRIM59 physically interacts with abhydrolase domain containing 5 (ABHD5) and directly induced the ubiquitination of ABHD5 and led to its proteasome-dependent degradation. ABHD5, an lipolytic co-activator, deficiency induced metabolic reprogramming and enabled NLRP3 inflammasome activation in macrophages. Further studies showed that the exacerbation of NLRP3 inflammasome activation by ABHD5 deficiency, provides a positive feedback loop to promote cancer progression by preferentially secrete the proinflammatory cytokine IL-1ß. CONCLUSIONS: Collectively, these data indicate that tumor-derived exosomal TRIM59 converts macrophages to tumor-promoting functions of macrophages via regulating ABHD5 proteasomal degradation, to activate NLRP3 inflammasome signaling pathway to promote lung cancer progression by IL-1ß secretion. Our findings also indicate that tumor-derived exosomal TRIM59 has an important role in intercellular communication for fostering an inflammatory microenvironment and promoting lung metastasis.

Primary bronchial myeloid sarcoma mimicking bronchogenic carcinoma: a case report.

BACKGROUND: Myeloid sarcoma (MS) rarely involves the bronchus, and primary bronchial MS has almost never been reported in mainland China. CASE PRESENTATION: A 65-year-old female patient was admitted with a 3-month history of cough. She was initially diagnosed with bronchogenic carcinoma according to chest computed tomography (CT). However, after a biopsy was taken from the endobronchial lesion by bronchoscopy and further immunohistochemical analysis was performed, the diagnosis of MS was made. Because her bone marrow was normal and she had no history of haematologic diseases, we further considered the diagnosis of primary bronchial MS. The patient received chemotherapy with HAG regimens, and the original mass completely resolved, as confirmed by chest CT scan after 3 cycles of treatment. Meanwhile, no abnormalities were found on re-examination via bronchoscopy. CONCLUSIONS: MS should be considered in the differential diagnosis in the presence of a suspicious pulmonary mass. Immunohistochemical analysis is necessary to confirm the diagnosis. Chemotherapy can lengthen the survival time for patients.

Impact of fruit-tree shade intensity on the growth, yield, and quality of intercropped wheat.

Agroforestry is a common traditional practice in China-especially in the southern Xinjiang of Northwest China. However, the productivity of many agroforestry systems has been lower than expected in recent years, highlighting the need for an actionably deep mechanistic understanding of the competition between crops and trees. Here, three different fruit tree/wheat (jujube/wheat, apricot /wheat, and walnut /wheat) intercropping agroforestry systems were chosen to investigate influence of different fruit tree shade intensity on the growth, yield and quality of intercropping wheat. Compared to the monoculture wheat system, the mean daily shade intensity of the jujube-, apricot-, and walnut-based intercropping systems were, respectively, 23.2%, 57.5%, and 80.7% shade. The photosynthetic rate of wheat in the jujube-, apricot-, and walnut-based intercropping systems decreased by, respectively, 11.3%, 31.9%, and 36.2% compared to monoculture wheat, and the mean number of fertile florets per spike decreased by 26.4%, 37.4%, and 49.5%. Moreover, the apricot- and walnut-based intercropping systems deleteriously affected grain yield (constituent components spike number, grains per spike, and thousand grain weight) and decreased the total N, P, and K content of intercropping wheat. Tree shading intensity strongly enhanced the grain protein content, wet gluten content, dough development time, and dough stability time of wheat, but significantly decreased the softening degree. Strong negative linear correlations were observed between tree shade intensity and the number of fertile florets, grain yield related traits (including spike number, grains per spike, and thousand grain weight), nutrient content (N, P and K), and softening degree of wheat. In contrast, Daily shade intensity was positively linearly correlated with grain protein content, wet gluten content, dough development time, and dough stability time. We conclude that jujube-based intercropping systems can be practical in the region, as they do not decrease the yield and quality of intercropping wheat.

[Airway epithelial cells increase macrophage chemotaxis and inflammatory cytokine secretion under hypoxic conditions].

OBJECTIVE: To investigate the effects of airway epithelial cells on macrophages chemotaxis and inflammatory cytokine expression under hypoxic conditions.
 Methods: Human bronchial epithelial cells (HBE) treated with different concentrations (0, 100, 200, 400, 800 µmol/L) of CoCl2 or transfected with HIF-1α siRNA were co-cultured with THP-1-derived M1 macrophages or M2 macrophages. The chemotactic effects on macrophages were analyzed by Transwell assay. The levels of TNF-α, IFN-γ, IL-4, IL-13 and IL-10 in the supernatants of macrophages were detected by ELISA, and HIF-1α or Cav-1 mRNA expression in HBE or macrophages was detected by RT-qPCR.
 Results: HBE cells promoted macrophages chemotaxis in a time- and concentration-dependent manner. Compared to un-transfected group, the chemotactic ability of HBE transfected with HIF-1α siRNA was significantly weakened (P<0.01). Under the same culture conditions, the chemotaxis of M2 macrophages was greater than that in THP1-derived M1 macrophages. The concentrations of TNF-α, IFN-γ, IL-4, IL-13 and IL-10 in the supernatants of macrophages were increased in a time-and concentration-dependent manner. The concentrations of TNF-α and IFN-γ were increased further after co-culturing for 8 and 12 h; while IL-4, IL-13 and IL-10 concentrations were increased further during 24 h of co-culture. The levels of cytokines in the supernatants of macrophages co-cultured with HBE and transfected with HIF-1α siRNA were significantly lower than those in un-transfected cells (P<0.05 or P<0.01). The reduction of TNF-α or IFN-γ was more obvious. The expression of HIF-1α or Cav-1 mRNA in HBE or macrophages was increased in a concentration-dependent manner after 8 or 12 h co-culture, which was significantly reduced when HBE was transfected with HIF-1α siRNA.
 Conclusion: Airway epithelial cells can enhance macrophages chemotaxis and pro-inflammatory cytokines expressions under hypoxic condition. HIF-1α and Cav-1 may be the important mediators in these processes.

[Heterogeneity of airway macrophage in different clinical phenotypes of COPD patients with frequent or infrequent exacerbations].

OBJECTIVE: To compare the clinical features and the heterogeneity of macrophages in different clinical phenotypes of chronic obstructive pulmonary disease (COPD) patients with frequent or infrequent exacerbations.
 Methods: Clinical characteristics of eighty COPD patients with chronic bronchitis (CB), emphysema (EM) or asthma-COPD overlap (ACO) phenotypes suffered from acute exacerbation were analyzed. The expressions of CCL3 and CD163 in sputum macrophages were detected by flow cytometry. The expressions of HIF-1α and Cav-1 in sputum macrophages were detected by quantitative PCR (qPCR).
 Results: The age, forced expiratory volume in one second (FEV1)/forced vital capacity (FVC), sputum bacteria positive rate, COPD Assessment Test (CAT) score, and Modified Medical Research Council (mMRC) score between the patients with FE and iFE were significantly different (P<0.05). Compared with iFE patients, the fluorescence intensity of CCL3 in sputum macrophages from patients with FE was significantly lower (P<0.01), while CD163 was significantly increased (P<0.01). Meanwhile, HIF-1α and Cav-1 mRNA levels were also significantly increased (P<0.01). The age, sputum bacteria positive rate, CAT score, and mMRC score between the patients of FE and iFE with CB phenotype were significantly different (P<0.05). Compared with iFE patients, the fluorescence intensity of CCL3 in sputum macrophages from FE patients was slightly decreased (P<0.05), while CD163 was significantly raised (P<0.01). Meanwhile, HIF-1α and Cav-1 mRNA levels were also significantly increased (P<0.01). The age, duration of disease, FEV1/FVC, sputum bacteria positive rate, CAT score, and mMRC score between the patients of FE and iFE with EM phenotype were significantly different (P<0.05). Compared with iFE patients, the fluorescence intensity of CCL3 in sputum macrophages from FE patients was slightly decreased (P>0.05), while CD163 was slightly raised (P>0.05). Meanwhile, HIF-1α levels were slightly elevated (P>0.05), while Cav-1 expression was significantly increased (P<0.01). There were no significant differences in all clinical features between FE and iFE patients with ACO phenotype. The fluorescence intensity of CCL3 in sputum macrophages from patients with FE was significantly lower than that in iFE patients (P<0.01); there was no significant difference in CD163 (P>0.05). At the same time, the expression of HIF-1α (P<0.01) and Cav-1(P<0.05) also increased significantly. There was a significant negative correlation between CCL3 and HIF-1α or Cav-1 in all FE and FE patients with CB phenotype. CD163 was only positively correlated with HIF-1α in those patients and FE patients with EM phenotype. There was a significant negative correlation between CCL3 and HIF-1α in FE patients with ACO phenotype, while CD163 was significantly positively correlated with HIF-1α.
 Conclusion: The clinical features of FE or iFE patients with CB, EM or ACO phenotype are different, and M2 in induced sputum from FE patients are dominant. HIF-1α may play a key role in the polarization process.

An TRIM59-CDK6 axis regulates growth and metastasis of lung cancer.

Lung cancer (LC) is a devastating malignancy with no effective treatments, due to its complex genomic profile. Using bioinformatics analysis and immunohistochemical of lung carcinoma tissues, we show that TRIM59 as a critical oncoprotein relating to LC proliferation and metastasis. In this study, high TRIM59 expression was significantly correlated with lymph node metastasis, distant metastasis, and tumour stage. Furthermore, up-regulation of TRIM59 expression correlated with poorer outcomes in LC patients. Mechanistically, TRIM59 play a key role in promoting LC growth and metastasis through regulation of extracellular-signal regulated protein kinase (ERK) signalling pathway and epithelial-to-mesenchymal transition (EMT)-markers, as validated by loss-of-function studies. In-depth bioinformatics analysis showed that there is preliminary evidence of co-expression of TRIM59 and cyclin dependent kinase 6 (CDK6) in LC. Notably, CDK6 expression significantly decreased when TRIM59 was knocked down in the LC cells. In contrast, exogenous up-regulation of TRIM59 expression also induced significant increases in the expression of CDK6. Moreover, the expression of CDK6 was also inhibited by the ERK signalling inhibitor, U0126. The results of both loss- and gain-of-function studies showed that TRIM59 could regulate the expression of CDK6. Collectively, these data provide evidence that TRIM59 is involved in lung carcinoma growth and progression possibly through the induction of CDK6 expression and EMT process by activation of ERK pathway.

Templated Sphere Phase Liquid Crystals for Tunable Random Lasing.

A sphere phase liquid crystal (SPLC) composed of three-dimensional twist structures with disclinations among them exists between isotropic phase and blue phase in a very narrow temperature range, about several degrees centigrade. A low concentration polymer template is applied to improve the thermal stability of SPLCs and broadens the temperature range to more than 448 K. By template processing, a wavelength tunable random lasing is demonstrated with dye doped SPLC. With different polymer concentrations, the reconstructed SPLC random lasing may achieve more than 40 nm wavelength continuous shifting by electric field modulation.

Clinical characteristics of chronic bronchitic, emphysematous and ACOS phenotypes in COPD patients with frequent exacerbations.

PURPOSE: Chronic bronchitis (CB), emphysematous (EM) and asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) phenotypes in COPD are well recognized. This study aimed to investigate distinguishing characteristics of these phenotypes in COPD patients with frequent exacerbations (FE). PATIENTS AND METHODS: A retrospective study was carried out. COPD patients with acute exacerbations were consecutively reviewed from November 2015 to October 2016. Patients were divided into FE and infrequent exacerbations (iFE) subgroups. RESULTS: A total of 142 eligible COPD subjects were reviewed. In the CB phenotype subgroup, age, body mass index, forced expiratory volume in 1 second (FEV1) % predicted, COPD assessment test (CAT), modified Medical Research Council breathlessness measurement (mMRC) dyspnea scale, emphysema scores and arterial carbon dioxide pressure (PaCO2) were significantly different in subjects with FE when compared to those in subjects with iFE of CB. In the EM phenotype subgroup, age, CAT, mMRC scores and history of COPD were different in subjects with FE when compared to those in CB subjects with iFE. Multivariate analysis indicated that FEV1% predicted (odds ratio [OR] =0.90, P=0.04) and PaCO2 (OR =1.22, P=0.02) were independent risk factors for FE in COPD with CB phenotype, and CAT (OR =2.601, P=0.001) was the independent risk factor for FE in COPD with EM phenotype. No significant differences in characteristics were observed in ACOS phenotype subgroups with FE or iFE. CONCLUSION: In CB or EM phenotypes, COPD patients with FE present several differential clinical characteristics compared to patients with iFE, while the characteristics of ACOS phenotype in patients with FE need more investigation.

Correction: De Novo Transcriptome Analysis for Kentucky Bluegrass Dwarf Mutants Induced by Space Mutation.

[This corrects the article DOI: 10.1371/journal.pone.0151768.].

De Novo Transcriptome Analysis for Kentucky Bluegrass Dwarf Mutants Induced by Space Mutation.

Kentucky bluegrass (Poa pratensis L.) is a major cool-season turfgrass requiring frequent mowing. Utilization of cultivars with slow growth is a promising method to decrease mowing frequency. In this study, two dwarf mutant selections of Kentucky bluegrass (A12 and A16) induced by space mutation were analyzed for the differentially expressed genes compared with the wild type (WT) by the high-throughput RNA-Seq technology. 253,909 unigenes were obtained by de novo assembly. 24.20% of the unigenes had a significant level of amino acid sequence identity to Brachypodium distachyon proteins, followed by Hordeum vulgare with 18.72% among the non-redundant (NR) Blastx top hits. Assembled unigenes were associated with 32 pathways using KEGG orthology terms and their respective KEGG maps. Between WT and A16 libraries, 4,203 differentially expressed genes (DEGs) were identified, whereas there were 883 DEGs between WT and A12 libraries. Further investigation revealed that the DEG pathways were mainly involved in terpenoid biosynthesis and plant hormone metabolism, which might account for the differences of plant height and leaf blade color between dwarf mutant and WT plants. Our study presents the first comprehensive transcriptomic data and gene function analysis of Poa pratensis L., providing a valuable resource for future studies in plant dwarfing breeding and comparative genome analysis for Pooideae plants.

Expression of Tumor-Related Macrophages and Cytokines After Surgery of Triple-Negative Breast Cancer Patients and its Implications.

BACKGROUND: Triple-negative breast cancer (TNBC) has negative expression of progesterone receptor (PR) and estrogen receptor (ER), and low expression of human epithelial growth factor receptor-2 (HER-2). This study aimed to investigate the expressional profile of cytokines in TNBC patients with significant expression of macrophages. MATERIAL/METHODS: Immunohistochemical (IHC) S-P staining method was used to detect the tumor-associated macrophages (TAMs) marker CD68 expression in 48 cases of TNBC samples. The correlation between CD68 expression and prognosis was analyzed. Expressions of key cytokines--interleukin-6 (IL-6), IL-10, IL-12, IL-1ß, chemokine (C-C motif) ligand-5 (CCL-5), and macrophage inflammatory protein-2 (MIP-2)--were quantified by RT-PCR and enzyme-linked immunosorbent assay (ELISA). RESULTS: Thirty-four out of 48 TNBC samples (71.4%) had CD68-positive expression. IL-6 and CCL-5 were up-regulated in high-infiltrated tumors when compared to low-infiltrated samples. Other cytokines had no significant difference regarding the expression level across groups. CONCLUSIONS: TAMs were up-regulated in most TNBC patients after the surgery. Its expression suggested unfavorable prognosis, especially in the high-infiltrated group. Those tumors with more macrophage also had elevated expression of cytokine IL-6 and chemotactic factor CCL-5, both of which have potency to be clinical index and drug target for TNBC.

Photoinduced hyper-reflective laminated liquid crystal film with simultaneous multicolor reflection.

A phototunable laminated liquid crystal film with simultaneous multicolor reflection is successfully fabricated by doping a light-driven chiral molecular switch into the laminated cholesteric liquid crystal structure. Upon UV-light irradiation, the reflection notches and their hyper-reflectivity properties can be precisely tuned, and their original state can be properly returned by visible-light irradiation.

Broadband reflection of polymer-stabilized chiral nematic liquid crystals induced by a chiral azobenzene compound.

A chiral nematic liquid crystal-photopolymerizable monomer-chiral azobenzene compound composite was prepared and then polymerized under UV irradiation. The reflection wavelength of the composite can be extended to cover the 1000-2400 nm range and also be adjusted to the visible light region by controlling the concentration of chiral compounds.

Light-controllable reflection wavelength of blue phase liquid crystals doped with azobenzene-dimers.

A new series of azobenzene-dimers were synthesized and doped into the blue phase liquid crystals to broaden the temperature range of BPs. It is found that not only can the reflection wavelength of BPI be reversibly controlled but BPI can also be transformed into the cholesteric phase owing to isomerization of azobenzene induced by light.