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Zhishu Li,1 Jiayue Chen,1 Jia Zeng,2 Ping Shi,2 Xiaomin Xiong,2 Meng Wang,1 Dong Zheng,1 Rui Zhao,1 Lixia Dong1 1Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Guangyuan Central Hospital, Guangyuan, People’s Republic of ChinaCorrespondence: Lixia Dong, Email luckydonglixia@163.comBackground: In patients with tuberculous pleural effusion (TPE) of various ages, the diagnostic accuracy of pleural biomarkers varies, and there are insufficient studies specifically in different age groups. Therefore, we investigated the adenosine deaminase cut-off value and its combination with the gamma interferon release assay for the diagnosis of TPE among patients aged ≥ 40 years.Methods: A retrospective analysis of 198 patients who underwent medical thoracoscopy and were admitted to the hospital between 2015 and 2020 with exudative pleural effusion and either fever, night sweats, fatigue, cough, or other clinical manifestations was performed. The medical thoracoscopy, ADA, and T-SPOT results were analysed in the pleural fluid. The patients were divided into groups based on age: 18– 39, 40– 59, and 60– 87.Results: The best cut-off values of ADA were 29.5, 31.5 and 19.5 U/L, respectively, for the aged 18– 39, aged 40– 87 and aged 60– 87 groups. The accuracy of 31.5 U/L was higher than 40 U/L for aged ≥ 40 years (86 vs 83%). The ADA diagnostic accuracy was higher than that of people under 40 years (83 vs 77%) when cut-off value of ADA was 40 U/L, but the IGRA accuracy was lower than that of people under 40 (87 vs 91%). The sensitivity of ADA or IGRA detection in patients over 40 years was 99%, and the specificity was 78%. The ADA specificity combined with IGRA for TPE was the highest (100%) in the ≥ 40 age group, and the sensitivity was 69%.Conclusion: Our study revealed the best cut-off values of ADA for TBE in different age groups. Combining ADA and IGRA in pleural fluid improves the detection rate of TPE in patients over 40 years of age with exudative pleural effusion. ADA combined with IGRA increases specificity, and ADA or IGRA increases sensitivity substantially.Keywords: adenosine deaminase, interferon gamma releasing assays, aged, diagnosis, pleural effusion, tuberculosis

Polycomb group proteins assemble into multi-protein complexes, known as Polycomb repressive complexes 1 and 2 (PRC1 and PRC2), that guide cell fate decisions during embryonic development. PRC1 forms an array of biochemically distinct canonical PRC1 (cPRC1) or non-canonical PRC1 (ncPRC1) complexes characterized by the mutually exclusive presence of PCGF (PCGF1-PCGF6) paralog subunit; however, whether each one of these subcomplexes fulfills a distinct role remains largely controversial. Here, by performing a CRISPR-based loss-of-function screen in embryonic stem cells (ESCs), we uncovered a previously unappreciated functional redundancy among PRC1 subcomplexes. Disruption of ncPRC1, but not cPRC1, displayed severe defects in ESC pluripotency. Remarkably, coablation of non-canonical and canonical PRC1 in ESCs resulted in exacerbation of the phenotype observed in the non-canonical PRC1-null ESCs, highlighting the importance of functional redundancy among PRC1 subcomplexes. Together, our studies demonstrate that PRC1 subcomplexes act redundantly to silence lineage-specific genes and ensure robust maintenance of ESC identity.

Primary central sleep apnea is classified as nonhypercapnic central sleep apnea. High loop gain, lower CO(2) reserves, and other reasons can lead to hypocapnia in patients who develop intermittent hyperventilation during sleep. Therefore, it is necessary to monitor nocturnal CO(2) level for these patients. We report a female patient diagnosed with nonhypercapnic primary central sleep apnea who complained of snoring, apnea, and excessive daytime sleepiness. With the monitoring of transcutaneous partial pressure of CO(2), manual noninvasive ventilation pressure titration was performed with continuous positive airway pressure, bilevel positive airway pressure in a spontaneous-timed mode, and adaptive servo-ventilation mode for 3 nights, respectively. Only adaptive servo-ventilation mode could stabilize the transcutaneous partial pressure of CO(2) above the apneic threshold (approximately 40 mm Hg) with successfully eliminating central apnea events. It is concluded that the level of CO(2) is the determinant of successful noninvasive ventilation pressure titration in patients with nonhypercapnic central sleep apnea. CITATION: Han X, Zhao D, Wang J, Wang Y, Dong L, Chen B-y. The level of carbon dioxide is the determinant of successful noninvasive ventilation pressure titration in patients with nonhypercapnic primary central sleep apnea: a case report. J Clin Sleep Med. 2022;18(1):319–324.

Yaoqian Cao,* Jiayue Chen,* Lixia Dong Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lixia Dong, Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, People’s Republic of China, Tel +86 13001385918, Email luckydonglixia@163.comBackground: Pneumocystis pneumonia (PCP) has a high mortality in HIV-negative immunocompromised patients. The occurrence and development of PCP are believed to be correlated with the level of lymphocytes and their subsets. The aim of this study was to determine if the levels of lymphocyte subpopulations and immunoglobulin are associated with PCP.Methods: A total of 74 immunocompromised patients were enrolled in this single-center cohort study. Diagnosis of PCP was based on the relevant pulmonary symptoms and radiological imaging, and the detection of Pneumocystis jirovecii in BAL fluid or biopsy tissue by metagenomic next-generation sequencing (mNGS). All patients were divided into two groups (PCP group and non-PCP group) and the patients in PCP group were then divided into two groupsbased on the outcome of the disease during the hospitalization.Results: We observed a significant lower level of IgG (p=0.000) and B lymphocyte counts (p=0.017) in the PCP group comparing to that in the non-PCP group. CD4+ T cell counts, as well as the ratio of CD4+/CD8+ T cells in circulation and BAL fluid were also lower in the PCP group comparing to those in the non-PCP group. Lactate dehydrogenase (LDH) in the PCP group was significantly higher than that in the non-PCP group (p=0.029). In the PCP group, a lower level of total lymphocytes (p=0.004), T cells (p=0.001), CD4+ cells (p=0.001), and CD8+ cells (p=0.007), as well as the proportion of lymphocytes in BAL fluid (p=0.000) were found in deceased patients comparing to those in the survived group.Conclusion: Our study revealed an important role of humoral immunity in the infection of Pneumocystis jirovecii. The level of B cells and IgG could be used as a supplement to predict the occurrence of PCP. The level of CD4+ and CD8+ lymphocytes was significantly correlated with the outcome of PCP.Keywords: Pneumocystis jirovecii pneumonia, immunosuppression, HIV-negative, lymphocytes, immunoglobulin

Background: To determine the risk of death and factors associated with survival in patients with primary pulmonary angiosarcoma(PPA).Methods: All patients diagnosed with small cell lung cancer (SCLC) or PPA between 1975 and 2019 were identified from the Surveillance, Epidemiology, and End Results (SEER) database. A further analysis of the PPA patient cohort was performed to assess the effect of surgery, chemotherapy, and radiotherapy on overall survival (OS). A multivariable analysis using the Cox proportional methods and a survival analysis using the Kaplan-Meier method were adopted.Results: A total of 127,126 patients with SCLC and 117 patients with PPA were identified. The majority of PPA patients were older than 60 years (64.1%), were more male (59.0%), and were predominantly white race (77.8%). The median survival time of PPA was 3.0 months (1.88-4.12 months), which was significantly lower than that of SCLC at 7.0 months (6.94-7.06 months, p < 0.01). The median survival with PPA surgery was 4.0 months (2.37-5.63 months), which was higher than that without surgery but not statistically different (4.0 months vs 3.0 months, aHR,0.80; 95% CI: 0.43-1.47; p = 0.46). Median survival with radiotherapy was higher but not statistically different (6.0 months vs 2.0 months, aHR, 0.79; 95% CI: 0.30-2.09; p = 0.63). Median survival with chemotherapy was significantly higher than in those without chemotherapy (9.0 months vs 1.0 month, aHR, 0.43; 95% CI: 0.23-0.80; p < 0.01).Conclusion: PPA is associated with poor outcomes, it has the same predilection site as SCLC, and chemotherapy significantly improves PPA survival outcomes.

Summary Polycomb group (PcG) proteins exist in distinct multi-protein complexes and play a central role in silencing developmental genes, yet the underlying mechanisms remain elusive. Here, we show that deficiency of retinoblastoma binding protein 4 (RBBP4), a component of the Polycomb repressive complex 2 (PRC2), in embryonic stem cells (ESCs) leads to spontaneous differentiation into mesendodermal lineages. We further show that Rbbp4 and core PRC2 share an important number of common genomic targets, encoding regulators involved in early germ layer specification. Moreover, we find that Rbbp4 is absolutely essential for genomic targeting of PRC2 to a subset of developmental genes. Interestingly, we demonstrate that Rbbp4 is necessary for sustaining the expression of Oct4 and Sox2 and that the forced co-expression of Oct4 and Sox2 fully rescues the pluripotency of Rbbp4-null ESCs. Therefore, our study indicates that Rbbp4 links maintenance of the pluripotency regulatory network with repression of mesendoderm lineages., Graphical Abstract, Highlights • RBBP4 deficiency in ESCs leads to spontaneous differentiation into mesendodermal lineages • Rbbp4 binding sites in ESCs substantially overlap with PRC2 binding • Rbbp4 is absolutely essential for PRC2 chromatin occupancy • Rbbp4 is necessary for sustaining the expression levels of Oct4 and Sox2, Polycomb group (PcG) proteins play a critical role in silencing developmental genes, yet the underlying mechanisms remain elusive. Yikai et al. report that PcG protein Rbbp4 represses developmental gene expression by recruiting PRC2 to the genes' promoter regions, thereby maintaining stem cell self-renewal and identity.

Increasing evidences indicate that unlimited capacity for self-renewal and pluripotency, two unique properties of embryonic stem cells (ESCs), are intrinsically linked to cell cycle control. However, the precise mechanisms coordinating cell fate decisions and cell cycle regulation remain to be fully explored. Here, using CRISPR/Cas9-mediated genome editing, we show that in ESCs, deficiency of components of the cell cycle regulatory MuvB complex Lin54 or Lin52, but not Lin9 or Lin37, triggers G2/M arrest, loss of pluripotency, and spontaneous differentiation. Further dissection of these phenotypes demonstrated that this cell cycle arrest is accompanied by the gradual activation of mesoendodermal lineage-specifying genes. Strikingly, the abnormalities observed in Lin54-null ESCs were partially but significantly rescued by ectopic coexpression of genes encoding G2/M proteins Cyclin B1 and Cdk1. Thus, our study provides new insights into the mechanisms by which the MuvB complex determines cell fate through regulation of the cell cycle machinery.

Purpose COPD-OSA (chronic obstructive pulmonary disease-obstructive sleep apnea) overlap syndrome is associated with more frequent COPD acute exacerbations than COPD without OSA. With the application of high-resolution computed tomography (HRCT) in COPD, bronchiectasis is commonly detected and is associated with disease severity. Sleep respiratory disease is also associated with bronchiectasis; however, the correlation between OSA and coexisted bronchiectasis in COPD (COPD-Bx) has not been reported yet. Patients and Methods A total of 124 consecutive patients with stable COPD were enrolled. All subjects completed the chest HRCT and nocturnal polysomnography (PSG). The scores of extent and severity in bronchiectasis were assessed based on the Smith method and the Bhalla scoring system. Clinical data, questionnaire, routine blood test data, blood levels of C-reactive protein (CRP) and Immunoglobulin E, and the lymphocyte subtype were collected. Results Among all enrolled patients, 56.45% (70/124) were diagnosed as COPD-OSA based on the results of PSG screening. Bronchiectasis was detected in 42.86% (30/70) of the patients with COPD-OSA, but in 18.52% (10/54) of the patients without OSA (χ2=8.264, p=0.004). PSG screening revealed that COPD with OSA had a significantly higher apnea-hypopnea index and percent of time spent with oxygen saturation below 90% (T90). Higher values of CRP, T90, and lower CD4/CD8 in the COPD-Bx with OSA were detected compared to COPD-Bx without OSA. Correlation analysis showed that the Bhalla severity score was related to CD8 cell count (r=0.446, p

Endometrial cancer (EC) ranks as the most prevalent malignancy occurring in the female genital tract. Non-SMC condensin I complex subunit G (NCAPG), a mitotic associated chromosomal condensing protein, is reported to be frequently abnormally expressed in several tumors and plays a vital role in carcinogenesis. Our study aimed to explore the effect of NCAPG on cell proliferation and apoptosis in EC cells and to determine the underlying mechanism. Expression and survival data of NCAPG in EC tissues were analyzed by bioinformatics methods. Cell proliferation was evaluated by EdU and CCK-8 assays. Apoptosis was assessed by flow cytometry analysis. Expression of NCAPG, proliferating cell nuclear antigen (PCNA), Ki67, Bcl-2, Bax, active caspase-3, active β-catenin, and c-Myc were determined by western blotting. NCAPG was highly expressed in EC tissues and cells and predicted poor survival for EC patients. NCAPG knockdown inhibited cell proliferation and induced apoptosis in EC cells. Additionally, NCAPG knockdown inactivated the Wnt/β-catenin pathway in EC cells. Mechanistically, β-catenin overexpression blocked the tumorigenic effects of NCAPG in EC cells. In conclusion, NCAPG silencing inhibited cell proliferation and induced apoptosis in EC cells via inhibiting the Wnt/β-catenin pathway.

Structural maintenance of chromosomes 4 (SMC4) has an important role in chromosome condensation and segregation, which is involved in regulating multiple tumor development. However, the role of SMC4 in endometrial cancer is uncertain. The expression and prognostic value of SMC4 were predicted by UALCAN, Gene Expression Omnibus (GEO), The Human Protein Atlas and Kaplan Meier plotter tools. SMC4-related genes were analyzed by LinkedOmics, Gene Ontology (GO) annotations, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Forkhead box protein O1 (FoxO1) activity was suppressed by AS1842856 (AS). SMC4, Ki67, B-cell lymphoma-2(Bcl-2), Bcl-2 associated X protein (Bax), FoxO1, phosphorylated FoxO1 (p-FoxO1), and p27 protein levels were detected by Western blotting. Cell proliferation was detected using Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) analyses. Cell apoptosis was measured using TUNEL analysis. SMC4 abundance was increased in endometrial cancer, and predicted a worse overall survival. SMC4 knockdown repressed proliferative ability of endometrial cancer cells and promoted cell apoptosis. SMC4 knockdown promoted FoxO1 transactivation by decreasing its phosphorylated level. Addition of AS inhibited FoxO1 activity by increasing the phosphorylated level of FoxO1. The inhibition of FoxO1 activity reversed the effect of SMC4 silencing on cell proliferation and apoptosis. In conclusion, SMC4 silencing restrained cell proliferation and facilitated apoptosis in endometrial cancer via regulating FoxO1 activity.

ObjectiveTo elucidate potential IL-17A- and TSA-mediated regulation of fibroblasts transformation.MethodsMTT assay, HDAC1 activity assay, cell immunofluorescence and Western blot were employed to detect the expression of related indicators.ResultsMRC5 cells expressed only a small amount of Vimentin. IL-17A treatment upregulated MRC5 cell proliferation, in a concentration-dependent manner. TSA treatment, however, suppressed MRC5 cell proliferation. IL-17A treatment also upregulated HDAC1 activity in MRC5 cells, in a concentration-dependent manner. Using immunofluorescence, we demonstrated that IL-17A-treated MRC5 cells had markedly elevated Vimentin, Collagen-I and a-SMA levels, compared to controls. However, a combined treatment of IL-17A and TSA resulted in markedly reduced levels of the Vimentin, Collagen-I and a-SMA, compared to IL-17A alone, yet the amount was higher than controls. Using western blot analysis, we also revealed that the IL-17A-treated MRC5 cells had markedly elevated levels of Vimentin, a-SMA, HDAC1, p-Smad2, and p-Smad3, and markedly reduced level of Smad7, compared to controls. In TSA intervention group, the expression effect of the above protein was opposite. Moreover, no discernible difference was observed in the levels of Smad2 and Smad3 among the treated and un-treated groups.ConclusionIL-17A stimulates proliferation of MRC5 cells and increases HDAC1 activity and protein expression. It also transforms MRC5 cells into myofibroblasts via activation of the TGF -β1/ Smads signaling network. TSA, on the other hand, strongly suppresses TGF -β1/ Smads pathway-mediated fibrosis by ceasing HDAC1 activity and protein expression.

Mga functions as a gatekeeper to prevent embryonic stem cells from entering into the endodermal lineage., Polycomb group (PcG) proteins form multiprotein complexes that affect stem cell identity and fate decisions by still largely unexplored mechanisms. Here, by performing a CRISPR-based loss-of-function screen in embryonic stem cells (ESCs), we identify PcG gene Mga involved in the repression of endodermal transcription factor Gata6. We report that deletion of Mga results in peri-implantation embryonic lethality in mice. We further demonstrate that Mga-null ESCs exhibit impaired self-renewal and spontaneous differentiation to primitive endoderm (PE). Our data support a model in which Mga might serve as a scaffold for PRC1.6 assembly and guide this multimeric complex to specific genomic targets including genes that encode endodermal factors Gata4, Gata6, and Sox17. Our findings uncover an unexpected function of Mga in ESCs, where it functions as a gatekeeper to prevent ESCs from entering into the PE lineage by directly repressing expression of a set of endoderm differentiation master genes.

Background: Venous thromboembolism (VTE) is a complex disease caused by both genetic and environmental risk factors. Although genetic determinants are known to be associated with VTE for individuals with European (EUR) ancestry, a large proportion of the VTE heritability remains unexplained, particularly the genetic architecture of VTE in the East Asian (EAS) population. Findings: We identified three independent genetic loci (FGG, ABO, AKAP12) associated with VTE from GWAS analysis, where AKAP12 is novel. TWAS further identified six (LRAT , KLKB1, GGT7, GSS, EDEM2 and PROCR) independent regulatory signals, of which three are associated with coagulation functions, and three are novel genes with metabolic functions (LRAT, GGT7, GSS). There are shared genetic effects of common variants between Han Chinese and EUR populations (genetic correlation = 0.93 ± 0.27). The individuals with the top 10% polygenic risk score had over three-fold increased risk for VTE relative to the general Han Chinese population. Interpretation: Our results suggest both shared and unique genetic characteristics of VTE between EAS and EUR populations. We identified novel loci suggesting the involvement of metabolic pathways in VTE occurrence in the Han Chinese population. Funding Information: The National Key Research and Development Program of China (No. 2016YFC0905600) National Natural Science Foundation of China (No. 81570049; 81970058); Beijing Natural Science Foundation (No.7152062). Declaration of Interests: Authors report no relevant conflicts of interest. Ethics Approval Statement: This study was conducted under the human and ethical research principles of The Ministry of Science and Technology, People's Republic of China (Regulation of the Administration of Human Genetic Resources, July 1, 2019). All the participants provided informed consent and agreed to participate in this research under a protocol approved by the Ethical Committee of China-Japan Friendship Hospital (Cases) and WeGene (Controls). The study's ethical approval was obtained from the Ethics Committee in China-Japan Friendship Hospital (2016-SSW-7).

Objective The study aimed to explore the correlations of long non‐coding RNA MALAT1 (lncRNA MALAT1) and its targets microRNA (miR)‐125b, miR‐133, miR‐146a, and miR‐203 with acute exacerbation risk, inflammation, and disease severity of chronic obstructive pulmonary disease (COPD). Methods Plasma samples were obtained from 120 acute exacerbation COPD (AECOPD) patients, 120 stable COPD patients, and 120 healthy controls (HCs). RT‐qPCR was conducted to detect lncRNA MALAT1 expression and its target miRNAs, and ELISA was performed to detect the inflammatory cytokines. Results LncRNA MALAT1 was highest in AECOPD patients followed by stable COPD patients and then HCs, which distinguished AECOPD patients from HCs (AUC: 0.969, 95% CI: 0.951‐0.987) and stable COPD patients (AUC: 0.846, 95% CI: 0.798‐0.894). Furthermore, lncRNA MALAT1 positively correlated with GOLD stage in both AECOPD and stable COPD patients. Regarding inflammatory cytokines, lncRNA MALAT1 positively correlated with tumor necrosis factor‐α (TNF‐α), interleukin (IL)‐1β, IL‐6, IL‐8, IL‐17, and IL‐23 in both AECOPD and stable COPD patients. Besides, lncRNA MALAT1 negatively correlated with miR‐125b, miR‐146a, and miR‐203 in AECOPD patients and reversely correlated with miR‐125b and miR‐146a in stable COPD patients. Notably, miR‐125b, miR‐133, miR‐146a, and miR‐203 were the lowest in AECOPD patients, followed by stable COPD patients, and then HCs; miR‐125b, miR‐133, miR‐146a, and miR‐203 negatively correlated with inflammation and GOLD stage in AECOPD and stable COPD patients. Conclusion LncRNA MALAT1 exhibits clinical implications in acute exacerbation risk prediction and management of COPD via the inner‐correlation with its targets miR‐125b, miR‐146a, and miR‐203.

Apoptosis plays a key role in the immune defense against pathogen infection, and caspase is one of the most important protease enzyme families, which could initiate and execute apoptosis. Among crustaceans, several caspase genes have been reported. However, caspase in mud crab Scylla paramamosain, have not been identified yet. Here, in the present study, we characterized a new caspase, named as Sp-caspase, from S. paramamosain. The full-length cDNA sequence of Sp-caspase contained 966 bp open reading frame, encoding 322 amino acids, and its molecular weight was 36 kDa. This gene has three conserved domains of the caspase family, a prodomain, a large subunit P20 and a small subunit P10. Phylogenetic analysis showed that Sp-caspase was clustered into an effector caspase group. Sp-caspase mainly distributed in midgut, hepatopancreas, hemocytes and female ovaries, and the transcript was significantly regulated in different tissues after being challenged with Vibrio parahaemolyticus, Vibrio alginolyticus or LPS. After infection with V. alginolyticus, the apoptosis rate of hemocytes notably increased, while the mRNA level of Sp-caspase and hydrolysis activity of caspase 3/7 significantly decreased. Furthermore, in vitro assays showed that the recombinant protein tSp-caspase (deletion of Sp-caspase prodomain) could efficiently recognize and cleave human caspase 3/7 substrate Ac-DEVD-pNA, functioning as an effector caspase. Meanwhile, heterologous expression of Sp-caspase in several cell lines (HEK293T cells, HeLa cells and HighFive cells) could specifically induce cell apoptosis. Taken together, these data demonstrated that Sp-caspase could perform apoptosis as an effector caspase. In addition, it might be a negative regulator of hemocytes apoptosis under pathogen infection, which would contribute to homeostasis and immune defense of hemocytes in S. paramamosain.

Objectives MicroRNAs have been reported to participate in various important cell biological processes, such as glucose metabolism. The aim of this study was to explore the roles of microRNA-15a (miR-15a) in regulating insulin sensitivity. Methods In L6 rat skeletal muscle cells, we observed the effect of miR-15a on glucose metabolism and glucose transporter 4 (GLUT4) translocation by targeting vesicle-associated membrane protein-associated protein A (VAP-A) after insulin treatment. Luciferase reporter assays were performed to demonstrate a direct interaction between miR-15a and the 3′-untranslated region of VAP-A microRNA. Results We identified miR-15a as an extremely important regulator of GLUT4 translocation via targeting of VAP-A. Additionally, knockdown of endogenous miR-15a or overexpression of VAP-A could increase extracellular glucose by inhibiting the translocation of GLUT4 to the cell membrane after insulin treatment. However, overexpression of miR-15a or knockdown of VAP-A had no significant effect on glucose metabolism. Conclusions These findings reveal the following: 1) VAP-A is a marker of skeletal muscle glucose disposal and 2) a novel mechanism for GLUT4 translocation by miR-15a.

Aim: We developed an overlap syndrome rat model of intermittent hypoxia based of emphysema exposure to explore whether OS can lead to more severe vascular endothelial injury and to assess the intervention effects of tempol. Methods: Male Wistar rats (n=60)were randomly distributed into 6 groups: normal oxygen control (NC), intermittent hypoxia (IH), continuous hypoxia (CH), exposure to smoke and IH (OS), exposure to OS and treated with tempol (OST), exposure to OS and treated with NaCl (OSN). After an 8-week challenge, lung tissues were stained with hematoxylin/eosin (H/E). The level of intracellular adhesion molecule-1 (ICAM-1) and vascular cellular adhesion molecule-1 (VCAM-1) were detected by enzyme-linked immunosorbent assay (ELISA), and the apoptosis of circulating endothelial cells (CECs) were analysed by flow cytometry. Results: The pathological changes in the lungs of the CH group were the formation of emphysema accompanied by infiltration of inflammatory cells, the partial fracture of the bronchial wall smooth muscle, and goblet cell hyperplasia, which were more severe in the OS group. The levels of ICAM-1, VCAM-1 and CEC apoptosis were highest in the OS group and lowest in the NC group. Administration of tempol in OS rats significantly reduced the levels described above compared with the non-tempol-treated group. Conclusion: Overlap syndrome-related inflammation and endothelial cell apoptosis may play important roles by promoting cardiovascular dysfunction and CVD. When IH is combined with emphysema, synergistic effects appear, and produce a more significant inflammatory status and endothelial injury. It is important that tempol treatment attenuated this effect

Sentiment analysis of text has tremendous value in many fields. But verb expression is absent, while lots of researchers concentrate on identifying opinions from adjective, adverb, and noun expressions in recent years. In this paper, we find that verb expressions in a sentence can be more important because verb expressions not only imply opinions but also give a direct way for enterprise to improve their products. It is meaningful that the verb expressions are extracted and analyzed. In order to deal with this problem, we propose a new method of linear regression optimized by particle swarm optimization to analyze verb expression extracted from reviews. Since our training data is obtained from titles of reviews whose labels are automatically inferred from review ratings, our method is able to work without manual involvement. Experimental results demonstrate our approach has great performance in terms of both precision and efficiency.

Innexins are a class of transmembrane proteins that are important for embryonic development, morphogenesis and electrical synapse formation. In the present study, a novel innexin2 gene from Scylla paramamosain was named Sp-inx2 and characterized. The complete cDNA and genomic DNA sequences of Sp-inx2 were revealed. Sp-inx2 mRNA transcripts were distributed in various tissues of S. paramamosain and were most abundant in the hemocytes. The Sp-inx2 was significantly upregulated in hemocyte, gill and hepatopancreas tissues with the challenge of either Vibrio alginolyticus, Vibrio parahaemolyticus or lipopolysaccharides (LPSs) when analyzed at 3 and 6 h using quantitative real-time PCR, suggesting that it could activate an immune response against the challenge of LPSs or Vibrio species. Using the chemical inhibitors carbenoxolone and probenecid, the absorption of the fluorescent dye Lucifer yellow decreased in the primary cultured hemocytes of crabs, thus confirming that hemichannels composed of Sp-inx2 existed in the crab hemocytes. With LPS stimulation, the level of mRNA transcripts and protein expression of Sp-inx2 in the same cultured hemocytes gradually increased from 6 to 48 h, while the activity of hemichannels was down-regulated at 6 and 12 h, demonstrating that LPSs could modulate the absorption activity of hemichannels in addition to its upregulation of Sp-inx2 gene expression. Furthermore, the dye uptake rate in HeLa cells in which Sp-inx2 was ectopically expressed increased dramatically but the increase was significantly down-regulated with the addition of 50 μg mL(-1) LPS, suggesting that the LPS stimulation could effectively reduce the activity of hemichannels. Interestingly, with the ectopic expression of Sp-inx2 in HeLa and EPC cells, apoptosis spontaneously occurred in both cultured cell lines when detected using TUNEL assay. In summary, a new Sp-inx2 gene was first characterized in a marine animal S. paramamosain and it had a function associated with immune response and cell apoptosis.

A wider variety of practical applications employ single photon avalanche diode (SPAD) operating in Geiger mode to detect the extremely weak optical signal due to many advantages, such as higher avalanche gain and faster response speed. In this paper, we report a high-performance linear scan SPAD detector with time delay integration (TDI) to enhance the dynamic range and signal to noise ratio (SNR). The detector is fabricated in 0.13μm CMOS technology and it comprises an array of 8×1k SPAD pixels, quenching circuits, readout modules and other necessary peripheral circuits.

This paper reports a laser diffraction measuring system based on a lab made 26M (5120×5120) pixels image sensor with a pixel pitch of 0.95μm. The long distance required in the traditional method to match the surface of the image sensor with large pixels is shortened, and the image sensor with submicron pixels becomes the key to capture the patterns at short range which is still meet the condition of fraunhofer approximation. The system refers to using a digital optoelectronic sensor array to sample the light transmitted through a specimen without the use of any imaging lenses between the object and the sensor planes. The hardware for such an imaging geometry is significantly simpler and much more compact and lightweight than that of conventional measuring system. In addition, an algorithm of image processing, termed super resolution image reconstruction, is used to further improve the resolution and is required to achieve subpixel spatial resolution in measuring system. In the experimental measurement, the final result can reach the accuracy of 0.98%.

Pathogens can enter their host cells by way of endocytosis in which the membrane lipid raft gene flotillins are probably involved in the invasion process and this is an important way to cause infection. In this study, a new gene SpFLT-1 was identified in Scylla paramamosain, which shared high identity with the flotillin-1 of other species. The SpFLT-1 gene was widely distributed in tissues and showed the highest level of mRNA transcripts in the hemocytes. This gene might be a maternal gene based on the evident results that it was highly expressed in maternal ovaries and in the early developmental stages of the zygote and early embryo stage whereas it gradually decreased in zoea 1. SpFLT-1 positively responded to the challenge of Vibrio alginolyticus with a significantly increased level of mRNA expression in the hemocytes and gills at 3 hours post infection (hpi). The SpFLT-1 protein was detected densely in the same fraction layer where the Vibrio protein was most present in the hemocytes and gills at 3 hpi. Furthermore, it was found that the expression of SpFLT-1 decreased to the base level following disappearance of the Vibrio protein at 6 hpi in the gills. Silencing SpFLT-1 inhibited the endocytosis rate of V. alginolyticus but overexpression of the gene could facilitate bacterial entry into the epithelioma papulosum cyprinid cells. Our study indicated that SpFLT-1 may act as a key protein involved in the process of bacterial infection and this sheds light on clarifying the pathogenesis of pathogens infecting S. paramamosain.

Purpose Obstructive sleep apnea and chronic obstructive pulmonary disease are independent risk factors of cardiovascular disease (CVD), and their coexistence is known as overlap syndrome (OS). Endothelial dysfunction is the initial stage of CVD; however, underlying mechanisms linking OS and CVD are not well understood. The aim of this study was to explore whether OS can lead to more severe inflammation and endothelial apoptosis by promoting endothelial dysfunction, and to assess the intervention effects of antioxidant tempol. Materials and Methods Male Wistar rats (n=66) were exposed to normal oxygen [normal control (NC) group], intermittent hypoxia (IH group), cigarette smoke (CH group), as well as cigarette smoke and IH (OS group). Tempol intervention was assessed in OS group treated with tempol (OST group) or NaCl (OSN group). After an 8-week challenge, lung tissues, serum, and fresh blood were harvested for analysis of endothelial markers and apoptosis. Results The levels of intracellular adhesion molecule-1, vascular cellular adhesion molecule-1, and apoptosis in circulating epithelial cells were the highest in OS group and the lowest in NC group. These levels were all greater in IH group than in CH group, and were lower in OST group than in OS and OSN groups (all p