Impact of post-dilatation on post-procedural physiology, microcirculatory resistance, and target vessel failure in STEMI patients undergoing PPCI: A single-center experience.

BACKGROUND: Suboptimal stent deployment is frequently observed in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PPCI). This study sought to investigate whether these patients could benefit from post-dilatation with respect to post-procedural physiology, microcirculatory resistance, and long-term clinical outcomes. METHODS: This was a retrospective study of consecutive STEMI patients who underwent successful stent implantation during PPCI from February 2016 to November 2021. Post-procedural physiology and microcirculatory resistance were assessed by Murray law-based quantitative flow ratio (µQFR) and angiographic microcirculatory resistance (AMR), respectively. The primary outcome was target vessel failure (TVF), a composite of cardiac death, target vessel-oriented myocardial infarction, and clinically driven target vessel revascularization. RESULTS: A total of 671 patients (671 culprit vessels) were included. Post-dilatation was selectively performed in 430 (64.1%) culprit vessels, resulting in a 0.02 (interquartile range: 0.00-0.05, p < 0.001) increase in post-procedural µQFR but no significant impact on AMR. During a median follow-up of 2.8 years (interquartile range: 1.4-3.0 years), TVF occurred in 47 (7.0%) patients. Post-dilatation demonstrated a trend toward a reduction in TVF (5.3% vs. 10.0%; adjusted hazard ratio: 0.60, 95% confidence interval: 0.33-1.09, p = 0.094), mainly driven by a lower incidence of clinically driven target vessel revascularization (1.6% vs. 4.1%; adjusted hazard ratio: 0.32, 95% confidence interval: 0.11-0.90, p = 0.030). CONCLUSIONS: In STEMI patients undergoing PPCI, selective post-dilatation was associated with improved post-procedural physiological results and a trend toward less TVF events without aggravating microcirculatory resistance.

Ambient noise-based weakly supervised manhole localization methods over deployed fiber networks.

We present a manhole localization method based on distributed fiber optic sensing and weakly supervised machine learning techniques. For the first time to our knowledge, ambient environment data is used for underground cable mapping with the promise of enhancing operational efficiency and reducing field work. To effectively accommodate the weak informativeness of ambient data, a selective data sampling scheme and an attention-based deep multiple instance classification model are adopted, which only requires weakly annotated data. The proposed approach is validated on field data collected by a fiber sensing system over multiple existing fiber networks.

Retracted: A Regulatory Axis of circ_0008193/miR-1180-3p/TRIM62 Suppresses Proliferation, Migration, Invasion, and Warburg Effect in Lung Adenocarcinoma Cells Under Hypoxia.

This publication has been retracted by the Editor due to non-original content and deficiencies in the conduct of the study. Reference: Minbiao Chen, Xiuming Huang, Liang Li, Mingfang Huang, Renzhong Cai, Xuqiang Liao.A Regulatory Axis of circ_0008193/miR-1180-3p/TRIM62 Suppresses Proliferation, Migration, Invasion, and Warburg Effect in Lung Adenocarcinoma Cells Under Hypoxia. Med Sci Monit, 2020; 26: e922900. DOI: 10.12659/MSM.922900.

lncRNA SLC9A3-AS1 Promotes Oncogenesis of NSCLC via Sponging microRNA-760 and May Serve as a Prognosis Predictor of NSCLC Patients.

Background: Non-small cell lung cancer (NSCLC) is a prevalent type of lung cancer worldwide. Long noncoding RNA (lncRNA) SLC9A3-AS1 is reported to play a carcinogenic role in nasopharyngeal carcinoma, but its full-scale role in NSCLC remains elusive. Methods: SLC9A3-AS1 expression was detected in serum and tissue of NSLCC patients and NSCLC cell lines. The effects of SLC9A3-AS1 on NSCLC proliferation, migration and invasion were evaluated using CCK-8 and transwell assays. In addition, the potential downstream molecules of SLC9A3-AS1 were searched and explored by bioinformatics analysis, RT-qPCR, dual-luciferase reporter, and rescue experiments. Results: SLC9A3-AS1 was upregulated in NSCLC tissues and cell lines. SLC9A3-AS1 possessed a favorable ability in diagnosing NSCLC. A high level of SLC9A3-AS1 was associated with poor prognosis in NSCLC patients. Functionally, SLC9A3-AS1 knockdown inhibited cell proliferation, migration, and invasion of NSCLC cells. Mechanistically, SLC9A3-AS1 acted as competing endogenous RNA for miR-760 to regulate NSCLC progression. In addition, rescue assay showed that downregulation of miR-760 could reverse the modulatory activity of SLC9A3-AS1 knockdown on NSCLC cells. Conclusion: SLC9A3-AS1 was upregulated in NSCLC, and SLC9A3-AS1 knockdown hindered NSCLC progression through targeting miR-760, suggesting that it may prove to be a novel biomarker and therapeutic target for NSCLC.

MiR-552-3p facilitated cell proliferation, migration and invasion by sponging Fibulin 5 in non-small cell lung cancer via activation of ERK/GSK3ß/ß-catenin signaling pathway.

Apart from the fact that miR-552-3p is known to promote cell progression among various cancers, its function on non-small cell lung cancer (NSCLC) is unknown which therefore emerges as the purpose of this research. TargetScan, Starbase, miRWalk, miRDB and the Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) were utilized to analyze the target genes of miR-552-3p. NSCLC cells were transfected with miR-552-3p mimic, miR-552-3p inhibitor, Fibulin 5 (FBLN5) overexpression plasmid, and small interfering FBLN5 (siFBLN5) and treated with extracellular regulated protein kinases (ERK) pathway inhibitor PD98059. MiR-552-3p, FBLN5, p-ERK, ERK, p-glycogen synthase kinase 3ß (GSK3ß) and ß-catenin levels were detected through quantitative reverse transcription-polymerase chain reaction and western blot. The binding sites between miR-552-3p and FBLN5 were predicted by TargetScan, which was tested through dual luciferase reporter analysis. Cell viability, migration and invasion were determined by cell counting kit-8 (CCK-8) assay, wound healing assay and transwell assay, respectively. MiR-552-3p expression was upregulated in NSCLC and FBLN5 functioned as its target. MiR-552-3p mimic promoted proliferation, migration, invasion, p-ERK, p-GSK3ß and ß-catenin expressions in NSCLC cells while miR-552-3p inhibitor did the opposite. Overexpressed FBLN5 suppressed proliferation, migration, invasion, p-ERK, p-GSK3ß and ß-catenin expressions in NSCLC cells whereas siFBLN5 exerted the effects opposite to overexpressed FBLN5. PD98059 enhanced the effect of overexpressed FBLN5 on NSCLC cell migration and invasion while reversing the effect of siFBLN5. MiR-552-3p facilitated cell proliferation, migration and invasion in NSCLC through sponging FBLN5 via activation of ERK/GSK3ß/ß-catenin pathway.

Comprehensive analysis of the long non-coding RNA expression profile and functional roles in a contrast-induced acute kidney injury rat model.

Long non-coding RNAs (lncRNAs) have been identified as a class of regulatory RNAs that participate in both physiological and pathological conditions, including acute kidney injury. However, the roles of lncRNA dysregulation in the pathogenesis of contrast-induced acute kidney injury (CI-AKI) are largely unknown. In the present study, the expression profiles of lncRNAs in kidney tissue were compared between rats with CI-AKI and controls using high-throughput RNA sequencing. In total, 910 differentially expressed (DE) lncRNAs (DElncRNAs), including 415 downregulated and 495 upregulated lncRNAs, were identified at 12 h after intra-arterial iodinated contrast medium injection (fold change ≥2; P<0.05). Eight DElncRNAs were further selected and validated using reverse transcription-quantitative polymerase chain reaction. A previous study defined microRNA (miRNA) and mRNA expression changes in the same CI-AKI model. In the present study, a lncRNA-mRNA co-expression network comprising 349 DElncRNAs and 202 DEmRNAs was constructed. The function of these DElncRNAs was mainly associated with oxidative stress and inflammation. Additionally, lncRNA-associated competing endogenous RNA (ceRNA) analysis revealed a network comprising 40 DElncRNA nodes, 5 DEmiRNA nodes and 59 DEmRNA nodes. Among which, the carnosine dipeptidase 1-specific and the transmembrane protein 184B-specific networks were likely to be associated with CI-AKI. The results of the present study revealed the expression profile and potential roles of lncRNAs in CI-AKI, and provide a framework for further mechanistic studies.

An analysis model of diagnosis and treatment for COVID-19 pandemic based on medical information fusion.

Exploring the complicated relationships underlying the clinical information is essential for the diagnosis and treatment of the Coronavirus Disease 2019 (COVID-19). Currently, few approaches are mature enough to show operational impact. Based on electronic medical records (EMRs) of 570 COVID-19 inpatients, we proposed an analysis model of diagnosis and treatment for COVID-19 based on the machine learning algorithms and complex networks. Introducing the medical information fusion, we constructed the heterogeneous information network to discover the complex relationships among the syndromes, symptoms, and medicines. We generated the numerical symptom (medicine) embeddings and divided them into seven communities (syndromes) using the combination of Skip-Gram model and Spectral Clustering (SC) algorithm. After analyzing the symptoms and medicine networks, we identified the key factors using six evaluation metrics of node centrality. The experimental results indicate that the proposed analysis model is capable of discovering the critical symptoms and symptom distribution for diagnosis; the key medicines and medicine combinations for treatment. Based on the latest COVID-19 clinical guidelines, this model could result in the higher accuracy results than the other representative clustering algorithms. Furthermore, the proposed model is able to provide tremendously valuable guidance and help the physicians to combat the COVID-19.

A Regulatory Axis of circ_0008193/miR-1180-3p/TRIM62 Suppresses Proliferation, Migration, Invasion, and Warburg Effect in Lung Adenocarcinoma Cells Under Hypoxia.

BACKGROUND Expression profiles of circular ribonucleic acids (circRNAs) have been recently reported in lung cancers including lung adenocarcinoma (LUAD). Hypoxia is a hallmark of lung cancers. However, the role of hsa_circ_0008193 (circ_0008193) in LUAD under hypoxia remains to be illuminated. MATERIAL AND METHODS Gene expression levels were detected using real-time quantitative polymerase chain reaction and western blotting. Cell proliferation, migration, invasion, and Warburg effect were detected using 3-(4, 5-dimethylthiazol-2-yl)-2, 5 diphenyltetrazolium bromide assay, transwell assays, special kits, and xenograft experiments. The relationship among circ_0008193, micro (mi)RNA (miR)-1180-3p, and tripartite motif containing 62 (TRIM62) was confirmed by dual-luciferase reporter assay and RNA immunoprecipitation. RESULTS Expression of circ_0008193 was downregulated in human LUAD tumor tissues and cell lines (A549 and H1975), accompanied by miR-1180-3p upregulation and TRIM62 downregulation. Moreover, circ_0008193 downregulation was correlated with tumor size and lymph node metastasis. Functionally, circ_0008193 overexpression inhibited cell viability, glucose uptake, lactate production, migration, and invasion, as well as expression of hexokinase II, lactate dehydrogenase A, matrix metalloproteinase 2 (MMP2), and MMP9 in hypoxic LUAD cells in vitro. Furthermore, tumor growth of A549 cells in vivo was also hindered by circ_0008193 overexpression. Mechanically, circ_0008193 regulated TRIM62 expression via sponging miR-1180-3p, and TRIM62 was targeted by miR-1180-3p. Both miR-1180-3p upregulation and TRIM62 downregulation could abolish the suppressive role of circ_0008193 in LUAD cells. CONCLUSIONS Upregulating circ_0008193 inhibited LUAD cell proliferation, migration, invasion, and Warburg effect under hypoxia in vitro and in vivo through regulation of the miR-1180-3p/TRIM62 axis.

Co-expression analysis reveals dysregulated miRNAs and miRNA-mRNA interactions in the development of contrast-induced acute kidney injury.

The pathogenesis of contrast-induced acute kidney injury (CI-AKI) is incompletely understood. MicroRNAs (miRNAs) are important mediators that normally function via post-transcriptional degradation of target mRNAs. Emerging evidence indicates the appearance of differentially expressed (DE) miRNAs in CI-AKI following the injection of intravenous contrast medium. However, there are differences in the pathological mechanism and incidence of CI-AKI between intravenous and intra-arterial contrast administration. The present study aimed to investigate the critical roles of dysregulated miRNAs and their associated mRNAs in kidney injury following intra-arterial contrast medium exposure. Based on a reliable CI-AKI rat model, we conducted genome-wide miRNA and mRNA expression profiling analysis using deep sequencing. In the study, 36 DE mature miRNAs were identified (fold change > 1.5 and p value < 0.05) in the kidneys of CI-AKI rats (n = 3) compared with that in the controls (n = 3), consisting of 23 up-regulated and 13 down-regulated DE miRNAs. Bioinformatic analysis revealed that wingnut (Wnt), transforming growth factor beta (TGF-ß), and 5'-AMP-activated protein kinase (AMPK) signaling pathways were most likely to be modulated by these dysregulated miRNAs. Around 453 dysregulated genes (fold change > 2.0 and p value < 0.05) were identified. Integrated analysis revealed 2037 putative miRNA-mRNA pairs with negative correlations. Among them, 6 DE miRNAs and 13 genes were selected for further quantitative real-time reverse transcription polymerase chain reaction validation (n = 6 for each group), and a good correspondence between the two techniques was observed. In conclusion, the present study provided evidence of miRNA-mRNA interactions in the development of kidney injury following an intra-arterial contrast injection. These findings provide insights into the underlying mechanisms of CI-AKI.

Multi-parameter distributed fiber sensing with higher-order optical and acoustic modes.

We propose a novel multi-parameter sensing technique based on a Brillouin optical time domain reflectometry in the elliptical-core few-mode fiber, using higher-order optical and acoustic modes. Multiple Brillouin peaks are observed for the backscattering of both the LP01 mode and LP11 mode. We characterize the temperature and strain coefficients for various optical-acoustic mode pairs. By selecting the proper combination of modes pairs, the performance of multi-parameter sensing can be optimized. Distributed sensing of temperature and strain is demonstrated over a 0.5-km elliptical-core few-mode fiber, with the discriminative uncertainty of 0.28°C and 5.81 µÎµ for temperature and strain, respectively.

Elevated Serum Angiopoietin-like Protein 2 in Patients with Acute Coronary Syndrome.

BACKGROUND AND AIMS: Angiopoietin-like protein 2 (Angptl2) is regarded as a proinflammatory factor in the pathogenesis of atherosclerosis and is expressed at high levels in patients with coronary artery disease. However, direct evidence of Angptl2 in acute coronary syndrome (ACS) is lacking. Our study was designed to investigate a possible relationship between serum Angptl2 and ACS. METHODS: We evaluated 251 consecutive patients undergoing coronary angiography, consisting of 132 patients with ACS (unstable angina pectoris n = 60, acute myocardial infarction n = 72), 50 patients with stable angina pectoris, and 69 control patients. Serum Angptl2 concentration was measured in peripheral venous blood by an enzyme-linked immunosorbent assay. RESULTS: Serum Angptl2 levels were significant higher in patients with ACS than in those with stable angina (p <0.05) or controls (p <0.001). The difference between angplt2 levels in unstable angina and acute myocardial infarction subgroups was statistically insignificant (p = 0.831). In multivariable logistic regression models, using quartiles of Angptl2, Angptl2 was closely associated with ACS following adjustment of age, gender, established risk factors and high sensitivity C-reactive protein levels (odds ratio for quartile 4 vs. quartile 1: 10.182, 95% confidence interval 2.440-42.485, p = 0.001). CONCLUSIONS: Serum Angptl2 is a new candidate biomarker for risk stratification of ACS.

CASP3 genetic variants and susceptibility to atrial fibrillation in Chinese Han population.

BACKGROUND: Caspase-3 plays an important role in the initiation and maintenance of atrial fibrillation (AF), but little is known about the role of CASP3 variants in the susceptibility to atrial fibrillation (AF). The purpose of this study was to comprehensively investigate the association between common genetic variants of CASP3 gene and AF in Chinese Han population. METHODS AND RESULTS: We investigated the association of five variants in CASP3 and the risk of AF in 889 AF patients and 1015 controls. The genotype distribution of the rs4647602 was significantly different between patients with AF and controls (p<0.001), and the A allele frequency was significantly higher in AF patients than in controls (61.0% vs 53.2%; p<0.001). Compared with CC genotype carriers, subjects with AA genotype had significantly increased susceptibility to AF (OR=1.84, p<0.001). Multivariable logistic regression analysis showed that the rs4647602 polymorphism was significantly associated with risk of AF under dominant, recessive and additive genetic model (OR, 1.44-1.64; all p<0.001). There was no association between the other four SNPs (rs6948, rs2696056, rs4647602 and rs4647610) and risk of AF. CONCLUSION: The rs4647602 polymorphism is independently associated with the risk of AF in Chinese Han population.

Association between SNP rs13376333 and rs1131820 in the KCNN3 gene and atrial fibrillation in the Chinese Han population.

BACKGROUND: The small conductance calcium-activated potassium, subfamily N, member 3 (KCNN3) gene rs13376333 and rs1131820 have been shown to be strongly associated with lone atrial fibrillation (AF), while replication association studies between rs13376333 in KCNN3 gene and risk of AF showed conflicting results. The current study tried to validate the impact of SNP rs13376333 and rs1131820 of KCNN3 gene on the risk of AF in the Chinese Han population. METHODS: A total of 889 AF patients and 1015 controls were enrolled. Two hundred and seventy-eight cases of AF were lone AF. KCNN3 gene SNP rs13376333 and rs1131820 were genotyped by allele-specific MALDI-TOF mass spectrometry. RESULTS: The genotype distribution and allele frequency of rs13376333 polymorphism were not different between total AF patients and controls. However, the genotype distribution of rs13376333 polymorphism was significantly different between lone AF and control group (p<0.001); and T allele frequency was significantly higher in lone AF group than that in controls (7.6% vs 3.6%, p<0.001). Multivariable logistic regression analysis showed that T allele carriers of rs13376333 was significantly associated with lone AF (OR=2.31, 95% CI 1.41-3.78, p=0.001). No relationship between rs1131820 polymorphism and total AF or lone AF was found in this study. CONCLUSIONS: KCNN3 rs13376333 polymorphism was associated with lone AF in the Chinese Han population and the T allele carriers may be an independent predictive factor for lone AF.

TheTGFB1 functional polymorphism rs1800469 and susceptibility to atrial fibrillation in two Chinese Han populations.

Transforming growth factor-ß1 (TGF-ß1) is related to the degree of atrial fibrosis and plays critical roles in the induction and perpetuation of atrial fibrillation (AF). To investigate the association of the common promoter polymorphism rs1800469 in the TGF-ß1 gene (TGFB1) with the risk of AF in Chinese Han population, we carried out a case-control study of two hospital-based independent populations: Southeast Chinese population (581 patients with AF and 723 controls), and Northeast Chinese population (308 AF patients and 292 controls). Two hundred and seventy-eight cases of AF were lone AF and 334 cases of AF were diagnosed as paroxysmal AF. In both populations, AF patients had larger left atrial diameters than the controls did. The rs1800469 genotypes in the TGFB1 gene were determined by polymerase chain reaction-restriction fragment length polymorphism. The genotype and allele frequencies of rs1800469 were not different between AF patients and controls of the Southeast Chinese population, Northeast Chinese population, and total Study Population. After adjustment for age, sex, hypertension and LAD, there was no association between the rs1800469 polymorphism and the risk of AF under the dominant, recessive and additive genetic models. Similar results were obtained from subanalysis of the lone and paroxymal AF subgroups. Our results do not support the role of the TGFB1 rs1800469 functional gene variant in the development of AF in the Chinese Han population.

[A study of relationship between dialectical classification according to traditional Chinese medicine of acute coronary syndrome with serum osteoprotegerin and its ligand].

OBJECTIVE: To investigate the relationship between osteoprotegerin (OPG) system and acute coronary syndrome (ACS) and its classification according to traditional Chinese medicine (TCM). METHODS: A prospective study was conducted. The patients with ACS (n=210) and the patients with stable angina pectoris (SAP, n=200) were enrolled. The serum OPG and its ligand (sRANKL) were determined by enzyme-linked immunosorbent assay (ELISA), the OPG/sRANKL ratio was calculated, and the number of coronary vessels was involved, finally their relationship with the typing according to TCM was evaluated. One hundred and fifty non-coronary heart disease patients were enrolled as control. RESULTS: The serum OPG, OPG/sRANKL in ACS and SAP groups were significantly higher than those in control group, and the sRANKL was significantly lower than that in control group (all P<0.01). The OPG, OPG/sRANKL in ACS groups were significantly higher than those in SAP group (both P<0.01). Serum OPG, OPG/sRANKL in ACS patients with different number of coronary vessel disease were significantly higher than those in control group, and the sRANKL was significantly lower than that in control group (all P<0.01). OPG and OPG/sRANKL were gradually increased with increase in number of diseased coronary vessels, but the sRANKL descended (P<0.05 or P<0.01). Serum OPG and OPG/sRANKL were descended according to dialectical classification of TCM: Yang Qi weakening syndrome>Qi and blood stagnation syndrome>Qi deficiency with blood stasis syndrome>stagnation of phlegm blocks the heart-vessels syndrome>Yin deficiencies of the heart and the kidney syndrome>deficiency of both Qi and Yin syndrome, among them they were significantly higher in Yang Qi failure syndrome and Qi and blood stagnation syndromes than those of both Qi and Yin syndrome [OPG(ng/L): 621.38±32.86, 617.63±39.60 vs. 593.86±36.19, OPG/sRANKL(g/mol): 1 018.98±106.03, 1 011.27±121.61 vs. 942.16±115.82, P<0.05 or P<0.01]. Among different types of TCM in ACS group the serum sRANKL was significantly lower than that in control group (all P<0.01), but the difference among different types was not significant. CONCLUSIONS: Serum OPG, sRANKL, OPG/sRANK levels were related with incidence and severity of coronary lesions in ACS patients. Serum OPG and OPG/sRANKL ratio may have correlation with Yang Qi weakening syndrome and Qi deficiency with blood stasis syndrome.

30Tb/s C- and L-bands bidirectional transmission over 10,181km with 121km span length.

We demonstrated the first 30Tb/s (350 × 85.74Gb/s) optical transmission over 10,181km using bidirectional C/L-bands, 121.2km hybrid fiber spans, DP-QPSK modulation and EDFAs. Achieved 306Petabit/s•km capacity × distance product is the highest reported to date for WDM transmission.

[Cilostazol inhibits proliferation and induces apoptosis in rat vascular smooth muscle cells through Rb-p53-p21 pathways].

OBJECTIVE: To explore the effects and related mechanisms of cilostazol on rat vascular smooth muscle cells (VSMCs)proliferation. METHODS: VSMCs were treated with DMEM (control) and various doses of cilostazol (1.0×10(-7), 2.5×10(-7), 5.0×10(-7), 7.5×10(-7) and 1.0×10(-6) mol/L) for 13 d (cell counting) or 72 h. Proliferation of VSMCs was investigated by cell-counting, MTT and flow cytometry analysis. Cell apoptosis was determined by TUNEL staining. mRNA and protein expressions of cell cycle regulatory proteins, such as Rb, p53 and p21 were detected by RT-PCR and Western blot, respectively. RESULTS: Cilostazol inhibited VSMCs proliferation and induced VSMCs arrest at G1 phase in a dose-dependent manner. High dose of cilostazol (7.5×10(-7) and 1.0×10(-6) mol/L) induced VSMCs apoptosis. p53 mRNA expression in 2.5×10(-7) mol/L to 7.5×10(-7) mol/L groups as well as 1.0×10(-6) mol/L group (3.22 ± 0.45 vs. 1.75 ± 0.32) and p53 protein expression in 7.5×10(-7) mol/L group and 1.0×10(-6) mol/L group (0.53 ± 0.11 vs. 0.18 ± 0.06) were significantly upregulated after 72 h culture (all P < 0.05 vs. control). Low dose of cilostazol (1.0×10(-7), 2.5×10(-7) and 5.0×10(-7) mol/L) significantly upregulated p21 mRNA expression compared to control group (1.86 ± 0.19, 2.20 ± 0.24 and 2.10 ± 0.18 vs. 1.210 ± 0.18, all P < 0.05). Similarly, Rb mRNA expression was significantly upregulated in 1.0×10(-7), 2.5×10(-7) and 5.0×10(-7) mol/L groups (0.89 ± 0.07 vs. 0.38 ± 0.04)compared with control group (all P < 0.05). However, high dose cilostazol (7.5×10(-7) and 1.0×10(-6) mol/L) significantly downregulated p21 mRNA expression (0.81 ± 0.09 vs. 1.21 ± 0.18, 0.36 ± 0.10 vs. 1.21 ± 0.18, all P < 0.05 vs. control) and Rb mRNA expression (0.12 ± 0.02 and 0.11 ± 0.02 vs. 0.38 ± 0.04, all P < 0.05 vs. control). p21 and Rb protein expressions also upregulated at low concentrations of cilostazol and downregulated at high concentrations of cilostazol. CONCLUSION: Cilostazol could inhibit the proliferation of rat VSMCs through modulating Rb-p53-p21 pathway and induce VSMCs apoptosis through upregulating p53.

Study of the toxicity of 1-Bromo-3-chloro-5,5-dimethylhydantoin to zebrafish.

OBJECTIVE: 1-Bromo-3-chloro-5,5-dimethylhydantoin (BCDMH) is a solid oxidizing biocide for water disinfection. The objective of this study was to investigate the toxic effect of BCDMH on zebrafish. METHODS: The developmental toxicity of BCDMH on zebrafish embryos and the dose-effect relationship was determined. The effect of BCDMH exposure on histopathology and tissue antioxidant activity of adult zebrafish were observed over time. RESULTS: Exposure to 4 mg/L BCDMH post-fertilization was sufficient to induce a number of developmental malformations, such as edema, axial malformations, and reductions in heart rate and hatching rate. The no observable effects concentration of BCDMH on zebrafish embryo was 0.5 mg/L. After 96 h exposure, the 50% lethal concentration (95% confidence interval (CI)) of BCDMH on zebrafish embryo was 8.10 mg/L (6.15-11.16 mg/L). The 50% inhibitory concentration (95% CI) of BCDMH on hatching rate was 7.37 mg/L (6.33-8.35 mg/L). Histopathology showed two types of responses induced by BCDMH, defensive and compensatory. The extreme responses were marked hyperplasia of the gill epithelium with lamellar fusion and epidermal peeling. The histopathologic changes in the gills after 10 days exposure were accompanied by significantly higher catalase activity and lipid peroxidation. CONCLUSION: These results have important implications for studies on the toxicity and use of BCDMH and its analogs.

1.92 Tb/s coherent DWDM-OFDMA-PON with no high-speed ONU-side electronics over 100 km SSMF and 1:64 passive split.

Record 1.92-Tb/s (40λ × 48 Gb/s/λ) coherent DWDM-OFDMA-PON without high-speed ONU-side ADCs/DACs/DSP/RF clock sources is demonstrated over 100 km straight SSMF with a 1:64 passive split. Novel optical-domain OFDMA sub-band selection, coherent detection, and simple RF components are exploited. As the first experimental verification of a next-generation optical platform capable of delivering 1 Gb/s to 1000(+) users over 100 km, the new architecture is promising for future optical access/metro systems.

[Tumor necrosis factor-α promote permeability of human umbilical vein endothelial cells via activating RhoA-ERK1/2 pathway].

OBJECTIVE: Tumor necrosis factor-α (TNF-α) is known to induce changes in endothelial cell morphology and permeability. The aim of this study is to determine the underlying signaling mechanisms involved in these responses. METHODS: Cultured human umbilical vein endothelial cells (HUVECs) were exposed to TNF-α, and HUVEC cytoskeletal changes were evaluated by observing fluorescence of F-actin following ligation with labeled antibodies. Endothelial permeability was detected by measuring the flux of horseradish peroxidase (HRP)-albumin across the EC monolayers. To explore the signaling pathways behind TNF-α-induced changes in HUVEC morphology and permeability, HUVECs were treated with either the Rho GTPase inhibitor Y27632 or the mitogen-activated protein kinases (MAPK) inhibitors PD98059 and SB203580 before TNF-α administration. To further elucidate possible involvement of the RhoA and ERK pathways in TNF-α-induced HUVEC changes, retrovirus-carried recombinant dominant-negative forms and constitutive-activative forms of RhoA, namely T19NRhoA and Q63LRhoA, were pre-infected into HUVECs prior to TNF-α exposure. RESULTS: TNF-α induced F-actin cytoskeleton rearrangement and increased HUVEC permeability in a dose and time-dependent manner. The maximal increase in the HRP-BSA flux (40 ng/ml) was seen in cells exposed to TNF-α at 100 ng/ml after 2 h. Preconditioning of HUVEC monolayer with Y27632 or PD98059 significantly reduced TNF-α induced permeability increase (HRP concentration from 40 ng/ml decreased to 12.5 ng/ml, P < 0.05) and F-actin cytoskeleton rearrangement, HUVEC pre-infection with activated forms of Q63LRhoA increased HUVEC permeability and upregulated pERK compared to GFP infection, while HUVEC pre-infection with inhibited forms of T19NRhoA attenuated the effects of TNF-α on HUVEC permeability. CONCLUSION: These results indicate that TNF-α-induced EC barrier dysfunction and morphological changes of the F-actin via activating RhoA-ERK/MAPK signal pathway.