A new integrative analysis of histopathology and single cell RNA-seq reveals the CCL5 mediated T and NK cell interaction with vascular cells in idiopathic pulmonary arterial hypertension.

BACKGROUND: Inflammation and dysregulated immunity play vital roles in idiopathic pulmonary arterial hypertension (IPAH), while the mechanisms that initiate and promote these processes are unclear. METHODS: Transcriptomic data of lung tissues from IPAH patients and controls were obtained from the Gene Expression Omnibus database. Weighted gene co-expression network analysis (WGCNA), differential expression analysis, protein-protein interaction (PPI) and functional enrichment analysis were combined with a hemodynamically-related histopathological score to identify inflammation-associated hub genes in IPAH. The monocrotaline-induced rat model of pulmonary hypertension was utilized to confirm the expression pattern of these hub genes. Single-cell RNA-sequencing (scRNA-seq) data were used to identify the hub gene-expressing cell types and their intercellular interactions. RESULTS: Through an extensive bioinformatics analysis, CXCL9, CCL5, GZMA and GZMK were identified as hub genes that distinguished IPAH patients from controls. Among these genes, pulmonary expression levels of Cxcl9, Ccl5 and Gzma were elevated in monocrotaline-exposed rats. Further investigation revealed that only CCL5 and GZMA were highly expressed in T and NK cells, where CCL5 mediated T and NK cell interaction with endothelial cells, smooth muscle cells, and fibroblasts through multiple receptors. CONCLUSIONS: Our study identified a new inflammatory pathway in IPAH, where T and NK cells drove heightened inflammation predominantly via the upregulation of CCL5, providing groundwork for the development of targeted therapeutics.

Risk factors and mortality of pulmonary embolism in COVID-19 patients: Evidence based on fifty observational studies.

BACKGROUND: At present, many studies have described acute pulmonary embolism (PE) as a frequent and prognostically relevant complication of coronavirus disease 2019 (COVID-19) infection. Thus we performed the present analysis of 50 studies to evaluate the risk factors and mortality of PE in COVID-19 patients. METHOD: Databases including PubMed, Embase, Cochrane Library and Web of Science were searched to October, 2021. Odds ratio (OR), mean difference (MD) or standard MD was used to evaluate the outcomes. The primary outcomes were the difference of mortality between PE and non-PE COVID-19 patients as well as relevant risk factors of PE in COVID-19 patients. All statistical analyses were performed using the standard statistical procedures provided in Review Manager 5.2. RESULT: A total of 50 studies including 10053 patients were included in this meta-analysis. Our results indicated that COVID-19 patients with PE experienced significantly higher mortality than non-PE patients (21.9% vs. 10.7%), with a pooled OR of 2.21 (95% CI 1.30 - 3.76; P = .003). In addition, COVID-19 patients with PE also experienced more mechanical ventilation (MV) (OR 2.21; 95% CI 1.30 - 3.75; P = .003) and invasive mechanical ventilation (IMV) (OR 3.58; 95% CI 2.47 - 5.20; P < .0001) respectively. Univariate analysis (UVA) results indicated the Sequential Organ Failure Assessment (SOFA) score, time to deep venous thrombosis (DVT), nonintensive care unit (non-ICU) patients and no anticoagulation as risk factors of PE for COVID-19 patients. In addition, multivariate analysis also found that SOFA score, D-dimer, BMI > 30 kg/m2 and history of PE were risk factors of PE for COVID-19 patients. CONCLUSION: The present analysis indicated that PE increased the mortality of COVID-19 patients. Mechanical ventilation, especially invasive mechanical ventilation, is correlated with an increased incidence of PE in patients with COVID-19. The incidence of PE for COVID-19 patients may be multifactorial and further researches focused on risk factors were needed in the future.

Clinical and hemodynamic features of acute pulmonary embolism patients diagnosed in cold weather predicts adverse clinical outcome.

Background: Acute pulmonary embolism (APE) is associated with peak incidence and mortality rate in winter. The present study sought to characterize the clinical and hemodynamic features of cold weather on APE patients. Methods: All enrolled 224 APE patients underwent clinical and hemodynamic evaluation and baseline parameters were collected. Recruited patients were grouped by weather pattern on admission into cold and warm weather group. The correlation and prognostic values among cold weather and other variables were analyzed. Results: Compared to warm weather group, patients in cold weather group present with more severe cardiac function, with adverse WHO-functional class (P = 0.032) and higher NT-proBNP concentration [1,853.0 (398.0, 5,237.0) pg/ml vs. 847.5 (56.8, 3,090.5) pg/ml, P = 0.001]. The cold weather group also displayed much critical hemodynamic status and heavier thrombosis load, with higher mPAP (29.1 ± 11.2mmHg vs. 25.6 ± 14.2mmHg, P = 0.045), higher PVR [3.3 (1.7, 6.0) wood units vs. 1.8 (0.9, 3.8) wood units, P < 0.001], higher Miller index (21.4 ± 5.9 vs. 19.1 ± 8.0, P = 0.024), and higher D-dimer levels [2,172.0 (854.5, 3,072.5) mg/L vs. 1,094.5 (210.5, 2,914.5) mg/L, P = 0.008]. Besides, cold weather showed well correlation with the above variables. Survival analysis showed APE patients in cold weather had significantly higher clinical worsening event rate (P = 0.010) and could be an independent predictor of adverse clinical outcome in the multivariate analysis (HR 2.629; 95% CI 1.127, 6.135; P = 0.025). Conclusion: APE patients in cold weather were associated with thrombus overload, cardiac dysfunction, hemodynamic collapse and higher clinical worsening event rate. Cold weather proves to be an independent predictor of adverse clinical outcome.

Relationship between quantitative contrast-enhanced ultrasonography parameters and angiogenesis in primary small hepatocellular carcinoma: A retrospective study.

ABSTRACT: To analyze the correlation between quantitative contrast-enhanced ultrasonography (CEUS) parameters and angiogenesis in primary small hepatocellular carcinoma (sHCC) with varying degrees of differentiation.According to varying degrees of differentiation, a total of 90 primary sHCC patients admitted to our hospital from July 2018 to January 2020 were selected and divided into poorly differentiated group (24 cases), moderately differentiated group (31 cases), and highly differentiated group (35 cases). All patients received real-time CEUS before surgery. The tumor diameter, microvascular morphology, grading of color blood flow, contrast-enhanced performance in different phases, quantitative CEUS parameters, expression of angiogenesis-related genes, and microvessel density (MVD) were compared among the 3 groups. The correlation between quantitative parameters of CEUS and angiogenesis indexes was analyzed by Spearman rank correlation analysis.Spearman rank correlation analysis showed that vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), epidermal growth factor receptor (EGFR), and angiopoietin-2 (Ang-2) expression and MVD were negatively correlated with the time to peak (TTP), wash-out time, and peak accelerating time (PAT) (r < 0, P < .05), and were positively correlated with enhancing slope rate (ESR) and peak intensity increasing rate (PIIR) (r > 0, P < .05).CEUS is able to identify varying degrees of differentiation in primary sHCC, and the quantitative CEUS parameters are closely related to angiogenesis.

A generic deep learning framework to classify thyroid and breast lesions in ultrasound images.

Breast and thyroid cancers are the two common cancers to affect women worldwide. Ultrasonography (US) is a commonly used non-invasive imaging modality to detect breast and thyroid cancers, but its clinical diagnostic accuracy for these cancers is controversial. Both thyroid and breast cancers share some similar high frequency ultrasound characteristics such as taller-than-wide shape ratio, hypo-echogenicity, and ill-defined margins. This study aims to develop an automatic scheme for classifying thyroid and breast lesions in ultrasound images using deep convolutional neural networks (DCNN). In particular, we propose a generic DCNN architecture with transfer learning and the same architectural parameter settings to train models for thyroid and breast cancers (TNet and BNet) respectively, and test the viability of such a generic approach with ultrasound images collected from clinical practices. In addition, the potentials of the thyroid model in learning the common features and its performance of classifying both breast and thyroid lesions are investigated. A retrospective dataset of 719 thyroid and 672 breast images captured from US machines of different makes between October 2016 and December 2018 is used in this study. Test results show that both TNet and BNet built on the same DCNN architecture have achieved good classification results (86.5% average accuracy for TNet and 89% for BNet). Furthermore, we used TNet to classify breast lesions and the model achieves sensitivity of 86.6% and specificity of 87.1%, indicating its capability in learning features commonly shared by thyroid and breast lesions. We further tested the diagnostic performance of the TNet model against that of three radiologists. The area under curve (AUC) for thyroid nodule classification is 0.861 (95% CI: 0.792-0.929) for the TNet model and 0.757-0.854 (95% CI: 0.658-0.934) for the three radiologists. The AUC for breast cancer classification is 0.875 (95% CI: 0.804-0.947) for the TNet model and 0.698-0.777 (95% CI: 0.593-0.872) for the radiologists, indicating the model's potential in classifying both breast and thyroid cancers with a higher level of accuracy than that of radiologists.

Prophylactic effect of rectal indomethacin plus nitroglycerin administration for preventing pancreatitis after endoscopic retrograde cholangiopancreatography in female patients.

BACKGROUND: Prophylactic pancreatic stent placement (PSP) and rectal indomethacin suppository are recommended to prevent post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) in high-risk cases. Clinical trials on the use of nitroglycerin to reduce PEP have reached no definitive conclusion. Our study aimed to determine whether treatment with rectal indomethacin plus nitroglycerin could eliminate the need for PSP in patients. METHODS: In this randomized clinical trial, patients were allocated into groups using a random number table, with each patient receiving a pre-made envelope containing their intervention prior to ERCP. The three treatment groups were: the placebo group, the indomethacin + nitroglycerin group, and the PSP group. The subjects were assessed for PEP and its severity by a panel of independent and blinded adjudicators. RESULTS: A total of 526 patients were eligible for inclusion. The placebo group included 176 patients, the indomethacin + nitroglycerin group included 176 patients and the PSP group included 174.A diagnosis of PEP was made in 64 (12.2%) cases. The rate of PEP in the three study groups placebo group, indomethacin + nitroglycerin group and the PSP group was 19.3%, 5.1%, and 12.1%, respectively. CONCLUSIONS: The risk of post-ERCP pancreatitis in the indomethacin + nitroglycerin group was 7% lower than that in the PSP. Indomethacin + nitroglycerin is superior to PSP in preventing and relieving the severity of post-ERCP pancreatitis in patients with difficult intubation. Indomethacin plus nitroglycerin can avoid the need for PSP in the prevention of post-ERCP pancreatitis. TRIAL REGISTRATION: Current Controlled Trials ChiCTR2000033944.

Traditional Uyghur medicine Quercus infectoria galls water extract triggers apoptosis and autophagic cell death in colorectal cancer cells.

BACKGROUND: The water extract of Quercuse infectoria galls (QIG) is the active ingredient of Uyghur medicine Xipayi Kui Jie'an (KJA) which has promising therapeutic effects on Ulcerative Colitis (UC) as an alternative medicine. Considering the relationship between UC and the development of colorectal cancer (CRC), the present work aims to explore the direct anti-CRC activity of QIG extract. METHODS: CCK8 assay and flow cytometry were used to detect cytotoxicity and apoptosis. Transmission electron microscopy (TEM), flow cytometry, laser confocal and western blotting were performed to examine autophagy. We also adopted Reactive Oxygen Assay kit, as well as transwell and wound healing tests to study the underlying mechanism of QIG against CRC cells. RESULTS: First, we found that QIG extract could suppress the viability of CRC cells and trigger caspases-dependent apoptosis. Subsequently, we proved for the first time that QIG extract also triggered autophagic cell death in CRC cells, which together with apoptosis contributed to the cytotoxic effect on CRC cells. Further investigation revealed that QIG-induced cytotoxicity associated with intracellular ROS accumulation which could suppress the AKT/mTOR signaling pathway, and then induce autophagy and inhibit cell growth. Besides, Erk signaling pathway was also involved in the process of autophagic cell death. Moreover, QIG extract also influenced EMT process and inhibited CRC cell migration. CONCLUSION: Altogether, this study provides a basis for the utilization of QIG as an alternative medicine for CRC prevention and treatment.

Clinical Characteristics and Eosinophils in Young SARS-CoV-2-Positive Chinese Travelers Returning to Shanghai.

Background: The COVID-19 outbreak, which was first reported in Wuhan, China, in December 2019, began to spread throughout the world, and now involves over 200 countries. Methods: A total of 37 overseas young and middle-aged people, who tested as SARS-CoV-2 positive upon their return to Shanghai, were enrolled for an analysis of their clinical symptoms, blood routine indexes, and lung CT images. Results: The clinical symptoms were characterized by fever (51.4%), dry cough (13.5%), expectoration (27.0%), hypodynamia (21.6%), pharyngalia (10.8%), pharynoxerosis (8.1%), rhinobyon (13.5%), rhinorrhea (8.1%), muscular soreness (16.2%), and diarrhea (2.7%). In 16.2% of cases, no symptoms were reported. Fever was the most common symptom (51.40%). The pneumonic changes referred to the latticed ground glass imaging and similar white lung imaging accompanied by consolidated shadows. The rate of pneumonia was high (81.10%). We found that the exclusive percent of eosinophils was abnormally low. By analyzing the correlation of eosinophils, fever, and pneumonia, we found that the percentage of eosinophils was low in the COVID-19 patients afflicted with fever or pneumonia (P < 0.01). Additionally, pneumonia and fever were negatively correlated with the percentage of eosinophils and eosinophils/neutrophils ratio (P < 0.01, respectively), but not associated with pneumonia severity (P > 0.05). Fever was not correlated with pneumonia (P > 0.05). Conclusion: A low percentage of eosinophils may be considered as a biomarker of pneumonia of COVID-19, but not as a biomarker of pneumonia severity.

Catalytic function of ferric oxide and effect of water on the formation of sulfur trioxide.

Sulfur trioxide (SO3) is not only environmentally harmful but also highly corrosive, taking a great threat to the safe operation of coal-fired power plants. A dominant pathway of SO3 formation in coal-fired power plant is through the catalytic oxidation of SO2 (SO2+1/2O2→SO3) on the surfaces of ash particles containing Fe2O3. The catalytic formation of SO3 could be affected by complex atmosphere, where the effect from H2O is still debatable. In this paper, density functional theory (DFT) is employed to explore the reaction pathway of SO3 formation catalyzed by α-Fe2O3 in complex atmosphere containing O, O2, SO2 and H2O. In order to get the stable adsorption sites of these species, the adsorption energy of potential adsorption configurations on the α-Fe2O3 (001) surface is calculated. The dissociations of O2 molecule on complete and defect α-Fe2O3 (001) surfaces with O vacancy are calculated, and the Langmuir-Hinshelwood and Eley-Rideal mechanisms for the O(ads) reaction with SO2(ads) or SO2 are compared. The effect of H2O besides of SO2 and O2 on the formation of SO3 is especially discussed. The DFT calculation results show that for the formation of SO3 in gas phase, the energy barrier of 'SO2+1/2O2→SO3' is 436.75 kJ mol-1, in contrast, for the catalytic formation of SO3 on α-Fe2O3 surfaces, this energy barrier becomes an order of magnitude smaller, 24.82 kJ mol-1. O2 molecules can dissociate on the defect α-Fe2O3 (001) surface with O vacancy spontaneously, indicating that the defect α-Fe2O3 is favorable for the dissociation of O2, thereby promotes the formation of SO3. The energy barrier of 'SO2(ads)+O(ads)→SO3(ads)' through Langmuir-Hinshelwood mechanism is much higher than that of 'SO2+O(ads)→SO3(ads)' through Eley-Rideal mechanism. The adsorption energy on the α-Fe2O3 (001) surface of H2O is much smaller than that of SO2 and O2, indicating that H2O has little effect on the adsorption of O, O2, SO2 and eventually the heterogeneous formation of SO3. The DFT analysis results in this study provide a deep understanding on the reaction pathway of SO3 catalytic formation by Fe2O3.

Hot corrosion behaviors of TP347H and HR3C stainless steel with KCl deposit in oxy-biomass combustion.

Oxy-combustion is one of the most promising technologies for carbon capture and sequestration. When CO2-neutral biomass is burned under oxy-combustion conditions, named "oxy-biomass combustion" a negative CO2 emission can be achieved. However, the high content of potassium and chlorine in biomass results in sever ash deposition and corrosion in air fired furnaces, which are further aggravated in oxy-combustion mode due to the enrichment of corrosive species by flue gas recycle. In this paper, the hot corrosion behaviors and mechanism of two representative materials (TP347H, HR3C) used for superheaters in furnaces are studied. The effects of oxy-combustion atmosphere, KCl deposition, effect of SO2, effect of water vapor, and temperature on the corrosion kinetics at the starting stage are investigated. The corrosion severity of the materials was determined using the weight gain method, and the microstructures and chemical compositions of corrosion layers were characterized by the scanning electron microscopy with energy dispersive spectroscopy, and X-ray diffraction. The results show that the hot corrosion rate is significantly sped up by KCl deposition, more than five times the gas corrosion rate under the same gas composition and temperature. HR3C with higher Cr and Ni contents is more likely to form Cr enrichment on the interface between the corrosion layer and the substrate than TP347H, resulting in stronger resistance to the hot corrosion than TP347H. When the corrosion atmosphere is changed from air-combustion to oxy-combustion, the hot corrosion rate is reduced with a denser Cr oxide film and less metal sulfides. The increase of temperature in the presence of KCl deposition significantly affects the hot corrosion rate, e.g. the corrosion rate at 650 °C is 16 times higher than that at 450 °C. Water vapor and SO2 concentrations have opposite influences on the hot corrosion, respectively. Compared to the dry environment, a high-humidity environment decreases the hot corrosion rate; however, a higher SO2 concentration facilitates the sulfation of KCl deposits, leading to stronger damage to the chromium oxide film and thereby an increased hot corrosion rate.

The evaluation of GI-pill gastrointestinal electronic capsule for colonic transit test in patients with slow transit constipation.

OBJECTIVE: The evaluation of GI-pill gastrointestinal electronic capsule for colonic transit test in patients with slow transit constipation (STC) was studied. MATERIALS AND METHODS: STC patients (n = 162) were randomly divided into experimental group (n = 84, orally taken GI-pill gastrointestinal electronic capsule and X-ray granule capsule) and control group (n = 78, orally taken X-ray granule capsule). Comparison of the time in colonic transit test between the two groups was conducted. The data of GI-pill gastrointestinal electronic capsule in vivo time, time of capsule passing through the colon, the number of high amplitude propagating contractions (HAPCs), and physiological response ratio were analyzed. RESULTS: There were no significant differences in the whole colonic transit test time, right colonic transit time, left colonic transit time, and rectosigmoid colonic transit time between experimental group and control group (p > 0.05). All patients had no abdominal pain, nausea, vomiting, black stool, difficulty in electronic capsule excretion, or any other discomfort during the test. CONCLUSION: GI-pill gastrointestinal electronic capsule can continuously evaluate the dynamic characteristics of digestive tract in STC patients and is consistent with X-ray granule capsule, which is meaningful to clinical application.

Biochemical composition distribution in different grain layers is associated with the edible quality of rice cultivars.

Clarifying the association of differences in endosperm biochemical composition with nutrient and edible quality can guide rice breeding and cultivation. In this study, very-low-amylose-content (LAC), Japanese good-taste (JTC), Northeast China good-taste (CTC), and Northeast China high-yield (CHC) cultivars were milled to obtain four layers (L1-L4) from outside-in, and then analyzed for apparent amylose content (AAC), protein content (PC), amino acids, soluble sugars, and minerals. The association of these compositions and Rapid-Visco analysis values with taste was also examined. LAC had low AAC, high amino acid and mineral content, and the highest taste value. Taste was significantly affected by AAC and soluble sugar in L3, and by PC in the L2 layer. High levels of amino acid in L2 and L3 improved the taste, as did Mg, P, and Ca in L1. On the whole, starch factors had the highest contribution to taste, followed by minerals, amino acids, and PC.

Prostate Cancer Vascularity: Superb Microvascular Imaging Ultrasonography with Histopathology Correlation.

BACKGROUND The aim of this study was to evaluate the association between prostate cancer (PCa) vascularity detected by superb microvascular imaging (SMI) and Gleason score in biopsy specimens. MATERIAL AND METHODS A total of 119 patients with suspected PCa before biopsy underwent gray-scale ultrasound (US), color Doppler ultrasound (CDUS), and SMI imaging between June 2018 and March 2019. Vascularity quantity was assessed by SMI and compared with that of CDUS. The vessel parameter was also compared with the Gleason score. The sensitivity of PCa was compared between transrectal ultrasound guided systematic biopsy (SB) and SMI-guided targeted biopsy (SMI-guided TB). RESULTS Pathology confirmed 74 of 119 patients had PCa. The microvascular quantity of PCa patients was significantly higher than that of non-malignant patients. SMI detected blood vessels in 97.3% (72/74) in the malignant group, while CDUS identified blood flow signals in 90.5% (67/74) of the PCa group. SMI visualized enriched microvascular in PCa of Gleason 8 (54.5%) and Gleason 9 (92.3%). There was a positive correlation between microvascular quantity detected by SMI and Gleason score, with a correlation coefficient of 0.373 (P<0.001). SMI-guided TB cores were significantly more likely than SB cores to detect PCa (OR=12.83, P<0.001). CONCLUSIONS SMI could be promising as a useful imaging technique in the detection and characterization of PCa. There was a positive correlation between microvascular quantity detected by SMI and Gleason score.

Strain Elastography-Targeted Biopsy: Does Prostate Volume Affect Prostate Cancer Detection?

BACKGROUND The present study aimed to assess the correlation between prostate volume and prostate cancer (PCa) detection by strain elastography (SE)-guided targeted biopsy (TB) compared with conventional transrectal ultrasound (TRUS)-guided systematic biopsy (SB). MATERIAL AND METHODS This retrospective study enrolled 357 patients suspected to have PCa. All patients received TRUS-guided 10-core SB and SE-guided TB. The sensitivity for PCa detected by SE-guided TB was compared with that by TRUS-guided SB, in combination with prostate biopsy pathology. The correlation between the prostate volume and the detection rate of SE-guided TB was investigated. RESULTS PCa was pathologically confirmed in 151 out of 357 patients. The by-patient detection rate of TRUS-guided SB was 72.8% (110/151). Subsequently, a further increase of 6.6% (10/151) in PCa determination was obtained by the SE-guided TB. The sensitivity of SE-guided TB for patients with prostate volume <30 ml, 30-50 ml, 51-80 ml, and >80 ml was 91.7% (44/48), 80.3% (53/66), 70.4% (19/27), and 40.0% (4/10), respectively (p=0.002). For patients with a prostate volume less than 30 ml, SE-guided TB (91.7%) had a higher sensitivity than SB (62.5%) (p<0.007). CONCLUSIONS SE-guided TB has a higher detection rate of PCa in comparison with TRUS-guided SB. There was also a negative correlation between prostate volume and SE-guided TB. Therefore, use of SE-guided TB may complement use of conventional SB, especially for patients with smaller prostate volume.

MicroRNA-326 suppresses iNOS expression and promotes autophagy of dopaminergic neurons through the JNK signaling by targeting XBP1 in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons, and substantia nigra is primarily one of the damaged brain regions. Evidence indicates that microRNAs (miRNAs) is involved in the pathophysiology of this disease. The present study aimed to investigate the biological function of miR-326 in PD through the JNK signaling pathway by targeting X-box binding protein 1 (XBP1). After liposome complexes were prepared, healthy male C57BL/6 mice were selected to construct a mouse model of PD. The targeting relationship between miR-326 and XBP1 was confirmed. The expression of miR-326 and XBP1 was measured in PD mice, and gain- and loss-function assay was conducted to examine the regulatory effect of miR-326 and XBP1 on inducible nitric oxide synthase (iNOS) expression and autophagy of dopaminergic neurons of PD mice. Mice treated with miR-326 mimic and siRNA-XBP1 showed increased traction test scores, activation of autophagy, expression of LC3-II, c-Jun, and p-α-Syn, but diminished climbing time and expressions of iNOS, α-Syn, and p-c-Jun. The siRNA-XBP1 treatment could reverse the effect of miR-326 inhibitor on PD mice. Overexpression of miR-326 inhibits iNOS expression and promotes autophagy of dopaminergic neurons through JNK signaling by targeting XBP1.

Experimental and kinetics study on SO3 catalytic formation by Fe2O3 in oxy-combustion.

Sulfur trioxide (SO3) is corrosive and environmentally harmful. Under oxy-combustion mode, the formation of SO3 is aggravated due to flue gas recirculation, and should be more concerned than that under traditional air-combustion mode. In this paper, the catalytic formation of SO3 by iron oxide (Fe2O3) under oxy-combustion mode was experimentally studied in a fixed-bed reactor, and effects of temperature (300-900 °C), atmosphere, catalyst particle size, SO2, O2, and H2O concentrations were discussed. Results show that Fe2O3 promotes SO3 formation, and the yield of SO3 reaches a maximum at 700 °C under both air- and oxy-combustion modes. Increasing O2 concentration in a range of 5-20% promotes the catalytic formation of SO3, whose effect is restricted at a higher O2 concentration. Both increases of SO2 concentration in a range of 500-3000 ppm and steam concentration in a range of 0-20% decrease the SO3 yield. A significant effect of Fe2O3 particle size on SO3 catalytic formation is observed. When the particle size decreases from 50-75 µm to 10-25 µm, the inflection temperature shifts from 700 °C to 600 °C, while the maximum SO3 yield increases by 33%. Kinetics analysis results show that in this case, the catalytic conversion from SO2 to SO3 by Fe2O3 has an apparent activation energy Ea of 18.9 kJ/mol and a pre-exponential factor A of 5.2 × 10-5. At 700 °C and with Fe2O3 particle size of 50-75 µm, the global reaction orders of SO2 and O2 for SO3 formation are 0.71 and 0.13, respectively.

MicroRNA-92 regulates vascular smooth muscle cell function by targeting KLF4 during vascular restenosis and injury.

MicroRNAs (miRNAs) contribute to multiple cellular processes in embryonic development and disorders. Several miRNAs are strongly associated with the progression of peripheral vascular disease. Recently, it was reported that miRNA (miR)-92 is one of the most upregulated miRNAs in vascular injury after intervention in the lower extremities; however, the function of miR-92 during proliferative vascular diseases remains unclear and the potential targets of miR-92 are poorly characterized. In this study, we investigated the expression of miR-92 in vitro and in vivo, and explored the associated underlying mechanism. qRT-PCR analysis showed that miR-92 expression was highly upregulated in patients with artery restenosis compared to those without restenosis. Platelet-derived growth factor (PDGF)-BB is regarded as a critical regulator of the phenotypic switch of VSMCs. miR-92 expression was significantly upregulated in PDGF-BB-stimulated VSMCs. Introducing an miR-92 mimic into VSMCs enhanced cell proliferation and migration, and induced S-phase arrest. The luciferase reporter assay revealed that KLF4 is a downstream target gene of miR-92. In vivo, miR-92 overexpression promoted neointimal formation, and thus resulted in a dramatic increase in intimal-medial area and thickness. These results reveal that miR-92 regulates VSMC function by directly targeting KLF4, which may be an important finding useful for the diagnosis and treatment of vascular restenosis and injury, arteriosclerosis, and other proliferative vascular diseases.

MicroRNA-488 inhibits progression of colorectal cancer via inhibition of the mitogen-activated protein kinase pathway by targeting claudin-2.

Colorectal cancer (CRC) affects people globally, and lymph node metastasis (LNM) is an important indicator of poor clinical outcome in CRC. The current study aims to evaluate the role of microRNA-448 (miR-488) and claudin-2 (CLDN2) in epithelial-mesenchymal transition (EMT) and LNM of CRC through the MAPK signaling pathway. First, microarray analysis indicated that miR-488 was poorly expressed in CRC, whereas CLDN2 was highly expressed. Additionally, the bioinformatics website MicroRNA.org and the dual luciferase reporter gene assay found that CLDN2 was a target gene of miR-488. Next, the results for the correlations between expression of miR-488 and clinicopathological characteristics of CRC indicated that the expression of miR-488 was closely associated with differentiation degree, LNM, and Dukes stages in CRC patients. Moreover, overexpression of miR-488 inhibited the activation of the MAPK signal transduction pathway. Notably, loss- and gain-of-function experiments demonstrated that upregulation of miR-488 suppressed SW480 cell viability, invasion, and migration and promoted apoptosis in SW480 cells. Finally, overexpression of miR-488 inhibited LNM, microlymphatic vessel density, and tumor growth in nude mice. We conclude that overexpression of miR-488 could suppress the cell proliferation, EMT, and LNM of CRC cells via inhibition of the CLDN2-mediated MAPK signaling pathway, which could be a new molecular therapy target for CRC.

LINC00312 represses proliferation and metastasis of colorectal cancer cells by regulation of miR-21.

Long non-coding RNAs (lncRNAs) have emerged as important regulators of cancer, including colorectal cancer (CRC). The exact expression pattern of long intergenic noncoding RNA 00312 (LINC00312) in CRC and its mechanisms of action have not been reported. Here, we found that LINC00312 is underexpressed in CRC tissues and cell lines. Functional experiments suggested that LINC00312 suppresses growth, migration and invasion of CRC cells in vitro and attenuates tumour proliferation and metastasis in vivo. Mechanistically, LINC00312 was found to regulate the malignancy of CRC cells by binding to miR-21 and by functioning as a tumour suppressor targeting PTEN. Overexpression of miR-21 or knockdown of PTEN attenuated the LINC00312-mediated inhibition of CRC cell proliferation and invasion. Taken together, our results elucidate the role of the LINC00312-miR-21-PTEN axis in CRC cell proliferation and tumour progression and may lead to new lncRNA-based diagnostics or therapeutics for CRC.