Declined plasma microfibrillar-associated protein 4 levels in acute coronary syndrome.

BACKGROUND: Microfibrillar-associated protein (MFAP4), initially identified as an extracellular matrix protein, has been demonstrated in multiple human disorders, but it is yet to be discovered following acute coronary syndrome (ACS) in clinical practice. Therefore, this study aimed to investigate the relationship between circulating MFAP4 levels and coronary stenosis in ACS. METHODS: We performed the study in 148 ACS subjects, including 75 ST-segment elevation myocardial infarction (STEMI), 27 non-ST-segment elevation myocardial infarction (non-STEMI) and 46 unstable angina (UA). Clinical variables were collected and Gensini and Syntax stenosis scoring systems were applied to assess the severity of coronary stenosis. Kaplan-Meier and logistic regression analysis were used to analyze the relationship between MFAP4 and the severity of coronary stenosis or ACS outcomes. Spearman analysis was used to describe the correlation between MFAP4 and clinical parameters. RESULTS: Circulating MFAP4 levels were significantly decreased in the STEMI group (0.008 ng/ml) compared with the non-STEMI group (0.014 ng/ml) and UA group (0.019 ng/ml) (p < 0.001). After adjusting for confounding factors, we found that MFAP4 was an independent risk factor for STEMI (odds ratio = 0.395, 95% CI 0.174-0.895, p = 0.026). MFAP4 level was negatively correlated with Gensini score and Syntax score (r = - 0.311 and - 0.211, p < 0.001 and 0.01, respectively). Based on the MFAP4 level of 0.117 ng/ml, ACS patients were divided into two groups: the low-MFAP4 group (< 0.117 ng/ml, n = 60) and the high-MFAP4 group (≥ 0.117 ng/ml, n = 88). After the median follow-up of 165 days, Kaplan-Meier survival analysis revealed that the MACE-free rate was significantly lower in ACS patients with lower MFAP4 levels (p = 0.009). CONCLUSIONS: MFAP4 has a potential as a biomarker for the degree of coronary stenosis in ACS. Confirmation of observations in larger cohorts and longer follow-up periods is warranted.

Spatiotemporal Dynamics of Surface Ozone and Its Relationship with Meteorological Factors over the Beijing-Tianjin-Tangshan Region, China, from 2016 to 2019.

In recent years, ozone pollution has been increasing in some parts of the world. In this study, we used the Beijing-Tianjin-Tangshan (BJ-TJ-TS) urban agglomeration region as a case study and used satellite remotely sensed inversion data and hourly ground monitoring observations of surface ozone concentrations, meteorological data, and other factors from 2016 to 2019 to explore the spatiotemporal dynamic characteristics of surface ozone concentration and its pollution levels. We also investigated their coupling relationships with meteorological factors, including temperature, pressure, relative humidity, wind velocity, and sunshine duration, in order to support the development of effective control measures for regional ozone pollution. The results revealed that the surface ozone concentration throughout the BJ-TJ-TS region from 2016 to 2019 exhibited an overall pattern of high values in the northwest and low values in the southeast, as well as an obvious difference between built-up and non-built-up areas (especially in Beijing). Meanwhile, a notable increasing trend of ozone levels was discovered in the BJ and TJ areas from 2016 to 2019, whereas this upward trend was not evident in the TS area. In all three areas, the highest monthly average ozone values occurred in the summer month of June, while the lowest monthly average levels occurred in the winter month of December. Their diurnal variation values reached a maximum value at approximately 3:00-4:00 p.m. and a minimum value at approximately 7:00 a.m. It is clear that high temperature, long sunshine duration, low atmospheric pressure, and weak wind velocity conditions, as well as certain relative humidity levels, readily led to high-concentration ozone pollution. Meanwhile, the daily average values of the five meteorological factors on days with Grade I and Grade II ozone pollution displayed different characteristics.

Elevated Plasma Thymic Stromal Lymphopoietin After Acute Myocardial Infarction.

Background: Thymic stromal lymphopoietin (TSLP), a distant paralog of the cytokine IL-7, has been shown to be associated with atherosclerosis. However, the effect of plasma TSLP level after acute myocardial infarction (AMI) remains largely unclear. Thus, we aimed to assess the relationship between the concentration of TSLP at admission and the risk of major adverse cardiovascular events (MACE) in AMI patients. Methods: A total of 175 patients with AMI and 145 unstable angina (UA) controls were recruited in the present study. The clinical characteristics were collected, and MACE was recorded during hospitalization and the follow-up period after discharge. Results: The median value (25, 75 percentiles) of TSLP concentrations in the AMI group was higher than that in the UA group [11.18 (8.14-15.22) vs. 8.56 (5.26-11.94) pg/ml, p < 0.001, respectively]. Multivariate linear regression analysis revealed that Troponin-I (standardized ß = 0.183, p = 0.004) was an independent factor for TSLP. According to the median of TSLP concentrations, all the AMI patients were divided into the high-level group (TSLP level ≥ 11.18 pg/ml, N = 91) and the low-level group (TSLP <11.18 pg/ml, N = 84). In a receiver operating characteristic curve analysis, the area under the curve for TSLP as a predictor of AMI was 0.674 with a cut-off value of 9.235 pg/ml. After a median follow-up of 14 months, Kaplan-Meier survival analysis showed no significant difference in MACE-free survival between the two groups (p = 0.648). Finally, the multivariate logistic regression analyses demonstrated that TSLP was a negative predictor of MACE in AMI patients (OR:0.778,95% CI:0.733-0.876, p = 0.032). Conclusions: Plasma TSLP levels were elevated in patients with AMI than those in UA. The lower TSLP concentration was associated with MACE after AMI.

Characterization of fecal metabolome changes in patients with obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is a clinical syndrome characterized by recurrent episodes of apnea or hypopnea of the upper airway, leading to increased negative intrathoracic pressure, sleep fragmentation, intermittent hypoxia during sleep, and increased risk for morbidity and mortality of affected patients. The gut microbiome plays a key role in OSA pathogenesis, and fecal metabolic profiling reflects the gut microbial functional readout and mediates host-microbiome interactions. METHODS: Herein, we conducted a cohort study to explore fecal metabolic signatures distinguishing OSA (44 patients) from healthy controls (22 healthy controls) by untargeted gas chromatography-time-of-flight mass spectroscopy. RESULTS: Significant metabolic signatures were detected in stool samples of patients with OSA: 246 metabolites of 24 ontology classes were identified, and 48 metabolites of 6 ontology classes were shifted. An enrichment of arachidonic acid, docosahexaenoic acid, and 11Z-eicosenoic acid and reduction in stearic acid, 5-hydroxyindoleacetic acid, gluconic acid, and α-hyodeoxycholic acid were observed in stool samples from patients with OSA. Fecal variance resulted in alterations in potential metabolic activities and was thereby strongly associated with host phenotypes, such as pulse blood oxygen saturation and apnea-hypopnea index. The prediction model based on feces metabolomics was established to distinguish OSA from healthy controls with high accuracy. CONCLUSIONS: This study revealed the metabolomic signatures of patients with OSA in feces, and the findings provide evidence of an association between metabolome and OSA. CITATION: Dong Y, Wang P, Lin J, et al. Characterization of fecal metabolome changes in patients with obstructive sleep apnea. J Clin Sleep Med. 2022;18(2):575-586.

Profile of gut flora in hypertensive patients with insufficient sleep duration.

Recently, the contribution of both insufficient sleep duration and gut microbiome dysbiosis to hypertension (HTN) have been revealed, yet the profile of gut flora in hypertensive patients with insufficient sleep duration remains unknown. To examine this condition, the specific shifts in the fecal microbiome of 53 participants with or without HTN were investigated. The patients were divided into those who slept short (≤6 h) or optimal (6-9 h) duration per day. Comprehensive metagenomic sequencing analysis of fecal specimens was performed in healthy controls with sufficient sleep (s-CTR, n = 10), healthy controls with insufficient sleep (ins-CTR, n = 6), hypertensive patients with sufficient sleep (s-HTN, n = 25), and HTNs complicated by short sleep duration (ins-HTN, n = 12). We found that the α-diversity and ß-diversity were quite similar between s-HTN and ins-HTN. Similarities were also observed in the enterotype distribution between s-HTN and ins-HTN subjects. In addition, the enrichment of gut bacteria was evident, such as Fusobacterium mortiferum and Roseburia inulinivorans in ins-HTN subjects. Several functional modules that were distinct between s-HTN and ins-HTN subjects were identified, which were unique to hypertensive patients with insufficient sleep duration. Overall, the data demonstrated that the gut microbial features were largely maintained in hypertensive participants with insufficient sleep duration.

Cigarette smoking status alters dysbiotic gut microbes in hypertensive patients.

Smoking not only is one of the most important risk factors of hypertension (HTN), but also alters the composition of gut microbiota (GM) in previous studies. Although dysbiosis of GM has been implicated in HTN, how GM alters in patients with HTN under smoking status is still not clear. This study aimed to explore the difference in intestinal microflora among smokers with HTN (S-HTN), nonsmokers with HTN (NS-HTN), and smokers without HTN (S-CTR) and identify whether cigarette smoking led to disordered intestinal microbiota in patients with HTN. Metagenomic sequencing analysis of fecal specimens was conducted in nonsmokers without HTN (NS-CTR, n = 9), S-CTR (n = 9), NS-HTN (n = 18), and S-HTN (n = 23). Compared with S-CTR or NS-HTN, the GM in S-HTN was disordered, with lower microbial α-diversity and significant difference of ß-diversity on axes as compared to S-CTR at genus and species level. The microbial enterotype in S-HTN was inclined to Prevotella-dominant type. Dramatic changes in the intestinal genera and species composition were observed in S-HTN, including reduced enrichment of Phycisphaera and Clostridium asparagiforme. Moreover, the intestinal function altered in S-HTN. Therefore, the findings of the present study revealed GM disorders in S-HTN and clarified the role of smoking in impairing the intestinal microbiome in HTN. Tobacco control is particularly important for improving GM in patients with HTN, and might be beneficial in preventing future cardiovascular events.

Characteristics and variation of fecal bacterial communities and functions in isolated systolic and diastolic hypertensive patients.

BACKGROUND: Hypertension (HTN) is one of the major cardiovascular risk factors, which contributes to increasing target organ damages and cardiovascular morbidity and mortality worldwide. Isolated systolic HTN (ISH) and isolated diastolic HTN (IDH) are two important subtypes of HTN. Previous researches have demonstrated the alteration of fecal bacteria in HTN, but not down to these two sub-types. In order to identify whether the composition of bacterial taxa and functional modules shift in ISH and IDH, we performed a metagenomic sequencing analysis of fecal samples from 15 controls, 14 ISH, and 11 IDH. RESULTS: Compared with control and ISH, IDH patients showed decreased gene number, bacterial richness, and evenness, although the bacterial alterations did not reach statistical significance in the Shannon index. Also, at the genus level, the ß-diversity for intestinal flora in IDH was distinguishable from those with ISH. Furthermore, the taxonomic composition of ISH or IDH was different from that of healthy control at genus and species levels. Patients with IDH or ISH were confirmed to be enriched with Rothia mucilaginosa, along with reduced Clostridium sp. ASBs410. Lastly, the altered KEGG modules were significantly decreased in IDH compared with the control group, such as sodium transport system; while for ISH, functions relevant to biotin biosynthesis were decreased. CONCLUSIONS: Overall, our results showed the disordered fecal bacteria profiles in subjects with ISH and especially IDH, emphasizing the significance of early intervention for IDH.

Chimney Detection Based on Faster R-CNN and Spatial Analysis Methods in High Resolution Remote Sensing Images.

Spatially location and working status of pollution sources are very important pieces of information for environment protection. Waste gas produced by fossil fuel consumption in the industry is mainly discharged to the atmosphere through a chimney. Therefore, detecting the distribution of chimneys and their working status is of great significance to urban environment monitoring and environmental governance. In this paper, we use an open access dataset BUAA-FFPP60 and the faster regions with convolutional neural network (Faster R-CNN) algorithm to train the preliminarily detection model. Then, the trained model is used to detect the chimneys in three high-resolution remote sensing images of Google Maps, which is located in Tangshan city. The results show that a large number of false positive targets are detected. For working chimney detection, the recall rate is 77.27%, but the precision is only 40.47%. Therefore, two spatial analysis methods, the digital terrain model (DTM) filtering, and main direction test are introduced to remove the false chimneys. The DTM is generated by ZiYuan-3 satellite images and then registered to the high-resolution image. We set an elevation threshold to filter the false positive targets. After DTM filtering, we use principle component analysis (PCA) to calculate the main direction of each target image slice, and then use the main direction to remove false positive targets further. The results show that by using the combination of DTM filtering and main direction test, more than 95% false chimneys can be removed and, therefore, the detection precision is significantly increased.

Metagenomic data-mining reveals enrichment of trimethylamine-N-oxide synthesis in gut microbiome in atrial fibrillation patients.

BACKGROUND: The gut bacteria-derived metabolite trimethylamine-N-oxide (TMAO) has been discussed in various cardiometabolic diseases. However, evidence characterizing the microbial population responsible for TMAO accumulation in patients with atrial fibrillation (AF), an increasingly prevalent arrhythmia, is yet lacking. In order to understand the key gut microorganisms that produce TMAO in AF, trimethylamine (TMA)-synthesis enzymes and metabolic pathways, as well as the potential TMA-producers in gut microbiome were assessed based on metagenomic data-mining in a northern Chinese cohort consisting of 50 non-AF controls and 50 patients with different types of AF. RESULTS: Compared to the control subjects, AF patients showed a marked increase in the microbial genes underlying TMA formation in the gut, which included 12 potential TMA-synthesis functional orthologs and 1 module. The specific bacterial genes, including choline-TMA lyase, carnitine monooxygenase, glycine betaine reductase, and TMAO reductase, were elevated in the gut of AF patients. Furthermore, 16 genera were assigned and significantly correlated with TMA-enzymatic genes, where 9 genera were remarkably enriched in the gut communities of AF patients. Neither of these TMA-synthesis pathways nor the microbial players showed a significant discrepancy between different types of AF in the current cohort. These gut microbes might participate in the formation of TMA by activating the key TMA-synthesis enzymes and contributing to the functional pathways in AF patients. CONCLUSIONS: The present study provides an in-depth insight into the potential bacteria and metabolic pathways involved in TMA production in the gut of AF patients. These findings emphasize a key role of the gut bacteria in driving TMAO formation during AF pathogenesis, thereby indicating its therapeutic potential as an intervention strategy of AF by targeting TMA-synthesis pathways and dysbiotic gut microbiota.

Three new isoquinoline alkaloids from the whole plants of Thalictrum tenue with cytotoxic activities.

Three new isoquinoline alkaloids, including two aporphines (1 and 2) and one oxoaporphine (3), were isolated from the 90% EtOH extract of the whole plants of Thalictrum tenue Franch. The structures of the isolated compounds were established based on 1D and 2D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy, in addition to high resolution mass spectrometry, respectively. The isolated alkaloids were tested in vitro for cytotoxic activity against six esophageal carcinoma cell lines. Consequently, alkaloids 1-3 exhibited some cytotoxic activities against all the tested tumor cell lines with IC50 values less than 20 µM. [Formula: see text].

Methyl 5-[(1H-indol-3-yl)selanyl]-1H-benzoimidazol-2-ylcarbamate (M-24), a novel tubulin inhibitor, causes G2/M arrest and cell apoptosis by disrupting tubulin polymerization in human cervical and breast cancer cells.

Methyl 5-[(1H-indol-3-yl)selanyl]-1H-benzoimidazol-2-ylcarbamate (M-24) is a newly synthesized analogue of nocodazole by our group and has been found to be active for some cancer cells. However, its sensitivity to different cell lines and the underlying anticancer mechanism are still unclear. In this study, we proved that M-24 had strong time- and dose-dependent anti-proliferative effects on human cervical cancer HeLa cells and human breast carcinoma MCF-7 cells. We demonstrated that the growth inhibitory effects of M-24 in both cell lines were associated with microtubule depolymerization. Furthermore, M-24 treatment resulted in cell cycle arrest at the G2/M phase in a dose-dependent manner with subsequent apoptosis induction. Western blotting analysis revealed that up-regulation of cyclin B1 and cdc2 was related with G2/M arrest in both cell lines. In addition, M-24-induced HeLa cell apoptosis was mainly associated with mitochondria-dependent intrinsic pathway. However, M-24-induced MCF-7 cell apoptosis was associated with both mitochondrial and death receptor pathway. In conclusion, M-24 caused apoptosis through disrupting microtubule assembly and inducing cell cycle arrest in HeLa and MCF-7 cells. Therefore, the novel compound M-24 is a promising microtubule-destabilizing agent that has great potential for the therapy of various malignancies especially human cervical and breast cancers.

Synthesis and evaluation of benzimidazole carbamates bearing indole moieties for antiproliferative and antitubulin activities.

A series of novel benzimidazole carbamates bearing indole moieties with sulphur or selenium atoms connecting the aromatic rings were synthesised and evaluated for their antiproliferative activities against three human cancer cell lines (SGC-7901, A-549 and HT-1080) using an MTT assay. Compounds 10a, 10b, 7a, 7b and 7f showed significant activities against these cell lines. The most potent compound in this series, 10a, was selected to investigate its antitumour mechanism. In addition, molecular docking studies suggested that compound 10a interacts very closely with the nocodazole docking pose through hydrogen bonds at the colchicine binding site of tubulin.