Cancer vulnerabilities unveiled by genomic loss.

Due to genome instability, most cancers exhibit loss of regions containing tumor suppressor genes and collateral loss of other genes. To identify cancer-specific vulnerabilities that are the result of copy number losses, we performed integrated analyses of genome-wide copy number and RNAi profiles and identified 56 genes for which gene suppression specifically inhibited the proliferation of cells harboring partial copy number loss of that gene. These CYCLOPS (copy number alterations yielding cancer liabilities owing to partial loss) genes are enriched for spliceosome, proteasome, and ribosome components. One CYCLOPS gene, PSMC2, encodes an essential member of the 19S proteasome. Normal cells express excess PSMC2, which resides in a complex with PSMC1, PSMD2, and PSMD5 and acts as a reservoir protecting cells from PSMC2 suppression. Cells harboring partial PSMC2 copy number loss lack this complex and die after PSMC2 suppression. These observations define a distinct class of cancer-specific liabilities resulting from genome instability.

Metabolite Profiles of Plant-Based Diets and Cardiometabolic Risk in the Mediators of Atherosclerosis in South Asians Living in America Study.

BACKGROUND: Healthy plant-based diets have been associated with lower risk of type 2 diabetes (T2D). Metabolomics can be leveraged to identify potential pathways through which diet influences disease risk. OBJECTIVES: This study aimed to identify profiles of serum metabolites reflective of plant-based diets of varying quality and examine associations with cardiometabolic risk and T2D. METHODS: We included data from 687 participants of the Mediators of Atherosclerosis in South Asians Living in America (MASALA) cohort. An overall plant-based diet index (PDI), healthy PDI (hPDI), and unhealthy PDI (uPDI) were estimated from food frequency questionnaires. Serum metabolites were assayed using ultraperformance liquid chromatography mass spectrometry. Elastic net regression was used to identify sets of metabolites predictive of each diet index, and metabolite profile scores were calculated as the weighted sum of the selected metabolites. Cross-sectional associations between metabolite profile scores and cardiometabolic measures and prospective associations with incident T2D were evaluated with multivariable-adjusted linear and logistic regressions. RESULTS: Metabolite profiles for PDI, hPDI, and uPDI consisted of n = 51, 55, and 45 metabolites, respectively. Metabolites strongly positively correlated with diet indices included phosphatidylcholine (16:0/18:3) for PDI, phosphatidylethanolamine (20:1/20:4) and pantothenate for hPDI, and lysophosphatidylglycerol (18:2/0:0), proline, and lauric acid for uPDI. Higher metabolite profile scores for PDI and hPDI were associated with lower glycemia and lipids measures, whereas a higher uPDI metabolite score was associated with higher triglycerides and lower low density lipoprotein cholesterol and high density lipoprotein cholesterol. A higher metabolite score for hPDI was additionally associated with lower adiposity measures, higher liver fat attenuation, higher adiponectin, lower odds of overweight (odds ratio [OR]: 0.64; 95% confidence interval [CI]: 0.51, 0.81) and obesity (OR: 0.59; 95% CI: 0.48, 0.74), and lower odds of incident T2D (OR: 0.66; 95% CI: 0.45, 0.97). CONCLUSIONS: Metabolite profiles of different plant-based diets were identified. Metabolite profiles of overall and healthy plant-based diets were associated with favorable cardiometabolic risk profiles.

Comparison of cardiac function and structure after left atrial appendage occlusion without versus with ablation in patients with non-valvular atrial fibrillation: a retrospective study.

The Aim of this study was to investigate the long-term impact of left atrial appendage occlusion (LAAO) on cardiac function and structure in patients with non-valvular atrial fibrillation (NVAF). 157 patients with NVAF who underwent LAAO or combined with ablation were included and divided into simple LAAO group or combined group. Long term impact of LAAO on cardiac function and structure were evaluated. Results showed that the procedures were performed successfully with 6.4% complications. During follow-up, there was a significant decrease of left atrial anteroposterior diameter (LAAD) at 6 months and a significant increase of left ventricular end-diastolic dimension (LVEDD) at 12 months after LAAO. A significant decrease in plasma N-terminal pro-brain natriuretic peptide (NT-proBNP) was noted at 3 months, 6 months and 12 months after procedure. There was a significant decrease of LAAD, LVEDD, left ventricular end-systolic dimension (LVESD) and NT-proBNP levels in combined group at 3 months, 6 months and 12 months post- procedure, while an increase of left ventricular ejection fraction (LVEF). Meanwhile, no significant change of LAAD, LVEDD, LVESD, NT-proBNP and LVEF was seen in simple LAAO group at 3 months follow-up, but a decrease of NT-proBNP during 6 months and 12 months follow-up. Compared with simple LAAO group, combined group was associated with a significant increase of residual flow. In conclusion, LAAO has no significant effect on cardiac structure and function but can significantly reduce NT-proBNP. The improvement of cardiac structure and function in combined therapy comes from the result of ablation, not LAAO.

The research hotspots and trends of volatile organic compound emissions from anthropogenic and natural sources: A systematic quantitative review.

Volatile organic compound (VOC) emissions have attracted wide attention due to their impacts on atmospheric quality and public health. However, most studies reviewed certain aspects of natural VOCs (NVOCs) or anthropogenic VOCs (AVOCs) rather than comprehensively quantifying the hotspots and evolution trends of AVOCs and NVOCs. We combined the bibliometric method with the evolution tree and Markov chain to identify research focus and uncover the trends in VOC emission sources. This study found that research mainly focused on VOC emission characteristics, effects on air quality and health, and VOC emissions under climate change. More studies concerned on AVOCs than on NVOCs, and AVOC emissions have shifted with a decreasing proportion of transport emissions and an increasing share of solvent utilization in countries with high emissions and publications (China and the USA). Research on AVOCs is imperative to develop efficient and economical abatement techniques specific to solvent sources or BTEX species to mitigate the detrimental effects. Research on NVOCs originating from human sources risen due to their application in medicine, while studies on sources sensitive to climate change grew slowly, including plants, biomass burning, microbes, soil and oceans. Research on the long-term responses of NVOCs derived from various sources to climate warming is warranted to explore the evolution of emissions and the feedback on global climate. It is worthwhile to establish an emission inventory with all kinds of sources, accurate estimation, high spatial and temporal resolution to capture the emission trends in the synergy of industrialization and climate change as well as to simulate the effects on air quality. We review VOC emissions from both anthropogenic and natural sources under climate change and their effects on atmospheric quality and health to point out the research directions for the comprehensive control of global VOCs and mitigation of O3 pollution.

Construction of atrial fibrillation-related circRNA/lncRNA-miRNA-mRNA regulatory network and analysis of potential biomarkers.

BACKGROUND: The specific pathogenesis of atrial fibrillation (AF) remains unclear. In this study, we examined the expression of differential messenger RNAs (mRNAs), circular RNAs (circRNAs), and long-stranded noncoding RNAs (lncRNAs) from human peripheral blood mononuclear cells to initially construct a circRNA/lncRNA-miRNA-mRNA ceRNA regulatory network to explore the pathogenesis of AF and to screen for potential biomarkers. METHODS: A total of four pairs of AF cases and healthy subjects were selected to detect differentially expressed mRNAs, circRNAs, and lncRNAs in peripheral blood mononuclear cells by microarray analysis. And 20 pairs of peripheral blood from AF patients and healthy subjects were selected for validation of mRNA, circRNA, and lncRNA by quantitative real-time PCR (qRT-PCR).The relevant ceRNA networks were constructed by GO and KEGG and correlation analysis. RESULTS: The results showed that compared with healthy subjects, there were 813 differentially expressed mRNAs (DEmRNAs) in peripheral blood monocytes of AF, including 445 upregulated genes and 368 downregulated genes, 120 differentially expressed circRNAs (DEcircRNAs), including 65 upregulated and 55 downregulated, 912 differentially expressed lncRNAs (DElncRNAs), including 531 upregulated and 381 downregulated lncRNAs. GO and KEGG analysis of DERNA revealed the biological processes and pathways involved in AF. Based on microarray data and predicted miRNAs, a ceRNA network containing 34 mRNAs, 212 circRNAs, 108 lncRNAs, and 38 miRNAs was constructed. CONCLUSION: We revealed a novel ceRNA network in AF and showed that downregulated XIST, circRNA_2773, and CADM1 were negatively correlated with miR-486-5p expression and had a potential targeting relationship with miR-486-5p.

Using the Perimeter-Derived Diameter and Ellipticity Index of the Left Atrial Appendage Landing Zone to Predict Watchman Occluder Size.

Objective: The Watchman 2.5 occluder device is a useful device to treat atrial fibrillation (AF), and predicting the size of the Watchman 2.5 occluder device is important to the therapeutic efficacy. To use cardiac computed tomography angiography (CCTA) to predict the size of a Watchman 2.5 occluder device is a potential approach. Methods: The CCTA was used to individually plan the left atrial appendage (LAA) landing zone and measure the longest and shortest diameters, in addition to the perimeter. The average diameter, the perimeter-derived diameter (PDD), and the ellipticity index (EI) are then calculated from the above values. The longest diameter, the shortest diameter, the average diameter, and PDD of the landing zone were used to predict the occluder size. The size of the occluder was predicted using the longest diameter, the shortest diameter, the average diameter, and the PDD, which is then compared to the actual size. Results: There were differences between the predicted and actual values of the four groups, with the smallest variability in PDD (P = .007). There was a strong positive correlation between the four groups and the actual occluder size, with the strongest PDD correlation (r = 0.941, P < .001). The prediction accuracy ranged from 44.1% to 90.1% for different methods, with PDD having the highest prediction accuracy. The ROC curve of EI was predicted and plotted using the longest diameter method recommended in the Watchman's instructions, and the area under the curve was 0.905 (95%Confidence Interval (CI) 0.847-0.963), with a cut-off value of 1.198, a sensitivity of 88.9% and a specificity of 82.7%. LAAs with an EI<1.198 had similar accuracy in predicting occluder size, regardless of whether the longest diameter (93.94%) or PDD (87.88%) (P = .344) method was used. However, the kappa test showed poor agreement between the two methods (Kappa = 0.093). When EI ≥ 1.198 (n = 45), the accuracy of PDD in predicting occluder size was 93.33%, which is significantly higher than predictions of the longest diameter (28.9%) (P < .001). Conclusions: The longest diameter and the PDD methods predicted occluder size with a high degree of accuracy when the LAAs EI < 1.198; the PDD method is suggested to be a preferred method to treatAF.

Synthesis of Cyclopropenes and Fluorinated Cyclopropanes via Michael Initiated Ring Closure of Alkyl Triflones.

A facile synthesis of cyclopropenes and fluorinated cyclopropanes from readily available alkyl triflones was developed. The reaction, regardless of electronic effect, gave products in good to excellent yields and moderate diastereoselectivity. The mechanism may involve tandem Michael addition of triflones/intramolecular nucleophilic cyclization (elimination of -SO2 CF3 )/elimination of fluoride.

Influencing Factors of Recurrence of Nonvalvular Atrial Fibrillation after Radiofrequency Catheter Ablation and Construction of Clinical Nomogram Prediction Model.

Purpose: This study sought to investigate the predictive factors for atrial fibrillation (AF) recurrence in patients after radiofrequency ablation (RFCA) and construct a nomogram prediction model for providing precious information of ablative strategies. Methods: A total of 221 patients with AF who underwent RFCA were enrolled. Univariate and multivariate Cox regression were used to screen the predictors of recurrence. The receiver operating characteristic (ROC) curve and the Kaplan-Meier (K-M) curve were drawn to analyze the value of predictors. The nomogram model was further constructed to predict the recurrence of AF in patients after RFCA. Results: There were 59 cases of AF recurrence after RFCA. Monocyte count/high-density lipoprotein cholesterol (MHR), AF course (COURSE), coronary heart disease (CHD), and AF type (TYPE) were the independent risk factors for predicting AF recurrence after RFCA. Accordingly, a nomogram prediction model based on MHR, COURSE, CHD, and TYPE was constructed with a C-index of 0.818 (95% CI: 0.681∼0.954), while the C-index of verification was 0.802 (95% CI: 0.658∼0.946). Conclusions: Preoperative MHR, COURSE, CHD, and TYPE were independent risk factors for predicting recurrence of AF after RFCA. The nomogram model based on MHR, COURSE, CHD, and TYPE can be used to predict the recurrence of AF after RFCA accurately and individually.

Spatiotemporal characteristics of NO2, PM2.5 and O3 in a coastal region of southeastern China and their removal by green spaces.

Understanding the spatio-temporal characteristics of air pollutants is essential to improving air quality. One aspect is the question of whether green spaces can reduce air pollutant concentrations. However, previous studies on this issue have reported mixed results. This study analyzed the spatio-temporal characteristics of NO2, PM2.5 and O3 in Fujian Province, Southeast China in 2015. In order to reduce uncertainties in the conclusions drawn, the effects landscape metrics describing green spaces have on air pollutants have been analyzed using Pearson correlation analysis at six different spatial scales for the four seasons, considering the influence of meteorological conditions. The results show that PM2.5 and O3 are major pollutants whose relative importance varies with the seasons. Significant differences in pollutant concentrations were observed in suburban and urban areas, highlighting the importance of ensuring a reasonable spatial distribution of monitoring stations. Moreover, significant correlations between air pollutants and green space landscape patterns during the four seasons were found, revealing increased air pollutant concentrations with increasing landscape fragmentation and reduced connectivity and aggregation. This probably indicates that interconnected green spaces have the potential to improve air quality. Utilizing green space function regulations can alleviate NO2 and PM2.5 pollution effectively, but it is still difficult to reduce O3 concentrations because green spaces are likely to not only serve as sinks for O3, but can also promote O3 formation.

On-Surface Synthesis of [3]Radialenes via [1+1+1] Cycloaddition.

[3]Radialenes are the smallest carbocyclic structures with unusual topologies and cross-conjugated π-electronic structures. Here, we report a novel [1+1+1] cycloaddition reaction for the synthesis of aza[3]radialenes on the Ag(111) surface, where the steric hindrance of the chlorine substituents guides the selective and orientational assembling of the isocyanide precursors. By combining scanning tunneling microscopy, non-contact atomic force microscopy, and time-of-flight secondary ion mass spectrometry, we determined the atomic structure of the produced aza[3]radialenes. Furthermore, two reaction pathways including synergistic and stepwise are proposed based on density functional theory calculations, which reveal the role of the chlorine substituents in the activation of the isocyano groups via electrostatic interaction.

Ladder Phenylenes Synthesized on Au(111) Surface via Selective [2+2] Cycloaddition.

Ladder phenylenes (LPs) composed of alternating fused benzene and cyclobutadiene rings have been synthesized in solution with a maximum length no longer than five units. Longer polymeric LPs have not been obtained so far because of their poor stability and insolubility. Here, we report the synthesis of linear LP chains on the Au(111) surface via dehalogenative [2+2] cycloaddition, in which the steric hindrance of the methyl groups in the 1,2,4,5-tetrabromo-3,6-dimethylbenzene precursor improves the chemoselectivity as well as the orientation orderliness. By combining scanning tunneling microscopy and noncontact atomic force microscopy, we determined the atomic structure and the electronic properties of the LP chains on the metallic substrate and NaCl/Au(111). The tunneling spectroscopy measurements revealed the charged state of chains on the NaCl layer, and this finding is supported by density functional theory calculations, which predict an indirect bandgap and antiferromagnetism in the polymeric LP chains.

Refined water security assessment for sustainable water management: A case study of 15 key cities in the Yangtze River Delta, China.

Water security represents ecological security and a policy priority for sustainable development; however, un-gridded assessment results cannot be used to support urban environmental management decisions. This study proposes a systematic framework to obtain a gridded regional water security assessment, which reflects the regional natural resource, based on the index system derived from the Pressure-State-Response (PSR) model and the Integrated Valuation of Ecosystem Services and Tradeoffs (InVEST) model. The results were applied to sustainable water management. Using 15 key cities in the Yangtze River Delta (YRD) region as a case study to apply the methodology, we found that the comprehensive water security was relatively high and high-value areas were widely distributed, accounting for about two-thirds of the study area. Low-value areas were mainly distributed in central and eastern regions, such as Shanghai, Suzhou, and Nanjing. There was evidence of a water resource shortage during the twelve-month period studied, particularly in August. The proportions of comprehensive water security in each administrative unit and the differences between simulated and target water quality could be used in the spatial planning and the exploration of payments for ecosystem services (PES) mechanism in county-level or smaller administrative units. Despite the premise requirement and the grid resolution problems of the InVEST model, it can be concluded that our assessment method proves capable of matching spatial and temporal differences in water supply and demand at a fine scale, and results can be used to supply useful information for urban management decision making.

Fluoride absorption, transportation and tolerance mechanism in Camellia sinensis, and its bioavailability and health risk assessment: a systematic review.

Tea is the one of the most popular non-alcoholic caffeinated beverages in the world. Tea is produced from the tea plant (Camellia sinensis (L.) O. Kuntze), which is known to accumulate fluoride. This article systematically analyzes the literature concerning fluoride absorption, transportation and fluoride tolerance mechanisms in tea plants. Fluoride bioavailability and exposure levels in tea infusions are also reviewed. The circulation of fluoride within the tea plantation ecosystems is in a positive equilibrium, with greater amounts of fluoride introduced to tea orchards than removed. Water extractable fluoride and magnesium chloride (MgCl2 ) extractable fluoride in plantation soil are the main sources of absorption by tea plant root via active trans-membrane transport and anion channels. Most fluoride is readily transported through the xylem as F- /F-Al complexes to leaf cell walls and vacuole. The findings indicate that tea plants employ cell wall accumulation, vacuole compartmentalization, and F-Al complexes to co-detoxify fluoride and aluminum, a possible tolerance mechanism through which tea tolerates higher levels of fluoride than most plants. Furthermore, dietary and endogenous factors influence fluoride bioavailability and should be considered when exposure levels of fluoride in commercially available dried tea leaves are interpreted. The relevant current challenges and future perspectives are also discussed. © 2020 Society of Chemical Industry.

An attention-based multi-task model for named entity recognition and intent analysis of Chinese online medical questions.

In this paper, we propose an attention-based multi-task neural network model for text classification and sequence tagging and then apply it to the named entity recognition and the intent analysis of Chinese online medical questions. We found that the use of both attention and multi-task learning improved the performance of these tasks. Our method achieved superior performance in named entity recognition and intent analysis compared with other baseline methods; the method is a light-weight solution that is suitable for deployment on small servers. Furthermore, we took advantage of the model's capabilities for these two tasks and built a simple question-answering system for cardiovascular issues. Users and service providers can monitor the logic of the answers generated by this system.

Selective Synthesis of 3-(9 H-Carbazol-2-yl)indolin-2-ones and Spiro[tetrahydrocarbazole-3,3'-oxindoles] via a HOTf Catalyzed Three-Component Reaction.

A HOTf catalyzed three-component reaction of indoles, acetophenones, and ( E)-3-phenacylideneoxindolinones resulted in the unexpected polysubstituted 3-(9 H-carbazol-2-yl)indolin-2-ones in good yields. A similar reaction with various cyclic ketones afforded the corresponding carbocyclic fused 3-(9 H-carbazol-2-yl)indolin-2-ones. On the other hand, ( E)-3-arylideneoxindolinones in the three-component reaction gave the expected spiro[tetrahydrocarbazole-3,3'-oxindoles] through a domino alkenylation/Diels-Alder reaction. The unusual different reactivity of ( E)-3-phenacylideneoxindolinones and ( E)-3-arylideneoxindolinones in the three-component reactions was believed to involve the different reaction paths caused by the existence of the carbonyl group.

Synthesis of functionalized dispiro[indoline-3,1[Formula: see text]-cyclopentane-3[Formula: see text],3[Formula: see text]-indolines] via cyclodimerization of 3-phenacylideneoxindolines with benzoylhydrazides and arylhydrazines.

The triethylamine-promoted domino cyclodimerization reaction of 3-phenacylideneoxindolines with benzohydrazides in acetonitrile afforded densely substituted dispiro[indoline-3,1[Formula: see text]-cyclopentane-3[Formula: see text],3[Formula: see text]-indolines] in good yields and with high diastereoselectivity. The similar domino reaction of 3-phenacylideneoxindoles with arylhydrazines also gave corresponding dispiro[indoline-3,1[Formula: see text]-cyclopentane-3[Formula: see text],3[Formula: see text]-indolines] with hydrazinyl or arylazo groups according to the structures of arylhydrazines.

Low Serum Adropin Levels are Associated with Coronary Slow Flow Phenomenon.

BACKGROUND: Adropin is a peptide hormone expressed in coronary artery endothelial cells, which plays a potential endothelial protective role. We sought to assess whether serum adropin levels are correlated with the coronary slow flow phenomenon (CSFP). METHODS: We enrolled 82 patients with angiographically confirmed CSFP and 184 age-matched controls. Serum adropin levels were measured by enzyme-linked immunosorbent assay (ELISA), and coronary flow rate was assessed using thrombolysis in myocardial infarction (TIMI) frame count (TFC). CSFP was defined as a corrected TIMI-TFC greater than two standard deviations from the normal range. RESULTS: Serum adropin levels were significantly lower in the CSFP patients (n = 82) than in the controls (n = 184) (4.03 ± 1.99 vs. 4.86 ± 1.88 ng/ml, p = 0.001). Multivariate logistic regression analysis revealed that serum adropin was the only independent negative predictor of CSFP (odds ratio 0.758, 95% confidence interval 0.647-0.888, p = 0.001). Serum adropin levels were independently and negatively correlated with mean TFC (r = -0.387, p < 0.001). CONCLUSIONS: We demonstrated that decreased serum adropin levels were independently associated with the presence and severity of angiographically proven CSFP. These findings suggest that serum adropin may be a potential biomarker to provide valuable information regarding the prediction of CSFP.

TfOH-Catalyzed One-Pot Domino Reaction for Diastereoselective Synthesis of Polysubstituted Tetrahydrospiro[carbazole-1,3'-indoline]s.

TfOH-catalyzed one-pot sequential reaction of indoles, acetophenones (cyclic ketones), and various 3-methyleneoxindolines in toluene afforded polysubstituted tetrahydrospiro[carbazole-1,3'-indoline]s in satisfactory yields. 1H NMR spectra and single-crystal structures indicated that the obtained tetrahydrospiro[carbazole-1,3'-indoline]s existing in an unusual trans-configuration. The reaction mechanism was believed to proceed with domino acid-catalyzed 3-alkenylation of indoles with acetophenones, Diels-Alder reaction of 3-alkyenylindoles with 3-methyleneoxindolines, and an acid-catalyzed diastereoisomerization process.

Selective construction of polycyclic spirooxindoles via a Cu(OTf)2/HOTf-catalyzed domino reaction of o-arylalkynylacetophenones and 3-phenacylideneoxindoles.

Under the combined catalysis of Cu(OTf)2/HOTf, the domino annulation reaction of o-arylalkynyl acetophenones with 3-phenacylideneoxindoles in refluxing acetonitrile selectively afforded functionalized spiro[indoline-3,7'-tetrapheno[7,6-bc]furans] and spiro[indeno[1,2-b]naphtho[2,1-d]furan-7,3'-indolines] depending on the electronic effect of the substituents on both substrates.