Stack growth of wafer-scale van der Waals superconductor heterostructures.

Two-dimensional (2D) van der Waals (vdW) heterostructures have attracted considerable attention in recent years1-5. The most widely used method of fabrication is to stack mechanically exfoliated micrometre-sized flakes6-18, but this process is not scalable for practical applications. Despite thousands of 2D materials being created, using various stacking combinations1-3,19-21, hardly any large 2D superconductors can be stacked intact into vdW heterostructures, greatly restricting the applications for such devices. Here we report a high-to-low temperature strategy for controllably growing stacks of multiple-layered vdW superconductor heterostructure (vdWSH) films at a wafer scale. The number of layers of 2D superconductors in the vdWSHs can be precisely controlled, and we have successfully grown 27 double-block, 15 triple-block, 5 four-block and 3 five-block vdWSH films (where one block represents one 2D material). Morphological, spectroscopic and atomic-scale structural analyses reveal the presence of parallel, clean and atomically sharp vdW interfaces on a large scale, with very little contamination between neighbouring layers. The intact vdW interfaces allow us to achieve proximity-induced superconductivity and superconducting Josephson junctions on a centimetre scale. Our process for making multiple-layered vdWSHs can easily be generalized to other situations involving 2D materials, potentially accelerating the design of next-generation functional devices and applications22-24.

A smartwatch sphygmomanometer-based model for predicting short-term new-onset hypertension in individuals with high-normal blood pressure: a cohort study.

OBJECTIVES: The objective was to utilize a smartwatch sphygmomanometer to predict new-onset hypertension within a short-term follow-up among individuals with high-normal blood pressure (HNBP). METHODS: This study consisted of 3180 participants in the training set and 1000 participants in the validation set. Participants underwent both ambulatory blood pressure monitoring (ABPM) and home blood pressure monitoring (HBPM) using a smartwatch sphygmomanometer. Multivariable Cox regressions were used to analyze cumulative events. A nomogram was constructed to predict new-onset hypertension. Discrimination and calibration were assessed using the C-index and calibration curve, respectively. RESULTS: Among the 3180 individuals with HNBP in the training set, 693 (21.8%) developed new-onset hypertension within a 6-month period. The nomogram for predicting new-onset hypertension had a C-index of 0.854 (95% CI, 0.843-0.867). The calibration curve demonstrated good agreement between the nomogram's predicted probabilities and actual observations for short-term new-onset hypertension. In the validate dataset, during the 6-month follow-up, the nomogram had a good C-index of 0.917 (95% CI, 0.904-0.930) and a good calibration curve. As the score increased, the risk of new-onset hypertension significantly increased, with an HR of 8.415 (95% CI: 5.153-13.744, p = .000) for the middle-score vs. low-score groups and 86.824 (95% CI: 55.071-136.885, p = .000) for the high-score vs. low-score group. CONCLUSIONS: This study provides evidence for the use of smartwatch sphygmomanometer to monitor blood pressure in individuals at high risk of developing new-onset hypertension in the near future. TRIAL REGISTRATION: ChiCTR2200057354.

BioCaster in 2021: automatic disease outbreaks detection from global news media.

SUMMARY: BioCaster was launched in 2008 to provide an ontology-based text mining system for early disease detection from open news sources. Following a 6-year break, we have re-launched the system in 2021. Our goal is to systematically upgrade the methodology using state-of-the-art neural network language models, whilst retaining the original benefits that the system provided in terms of logical reasoning and automated early detection of infectious disease outbreaks. Here, we present recent extensions such as neural machine translation in 10 languages, neural classification of disease outbreak reports and a new cloud-based visualization dashboard. Furthermore, we discuss our vision for further improvements, including combining risk assessment with event semantics and assessing the risk of outbreaks with multi-granularity. We hope that these efforts will benefit the global public health community. AVAILABILITY AND IMPLEMENTATION: BioCaster web-portal is freely accessible at http://biocaster.org.

Elevated levels of body mass index and waist circumference, but not high variability, are associated with an increased risk of atrial fibrillation.

BACKGROUND: Although obesity has been associated with risk of atrial fibrillation (AF), the associations of variability of obesity measures with AF risk are uncertain, and longitudinal studies among Chinese population are still lacking. We aimed to evaluate the impacts of obesity and variability of body mass index (BMI) and waist circumference (WC) on the risk of atrial fibrillation (AF) in a large Chinese cohort study. METHODS: A total of 44,135 participants of the Kailuan Study who were free of cancer and cardiovascular disease and underwent three consecutive surveys from 2006 to 2010 were followed for incident AF until 2020. Average BMI and WC over time and variability were calculated. Cox proportional hazards regression models were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of obesity and variability in BMI and WC with AF risk. RESULTS: During a mean follow-up of 9.68 years, there were 410 cases of incident AF. In multivariable-adjusted models, compared with normal BMI/WC, individuals with general obesity and abdominal obesity had increased risk of AF, with corresponding HRs of 1.73 (95% CI: 1.31-2.30) and 1.38 (95% CI: 1.11-1.60), respectively. The short-term elevation in AF risk persisted for the obese even after adjustment for updated biologic intermediaries and weight. Variability in BMI and WC were not associated with the risk of AF. The restricted cubic spline models indicated significant linear relationships between levels of WC and BMI and risk of AF. CONCLUSIONS: Elevated levels of BMI and WC were associated with an increased risk of AF, whereas variability in BMI and WC were not. Therefore, achieving optimal levels of BMI and WC could be valuable in AF prevention.

Controllable growth of wafer-scale monolayer transition metal dichalcogenides ternary alloys with tunable band gap.

The tuning of band gap is very important for the application of two-dimensional (2D) materials in optoelectronic devices. Alloying of 2D transition metal dichalcogenides (TMDCs) is an important way to tune the wide band gap. In this study, we report a multi-step vapor deposition method to grow monolayer TMDC ternary alloy films with wafer scale, including Mo1-xWxS2, Mo1-xWxSe2and MoS2xSe2(1-x), which are accurately controllable in the elemental proportion (xis from 0 to 1). The band gap of the three 2D ternary alloy materials are continuously tuned for the whole range of metal and chalcogen compositions. The metal compositions are controlled by the as-deposited thickness. Raman, photoluminescence, elemental maps and TEM show the high spatial homogeneity in the compositions and optical properties across the whole wafer. The band gap can be continuously tuned from 1.86 to 1.99 eV for Mo1-xWxS2, 1.56 to 1.65 eV for Mo1-xWxSe2, 1.56 to 1.86 eV for MoS2xSe2(1-x). Electrical transport measurements indicate that Mo1-xWxS2and MoS2xSe2(1-x)monolayers shown-type semiconductor behaviors, and the carrier types of Mo1-xWxSe2can be tuned asn-type, bipolar andp-type. Moreover, this control process can be easily generalized to other 2D alloy films, even to quaternary or multi-element alloy materials. Our study presents a promising route for the preparation of large-scale homogeneous monolayer TMDC alloys and the application for future functional devices.

Atmospheric Autoxidation of Organophosphate Esters.

Organophosphate esters (OPEs), widely used as flame retardants and plasticizers, have frequently been identified in the atmosphere. However, their atmospheric fate and toxicity associated with atmospheric transformations are unclear. Here, we performed quantum chemical calculations and computational toxicology to investigate the reaction mechanism of peroxy radicals of OPEs (OPEs-RO2•), key intermediates in determining the atmospheric chemistry of OPEs, and the toxicity of the reaction products. TMP-RO2• (R1) and TCPP-RO2• (R2) derived from trimethyl phosphate and tris(2-chloroisopropyl) phosphate, respectively, are selected as model systems. The results indicate that R1 and R2 can follow an H-shift-driven autoxidation mechanism under low NO concentration ([NO]) conditions, clarifying that RO2• from esters can follow an autoxidation mechanism. The unexpected autoxidation mechanism can be attributed to the distinct role of the ─(O)3P(═O) phosphate-ester group in facilitating the H-shift of OPEs-RO2• from commonly encountered ─OC(═O)─ and ─ONO2 ester groups in the atmosphere. Under high [NO] conditions, NO can mediate the autoxidation mechanism to form organonitrates and alkoxy radical-related products. The products from the autoxidation mechanism have low volatility and aquatic toxicity compared to their corresponding parent compounds. The proposed autoxidation mechanism advances our current understanding of the atmospheric RO2• chemistry and the environmental risk of OPEs.

Formation of Low-Volatile Products and Unexpected High Formaldehyde Yield from the Atmospheric Oxidation of Methylsiloxanes.

With stricter regulation of atmospheric volatile organic compounds (VOCs) originating from fossil fuel-based vehicles and industries, the use of volatile chemical products (VCPs) and the transformation mechanism of VCPs have become increasingly important to quantify air quality. Volatile methylsiloxanes (VMS) are an important class of VCPs and high-production chemicals. Using quantum chemical calculations and kinetics modeling, we investigated the reaction mechanism of peroxy radicals of VMS, which are key intermediates in determining the atmospheric chemistry of VMS. L2-RSiCH2O2• and D3-RSiCH2O2• derived from hexamethyldisiloxane and hexamethylcyclotrisiloxane, respectively, were selected as representative model systems. The results indicated that L2-RSiCH2O2• and D3-RSiCH2O2• follow a novel Si-C-O rearrangement-driven autoxidation mechanism, leading to the formation of low volatile silanols and high yield of formaldehyde at low NO/HO2• conditions. At high NO/HO2• conditions, L2-RSiCH2O2• and D3-RSiCH2O2• react with NO/HO2• to form organic nitrate, hydroperoxide, and active alkoxy radicals. The alkoxy radicals further follow a Si-C-O rearrangement step to finally form formate esters. The novel Si-C-O rearrangement mechanism of both peroxy and alkoxy radicals are supported by available experimental studies on the oxidation of VMS. Notably, the high yield of formaldehyde is estimated to significantly contribute to formaldehyde pollution in the indoor environment, especially during indoor cleaning.

A novel methodology for rat aortic pulse wave velocity assessment by Doppler ultrasound: validation against invasive measurements.

There is still lack of a simple, accurate, and noninvasive method for rat aortic pulse wave velocity (PWV) measurement, especially the transit distance cannot be accurately measured. Thus, we aimed to derive an equation for aortic transit distance as a function of the nose-to-rump length (L) and to test the hypothesis that aortic PWV measured by new equation combined with Doppler ultrasound (the "equation method") may have stronger correlation with invasive measurements than traditional "body surface method." Two-hundred male Sprague-Dawley (SD) rats (age ranged 5-24 wk) were included in protocol 1, and the aortic transit distances were measured postmortem. In protocol 2, heart-femoral PWV and carotid-femoral PWV were measured by equation method (hfPWVE, cfPWVE) and also by traditional body surface method (hfPWVS, cfPWVS) in another 30 young and 28 old rats. These measurements were then validated against invasively measured hfPWVI and cfPWVI from the same animal. Protocol 1 showed that the heart-femoral transit distance could be calculated by 0.6086 × L - 1.6523, and the carotid-femoral transit distance by 0.4614 × L + 1.8335. In protocol 2, in young rats, the Pearson r between hfPWVE, cfPWVE, hfPWVS, and cfPWVS and their corresponding invasive measurement were 0.8962, 0.8509, 0.8387, and 0.7828, respectively (all P < 0.0001). In the old group, the results were 0.8718, 0.7999, 0.8330, and 0.7112, respectively (all P < 0.0001). The hfPWVE and cfPWVE showed better agreement with hfPWVI and cfPWVI and lower intra- and interobserver variability compared with hfPWVS and cfPWVS in both groups. These findings demonstrate that this novel methodology provides a simple and reliable method for rat noninvasive aortic PWV measurement.NEW & NOTEWORTHY First, when measuring aortic PWV in SD rat models, the heart-femoral transit distance can be estimated by 0.6086 × L - 1.6523, and the carotid-femoral distance transit distance can be estimated by 0.4614 × L + 1.8335, where L (in mm) is nose-to-rump length. Second, this novel methodology for aortic PWV measurement was validated with a closer correlation with the invasive measurements than traditional approach in young and old rats. Third, this study provides a simple and reliable method for rat noninvasive aortic PWV measurement.

NRT1.1B improves selenium concentrations in rice grains by facilitating selenomethinone translocation.

Selenium (Se) is an essential trace element for humans and other animals, yet approximately one billion people worldwide suffer from Se deficiency. Rice is a staple food for over half of the world's population that is a major dietary source of Se. In paddy soils, rice roots mainly take up selenite. Se speciation analysis indicated that most of the selenite absorbed by rice is predominantly transformed into selenomethinone (SeMet) and retained in roots. However, the mechanism by which SeMet is transported in plants remains largely unknown. In this study, SeMet uptake was found to be an energy-dependent symport process involving H+ transport, with neutral amino acids strongly inhibiting SeMet uptake. We further revealed that NRT1.1B, a member of rice peptide transporter (PTR) family which plays an important role in nitrate uptake and transport in rice, displays SeMet transport activity in yeast and Xenopus oocyte. The uptake rate of SeMet in the roots and its accumulation rate in the shoots of nrt1.1b mutant were significantly repressed. Conversely, the overexpression of NRT1.1B in rice significantly promoted SeMet translocation from roots to shoots, resulting in increased Se concentrations in shoots and rice grains. With vascular-specific expression of NRT1.1B, the grain Se concentration was 1.83-fold higher than that of wild type. These results strongly demonstrate that NRT1.1B holds great potential for the improvement of Se concentrations in grains by facilitating SeMet translocation, and the findings provide novel insight into breeding of Se-enriched rice varieties.

Stiffening of aorta is more preferentially associated with rheumatoid arthritis than peripheral arteries.

The objective of this study is to investigate the relative impact of rheumatoid arthritis (RA) and other factors on arterial stiffness of different regions assessed by regional pulse wave velocity (PWV). Seventy-two patients with RA and 55 strictly matched healthy controls were included. Doppler ultrasound was used to measure the PWV of heart-carotid (hcPWV), heart-femoral (hfPWV), brachial-radial (brPWV), femoral-ankle (faPWV) and carotid-femoral segments (cfPWV) in all subjects. The reproducibility of regional PWV measurement was evaluated in 30 random RA patients. In RA patients, the hfPWV and cfPWV were significantly higher than that in controls (P = 0.0006, P = 0.0001, respectively), and the hcPWV, brPWV and faPWV only showed an increase trend without significance. The mean increase magnitude of hfPWV (17.5%) and cfPWV (18.5%) were greater than brPWV (7.2%) and faPWV (1.7%) in RA patients. The association between RA and both hfPWV, cfPWV remained significant after adjustments for other confounders (P < 0.001). However, the association between RA and brPWV (P = 0.199), faPWV (P = 0.599) was not significant. In addition, age and systolic blood pressure were also significant independent factors associated with hfPWV and cfPWV. The reproducibility analysis showed that hfPWV and cfPWV measurements had lower coefficient of variation than others. The stiffness of different arterial regions is not equally affected by RA. The stiffening of aorta is more preferentially associated with RA than that of the peripheral arteries in extremities. The discrepant stiffening between aorta and peripheral arteries may provide a new insight into the pathogenesis of cardiovascular and microvascular dysfunction frequently occurred in RA.

[miR-494-3p reduces insulin sensitivity in diabetic cardiomyocytes by down-regulation of insulin receptor substrate 1].

More and more evidence suggests that microRNA is widely involved in the regulation of cardiovascular function. Our preliminary experiment showed that miR-494-3p was increased in heart of diabetic rats, and miR-494-3p was reported to be related to metabolism such as obesity and exercise. Therefore, this study was aimed to explore the role of miR-494-3p in diabetic myocardial insulin sensitivity and the related mechanism. The diabetic rat model was induced by high fat diet (45 kcal% fat, 12 weeks) combined with streptozotocin (STZ, 30 mg/kg), and cardiac tissue RNA was extracted for qPCR. The results showed that the level of miR-494-3p was significantly up-regulated in the myocardium of diabetic rats compared with the control (P < 0.05). The level of miR-494-3p in H9c2 cells cultured in high glucose and high fat medium (HGHF) was significantly increased (P < 0.01) with the increase of sodium palmitate concentration, whereas down-regulation of miR-494-3p in HGHF treated cells led to an increase in insulin-stimulated glucose uptake (P < 0.01) and the ratio of p-Akt/Akt (P < 0.05). Over-expression of miR-494-3p in H9c2 cell line significantly inhibited insulin-stimulated glucose uptake and phosphorylation of Akt (P < 0.01). Bioinformatics combined with Western blotting experiments confirmed insulin receptor substrate 1 (IRS1) as a target molecule of miR-494-3p. These results suggest that miR-494-3p reduces insulin sensitivity in diabetic cardiomyocytes by down-regulating IRS1.

Cu(I)-Catalyzed Coupling of Bis(trimethylsilyl)diazomethane with Terminal Alkynes: A Synthesis of 1,1-Disilyl Allenes.

A Cu(I)-catalyzed cross-coupling reaction of terminal alkynes and bis(trimethylsilyl)diazomethane is reported. Mechanistically, the reaction is based on the recently developed cross-coupling reactions through metal-carbene migratory insertion. This reaction provides an efficient synthetic method for 1,1-disilyl allenes. Subsequent transformations of 1,1-disilyl allenes are investigated, which show diverse reactivities of these allenes.

Long-term simulated microgravity fosters carotid aging-like changes via Piezo1.

AIMS: Elucidating the impacts of long-term spaceflight on cardiovascular health is urgently needed in face of the rapid development of human space exploration. Recent reports including the NASA Twins Study on vascular deconditioning and aging of astronauts in spaceflight are controversial. The aims of this study were to elucidate whether long-term microgravity promotes vascular aging and the underlying mechanisms. METHODS AND RESULTS: Hindlimb unloading (HU) by tail suspension was used to simulate microgravity in rats and mice. The dynamic changes of carotid stiffness in rats during 8 weeks of HU were determined. Simulated microgravity led to carotid artery aging-like changes as evidenced by increased stiffness, thickness, fibrosis, and elevated senescence biomarkers in the HU rats. Specific deletion of the mechanotransducer Piezo1 in vascular smooth muscles significantly blunted these aging-like changes in mice. Mechanistically, mechanical stretch-induced activation of Piezo1 elevated microRNA-582-5p in vascular smooth muscle cells, with resultant enhanced synthetic cell phenotype and increased collagen deposition via PTEN/PI3K/Akt signalling. Importantly, inhibition of miRNA-582-5p alleviated carotid fibrosis and stiffness not only in HU rats but also in aged rats. CONCLUSIONS: Long-term simulated microgravity induces carotid aging-like changes via the mechanotransducer Piezo1-initiated and miRNA-mediated mechanism.

Association between gut microbiota and Hirschsprung disease: a bidirectional two-sample Mendelian randomization study.

Background: Several studies have pointed to the critical role of gut microbiota (GM) and their metabolites in Hirschsprung disease (HSCR) pathogenesis. However, the detailed causal relationship between GM and HSCR remains unknown. Methods: In this study, we used two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between GM and HSCR, based on the MiBioGen Consortium's genome-wide association study (GWAS) and the GWAS Catalog's HSCR data. Reverse MR analysis was performed subsequently, and the sensitivity analysis, Cochran's Q-test, MR pleiotropy residual sum, outlier (MR-PRESSO), and the MR-Egger intercept were used to analyze heterogeneity or horizontal pleiotropy. 16S rDNA sequencing and targeted mass spectrometry were developed for initial validation. Results: In the forward MR analysis, inverse-variance weighted (IVW) estimates suggested that Eggerthella (OR: 2.66, 95%CI: 1.23-5.74, p = 0.01) was a risk factor for HSCR, while Peptococcus (OR: 0.37, 95%CI: 0.18-0.73, p = 0.004), Ruminococcus2 (OR: 0.32, 95%CI: 0.11-0.91, p = 0.03), Clostridiaceae1 (OR: 0.22, 95%CI: 0.06-0.78, p = 0.02), Mollicutes RF9 (OR: 0.27, 95%CI: 0.09-0.8, p = 0.02), Ruminococcaceae (OR: 0.16, 95%CI: 0.04-0.66, p = 0.01), and Paraprevotella (OR: 0.45, 95%CI: 0.21-0.98, p = 0.04) were protective factors for HSCR, which had no heterogeneity or horizontal pleiotropy. However, reverse MR analysis showed that HSCR (OR: 1.02, 95%CI: 1-1.03, p = 0.049) is the risk factor for Eggerthella. Furthermore, some of the above microbiota and short-chain fatty acids (SCFAs) were altered in HSCR, showing a correlation. Conclusion: Our analysis established the relationship between specific GM and HSCR, identifying specific bacteria as protective or risk factors. Significant microbiota and SCFAs were altered in HSCR, underlining the importance of further study and providing new insights into the pathogenesis and treatment.

Growth of wafer-scale chromium sulphide and selenide semiconductor films.

Two-dimensional (2D) transition metal chalcogenides have attracted enormous attention due to their stunning properties and great prospects for applications. Most of the reported 2D materials have layered structure, and non-layered transition metal chalcogenides are rare. Particularly, chromium chalcogenides are highly complexed in terms of structural phases. Researches on their representative chalcogenides, Cr2S3and Cr2Se3, are insufficient and most of them focus on individual crystal grains. In this study, large-scale Cr2S3and Cr2Se3films with controllable thickness are successfully grown, and their crystalline qualities are confirmed by multiple characterizations. Moreover, the thickness-dependent Raman vibrations are investigated systematically, presenting slight redshift with increasing thickness. The fundamental physical properties of grown Cr2S3and Cr2Se3films, including optical bandgap, activation energy and electrical properties, are measured with different thicknesses. The 1.9 nm thick Cr2S3and Cr2Se3films show narrow optical bandgap of 0.732 and 0.672 eV, respectively. The electrical properties of Cr2S3films demonstratep-type semiconductor behaviours, while the Cr2Se3films exhibit no gate response. This work can provide a feasible method for growing large-scale Cr2S3and Cr2Se3films, and reveal fundamental information of their physical properties, which is helpful for future applications.

Sensitive detection of single-nucleotide polymorphisms by conjugated polymers for personalized treatment of hypertension.

Genetic variants among individuals have been associated with ineffective control of hypertension. Previous work has shown that hypertension has a polygenic nature, and interactions between these loci have been associated with variations in drug response. Rapid detection of multiple genetic loci with high sensitivity and specificity is needed for the effective implementation of personalized medicine for the treatment of hypertension. Here, we used a cationic conjugated polymer (CCP)-based multistep fluorescence resonance energy transfer (MS-FRET) technique to qualitatively analyze DNA genotypes associated with hypertension in the Chinese population. Assessment of 10 genetic loci using this technique successfully identified known hypertensive risk alleles in a retrospective study of whole-blood samples from 150 patients hospitalized with hypertension. We then applied our detection method in a prospective clinical trial of 100 patients with essential hypertension and found that personalized treatment of patients with hypertension based on results from the MS-FRET technique could effectively improve blood pressure control rate (94.0% versus 54.0%) and shorten the time duration to controlling blood pressure (4.06 ± 2.10 versus 5.82 ± 1.84 days) as compared with conventional treatment. These results suggest that CCP-based MS-FRET genetic variant detection may assist clinicians in rapid and accurate classification of risk in patients with hypertension and improve treatment outcomes.

Predictive validation of existing bleeding and thromboembolic scores in elderly patients with comorbid atrial fibrillation and acute coronary syndrome.

BACKGROUND: The validation of various risk scores in elderly patients with comorbid atrial fibrillation (AF) and acute coronary syndrome (ACS) has not been reported. The present study compared the predictive performance of existing risk scores in these patients. METHODS: A total of 1252 elderly patients with AF and ACS comorbidities (≥ 65 years old) were consecutively enrolled from January 2015 to December 2019. All patients were followed up for one year. The predictive performance of risk scores in predicting bleeding and thromboembolic events was calculated and compared. RESULTS: During the 1-year follow-up, 183 (14.6%) patients had thromboembolic events, 198 (15.8%) patients had BARC class ≥ 2 bleeding events, and 61 (4.9%) patients had BARC class ≥ 3 bleeding events. For the BARC class ≥ 3 bleeding events, discrimination of the existing risk scores was low to moderate, PRECISE-DAPT (C-statistic: 0.638, 95% CI: 0.611-0.665), ATRIA (C-statistic: 0.615, 95% CI: 0.587-0.642), PARIS-MB (C-statistic: 0.612, 95% CI: 0.584-0.639), HAS-BLED (C-statistic: 0.597, 95% CI: 0.569-0.624) and CRUSADE (C-statistic: 0.595, 95% CI: 0.567-0.622). However, the calibration was good. PRECISE-DAPT showed a higher integrated discrimination improvement (IDI) than PARIS-MB, HAS-BLED, ATRIA, and CRUSADE (P < 0.05) and the best decision curve analysis (DCA). For thromboembolic events, the discrimination of GRACE (C-statistic: 0.636, 95% CI: 0.608-0.662) was higher than CHA2DS2-VASc (C-statistic: 0.612, 95% CI: 0.584-0.639), OPT-CAD (C-statistic: 0.602, 95% CI: 0.574-0.629) and PARIS-CTE (C-statistic: 0.595, 95% CI: 0.567-0.622). The calibration was good. Compared to OPT-CAD and PARIS-CTE, the IDI of the GRACE score slightly improved (P < 0.05). However, NRI analysis showed no significant difference. DCA showed that the clinical practicability of thromboembolic risk scores was similar. CONCLUSIONS: The discrimination and calibration of existing risk scores in predicting 1-year thromboembolic and bleeding events were unsatisfactory in elderly patients with comorbid AF and ACS. PRECISE-DAPT showed higher IDI and DCA than other risk scores in predicting BARC class ≥ 3 bleeding events. The GRACE score showed a slight advantage in predicting thrombotic events.

An overlooked oxidation mechanism of toluene: computational predictions and experimental validations.

Secondary organic aerosols (SOAs) influence the Earth's climate and threaten human health. Aromatic hydrocarbons (AHs) are major precursors for SOA formation in the urban atmosphere. However, the revealed oxidation mechanism dramatically underestimates the contribution of AHs to SOA formation, strongly suggesting the importance of seeking additional oxidation pathways for SOA formation. Using toluene, the most abundant AHs, as a model system and the combination of quantum chemical method and field observations based on advanced mass spectrometry, we herein demonstrate that the second-generation oxidation of AHs can form novel epoxides (TEPOX) with high yield. Such TEPOX can further react with H2SO4 or HNO3 in the aerosol phase to form less-volatile compounds including novel non-aromatic and ring-retaining organosulfates or organonitrates through reactive uptakes, providing new candidates of AH-derived organosulfates or organonitrates for future ambient observation. With the newly revealed mechanism, the chemistry-aerosol box modeling revealed that the SOA yield of toluene oxidation can reach up to 0.35, much higher than 0.088 based on the original mechanism under the conditions of pH = 2 and 0.1 ppbv NO. This study opens a route for the formation of reactive uptake SOA precursors from AHs and significantly fills the current knowledge gap for SOA formation in the urban atmosphere.

A Binary Solution Strategy Enables High-Efficiency Quasi-2D Perovskite Solar Cells with Excellent Thermal Stability.

Quasi-two-dimensional (2D) perovskites are highly promising light-harvesting materials for commercialization of perovskite solar cells (PSCs) owing to the excellent materials stability. However, the coexistence of multiple n-value species in 2D perovskites often causes increased complexities in crystallization that can negatively affect the eventual photovoltaic performance. Herein, we present a binary solution based strategy via introducing nontoxic and widely accessible CH3COOH (HAc) as a co-solvent for preparing high-quality 2D perovskite films. Based on a 2D perovskite model system, (AA)2MA4Pb5I16 (n = 5), we show that the prenucleation and grain growth kinetics are appreciably modified with HAc, which benefits from the strong electron-donating ability of HAc with the key component of PbI2, leading to formation of favorable cluster aggregates and resultant modulation of crystal growth. With the HAc-based method, the devices yield a boosted photovoltaic efficiency of 18.55% with an impressive photovoltage of 1.26 V. The champion cells exhibit a supreme thermal stability, showing <3% efficiency degradation under continuous thermal aging for 800 h.

Association Between Familial Hypercholesterolemia and Risk of Cardiovascular Events and Death in Different Cohorts: A Meta-Analysis of 1.1 Million Subjects.

Background and Aims: The association of familial hypercholesterolemia (FH) with risk of cardiovascular events (CVE) and death in different cohorts is controversial. We aimed to assess the risk of CVE and death in patients with FH in different cohorts, including CHD and ACS patients, White and Asian, different diagnostic criteria. Methods: We searched PubMed, MEDLINE, and Web of Science electronic databases through May 2021 to identify cohort studies of CVE and death in patients with FH. Results: We found 18 eligible studies with 1,139,788 participants, including 34,261 patients. There were 31,287 ACS patients, of whom 2,338 were combined with FH. Randomized-effects meta-analysis showed that in patients with FH, relative risk (RR) of CVE and death was 1.87 (95% CI 1.21-2.88), among which CVE was 2.14 (95%CI 1.26-3.64), all-cause of death RR = 1.12 (95% CI 0.89-1.41), and cardiac death RR = 1.03 (95% CI 0.59-1.79). Risk of CVE and death in general population with FH was 2.85 (95% CI 0.72-11.21), hyperlipidemia population RR = 1.59 (95% CI 1.05-2.41), coronary heart disease patients (CHD) RR = 1.46 (95% CI 1.24-1.72), and acute coronary syndrome patients (ACS) RR = 1.71 (95% CI 1.19-2.46). Among ACS patients, the RR of CVE in patients with FH was 1.91 (95% CI 1.55-2.35), the RR of all-cause of death was 1.03 (95% CI 0.80-1.32), and the RR of cardiac death was 1.03 (95% CI 0.59-1.79). The risk of CVE and death in ACS patients with FH in White was 1.69 (95% CI 1.09-2.64) and Asian 1.90 (95% CI 1.31-2.75). RR in patients with Dutch Lipid Network criteria (DLCN) ≥6 vs. <3 points was higher (RR = 2.24, 95% CI 1.69-2.97). RR for long-term follow-up was 1.68 (95% CI 1.09-2.61) and for short-term follow-up was 1.80 (95% CI 1.16-2.78). The results of the overall population were similar, but RR for overall population during a short-term follow-up was 1.49 (95% CI 0.81-2.73). We followed PRISMA checklist to complete meta-analysis. Conclusions: The risk of CVE and death was increased in patients with CHD, especially in patients with ACS. DLCN ≥ 6 points was suggested for clinical diagnosis of FH. The risk of long-term and short-term CVE and death increased in ACS patients with FH. Registration Number: INPLASY2021110010.