Medical record data-enabled machine learning can enhance prediction of left atrial appendage thrombosis in nonvalvular atrial fibrillation.

BACKGROUND: As a major complication of non-valvular atrial fibrillation (NVAF), left atrial appendage (LAA) thrombosis is associated with cerebral ischemic strokes, as well as high morbidity. Due to insufficient incorporation of risk factors, most current scoring methods are limited to the analysis of relationships between clinical characteristics and LAA thrombosis rather than detecting potential risk. Therefore, this study proposes a clinical data-driven machine learning method to predict LAA thrombosis of NVAF. METHODS: Patients with NVAF from January 2014 to June 2022 were enrolled from Southwest Hospital. We selected 40 variables for analysis, including demographic data, medical history records, laboratory results, and the structure of LAA. Three machine learning algorithms were adopted to construct classifiers for the prediction of LAA thrombosis risk. The most important variables related to LAA thrombosis and their influences were recognized by SHapley Addictive exPlanations method. In addition, we compared our model with CHADS2 and CHADS2-VASc scoring methods. RESULTS: A total of 713 participants were recruited, including 127 patients with LAA thrombosis and 586 patients with no obvious thrombosis. The consensus models based on Random Forest and eXtreme Gradient Boosting LAA thrombosis prediction (RXTP) achieved the best accuracy of 0.865, significantly outperforming CHADS2 score and CHA2DS2-VASc score (0.757 and 0.754, respectively). The SHAP results showed that B-type natriuretic peptide, left atrial appendage width, C-reactive protein, Fibrinogen and estimated glomerular filtration rate are closely related to the risk of LAA thrombosis in nonvalvular atrial fibrillation. CONCLUSIONS: The RXTP-NVAF model is the most effective model with the greatest ROC value and recall rate. The summarized risk factors obtained from SHAP enable the optimization of the treatment strategy, thereby preventing thromboembolism events and the occurrence of cardiogenic ischemic stroke.

Catalytic Asymmetric Deoxygenative Cyclopropanation Reactions by a Chiral Salen-Mo Catalyst.

The catalytic asymmetric cyclopropanation reaction of alkenes with diazo compounds is a direct and powerful method to construct chiral cyclopropanes that are essential to drug discovery. However, diazo compounds are potentially explosive and often require hazardous reagents for their preparation. Here, we report on the use of 1,2-dicarbonyl compounds as safe and readily available surrogates for diazo compounds in the direct catalytic asymmetric deoxygenative cyclopropanation reaction. Enabled by a class of simple and readily accessible chiral salen-Mo catalysts, the reaction proceeded with generally good enantioselectivities and yields toward a wide range of substrates (80 examples). Preliminary mechanistic studies suggested that the proposed µ-oxo bridged dinuclear Mo(III)-species was the catalytically active species. This strategy not only provides a promising route for the synthesis of chiral cyclopropanes but also opens a new window for the potential applications of chiral salen-Mo complexes in asymmetric catalysis.

Ocular adverse events associated with anti-VEGF therapy: A pharmacovigilance study of the FDA adverse event reporting system (FAERS).

Background: The purpose of this study is to identify and characterize ocular adverse events (AEs) that are significantly associated with anti-VEGF drugs for treatment of neovascular age-related macular degeneration and compare the differences between each drug, and provide clinical reference. Methods: Ocular AEs submitted to the US Food and Drug Administration were analyzed to map the safety profile of anti-VEGF drugs. The Pharmacovigilance tools used for the quantitative detection of signals were reporting odds ratio and bayesian confidence propagation neural network. Results: A total of 10,608,503 AE reports were retrieved from FAERS, with 20,836 for ranibizumab, 19,107 for aflibercept, and 2,442 for brolucizumab between the reporting period of Q1, 2004 and Q3, 2021. We found and analyzed the different AEs with the strongest signal in each drug-ranibizumab-macular ischaemia (ROR = 205.27, IC-2SD = 3.70), retinal pigment epithelial tear (ROR = 836.54, IC-2SD = 7.19); aflibercept-intraocular pressure increased (ROR = 31.09, IC-2SD = 4.61), endophthalmitis (ROR = 178.27, IC-2SD = 6.70); brolucizumab-retinal vasculitis (ROR = 2930.41, IC-2SD = 7.47) and/or retinal artery occlusion (ROR = 391.11, IC-2SD = 6.10), dry eye (ROR = 12.48, IC-2SD = 2.88). Conclusion: The presence of AEs should bring clinical attention. The use of anti-VEGF drugs should be based on the patient's underlying or present medical condition to reduce any adverse event associated with the treatment.

Solvent- and initiator-free fabrication of efficient and stable perovskite-polystyrene surface-patterned thin films for LED backlights.

We report a one-pot route for the synthesis of CsPbBr3 perovskite nanocrystals (PNCs) in styrene to form a glue-like polystyrene (PS) pre-polymer incorporating mono-dispersed PNCs. The pre-polymer enables solvent- and initiator-free fabricating and patterning PNC-PS light down-conversion films for liquid crystal display application. The mechanistic study reveals that the styrene molecules adsorbed on the PNC surface undergo self-initiated polymerization in the pre-polymerization process, forming stable surface capsulation over the PNCs. The PNC-PS pre-polymer and composite film display high photoluminescent quantum yield (PLQY) and resistance to air, light irradiation and water. The micropatterned PNC-PS film with a period of 1000 nm was fabricated through imprinting of the pre-polymer. The micropatterned thin film displays an enlarged viewing angle, improved light distribution and PLQY of >90%. The backlight employing the PNC-PS film displays bright green color and a wide color gamut of >120% NTSC. This solvent-free and one-pot strategy could find promising potential in the development of diverse luminescent nanocomposites to meet the requirements of micro/nano-manufacturing and high performance display application.

Molybdenum-Catalyzed Deoxygenative Cyclopropanation of 1,2-Dicarbonyl or Monocarbonyl Compounds.

The transition-metal-catalyzed cyclopropanation of alkenes by the decomposition of diazo compounds is a powerful and straightforward strategy to produce cyclopropanes, but is tempered by the potentially explosive nature of diazo substrates. Herein we report the Mo-catalyzed regiospecific deoxygenative cyclopropanation of readily available and bench-stable 1,2-dicarbonyl compounds, in which one of the two carbonyl groups acts as a carbene equivalent upon deoxygenation and engages in the subsequent cyclopropanation process. The use of a commercially available Mo catalyst afforded an array of valuable cyclopropanes with exclusive regioselectivity in up to 90 % yield. The synthetic utility of this method was further demonstrated by gram-scale syntheses, late-stage functionalization, and the cyclopropanation of a simple monocarbonyl compound. Preliminary mechanistic studies suggest that phosphine (or silane) acts as both a mild reductant and a good oxygen acceptor that efficiently regenerates the catalytically active Mo catalyst through reduction of the Mo-oxo complexes.

Dysregulation of serum miR-361-5p serves as a biomarker to predict disease onset and short-term prognosis in acute coronary syndrome patients.

BACKGROUND: Serum microRNAs (miRNAs) have been used as novel biomarkers for various diseases, including acute coronary syndrome (ACS). This study aimed to investigate the expression and clinical significance of microRNA-361-5p (miR-361-5p) in patients with ACS. METHODS: This study included 118 ACS patients, 78 patients with stable coronary heart disease (SCHD) and 66 healthy controls. MiR-361-5p expression was measured by qRT-PCR. The diagnostic value of miR-361-5p was evaluated by the ROC analysis. A 30-day follow-up was performed for the patients from hospitalization, and Kaplan-Meier curves and logistics analysis were used to evaluate the ability of miR-361-5p to predict the occurrence of major adverse cardiac events (MACE). ELISA kits were used to detect the levels of endothelial dysfunction (ED) markers, including vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1) and E-selectin. RESULTS: The expression of miR-361-5p was significantly increased in patients with SCHD and ACS, and positively correlated with Gensini scores. Serum miR-361-5p expression had a high diagnostic accuracy for distinguishing ACS from health controls and SCHD patients. ACS patients with high expression of miR-361-5p had a higher probability of developing MACE. MiR-361-5p expression was an independent risk factor for the occurrence of MACE in ACS patients, and was positively correlated with the levels of VCAM-1, ICAM-1 and E-selectin. CONCLUSION: All data indicated that miR-361-5p expression was significantly increased in ACS patients. Aberrant miR-361-5p expression in ACS might be a candidate biomarker for ACS diagnosis and the the prediction of MACE onset.

Inhibition of Microrna-766-5p Attenuates the Development of Cervical Cancer Through Regulating SCAI.

PURPOSE: MicroRNAs (miRNAs) are considered to play anti-tumor roles in cancers. This study is designed to illustrate the role and potential mechanism of miR-766-5p in cervical cancer (CC) progression. METHODS: MiR-766-5p expression in tissues and serum of CC patients was detected by quantitative reverse-transcription PCR (qRT-PCR). Receiver operating characteristic (ROC) curve was performed to evaluate the diagnostic value of serum miR-766-5p in CC. The 5-ethynyl-2'-deoxyuridine (EdU) assay, flow cytometry, wound healing as well as transwell assay were utilized to detect the proliferation, apoptosis, migration and invasion of CC cells, respectively. The interaction between miR-766-5p and SCAI was confirmed by dual-luciferase reporter gene assay. Xenografted tumor model was established to measure the growth of tumor xenograft in vivo. RESULTS: MiR-766-5p was significantly increased in tissues and serum of CC patients. ROC curve suggested that serum miR-766-5p could serve as a biomarker for the diagnosis of CC. Inhibition of miR-766-5p suppressed the proliferation, migration and invasion, and promoted the apoptosis of CC cells. SCAI was proved to be a target of miR-766-5p. Silencing of SCAI eliminated the inhibiting effects of miR-766-5p inhibitor on the proliferation, migration and invasion of CC cells in vitro. Additionally, down-regulation of SCAI also reversed the inhibitory effect of miR-766-5p inhibitor on the growth of tumor xenograft in vivo. CONCLUSIONS: Inhibition of miR-766-5p restrains the cell proliferation, migration and invasion, and promotes the apoptosis in CC through negatively regulating SCAI.

Antimicrobial resistance surveillance and prediction of Gram-negative bacteria based on antimicrobial consumption in a hospital setting: A 15-year retrospective study.

Antimicrobial resistance, a major threat to human health, is mainly driven by the overuse of antimicrobials. The purpose of this study was to further investigate the relationship between antimicrobial use and resistance with a 15-year record in Southwest hospital, one of the largest hospitals in Southwest China and a university affiliated hospital, thus to further predict the antimicrobial resistance in an autoregressive integrated moving average (ARIMA) manner. Kirby-Bauer tests were carried out to figure out the drug sensitivity of Gram-negative bacterial. Antimicrobials (ß-lactamase inhibitor complex, aminoglycosides, quinolones, third and fourth-generation cephalosporins, carbapenems, cephamycins, oxacephems, and sulfonamides) consumption were calculated according to World Health Organization (WHO) anatomical therapeutic chemical classification index and expressed as annual defined daily dose (DDD) or DDD per 1000 out patients. Resistance rates of levofloxacin-resistant Escherichia coli, ceftazidime-resistant Klebsiella pneumoniae, amikacin-resistant Bacterium levans, imipenem-resistant Pseudomonas aeruginosa is positively correlated with the usage of aminoglycosides and quinolones; resistance rates of imipenem-resistant Acinetobacter baumanii is positively correlated with the usage of carbapenemes (P-value between the drug resistance of levofloxacin-resistant E. coli, ceftazidime-resistant K. pneumoniae and the usage of aminoglycosides is under .05, the other P-value are under .01); resistance rates of the drug resistance of levofloxacin-resistant E. coli is positively correlated with the usage of oxacephems (P < .01); resistance rates of imipenem-resistant P. aeruginosa is positively correlated with the usage of oxacephems and sulfonamides (P < .01).The present study presents one of the largest and longest retrospective analyses in China between antimicrobial consumption and antimicrobial resistance. Change of the usage of several antibacterial drugs has great influence on the drug resistance of Gram-negative bacterial. Of particular, ARIMA forecasting revealed that carbapenem related bacterial resistance should be closely watched.

Controlled Growth of CH3 NH3 PbBr3 Perovskite Nanocrystals via a Water-Oil Interfacial Synthesis Method.

Fundamental insights into the reaction kinetics of organic-inorganic lead halide perovskite nanocrystals (LHP NCs) are still limited due to their ultrafast formation rate. Herein, we develop a water-oil interfacial synthesis of MAPbBr3 NCs (MA=CH3 NH3 + ), which prolongs the reaction time to tens of minutes. This method makes it possible to monitor in situ the formation process of MAPbBr3 NCs and observe successive spectral evolutions from 438 to 534 nm in a single reaction by extending reaction time. The implementation of this method depends on reducing the formation rate of PbBr6 4- octahedra and the diffusion rate of MA. The formation of PbBr6 4- is a rate-determining step, and the biphasic system offers a favorable reaction condition to control the mass transfer of MA. The effects of temperature and concentration of precursor and ligand are investigated in detail.

Iron-Catalyzed Aerobic Dehydrogenative Kinetic Resolution of Cyclic Secondary Amines.

A nonenzymatic iron-catalyzed dehydrogenative kinetic resolution of cyclic secondary amines using air as an oxidant has been reported. The economical and practical method is applicable to a series of cyclic benzylic amines, including 5,6-dihydrophenanthridines and 1,2-dihydroquinolines, with diverse functional groups at the α position in high yields with excellent enantioselectivities. The direct dehydrogenative kinetic resolution of advanced intermediates of bioactive molecules that are difficult to access using existing catalytic asymmetric synthetic strategy was also demonstrated.

Influence of alkyl polyglucoside, citric acid, and nitrilotriacetic acid on phytoremediation in pyrene-Pb co-contaminated soils.

At present, the remediation for organic pollutants and heavy metals co-contaminated soils is a challenge which needs to be broken through. In this study, alkyl polyglucoside (APG), citric acid (CA), and nitrilotriacetic acid (NTA) were chosen to enhance the phytoremediation of pyrene and Pb co-contaminated soils by perennial ryegrass. Through the comparison of the results with different applications, it could be found that the application of NTA was beneficial to the growth of perennial ryegrass, the underground and aboveground biomass were increased by 172.9-236.1% and 61.9-142.8%, respectively, meanwhile, photosynthetic activity of perennial ryegrass was affected positively. More importantly, the combined application of APG and NTA maximally promoted the accumulation and translocation of Pb (BF/TF, 0.44/0.61) and dissipation of pyrene (71.6%). These results indicated that the combined application of APG and NTA could be promising for future practical application of phytoremediation. However, the optimal dosage ratio of APG and NTA for phytoremediation needs to be further researched.

Increased accumulation of Pb and Cd from contaminated soil with Scirpus triqueter by the combined application of NTA and APG.

Phytoremediation of heavy metals contaminated soils shows many advantages and it can be improved by adding chelating agents and surfactants. In this study, pot culture experiments were set up to explore the effect of alone application of nitrilotriacetic acid (NTA) and combined application of NTA and alkyl polyglucoside (APG) on changes in absorption and adsorption of heavy metals by root of Scirpus triqueter and bioaccumulation of metals in single or co-contamination. Different additives were added into the soils artificially after 10 d and heavy metals extracted from different plant tissues were analyzed after 60 d. Results showed that more cadmium (Cd) was adsorbed on the root surface while more lead (Pb) was absorbed in root interior with the combined application of NTA and APG during phytoremediation of single contaminated soil. In co-contaminated soils, such a combined application not only strengthened the plant growth, but also promoted accumulation of Pb and Cd by Scirpus triqueter. NTA improved absorption amounts of Pb (9.7-fold) and Cd (1.0-fold) in root interior significantly. APG induced more metals to gather on the root surface in the presence of NTA and the adsorption amounts of Pb and Cd ranged from 26.2 and 17.7 mg kg-1 to 412 and 46.0 mg kg-1 respectively. Besides, the coexistence metal increased bioaccumulation of another metal under combined application of NTA and APG in co-contamination of Pb and Cd. In conclusion, the combined application of NTA and APG would be beneficial to accumulate Pb and Cd from contaminated soils by Scirpus triqueter.

Assessment of Pb and pyrene accumulation in Scirpus triqueter assisted by combined alkyl polyglucoside and nitrilotriacetic acid application.

To understand the accumulation and uptake of polycyclic aromatic hydrocarbons (PAHs) and heavy metals by plants is an important part of the assessment of phytoremediation for PAHs and heavy metals co-contaminated soil. This study was an investigation of the accumulation and uptake of pyrene and lead (Pb) by Scirpus triqueter under the condition of alkyl polyglucoside (APG) and nitrilotriacetic acid (NTA) combined application. The results indicated that the accumulation of Pb by S. triqueter was significantly improved by NTA and APG addition into the soil. The pyrene accumulation in plant was also increased after application of APG when compared to the control treatment. However, the pyrene accumulation was decreased when APG was applied together with NTA. SEM and TEM images of root surface suggested that more Pb in the soil transferred to the plant by combined application of APG and NTA. More importantly, TEM images of xylem cells of S.triqueter root showed that permeability of cell membrane was improved by application of APG.

Effect of tea saponin on phytoremediation of Cd and pyrene in contaminated soils by Lolium multiflorum.

Tea saponin (TS), a kind of green biosurfactant produced by plants, was added into the Cd-pyrene co-contaminated soils to evaluate its influence on phytoremediation of Cd and pyrene by Lolium multiflorum. The results showed that the accumulation of pyrene in L. multiflorum was significantly promoted by the TS. Compared with no TS treatments (PL and ML), the aboveground concentrations of pyrene in TS treatments (PLT and MLT) increased by 135 and 30%, respectively, and the underground concentrations of pyrene in TS treatments (PLT and MLT) increased by 40 and 25%. The concentrations of Cd in the aboveground and underground parts in single contaminated treatments were all significantly more than those in co-contaminated treatments, while the situation of pyrene was quite the reverse. Besides, the addition of TS enhanced activities of dehydrogenase and polyphenol oxidase in soils and increased the biomass of L. multiflorum. The micromorphology of L. multiflorum was not affected by TS. The study suggests that the use of L. multiflorum with TS is an alternative technology for remediation of Cd-pyrene co-contaminated soils.

Medium-Sized Cyclic Ethers via Stevens [1,2]-Shift of Mixed Monothioacetal-Derived Sulfonium Ylides: Application to Formal Synthesis of (+)-Laurencin.

A novel approach to medium-sized cyclic ethers was devised using a Stevens [1,2]-shift of a sulfonium ylide derived from a readily accessible six-membered mixed-monothioacetal precursor. The concise and efficient transformation offers a surprising degree of chirality transfer with observed retention of stereochemical configuration on the anomeric migrating carbon and has been applied as the key step in an enantioselective formal synthesis of (+)-laurencin.

Phytoremediation effect of Scirpus triqueter inoculated plant-growth-promoting bacteria (PGPB) on different fractions of pyrene and Ni in co-contaminated soils.

At present, few reveal the mechanism of inoculation plants with PGPB to remediate PAH-metal co-contaminated soil by analyzing the chemical speciations of contaminants. This study investigated the influence of inoculation plants with PGPB on different fractions of pyrene and Ni in rhizospheric and non-rhizospheric soil. The results demonstrated that the addition of PGPB brought the extensive increase of FDA activities in pyrene-Ni co-contaminated soil. PGPB increased the resistance of plants in nickel and pyrene-Ni contaminated soil, but decreased the plant biomass in single pyrene contaminated soil. The addition of PGPB efficiently decreased bioaccessible fractions of pyrene and increased the bioavailability of Ni in both rhizospheric and non-rhizospheric soil. Although inoculation plants with PGPB significantly increased the accumulation of Ni in single Ni and pyrene-Ni co-contaminated soil, the poor bioavailability of Ni in rhizospheric soil still restricted the phytoremediation of the heavy metal. The presence of pyrene hindered the inoculated plant from accumulating Ni to some extent. On the contrary, the presence of Ni significantly promoted the degradation of pyrene in both rhizospheric and non-rhizospheric soil after inoculation plants with PGPB.

Biodegradation of crude oil by a defined co-culture of indigenous bacterial consortium and exogenous Bacillus subtilis.

The aim of this work was to study biodegradation of crude oil by defined co-cultures of indigenous bacterial consortium and exogenous Bacillus subtilis. Through residual oil analysis, it is apparent that the defined co-culture displayed a degradation ratio (85.01%) superior to indigenous bacterial consortium (71.32%) after 7days of incubation when ratio of inoculation size of indigenous bacterial consortium and Bacillus subtilis was 2:1. Long-chain n-alkanes could be degraded markedly by Bacillus subtilis. Result analysis of the bacterial community showed that a decrease in bacterial diversity in the defined co-culture and the enrichment of Burkholderiales order (98.1%) degrading hydrocarbons. The research results revealed that the promising potential of the defined co-culture for application to degradation of crude oil.

Combined remediation of pyrene-contaminated soil with a coupled system of persulfate oxidation and phytoremediation with ryegrass.

The in situ chemical oxidation technology (ISCO) and phytoremediation for PAHs have been studied respectively, but few focus on the feasibility of combining persulfate with ryegrass. This literature revealed the effect of persulfate oxidation on the growth of ryegrass and the removal ratios of pyrene in the couple system of persulfate oxidation and phytoremediation. The results demonstrated that half of pyrene in test soil was oxidized by persulfate in 7 days and then the residual pyrene concentration was decreased to a lower level by ryegrass in the following 2 months in oxidation treatment and drip washing and plants (OWP) and oxidation treatment and drip washing and plants and fertilization (OWFP) treatment. Ryegrass could grow well after persulfate oxidation with the oxidized soil washed by water. Ryegrass in OWP and OWFP treatments had higher ratios of overground and underground biomass. However, the seeds of ryegrass cannot germinate when drip washing was omitted. Pyrene together with residual persulfate changed soil enzyme activities. Drip washing and the growth of ryegrass made soil enzyme activities tend to returned to normal levels. Persulfate oxidation and phytoremediation were compatible to make contributions to the dissipation of pyrene. Persulfate oxidation activated by heat had higher removal efficiency of PAHs and phytoremediation could further decrease the pyrene concentration in spiked soil.

Characterization of OfWRKY3, a transcription factor that positively regulates the carotenoid cleavage dioxygenase gene OfCCD4 in Osmanthus fragrans.

The sweet osmanthus carotenoid cleavage dioxygenase 4 (OfCCD4) cleaves carotenoids such as ß-carotene and zeaxanthin to yield ß-ionone. OfCCD4 is a member of the CCD gene family, and its promoter contains a W-box palindrome with two reversely oriented TGAC repeats, which are the proposed binding sites of WRKY transcription factors. We isolated three WRKY cDNAs from the petal of Osmanthus fragrans. One of them, OfWRKY3, encodes a protein containing two WRKY domains and two zinc finger motifs. OfWRKY3 and OfCCD4 had nearly identical expression profile in petals of 'Dangui' and 'Yingui' at different flowering stages and showed similar expression patterns in petals treated by salicylic acid, jasmonic acid and abscisic acid. Activation of OfCCD4pro:GUS by OfWRKY3 was detected in coinfiltrated tobacco leaves and very weak GUS activity was detected in control tissues, indicating that OfWRKY3 can interact with the OfCCD4 promoter. Yeast one-hybrid and electrophoretic mobility shift assay showed that OfWRKY3 was able to bind to the W-box palindrome motif present in the OfCCD4 promoter. These results suggest that OfWRKY3 is a positive regulator of the OfCCD4 gene, and might partly account for the biosynthesis of ß-ionone in sweet osmanthus.

High-throughput prediction of tablet weight and trimethoprim content of compound sulfamethoxazole tablets for controlling the uniformity of dosage units by NIR.

This paper establishes a novel method to simultaneously predict the tablet weight (TW) and trimethoprim (TMP) content of compound sulfamethoxazole tablets (SMZCO) by near infrared (NIR) spectroscopy with partial least squares (PLS) regression for controlling the uniformity of dosage units (UODU). The NIR spectra for 257 samples were measured using the optimized parameter values and pretreated using the optimized chemometric techniques. After the outliers were ignored, two PLS models for predicting TW and TMP content were respectively established by using the selected spectral sub-ranges and the reference values. The TW model reaches the correlation coefficient of calibration (R(c)) 0.9543 and the TMP content model has the R(c) 0.9205. The experimental results indicate that this strategy expands the NIR application in controlling UODU, especially in the high-throughput and rapid analysis of TWs and contents of the compound pharmaceutical tablets, and may be an important complement to the common NIR on-line analytical method for pharmaceutical tablets.