Short-term antithrombotic strategies after left atrial appendage occlusion: a systematic review and network meta-analysis.

Background: Percutaneous left atrial appendage occlusion (LAAO) has emerged as a stroke prevention strategy in patients with nonvalvular atrial fibrillation (NVAF), and these patients were required to receive antithrombotic therapy post-procedure. However, the optimal antithrombotic strategy after LAAO remains controversial. This study explored the safety and efficacy of different antithrombotic strategies after LAAO through a network comparison method. Methods: We systematically searched the MEDLINE, Embase, and Cochrane Library databases for studies that reported the interested efficacy and safety outcomes (stroke, device-related thrombus (DRT), and major bleeding) of different antithrombotic strategies [DAPT (dual antiplatelet therapy), DOACs (direct oral anticoagulants), and VKA (vitamin k antagonist)] in patients who had experienced LAAO. Pairwise comparisons and network meta-analysis were performed for the interested outcomes. Risk ratios (RRs) with their confidence intervals (CIs) were calculated using a random-effects model. The rank of the different strategies was calculated using the surface under the cumulative ranking curve (SUCRA). Results: Finally, 10 observational studies involving 1,674 patients were included. There was no significant difference in stroke, DRT, and major bleeding among the different antithrombotic strategies (DAPT, DOACs, and VKA). Furthermore, DAPT ranked the worst in terms of stroke (SUCRA: 19.8%), DRT (SUCRA: 3.6%), and major bleeding (SUCRA: 6.6%). VKA appeared to be superior to DOACs in terms of stroke (SUCRA: 74.9% vs. 55.3%) and DRT (SUCRA: 82.3% vs. 64.1%) while being slightly inferior to DOACs in terms of major bleeding (SUCRA: 71.0% vs. 72.4%). Conclusion: No significant difference was found among patients receiving DAPT, DOACs, and VKA in terms of stroke, DRT, and major bleeding events after LAAO. The SUCRA indicated that DAPT was ranked the worst among all antithrombotic strategies due to the higher risk of stroke, DRT, and major bleeding events, while VKAs were ranked the preferred antithrombotic strategy. However, DOACs are worthy of consideration due to their advantage of convenience.

Inconsistency between polyphenol-enzyme binding interactions and enzyme inhibition: Galloyl moiety decreases amyloglucosidase inhibition of catechins.

Inhibiting carbohydrate-hydrolyzing enzymes has been considered as an effective approach for controlling starch digestion and postprandial blood glucose level. α-Amylase and amyloglucosidase (AMG) are commonly applied in analysis of starch digestion behaviour. Catechins have been shown with the inhibiting effects on α-amylase. However, the inhibitory activity of catechins against AMG needs to be further studied. Therefore, AMG inhibition of 8 catechins and the mechanisms were studied in this work through substrate depletion, inhibition kinetics, molecular docking, fluorescence quenching, differential scanning calorimetry, and isothermal titration calorimetry. The inhibitory activity of catechins with galloyl moiety (CGMs) was found to be lower than the corresponding catechins without the moiety (Cs). All catechins were anti-competitive inhibitors, indicating that they tended to bind with AMG-starch complex in the digestion system, rather than with AMG directly. Interestingly, CGMs had higher quenching effects on AMG fluorescence than Cs, due to the additional π-stacking between aromatic rings of GM and AMG fluorophores. Also, CGMs had a higher binding affinity to AMG, due to the tendency of GM to AMG active site, although the affinity was much weaker than that of starch to AMG. Besides, catechins did not affect AMG thermostability. Therefore, there was an inconsistency between catechins-AMG binding interactions and the enzyme inhibition because the predominant sites for catechins binding were the non-active sites on AMG-starch complex, rather than the enzyme active ones. Conclusively, inhibition mode should also be considered when evaluating the inhibitory activity of a polyphenol based on the polyphenol-enzyme binding affinity.

Soluble dietary fibres decrease α-glucosidase inhibition of epigallocatechin gallate through affecting polyphenol-enzyme binding interactions.

The effects of soluble dietary fibres (SDFs) on α-glucosidase inhibition of EGCG were studied. Three arabinoxylans and polygalacturonic acid (PGA) significantly decreased inhibitory activity of EGCG against α-glucosidase, while two ß-glucans hardly affected the inhibition. Although arabinoxylans and PGA weakened the competitive inhibition character of EGCG, they maintained the fluorescence quenching effect of EGCG. Then, arabinoxylans and PGA significantly decreased the particle size and turbidity of EGCG-enzyme complex. These results suggest that there formed SDFs-EGCG-enzyme ternary complexes. The stronger decreasing-effects of arabinoxylans and PGA on α-glucosidase inhibition of EGCG than ß-glucans resulted from the stronger non-covalent interactions of arabinoxylans and PGA with EGCG. This is considered to arise from the short-branches of arabinoxylans that provided more opportunity for capturing EGCG, and from the strong polarity of PGA carboxyl that promoted hydrogen bondings with EGCG. Conclusively, SDFs should be considered as an impact factor when evaluating α-glucosidase inhibition of dietary polyphenols.

Clinical Characteristics of 606 Patients with Community-Acquired Pyogenic Liver Abscess: A Six-Year Research in Yantai.

Objective: This study was designed to analyze the clinical characteristics, etiological characteristics, drug resistance, and empirical use of antibiotics for community-acquired pyogenic liver abscess (PLA) to provide a basis for rational and effective empirical treatment of PLA in the local area. Methods: The clinical data, etiological characteristics, drug resistance, and empirical anti-infective therapy schemes of 606 patients with PLA were collected and analyzed retrospectively. Results: The included patients were mainly males, with a male-to-female ratio of 1.3:1. The average age of the patients was 60.3 ± 14.1 years. The underlying diseases were diabetes and biliary tract disease, accounting for 38.7% and 22.3%, respectively. The main clinical manifestations were fever (92.9%), abdominal pain (44.7%), and nausea (33.3%). Imaging findings: the proportion of patients with a single lesion was 74.7%, and 67% of the patients had involvement in the right lobe of the liver. The main pathogen was Klebsiella pneumoniae accounted for 74.9% in blood culture and 84.1% in pus culture, mainly extended-spectrum ß-lactamase. In 272 strains negative for extended-spectrum ß-lactamase (ESBLs), 100% were resistant to ampicillin and less than 50% were sensitive to nitrofurantoin. Only 36 ESBL-positive strains had higher than 80% sensitivity to carbapenems, ß-lactamase inhibitor compound, and amikacin. Patients treated with different treatment methods showed significantly different average length of hospital stay (14 [9-21] vs 13 [8-18]). Empirical anti-infective therapy: Beta-lactamase complex, carbapenems, cephalosporins, and quinolones were used in 280 (37.6%), 180 (29.7%), 180 (29.7%), and 147 (24.3%) patients, respectively. Conclusion: Patients with community-acquired PLA in this area are mainly males, and the underlying diseases are mainly diabetes and hepatobiliary system disease. The main clinical manifestation is fever, so patients with fever of unknown cause should pay attention to possible liver abscesses. Based on drug sensitivity tests, the empirical use of antibiotics is somewhat unreasonable.

Accurate extraction of the +1 term spectrum with spurious spectrum elimination in off-axis digital holography.

In off-axis digital holography, spatial filtering is a key problem limiting the quality of reconstructed image, especially in the case of spurious spectrum generated by coherent noise in the hologram spectrum. In this paper, a new spatial filtering method with spurious spectrum elimination is proposed. Side band centering judgment is firstly implemented to locate the center point of the +1 term in the hologram spectrum. Then by roughly recognizing the region of +1 term spectrum, most of the -1 term, 0 term and the spurious spectral components are eliminated. Finally, Butterworth filtering is performed to extract the +1 term spectrum as enough as possible without introducing the spurious spectrum. Simulated hologram of E-shaped specimen with the spurious spectrum is generated to evaluate the performance of the proposed method. Experimental data of USAF 1951 resolution target, ovarian slice and microlens array are adopted to verify the effectiveness of the proposed method. Simulation and experimental results demonstrated that the proposed method is able to accurately extract the +1 term spectrum with spurious spectrum elimination and achieve a relatively good balance between the structural detail characterization and noise suppression.

Warfarin anticoagulation management during the COVID-19 pandemic: The role of internet clinic and machine learning.

Background: Patients who received warfarin require constant monitoring by hospital staff. However, social distancing and stay-at-home orders, which were universally adopted strategies to avoid the spread of COVID-19, led to unprecedented challenges. This study aimed to optimize warfarin treatment during the COVID-19 pandemic by determining the role of the Internet clinic and developing a machine learning (ML) model to predict anticoagulation quality. Methods: This retrospective study enrolled patients who received warfarin treatment in the hospital anticoagulation clinic (HAC) and "Internet + Anticoagulation clinic" (IAC) of the Nanjing Drum Tower Hospital between January 2020 and September 2021. The primary outcome was the anticoagulation quality of patients, which was evaluated by both the time in therapeutic range (TTR) and international normalized ratio (INR) variability. Anticoagulation quality and incidence of adverse events were compared between HAC and IAC. Furthermore, five ML algorithms were used to develop the anticoagulation quality prediction model, and the SHAP method was introduced to rank the feature importance. Results: Totally, 241 patients were included, comprising 145 patients in the HAC group and 96 patients in the IAC group. In the HAC group and IAC group, 73.1 and 69.8% (p = 0.576) of patients achieved good anticoagulation quality, with the average TTR being 79.9 ± 20.0% and 80.6 ± 21.1%, respectively. There was no significant difference in the incidence of adverse events between the two groups. Evaluating the five ML models using the test set, the accuracy of the XGBoost model was 0.767, and the area under the receiver operating characteristic curve was 0.808, which showed the best performance. The results of the SHAP method revealed that age, education, hypertension, aspirin, and amiodarone were the top five important features associated with poor anticoagulation quality. Conclusion: The IAC contributed to a novel management method for patients who received warfarin during the COVID-19 pandemic, as effective as HAC and with a low risk of virus transmission. The XGBoost model could accurately select patients at a high risk of poor anticoagulation quality, who could benefit from active intervention.

A Strategy to Design Cu2MoS4@MXene Composite With High Photothermal Conversion Efficiency Based on Electron Transfer Regulatory Effect.

Using photothermal therapy to treat cancer has become an effective method, and the design of photothermal agents determines their performance. However, due to the major radiative recombination of a photogenerated electron in photothermal materials, the photothermal performance is weak which hinders their applications. In order to solve this issue, preventing radiative recombination and accelerating nonradiative recombination, which can generate heat, has been proved as a reasonable way. We demonstrated a Cu2MoS4@MXene nanocomposite with an obviously enhanced photothermal conversion efficiency (η = 87.98%), and this improvement can be attributed to the electron migration. Then, a mechanism is proposed based on the electron transfer regulatory effect and the localized surface plasmon resonance effect, which synergistically promote nonradiative recombination and generate more heat. Overall, our design strategy shows a way to improve the photothermal performance of Cu2MoS4, and this method can be extended to other photothermal agents to let them be more efficient in treating cancer.

α-Amylase inhibition of a certain dietary polyphenol is predominantly affected by the concentration of α-1, 4-glucosidic bonds in starchy and artificial substrates.

To elucidate why the inhibitory activity of one same polyphenol against α-amylase varies in different works. Seven starchy and three artificial substrates, and a polyphenolic competitive inhibitor, tannic acid (TA) were applied to study the enzyme inhibition in different digestion systems. The results showed that the IC50 values of TA were similar for all starches at the same starch concentration, although there existed difference in starch physiochemical properties, like branching degree, amylose chain distribution, viscosity, and digestion rate. However, the IC50 values significantly decreased with the substrate concentration decreasing, regardless of substrate types. Notably, TA had a similar competitive inhibition constant (Kic) for all the starches, despite the difference in substrate concentration, indicating that the fixed constant unconditionally describes the inhibitor-enzyme binding property. In the TA/amylase/starch system, the physical adsorption of TA with starch was much weaker than the specific binding of TA with α-amylase that was driven by hydrogen bondings and π-stackings. Therefore, it was the substrate, i.e., α-1,4-glucosidic bond concentration, rather than the existing matrix of the bonds, that predominantly affected the inhibitory activity of a polyphenol, because of the competitive action between α-1,4-glucosidic bond and the polyphenol regarding binding with the enzyme.

RNA-Seq Based Toxicity Analysis of Mesoporous Polydopamine Nanoparticles in Mice Following Different Exposure Routes.

Mesoporous polydopamine nanoparticles (MPDA NPs) are promising nanomaterials that have the prospect of clinical application for multi-strategy antitumor therapy, while the biosecurity of MPDA NPs remains indistinct. Here, transcriptome sequencing (RNA-Seq) was performed to systematically reveal the toxicity of MPDA NPs to five categories of organs after three different exposure routes, including intravenous injection, intramuscular injection, and intragastric administration. Our results uncovered that MPDA NPs could be deposited in various organs in small amounts after intravenous administration, not for the other two exposure routes. The number of differentially expressed genes (DEGs) identified in the heart, liver, spleen, lung, and kidney from the intragastric administration group was from 22 to 519. Similarly, the corresponding number was from 23 to 64 for the intramuscular injection group and was from 11 to 153 for the intravenous injection group. Functional enrichment analyses showed 6, 39, and 4 GO terms enriched for DEGs in intragastric administration, intramuscular injection, and intravenous injection groups, respectively. One enriched pathway was revealed in intragastric administration group, while no enriched pathway was found in other groups. Our results indicated that MPDA NPs produced only slight changes at the transcriptome level in mice, which provided new insights for further clinical application of MPDA NPs.

SAIL: a new conserved anti-fibrotic lncRNA in the heart.

Long non-coding RNAs (lncRNAs) account for a large proportion of genomic transcripts and are critical regulators in various cardiac diseases. Though lncRNAs have been reported to participate in the process of diverse cardiac diseases, the contribution of lncRNAs in cardiac fibrosis remains to be fully elucidated. Here, we identified a novel anti-fibrotic lncRNA, SAIL (scaffold attachment factor B interacting lncRNA). SAIL was reduced in cardiac fibrotic tissue and activated cardiac fibroblasts. Gain- and loss-of-function studies showed that knockdown of SAIL promoted proliferation and collagen production of cardiac fibroblasts with or without TGF-ß1 (transforming growth factor beta1) treatment, while overexpression of SAIL did the opposite. In mouse cardiac fibrosis induced by myocardial infarction, knockdown of SAIL exacerbated, whereas overexpression of SAIL alleviated cardiac fibrosis. Mechanically, SAIL inhibited the fibrotic process by directly binding with SAFB via 23 conserved nucleotide sequences, which in turn blocked the access of SAFB to RNA pol II (RNA polymerase II) and reduced the transcription of fibrosis-related genes. Intriguingly, the human conserved fragment of SAIL (hSAIL) significantly suppressed the proliferation and collagen production of human cardiac fibroblasts. Our findings demonstrate that SAIL regulates cardiac fibrosis by regulating SAFB-mediated transcription of fibrotic related genes. Both SAIL and SAFB hold the potential to become novel therapeutic targets for cardiac fibrosis.

LncRNA ACART protects cardiomyocytes from apoptosis by activating PPAR-γ/Bcl-2 pathway.

Cardiomyocyte apoptosis is an important process occurred during cardiac ischaemia-reperfusion injury. Long non-coding RNAs (lncRNA) participate in the regulation of various cardiac diseases including ischaemic reperfusion (I/R) injury. In this study, we explored the potential role of lncRNA ACART (anti-cardiomyocyte apoptosis-related transcript) in cardiomyocyte injury and the underlying mechanism for the first time. We found that ACART was significantly down-regulated in cardiac tissue of mice subjected to I/R injury or cultured cardiomyocytes treated with hydrogen peroxide (H2 O2 ). Knockdown of ACART led to significant cardiomyocyte injury as indicated by reduced cell viability and increased apoptosis. In contrast, overexpression of ACART enhanced cell viability and reduced apoptosis of cardiomyocytes treated with H2 O2 . Meanwhile, ACART increased the expression of the B cell lymphoma 2 (Bcl-2) and suppressed the expression of Bcl-2-associated X (Bax) and cytochrome-C (Cyt-C). In addition, PPAR-γ was up-regulated by ACART and inhibition of PPAR-γ abolished the regulatory effects of ACART on cell apoptosis and the expression of Bcl-2, Bax and Cyt-C under H2 O2 treatment. However, the activation of PPAR-γ reversed the effects of ACART inhibition. The results demonstrate that ACART protects cardiomyocyte injury through modulating the expression of Bcl-2, Bax and Cyt-C, which is mediated by PPAR-γ activation. These findings provide a new understanding of the role of lncRNA ACART in regulation of cardiac I/R injury.

lncRNA H19 Alleviated Myocardial I/RI via Suppressing miR-877-3p/Bcl-2-Mediated Mitochondrial Apoptosis.

Ischemic cardiac disease is the leading cause of morbidity and mortality in the world. Despite the great efforts and progress in cardiac research, the current treatment of cardiac ischemia reperfusion injury (I/RI) is still far from being satisfactory. This study was performed to investigate the role of long non-coding RNA (lncRNA) H19 in regulating myocardial I/RI. We found that H19 expression was downregulated in the I/R hearts of mice and cardiomyocytes treated with H2O2. Overexpression of H19 alleviated myocardial I/RI of mice and cardiomyocyte injury induced by H2O2. We found that H19 functioned as a competing endogenous RNA of miR-877-3p, which decreased the expression of miR-877-3p through the base-pairing mechanism. In parallel, miR-877-3p was upregulated in H2O2-treated cardiomyocytes and mouse ischemia reperfusion (I/R) hearts. miR-877-3p exacerbated myocardial I/RI and cardiomyocyte apoptosis. We further established Bcl-2 as a downstream target of miR-877-3p. miR-877-3p inhibited the mRNA and protein expression of Bcl-2. Furthermore, H19 decreased the Bcl-2/Bax ratio at mRNA and protein levels, cytochrome c release, and activation of caspase-9 and caspase-3 in myocardial I/RI mice, which were canceled by miR-877-3p. In summary, the H19/miR-877-3p/Bcl-2 pathway is involved in regulation of mitochondrial apoptosis during myocardial I/RI, which provided new insight into molecular mechanisms underlying regulation of myocardial I/RI.

LncRNA PCFL promotes cardiac fibrosis via miR-378/GRB2 pathway following myocardial infarction.

Long noncoding RNAs (lncRNAs) are a class of novel molecular regulators in cardiac development and diseases. However, the role of specific lncRNAs in cardiac fibrosis remains to be fully explored. The aim of the present study was to investigate the effects and underlying mechanisms of lncRNA PCFL (pro-cardiac fibrotic lncRNA) on cardiac fibrosis after myocardial infarction (MI). Cardiac fibroblasts (CFs) with gain and loss of function of PCFL and mice with global knockout or overexpression of PCFL were used to explore the effects of PCFL on cardiac fibrosis. The data showed that PCFL was significantly increased in hearts of mice subjected to MI and CFs treated with transforming growth factor-ß1 (TGF-ß1). Overexpression of PCFL promoted collagen production and CF proliferation, while silencing PCFL exhibited the opposite effects. Compared with wild type MI mice, heterozygous knockout of PCFL (PCFL+/-) in mice significantly improved heart function and reduced cardiac fibrosis after MI. While overexpression of PCFL impaired cardiac function and aggravated MI-induced cardiac fibrosis. The mechanistic data demonstrated that PCFL functioned as a sponge of miR-378. Luciferase reporter assay confirmed the interaction of PCFL with miR-378. MiR-378 inhibited collagen production by suppressing its target gene, GRB2 (growth factor receptor bound protein 2). Knockdown of PCFL led to an increase of miR-378. Silencing of miR-378 reserved the inhibitory effects of PCFL knockdown on collagen production, cell proliferation and GRB2 expression. In conclusion, the study identifies a novel pro-fibrotic lncRNA, PCFL, and the mechanism involves the direct interaction of PCFL with miR-378, which in turn relieves the inhibition effect of miR-378 on GRB2 and promotes cardiac fibrosis.