Safety and efficacy of apixaban versus vitamin K antagonists in patients undergoing dialysis: a systematic review and meta-analysis.

BACKGROUND: This review aims to evaluate the safety and efficacy of apixaban vs. vitamin K antagonists (VKAs) in patients on dialysis. METHODS: All types of studies published on PubMed, Embase, CENTRAL, and Web of Science up to 10 September 2023 and comparing outcomes of apixaban vs. VKA in dialysis patients were eligible. RESULTS: Two randomized controlled trials (RCTs) and six retrospective studies were included. Apixaban treatment was associated with significantly lower risk of major bleeding (RR: 0.61; 95% CI: 0.48, 0.77; I2 = 50%) and clinically relevant non-major bleeding (RR: 0.82, 95% CI: 0.68, 0.98, I2 = 9%) compared to VKA. Meta-analysis also showed that the risk of gastrointestinal bleeding (RR: 0.74, 95% CI: 0.64, 0.85, I2 = 16%) and intracranial bleeding (RR: 0.64, 95% CI: 0.49, 0.84, I2 = 0%) was significantly reduced with apixaban. Meta-analysis showed no difference in the risk of ischemic stroke (RR: 0.40, 95% CI: 0.06, 2.69, I2 = 0%), mortality (RR: 1.26, 95% CI: 0.74, 2.16, I2 = 94%) and recurrent venous thromboembolism (RR: 1.02, 95% CI: 0.87, 1.21, I2 = 0%) between the two groups. Subgroup analysis of RCTs showed no difference in bleeding outcomes. CONCLUSIONS: Low-quality evidence from a mix of RCTs and retrospective studies shows that apixaban may have better safety and equivalent efficacy as compared to VKA in dialysis patients. Apixaban treatment correlated with significantly reduced risk of major bleeding and clinically relevant nonmajor bleeding in observational studies but not in RCTs. The predominance of retrospective data warrants caution in the interpretation of results.

An Updated Pooled Analysis of Off-Label Under and Over-Dosed Direct Oral Anticoagulants in Patients with Atrial Fibrillation.

INTRODUCTION: Off-label, under-, and overdosed direct oral anticoagulants (DOACs) are commonly prescribed to patients with atrial fibrillation (AF), but real-world evidence on their effectiveness and safety is limited. METHODS: MEDLINE, Embase, and Cochrane Library databases were systematically searched from 01 July 2020 to 28 February 2022 to update a previous systematic review with the same search strategy from the inception to 30 June 2020. Eligible studies were those that reported effectiveness (stroke/systemic embolism and myocardial infarction) or safety (gastrointestinal or major bleeding and death) outcomes of off-label doses of DOACs compared to on-label doses in AF patients. A random-effects meta-analysis was performed to estimate the pooled hazard ratio (HR) and 95% confidence interval (CI). Subgroup analyses were performed by specific DOACs and geographic regions. RESULTS: Twenty-two studies were included. Off-label, underdosed DOACs, compared to on-label doses, were not associated with an increased risk of stroke (HR 1.03, 95%CI: 0.88-1.17) but were associated with an increased risk of death (HR 1.26, 95%CI: 1.09-1.43). However, risk varied depending on the active ingredient. No other safety outcomes were associated with underdosed DOACs. No significant differences were observed by geographic regions. Compared to on-label DOACs, overdosing increased the risk of stroke (HR 1.17, 95%CI: 1.04-1.31), major bleeding (HR 1.18, 95%CI: 1.05-1.31), and death (HR 1.19, 95%CI: 1.03-1.35). Risk varied between geographical regions. CONCLUSIONS: Off-label underdoses, compared to on-label dosing of DOACs, did not increase the risk of stroke but did increase overall mortality. Overdosed DOACs, compared to on-label doses, were associated with an increased risk of stroke, major bleeding, and death. Future studies must examine these associations, focusing on specific active ingredients and geographic settings.

Bioinspired Active Site with a Coordination-Adaptive Organosulfonate Ligand for Catalytic Water Oxidation at Neutral pH.

Many enzymes use adaptive frameworks to preorganize substrates, accommodate various structural and electronic demands of intermediates, and accelerate related catalysis. Inspired by biological systems, a Ru-based molecular water oxidation catalyst containing a configurationally labile ligand [2,2':6',2″-terpyridine]-6,6″-disulfonate was designed to mimic enzymatic framework, in which the sulfonate coordination is highly flexible and functions as both an electron donor to stabilize high-valent Ru and a proton acceptor to accelerate water dissociation, thus boosting the catalytic water oxidation performance thermodynamically and kinetically. The combination of single-crystal X-ray analysis, various temperature NMR, electrochemical techniques, and DFT calculations was utilized to investigate the fundamental role of the self-adaptive ligand, demonstrating that the on-demand configurational changes give rise to fast catalytic kinetics with a turnover frequency (TOF) over 2000 s-1, which is compared to oxygen-evolving complex (OEC) in natural photosynthesis.

MicroRNA expression in osteoarthritis: a meta-analysis.

Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases globally, leading to chronic disability and poor prognosis. One of the approaches for optimizing OA treatment is to find early effective diagnostic biomarkers. The contribution of microRNAs (miRNAs) in OA progression is now being increasingly recognized. This review provides a comprehensive summary on studies reporting the expression profiling of miRNAs in OA and associated signaling pathways. We performed a systematic search of the Embase, Web of Science, PubMed, and Cochrane library databases. This systematic review is reported according to the PRISMA checklist. Studies which identified miRNAs with aberrant expression compared to controls during OA progression were included, and a meta-analysis was performed. Results from the random effects model were provided as log10 odds ratios (logORs) and 95% confidence intervals. Sensitivity analysis was conducted to confirm the accuracy of the results. Subgroup analysis was conducted based on tissue source. The target genes of miRNAs identified in this study were extracted from the MiRWalk database, and these target genes were enriched in Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. A total of 191 studies reporting 162 miRNAs were included in our meta-analysis. Among them, 36 miRNAs distributed across 96 studies were expressed in the same direction in at least two studies (13 up-regulated and 23 down-regulated). Subgroup analysis of tissue source revealed that the highest number of studies was conducted using articular cartilage, where the most up-regulated miRNAs were miR-146a-5p (logOR 7.355; P < 0.001) and miR-34a-5p (logOR 6.955; P < 0.001), and the most down-regulated miRNAs were miR-127-5p (logOR 6.586; P < 0.001) and miR-140-5p (logOR 6.373; P < 0.001). Enrichment analysis of 752 downstream target genes of all identified miRNAs was performed, and the regulatory relationships among them were displayed. Mesenchymal stem cells and transforming growth factor-ß were found to be the most important downstream effectors regulated by miRNA in OA. This study highlighted the importance of miRNA signaling in OA progression and identified a number of prominent miRNAs including miR-146a-5p, miR-34a-5p, miR-127-5p, and miR-140-5p which might be considered as potential biomarkers for OA.

The microRNA Expression Profiling in Heart Failure: A Systematic Review and Meta-Analysis.

Background: Heart failure (HF) is a main consequence of cardiovascular diseases worldwide. Abnormal expression levels of microRNAs (miRNAs) in HF are observed in current studies. Novel biomarkers miRNAs may play an important role in the development of HF. Nevertheless, the inconsistency of miRNA expression limits the clinical application. We thus perform this systematic review of the miRNAs expression profiling to identify potential HF biomarkers. Methods: The electronic databases of Embase, Medline, and Cochrane Library were systematically searched to identify the miRNA expression profiles between HF subjects and non-HF controls before May 26th, 2021. The pooled results were shown as log10 odds ratios (logORs) with 95% confidence intervals (CI) using random-effect models. Subgroup analyses were conducted according to species, region, and sample source. The quality assessment of included studies was independently conducted based on Diagnostic Accuracy Study 2 (QUADAS-2). The sensitivity analysis was conducted based on sample size. Results: A total of 55 miRNA expression articles reporting 276 miRNAs of HF were included. 47 consistently up-regulated and 10 down-regulated miRNAs were identified in the overall analysis, with the most up-regulated miR-21 (logOR 8.02; 95% CI: 6.76-9.27, P < 0.001) and the most down-regulated miR-30c (logOR 6.62; 95% CI: 3.04-10.20, P < 0.001). The subgroup analysis of sample source identified 35 up-regulated and 10 down-regulated miRNAs in blood sample, the most up-regulated and down-regulated miRNAs were miR-210-3p and miR-30c, respectively. In the region sub-groups, let-7i-5p and miR-129 were most up-regulated and down-regulated in Asian countries, while in non-Asian countries, let-7e-5p and miR-30c were the most dysregulated. It's worth noting that miR-622 was consistently up-regulated in both Asian and non-Asian countries. Sensitivity analysis showed that 46 out of 58 (79.31%) miRNAs were dysregulated. Conclusion: A total of 57 consistently dysregulated miRNAs related to HF were confirmed in this study. Seven dysregulated miRNAs (miR-21, miR-30c, miR-210-3p, let-7i-5p, miR-129, let-7e-5p, and miR-622) may be considered as potential non-invasive biomarkers for HF. However, further validation in larger-scale studies are needed to verify our conclusions.

Valuation of Ecosystem Services for the Sustainable Development of Hani Terraces: A Rice-Fish-Duck Integrated Farming Model.

As a complementary and symbiotic agro-ecological cycle system, a nature-based integrated rice-fish-duck farming ecosystem was developed in the Honghe Hani Rice Terraces. The main research objective was to evaluate the ecosystem services based on case studies of the Hani integrated rice-fish-duck terraced farming system and determine its potential and its importance as an ecological asset. We developed a valuation model to assess the value of the integrated farming system based on the three aspects of provisioning, regulation and maintenance, and cultural services; we selected eight groups and 10 indictors to evaluate the ecosystem services of the integrated ecosystem in Honghe Hani Rice Terraces was 3.316 billion CNY, of which the provisioning service value was 1.76 billion CNY, the regulation and maintenance service value was 1.32 billion CNY, and the cultural services value was 230.85 million CNY. The evaluation will be useful as a theoretical reference for poverty alleviation policy makers in similar poverty-stricken areas, enabling them to better protect and promote this mode of farming and further promote the protection of the natural environment and cultural heritage alongside the sustainable development of natural resources and human well-being.

Promoting Proton Transfer and Stabilizing Intermediates in Catalytic Water Oxidation via Hydrophobic Outer Sphere Interactions.

The outer coordination sphere of metalloenzyme often plays an important role in its high catalytic activity, however, this principle is rarely considered in the design of man-made molecular catalysts. Herein, four Ru-bda (bda=2,2'-bipyridine-6,6'-dicarboxylate) based molecular water oxidation catalysts with well-defined outer spheres are designed and synthesized. Experimental and theoretical studies showed that the hydrophobic environment around the Ru center could lead to thermodynamic stabilization of the high-valent intermediates and kinetic acceleration of the proton transfer process during catalytic water oxidation. By this outer sphere stabilization, a 6-fold rate increase for water oxidation catalysis has been achieved.

The Effect of a Combined Ganciclovir, Methylprednisolone, and Immunoglobulin Regimen on Survival and Functional Outcomes in Patients With Japanese Encephalitis.

Objective: There is currently no effective treatment for Japanese encephalitis, which has a high rate of morbidity and mortality. This study assessed the effectiveness of a ganciclovir, methylprednisolone, and immunoglobulin combination (TAGMIC) therapy in decreasing cognitive impairment and mortality among patients with Japanese encephalitis. Methods: We retrospectively assessed the clinical data of 31 patients diagnosed with Japanese encephalitis, who were admitted to an intensive care unit. Patients were divided into the TAGMIC and non-TAGMIC group according to their treatment regime. We compared the 60-day, 6-month, and overall mortality and survival curves between groups. We also compared Barthel Index scores, Montreal Cognitive Assessment (MoCA) scores, and diffusion tensor imaging (DTI) results. Results: There was no significant difference in the 30-day mortality rate or Kaplan-Meier survival curve between groups. The 60-day, 6-month, and overall mortality rates in the TAGMIC group were significantly reduced (P = 0.043, P = 0.018, and P = 0.018, respectively) compared with the non-TAGMIC group (0, 0, 0 vs. 31.25, 37.5, 37.5%, respectively). The 60-day, 6-month, and overall Kaplan-Meier survival curves were significantly different between groups (P = 0.020, P = 0.009, P = 0.009, respectively). There was no significant difference in the Barthel Index scores of surviving patients. Among the five patients who underwent MoCA and DTI, four had a score of 0/5 for delayed recall (no cue), while the remaining patient had a score of 2/5. All five patients were able to achieve a score of 5/5 with classification and multiple-choice prompts, and had sparse or broken corpus callosum (or other) fibre bundles. Conclusion: TAGMIC treatment can reduce mortality due to severe Japanese encephalitis. The memory loss of surviving patients is mainly due to a disorder of the memory retrieval process, which may be related to the breakage of related fibre bundles.

Task-Specific Tailored Cationic Polymeric Network with High Base-Resistance for Unprecedented 99TcO4 - Cleanup from Alkaline Nuclear Waste.

Direct removal of 99TcO4 - from alkaline nuclear waste is desirable because of the nuclear waste management and environmental protection relevant to nuclear energy but is yet to be achieved given that combined features of decent base-resistance and high uptake selectivity toward anions with low charge density have not been integrated into a single anion-exchange material. Herein, we proposed a strategy overcoming these challenges by rationally modifying the imidazolium unit of a cationic polymeric network (SCU-CPN-4) with bulky alkyl groups avoiding its ring-opening reaction induced by OH- because of the steric hindrance effect. This significantly improves not only the base-resistance but also the affinity toward TcO4 - as a result of enhanced hydrophobicity, compared to other existing anion-exchange materials. More importantly, SCU-CPN-4 exhibits record high uptake selectivity, fast sorption kinetics, sufficient robustness, and promising reusability for removing 99TcO4 - from the simulated high-level waste stream at the U.S. Savannah River Site, a typical alkaline nuclear waste, in both batch experiment and dynamic column separation test for the first time.

Crystalline-Phase-Recognition-Induced Domino Phase Transition and Luminescence Switching for Advanced Information Encryption.

Herein, a new mechanism, namely, crystalline phase recognition (CPR), is proposed for the single-crystal-to-single-crystal (SCSC) transition of metal halides. Chiral ß-[Bmmim]2 SbCl5 (Bmmim=1-butyl-2,3-methylimidazolium) can recognize achiral α-[Bmmim]2 SbCl5 on the basis of a key-lock feature through intercontact of their single crystals, resulting in a domino phase transition (DPT). The concomitant photoluminescence (PL) switching enables observation of the DPT in situ. The liquid eutectic interface, stress-strain transfer, and feasible thermodynamics are key issues for the CPR. DFT calculations and PL measurements revealed that the optical absorption and emission of the isomers mainly originate from [SbCl5 ]2- anions. The structural effects (e.g., supramolecular interactions and [SbCl5 ]2- distortion) on the optical emission are clarified. As a novel type of stimuli response, the CPR-induced DPT and luminescence switching exhibit potential for application in advanced time-resolved information encryption.

Real-World Prevalence of Direct Oral Anticoagulant Off-Label Doses in Atrial Fibrillation: An Epidemiological Meta-Analysis.

Background: The use of direct oral anticoagulant (DOAC) off-label doses in atrial fibrillation (AF) patients may result in poor clinical outcomes. However, the true prevalence remains scarce. This study aims at estimating the prevalence of DOAC off-label doses in AF patients. Methods: Databases of MEDLINE, EMBASE, and COCHRANE were searched from inception through February 2020 for real-world studies that reported the off-label definition and prevalence data of AF patients using DOACs. The primacy outcomes were the overall prevalence of DOAC off-label doses and the corresponding underdose and overdose. The random-effects model was used for data synthesis. Variations on individual DOAC and different regions were examined by subgroup analyses. Results: A total of 23 studies involving 162,474 AF patients were finally included. The overall prevalence of DOAC off-label doses was 24% (95% CI, 19-28%), with 18% for dabigatran, 27% for rivaroxaban, 24% for apixaban, and 26% for edoxaban. The prevalence of underdosed DOACs was 20% (95% CI, 16-24%) with significant difference among individual anticoagulants (13% for dabigatran, 22% for rivaroxaban, 22% for apixaban, and 18% for edoxaban; P interaction =0.02). The prevalence of overdosed DOACs was 5% (95% CI, 3-7%), with the lowest prevalence observed in apixaban (2%). Subgroup analyses by regions demonstrated that the prevalence of DOAC off-label doses was higher in Asia (32%) than in North America (14%) and in Europe (22%), with underdose being predominant. Regardless of different regions, the prevalence of overdose was relatively low (4-6%). Conclusion: This study provides an estimation of DOAC off-label doses in the real-world setting. The prevalence rate of DOAC off-label doses in AF patients was relatively high, with underdose being predominant. Clinicians in Asia preferred to prescribe underdose of DOACs to AF patients. More evidence about the appropriateness of DOAC off-label doses in AF patients is urgently needed. Education programs concerning the appropriate prescription of DOACs within the drug labels and accepted guidelines are necessary to DOAC prescribers to ensure the safety and effectiveness of anticoagulation therapy for patients with AF.

Effectiveness and Safety of Under or Over-dosing of Direct Oral Anticoagulants in Atrial Fibrillation: A Systematic Review and Meta-analysis of 148909 Patients From 10 Real-World Studies.

Background: In routine clinical practice, non-standard doses of direct oral anticoagulants (DOACs) are commonly used in patients with atrial fibrillation (AF). However, data on the clinical outcomes of non-standard doses of DOACs are limited. Methods: The MEDLINE, Embase, and Cochrane Library databases were systematically searched from their inception until 30 June 2020 for studies that reported the effectiveness or safety outcomes of non-standard doses of DOACs compared with on-label doses of DOACs in patients with atrial fibrillation. Non-standard doses of DOACs were defined as under or over-dose of DOACs based on the recommended standard doses in drug labels. A random-effects meta-analysis was performed to calculate the pooled hazard ratio and associated 95% confidence interval (95% confidence interval). Subgroup analyses were conducted according to individual DOACs and different geographic regions. Results: Ten articles involving 148,909 patients with AF were included. There were no significant differences between under-dosing and on-label dosing with respect to stroke/systematic embolism (HR: 1.01, 95% CI: 0.93-1.09), major bleeding (HR: 0.98, 95% CI: 0.77-1.19), intracranial haemorrhage (HR: 1.07, 95% CI: 0.74-1.40), gastrointestinal bleeding (HR: 1.10, 95% CI: 0.82-1.39), and myocardial infarction (HR: 1.07, 95% CI: 0.89-1.25), except for an increased risk of death (HR: 1.37, 95% CI: 1.01-1.73). We observed a significant association between over-dosing of DOACs and increased risk of stroke/systematic embolism (HR: 1.18, 95% CI: 1.04-1.32), major bleeding (HR: 1.16, 95% CI: 1.03-1.29), and death (HR: 1.21, 95% CI: 1.03-1.38) compared with on-label dosing. Furthermore, over-dosing of DOACs increased the risk of stroke/systematic embolism (HR: 1.16; 95% CI: 1.00-1.33) and major bleeding events (HR: 1.18; 95% CI: 1.00-1.37) in Asian patients. Conclusion: A reduced dose of DOACs might be safely and effectively used in clinical practice, especially in Asian patients, whereas high-dose DOACs might not be well tolerated by Asian patients.

99TcO4- Separation through Selective Crystallization Assisted by Polydentate Benzene-Aminoguanidinium Ligands.

99Tc is one of the most abundant radiotoxic isotopes in used nuclear fuel with a high fission yield and a long half-life. Effective removal of pertechnetate (TcO4-) from an aqueous solution is important for nuclear waste separation and remediation. Herein, we report a series of facilely obtained benzene-linked guanidiniums that could precipitate TcO4- and its nonradioactive surrogate ReO4- from a high-concentration acidic solution through self-assembly crystallization. The resulting perrhenate and pertechnetate solids exhibit exceptionally low aqueous solubility. The benzene-linked guanidiniums hold one of the highest TcO4- removal capacities (1279 mg g-1) among previously reported materials and possess a removal percentage of 59% for ReO4- in the presence of Cl- over 50 times. The crystallization mechanism was clearly illustrated by the single-crystal structures and density functional theory calculations, indicating that TcO4- is captured through a charge-assisted hydrogen bonding interaction and stabilized by π-π stacking layers. In addition, the removal process is easily recycled and no toxic organic reagents are introduced. This work provides a green approach to preliminarily separate TcO4- from high-level nuclear wastes.

Electron Beam Irradiation-Induced Formation of Defect-Rich Zeolites under Ambient Condition within Minutes.

Zeolites are a well-known family of microporous aluminosilicate crystals with a wide range of applications. Their industrial synthetic method under hydrothermal condition requires elevated temperature and long crystallization time and is therefore quite energy-consuming. Herein, we utilize high-energy electron beam irradiation generated by an industrial accelerator as a distinct type of energy source to activate the formation reaction of Na-A zeolite. The initial efforts afford an attractive reaction process that can be achieved under ambient conditions and completed within minutes with almost quantitative yield, leading to notable energy saving of one order of magnitude compared to the hydrothermal reaction. More importantly, electron beam irradiation simultaneously exhibits an etching effect during the formation of zeolite generating a series of crystal defects and additional pore windows that can be controlled by irradiation dose. These observations give rise to significantly enhanced surface area and heavy metal removal capabilities in comparison with Na-A zeolite synthesized hydrothermally. Finally, we show that this method can be applied to many other types of zeolites.

Unveiling the Uncommon Fluorescent Recognition Mechanism towards Pertechnetate Using a Cationic Metal-Organic Framework Bearing N-Heterocyclic AIE Molecules.

As one of most problematic radionuclides, technetium-99, mainly in the form of anionic pertechnetate (TcO4 - ), exhibits high environmental mobility, long half-life, and radioactive hazard. Due to low charge density and high hydrophobicity for this tetrahedral anion, it is extremely difficult to recognize it in water. Seeking efficient and selective recognition method for TcO4 - is still a big challenge. Herein, a new water-stable cationic metal-organic framework (ZJU-X8) was reported, bearing tetraphenylethylene pyrimidine-based aggregation-induced emission (AIE) ligands and attainable silver sites for TcO4 - detection. ZJU-X8 underwent an obvious spectroscopic change from brilliant blue to flavovirens and exhibited splendid selectivity towards TcO4 - . This uncommon fluorescent recognition mechanism was well elucidated by batch sorption experiments and DFT calculations. It was found that only TcO4 - could enter into the body of ZJU-X8 through anion exchange whereas other competing anions were excluded outside. Subsequently, after interaction between TcO4 - and silver ions, the electron polarizations from pyrimidine rings to Ag+ cations significantly lowered the energy level of the π* orbital and thus reduced the π-π* energy gap, resulting in a red-shift in the fluorescent spectra.

Direct Oral Anticoagulants vs. Vitamin-K Antagonists in the Elderly With Atrial Fibrillation: A Systematic Review Comparing Benefits and Harms Between Observational Studies and Randomized Controlled Trials.

Background: The publication of high-quality observational studies (OSs) has fueled reassessment of the treatment effects of direct oral anticoagulants (DOACs) in the elderly with atrial fibrillation (AF). Methods: The MEDLINE, EMBASE, and Cochrane Library databases were systematically searched (through July 1, 2019) for eligible OSs and randomized controlled trials (RCTs) that reported effectiveness outcomes [stroke or systemic embolism (SE)] or safety outcomes [intracranial hemorrhage (ICH), major bleeding, gastrointestinal bleeding (GIB), myocardial infarction (MI), and all-cause mortality] for DOACs and vitamin-K antagonists (VKAs) in elderly AF patients. A random-effects model was applied to calculate adjusted hazard ratios (HRs) for OSs and relative risks (RRs) for RCTs. Interaction analyses and the ratio of HR (RHR) were used to assess and compare OSs and RCTs. Results: A total of 32 studies involving 547,419 patients were included. No significant difference in treatment effect estimates was found between 27 OSs and 5 RCTs [P interaction > 0.05 for each and all 95% confidence interval (CI) of RHR crossed 1.0]. Compared with VKAs, DOACs significantly reduced risk for stroke/SE (OSs, HR: 0.87, 95% CI: 0.81-0.94; RCT, RR: 0.82, 95% CI: 0.67-0.96), and ICH (OSs: 0.47 [0.37-0.57]; RCTs: 0.47 [0.31-0.63]), without increasing risk for GIB (OSs: 1.21 [0.98-1.43]; RCTs: 1.34 [0.91-1.77]), and all-cause mortality (OSs: 1.01 [0.92-1.11]; RCTs: 0.94 [0.87-1.00]). Among OSs, DOACs significantly decreased risk for major bleeding (0.87 [0.77-0.98]) and MI (0.89 [0.79-0.99]). It was found that dabigatran, but not other DOACs, significantly increased risk for GIB (1.48 [1.23-1.72]). Conclusions: DOACs were demonstrated to be more effective and safer than VKAs in elderly AF patients, whereas dabigatran users had a 48% increase in risk for GIB.

99TcO4- removal from legacy defense nuclear waste by an alkaline-stable 2D cationic metal organic framework.

Removal of 99TcO4- from legacy defense nuclear tank waste at Savannah River Site is highly desirable for the purpose of nuclear safety and environmental protection, but currently not achievable given the extreme conditions including high alkalinity, high ionic strength, and strong radiation field. Herein, we present a potential solution to this long-term issue by developing a two-dimensional cationic metal organic framework SCU-103, showing ultrahigh stability in alkaline aqueous media and great resistance to both ß and γ radiation. More importantly, it is very effective for 99TcO4- separation from aqueous media as demonstrated by fast exchange kinetics, high sorption capacity, and superior selectivity, leading to the successful removal of 99TcO4- from actual Savannah River Site high level tank waste for the first time, to the best of our knowledge. In addition, the uptake mechanism is comprehensively elucidated by molecular dynamics simulation and density functional theory calculation, showing a unique chemical recognition of anions with low charge density.

miR-150 regulates glucose utilization through targeting GLUT4 in insulin-resistant cardiomyocytes.

MicroRNAs (miRNAs) play an important role in cardiac function and metabolism. However, whether they regulate insulin resistance (IR) of cardiomyocytes remains unclear. The aim of the present study was to shed light on this issue with a focus on miR-150. We found here that miR-150 level was elevated in myocardium of type 2 diabetes mellitus (T2DM) rat model and in insulin-resistant cardiomyocytes induced by high glucose (25 mM) and high insulin (1 µM). Deregulation of miR-150 downregulated the protein and mRNA levels of glucose transporter 4 (GLUT4) as assessed by western blot, real-time polymerase chain reaction (qPCR), and immunofluorescence assays. Overexpression of miR-150 inhibited glucose utilization in cardiomyocytes as detected by 2-deoxyglucose transport and glucose consumption assays. In contrast, knockdown of miR-150 significantly increased glucose uptake in cardiomyocytes. Moreover, GLUT4 translocation was increased after transfection of miR-150 inhibitor (AMO-150). Collectively, miR-150 reduced glucose utilization by directly decreasing the expression and translocation of GLUT4 in the cardiomyocytes with IR and therefore might be a new therapeutic target for metabolic diseases such as T2DM.

Modulation of the Structure and Photoluminescence of Bismuth(III) Chloride Hybrids by Altering the Ionic-Liquid Cations.

Two bismuth(III) halides hybrids with room-temperature phosphorescence (RTP), namely, [BPy]2[Bi2Cl8(bpym)] (1, BPy = N-butylpyridinium) and [EPy]2[Bi2Cl8(bpym)] (2, EPy = N-ethylpyridinium), were synthesized and characterized. Structural comparison reveals that 1 and 2 possess similar anionic zigzaglike chain of [Bi2Cl8(bpym)]n2n-; however, different packing modes of anion/cations and thus different weak interactions. Interestingly, the utilization of pyridinium cations with different length of alkyl chain could tune the RTP behaviors efficiently. The RTP quantum yield (QY) is increased more than 5-fold from 1 to 2 probably due to more rigid structure of 2 arising from the additional H-bond and anion-π interactions, as confirmed by Hirshfeld surfaces analyses and PLATON calculations. Moreover, additional π-π interactions in 1 could stabilize the triplet excitons, leading to an average lifetime of 1 (11.36 ms at 77 K and 1.407 ms at 298 K) being higher than 2 (0.3618 ms at 77 K and 0.07511 ms at 298 K). Density functional theory (DFT) calculations confirm that inorganic moiety to organic ligand charge-transfer (IOCT) is involved in the phosphorescence process. The present work provides a new sight into the design of RTP metal halides through studying the structure-RTP relationship.

Comparison of effectiveness and safety of direct oral anticoagulants versus vitamin-k antagonists in elderly patients with atrial fibrillation: a systematic review and cost-effectiveness analysis protocol.

BACKGROUND: Current evidence regarding the effectiveness and safety of direct oral anticoagulants (DOACs) in the elderly with atrial fibrillation (AF) remains scarce. Based on the emerging evidence from real-world studies (RWSs) associated with DOACs, we will perform a systematic review and meta-analysis of data from RWSs and randomized controlled trials (RCTs) to compare the effectiveness, safety and cost of DOACs versus Vitamin K antagonists (VKAs) in elderly patients with AF. METHODS: The MEDLINE, EMBASE and Cochrane Library databases will be systematically searched until June 30, 2019 for eligible RWSs and RCTs that reported the clinical outcomes between DOACs and VKAs in elderly patients with AF. The effectiveness outcome is stroke or systemic embolism (SE), and the safety outcomes are major bleeding, intracranial haemorrhage (ICH), gastrointestinal bleeding (GIB), myocardial infarction (MI) and all-cause mortality. A random-effects model will be used to calculate adjusted hazard ratios (HRs) for RWSs and relative risks (RRs) for RCTs, separately. The interaction analysis and the ratio of HRs (RHRs) will be applied to compare the treatment effect difference between RWSs and RCTs. A Markov model will be constructed to evaluate the cost-effectiveness of DOACs versus VKAs in elderly AF patients in real-world setting. DISCUSSION: This study will summarize all available evidences from RWSs and RCTs for a comprehensive and rigorous systematic review on the effectiveness and safety associated with DOACs, as well as perform a cost-effectiveness analysis to evaluate the price performance of DOACs among elderly AF patients in real clinical setting. TRIAL REGISTRATION: PROSPERO register platform (CRD42019142881, www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID =142881).