Aging and atrial fibrillation: A vicious circle.

Atrial fibrillation (AF) is the commonest sustained cardiac arrhythmia observed in clinical practice. Its prevalence increases dramatically with advancing age. This review article discusses the recent advances in studies investigating the relationship between aging and AF and the possible underlying mechanisms.

Resveratrol activation of SIRT1/MFN2 can improve mitochondria function, alleviating doxorubicin-induced myocardial injury.

Background: Doxorubicin is a widely used cytotoxic chemotherapy agent for treating different malignancies. However, its use is associated with dose-dependent cardiotoxicity, causing irreversible myocardial damage and significantly reducing the patient's quality of life and survival. In this study, an animal model of doxorubicin-induced cardiomyopathy was used to investigate the pathogenesis of doxorubicin-induced myocardial injury. This study also investigated a possible treatment strategy for alleviating myocardial injury through resveratrol therapy in vitro. Methods: Adult male C57BL/6J mice were randomly divided into a control group and a doxorubicin group. Body weight, echocardiography, surface electrocardiogram, and myocardial histomorphology were measured. The mechanisms of doxorubicin cardiotoxicity in H9c2 cell lines were explored by comparing three groups (phosphate-buffered saline, doxorubicin, and doxorubicin with resveratrol). Results: Compared to the control group, the doxorubicin group showed a lower body weight and higher systolic arterial pressure, associated with reduced left ventricular ejection fraction and left ventricular fractional shortening, prolonged PR interval, and QT interval. These abnormalities were associated with vacuolation and increased disorder in the mitochondria of cardiomyocytes, increased protein expression levels of α-smooth muscle actin and caspase 3, and reduced protein expression levels of Mitofusin2 (MFN2) and Sirtuin1 (SIRT1). Compared to the doxorubicin group, doxorubicin + resveratrol treatment reduced caspase 3 and manganese superoxide dismutase, and increased MFN2 and SIRT1 expression levels. Conclusion: Doxorubicin toxicity leads to abnormal mitochondrial morphology and dysfunction in cardiomyocytes and induces apoptosis by interfering with mitochondrial fusion. Resveratrol ameliorates doxorubicin-induced cardiotoxicity by activating SIRT1/MFN2 to improve mitochondria function.

Investigation of internal damage evolution in gneiss considering water softening.

In soft rock tunnels, there are often large deformations during construction, especially when the groundwater seepage and softens the surrounding rock. For achieving the purpose of studying the softening effect of water immersion on strength and stability of surrounding rock, 15 rock samples were selected for physical and mechanical tests under 5 conditions: natural state and free immersion for 1, 3, 6, and 9 months, and nuclear magnetic resonance technology(NMR) was also adopted to test the internal pore structure of specimens with different immersion durations, thus the micro structure features of the gneiss, such as the NMR relaxation time T2 spectrum distribution, porosity, and pore volume ratio of different pore sizes under water softening were then obtained. The NMR results shows that the longer the free immersion duration of the rock sample, the greater the porosity; at the same time, the number of micropores in the rock gradually decreases under the interaction of water and rock, and the mesopores increase slightly first and then decrease all the time. The number of macropores is gradually increasing. When the immersion duration is 6 months, the number of macropores begins to increase significantly, and the mechanical properties of the specimens begin to drop significantly. By 9 months, the proportion of macropores in the rock has reached 57.6%. The results showed that the number growth of macropores is the root cause of the macroscopic failure of rock sample. The study results have significance for on-site construction in water-rich areas.

Unsupervised machine learning model to predict cognitive impairment in subcortical ischemic vascular disease.

INTRODUCTION: It is challenging to predict which patients who meet criteria for subcortical ischemic vascular disease (SIVD) will ultimately progress to subcortical vascular cognitive impairment (SVCI). METHODS: We collected clinical information, neuropsychological assessments, T1 imaging, diffusion tensor imaging, and resting-state functional magnetic resonance imaging from 83 patients with SVCI and 53 age-matched patients with SIVD without cognitive impairment. We built an unsupervised machine learning model to isolate patients with SVCI. The model was validated using multimodal data from an external cohort comprising 45 patients with SVCI and 32 patients with SIVD without cognitive impairment. RESULTS: The accuracy, sensitivity, and specificity of the unsupervised machine learning model were 86.03%, 79.52%, and 96.23% and 80.52%, 71.11%, and 93.75% for internal and external cohort, respectively. DISCUSSION: We developed an accurate and accessible clinical tool which requires only data from routine imaging to predict patients at risk of progressing from SIVD to SVCI. HIGHLIGHTS: Our unsupervised machine learning model provides an accurate and accessible clinical tool to predict patients at risk of progressing from subcortical ischemic vascular disease (SIVD) to subcortical vascular cognitive impairment (SVCI) and requires only data from imaging routinely used during the diagnosis of suspected SVCI. The model yields good accuracy, sensitivity, and specificity and is portable to other cohorts and to clinical practice to distinguish patients with SIVD at risk for progressing to SVCI. The model combines assessment of diffusion tensor imaging and functional magnetic resonance imaging measures in patients with SVCI to analyze whether the "disconnection hypothesis" contributes to functional and structural changes and to the clinical presentation of SVCI.

Cardiovascular Toxicity of Proteasome Inhibitors in Multiple Myeloma Therapy.

The treatment for multiple myeloma has advanced significantly over the past few decades. Proteasome inhibitors have become the cornerstone of the treatment of multiple myeloma. However, proteasome inhibitors have shown cardiovascular complications such as hypertension, pulmonary hypertension, heart failure, arrhythmias, ischaemic heart disease and thromboembolism. Detection, monitoring and management of proteasome inhibitor-related cardiovascular toxicity are essential to improve clinical outcomes for patients. Proposed mechanisms of proteasome inhibitor-related cardiovascular toxicity are apoptosis, prolonged inhibition of the ubiquitin-proteasome system, accumulation of improperly folded proteins within cardiomyocytes and higher protein phosphatase 2A activity. To better understand the mechanisms underlying cardiotoxicity, further in vitro and in vivo experiments are required to investigate these hypotheses. Combined use of metformin or angiotensin II receptor blockers with the proteasome inhibitor, carfilzomib, showed an emerging role as a prophylactic therapy because they can preserve heart function in multiple myeloma patients. Metformin is expected to be an effective therapeutic intervention for the management of carfilzomib-induced cardiotoxicity. There has been evidence that three compounds, apremilast, rutin, and dexrazoxane, can reverse carfilzomib-induced cardiotoxicity in rats. The future transition from animal experiments to clinical trials is worth waiting for.

Efficacy of Yiqi Yangyin Jiedu decoction in postoperative patients with thyroid cancer: A protocol for systematic review and meta-analysis.

BACKGROUND: There is no evidence-based data to confirm the efficacy of Yiqi Yangyin Jiedu Decoction (YYJD) in postoperative thyroid cancer patients. Therefore, in order to provide new evidence-based medical evidence for clinical treatment, we used this protocol to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of YYJD in postoperative patients with thyroid cancer. METHODS: This systematic review and meta-analysis has been prospectively registered in the PROSPERO (No. CRD42022365826). Six databases, including Medicine, Embase, Cochrane, CNKI, Wan Fang, and VIP, will be searched from their inception to February 1, 2023. Clinical controlled studies investigating the efficacy and safety of YYJD in patients after thyroid cancer surgery will all be considered for inclusion. The primary outcomes are tumor recurrence rate and overall survival. The secondary outcomes include treatment-related adverse effects, length of hospital stay, and patient satisfaction. All data will be analyzed using R version 3.4.3 to calculate pooled standardized mean differences for outcomes. Data that can not be retrieved will be interpreted from graphs using digital ruler software. RESULTS: The results of this paper will fill a gap in the literature regarding this project. CONCLUSION: We assume that the YYJD has a positive effect.

Culture Effects on the Chinese Version Boston Naming Test Performance and the Normative Data in the Native Chinese-Speaking Elders in Mainland China.

Background: The Chinese version of Boston Naming Test (BNT-C) is administered in China widely. However, the neuropsychological parameter of BNT-C in native Chinese-speaking elders in mainland China has not been explored systematically. The aim of this study was to explore cultural influences on BNT-C performance and establish norms among native Chinese-speaking elders in Beijing. Methods: A total of 161 native, Chinese-speaking, cognitively normal elders aged ≥55 years were enrolled from various communities in Beijing. The BNT-C was conducted on all the participants. The internal consistency, participants' familiarity, and naming accuracy were analyzed and compared with data from Chinese areas outside the mainland and from American published previously. The influencing factors and stratified norms for BNT-C were established. Results: The BNT-C showed good internal consistency (α = 0.738). Strong correlation between naming accuracy and object familiarity was found (r = 0.962, P < 0.001). Participants' familiarity and correct naming rate for many items were notably different between the Chinese-speaking elders and English-speaking elders in America. The difference in some items' correct naming rate also existed between Beijing, Taiwan, and Hongkong. Higher education was associated with higher scores, whereas age and gender had no effect on BNT-C performance. The recommended norms of total naming scores for elders with education ≤ 9 and >9 years were 16 and 23, respectively. Conclusion: The participants' familiarity with BNT items differed between different cultures, which further affected the naming accuracy and total scores. The education stratified norms established here are helpful for the better application of BNT-C in mainland China.

Applicability of five nutritional screening tools in Chinese patients undergoing colorectal cancer surgery: a cross-sectional study.

OBJECTIVES: To identify the most appropriate nutritional risk screening tool for patients undergoing colorectal cancer surgery, five nutritional screening tools, including the Nutritional Risk Screening 2002 (NRS 2002), Short Form of Mini Nutritional Assessment (MNA-SF), Malnutrition Universal Screening Tool (MUST), Malnutrition Screening Tool (MST) and Nutritional Risk Index (NRI), were employed to evaluate the nutritional risk at admission and short-term clinical outcome prediction. DESIGN: A cross-sectional study. SETTING: A comprehensive affiliated hospital of a university in Shenyang, Liaoning Province, China. PARTICIPANTS: 301 patients diagnosed with colorectal cancer were continuously recruited to complete the study from October 2020 to May 2021. PRIMARY AND SECONDARY OUTCOME MEASURES: Within 48 hours of hospital admission, five nutritional screening tools were used to measure the nutritional risk and to determine their relationship with postoperative short-term clinical outcomes. RESULTS: The nutritional risk assesed by the five tools ranged from 25.2% to 46.2%. Taking the Subject Global Assessment as the diagnostic standard, MNA-SF had the best consistency (κ=0.570, p<0.001) and MST had the highest sensitivity (82.61%). Multivariate Logistic regression analysis after adjusting confounding factors showed that the NRS 2002 score ≥3 (OR 2.400, 95% CI 1.043 to 5.522) was an independent risk factor for postoperative complications and was the strongest predictor of postoperative complications (area under the curve 0.621, 95% CI 0.549 to 0.692). The scores of NRS 2002 (r=0.131, p<0.001), MNA-SF (r=0.115, p<0.05) and NRI (r=0.187, p<0.05) were poorly correlated with the length of stay. There was no correlation between the five nutritional screening tools and hospitalisation costs (p>0.05). CONCLUSIONS: Compared with the other four nutritional screening tools, we found that NRS 2002 is the most appropriate nutritional screening tool for Chinese patients with colorectal cancer.

IP3R1/GRP75/VDAC1 complex mediates endoplasmic reticulum stress-mitochondrial oxidative stress in diabetic atrial remodeling.

RATIONALE: Endoplasmic reticulum (ER) stress and mitochondrial dysfunction are important mechanisms of atrial remodeling, predisposing to the development of atrial fibrillation (AF) in type 2 diabetes mellitus (T2DM). However, the molecular mechanisms underlying these processes especially their interactions have not been fully elucidated. OBJECTIVE: To explore the potential role of ER stress-mitochondrial oxidative stress in atrial remodeling and AF induction in diabetes. METHODS AND RESULTS: Mouse atrial cardiomyocytes (HL-1 cells) and rats with T2DM were used as study models. Significant ER stress was observed in the diabetic rat atria. After treatment with tunicamycin (TM), an ER stress agonist, mass spectrometry (MS) identified several known ER stress and calmodulin proteins, including heat shock protein family A (HSP70) member [HSPA] 5 [GRP78]) and HSPA9 (GRP75, glucose-regulated protein 75). In situ proximity ligation assay indicated that TM led to increased protein expression of the IP3R1-GRP75-VDAC1 (inositol 1,4,5-trisphosphate receptor 1-glucose-regulated protein 75-voltage-dependent anion channel 1) complex in HL-1 cells. Small interfering RNA silencing of GRP75 in HL-1 cells and GRP75 conditional knockout in a mouse model led to impaired calcium transport from the ER to the mitochondria and alleviated mitochondrial oxidative stress and calcium overload. Moreover, GRP75 deficiency attenuated atrial remodeling and AF progression in Myh6-Cre+/Hspa9flox/flox + TM mice. CONCLUSIONS: The IP3R1-GRP75-VDAC1 complex mediates ER stress-mitochondrial oxidative stress and plays an important role in diabetic atrial remodeling.

Investigation on the Properties of Gneiss under Different Ground Stresses.

Initial geostress has great influence on the properties of gneiss. The physical and mechanical properties of gneiss vary considerably due to different initial geostresses, which exert a huge effect on the stability of underground engineering. In order to explore the influence of initial ground stress on the properties of gneiss. Changes in the physical properties (e.g., P-wave velocity and volumetric weight), mechanical properties (e.g., compressive strength, elastic modulus, and residual strength) and failure mode of gneiss are analyzed by conducting physical and mechanical tests on gneiss in different ground stress areas. The results show that high geostress can improve the pre-peak mechanical properties of gneiss, and weaken its post-peak mechanical properties. When the initial geostress is greater, the pre-peak mechanical properties are better, and the post-peak mechanical properties are worse. The failure mode of gneiss under high ground stress is primarily brittle failure. When the initial ground stress is greater, brittleness is stronger. According to the research results of this paper, it can provide the basis for the optimization and improvement of underground engineering support in gneiss strata with high geostress. The research results have important reference value and guiding significance for underground engineering construction in high geostress gneiss areas.

Release characteristics of polycyclic aromatic hydrocarbons (PAHs) leaching from oil-based drilling cuttings.

Drilling cuttings, the primary byproduct from the exploration and mining of shale gas, are potentially hazardous wastes that are associated with the serious depletion of land resources and environmental safety problems. In this work, the distribution of polycyclic aromatic hydrocarbons (PAHs) in oil-based residues of shale gas drilling cuttings was studied. Furthermore, a column leaching test was carried out to investigate the leaching behaviour of PAHs. The results showed that (1) the concentrations of 4-ring PAHs were highest among the PAH concentrations detected from the oil-based residues, and the concentration of PAHs decreased with increasing particle size of the residues. (2) The PAH concentration in leachates from all the tested residues differed during the leaching process, and the cumulative amount of each leached PAH accounted for 1.50-3.20% of the total PAHs. (3) The first-order diffusion model (FRDM) was the most applicable model for describing the leaching characteristics of the PAHs, and the leaching rate was initially controlled by surface wash-off and then by diffusion.

mTOR-mediated autophagy in the hippocampus is involved in perioperative neurocognitive disorders in diabetic rats.

INTRODUCTION: Perioperative neurocognitive disorders (PND) are common neurological complications after surgery. Diabetes mellitus (DM) has been reported to be an independent risk factor for PND, but little is known about its mechanism of action. Mammalian target of rapamycin (mTOR) signaling is crucial for neuronal growth, development, apoptosis, and autophagy, but the dysregulation of mTOR signaling leads to neurological disorders. The present study investigated whether rapamycin can attenuate PND by inhibiting mTOR and activating autophagy in diabetic rats. METHODS: Male diabetic Sprague-Dawley rats underwent tibial fracture surgery under isoflurane anesthesia to establish a PND model. Cognitive functions were examined using the Morris water maze test. The levels of phosphorylated mTOR (p-mTOR), phosphorylated tau (p-tau), autophagy-related proteins (Beclin-1, LC3), and apoptosis-related proteins (Bax, Bcl-2, cleaved caspase-3) in the hippocampus were examined on postoperative days 3, 7, and 14 by Western blot. Hippocampal amyloid ß (Aß) levels were examined by immunohistochemistry. RESULTS: The data showed that surgical trauma and/or DM impaired cognitive function, induced mTOR activation, and decreased Beclin-1 levels and the LC3-II/I ratio. The levels of Aß and p-tau and the hippocampal apoptotic responses were significantly higher in diabetic or surgery-treated rats than in control rats and were further increased in diabetic rats subjected to surgery. Pretreatment of rats with rapamycin inhibited mTOR hyperactivation and restored autophagic function, effectively decreasing tau hyperphosphorylation, Aß deposition, and apoptosis in the hippocampus. Furthermore, surgical trauma-induced neurocognitive disorders were also reversed by pretreatment of diabetic rats with rapamycin. CONCLUSION: The results demonstrate that mTOR hyperactivation regulates autophagy, playing a critical role in the mechanism underlying PND, and reveal that the modulation of mTOR signaling could be a promising therapeutic strategy for PND in patients with diabetes.

Volatilization behavior of polycyclic aromatic hydrocarbons from the oil-based residues of shale drill cuttings.

Shale gas, an emerging oil-bearing and pillar industry at home and abroad, has a very large impact on economic development and industry, but the resulting emerging pollutants pose a serious threat to the environment. Drilling cuttings, the primary byproduct of the exploration and mining of shale gas, are potentially hazardous types of waste that seriously deplete land resources and pose environmental safety problems. In this paper, a long-term static volatilization experiment was conducted to study the volatilization of polycyclic aromatic hydrocarbons (PAHs) in the oil-based residue of shale gas drill cuttings. Furthermore, the effects of some relevant environmental factors controlling the volatilization behavior were evaluated, including different particle sizes, temperatures and illuminances. The results showed that (1) the volatilization concentrations of PAHs gradually increased with prolonged volatilization time. PAHs with smaller ring numbers were present at the highest concentrations among the detected PAHs, and they were more readily volatilized and could be detected earlier. (2) The C-history method was found to significantly describe the kinetic process of the volatilization of PAHs. (3) Different environmental factors had different effects on the volatilization of PAHs. We found that increasing the temperature and illuminance and decreasing the particle size increased volatility. Through canonical correspondence analysis, PAHs volatilization was found to be a complex process, so volatilization tests under simulated environmental conditions are of scientific and environmental interest.

Efficacy and safety of Yiqi Huoxue Yangxin decoction combined with western medicine in patients with chronic coronary heart disease: A protocol for systematic review and meta-analysis.

BACKGROUND: There is no evidence-based data to confirm the efficacy of Yiqi Huoxue Yangxin Decoction combined with Western medicine in patients with coronary heart disease (CHD). Therefore, in order to provide new medical evidence for clinical treatment, we used this protocol to conduct a systematic review and meta-analysis on the effectiveness and safety of Yiqi Huoxue Yangxin Decoction combined with Western medicine in patients with CHD. METHODS: The systematic review protocol is registered in PROSPERO under registration number CRD42022372800. The systematic literature review will follow PRISMA guidelines (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). The following search terms will be used in PUBMED, Scopus, EMBASE, Cochrane Library, CNKI, Wan Fang, and VIP on December 1, 2022. Two independent authors extract the following descriptive raw information from selected studies: study characteristics such as authors, year of publication, study design; patient demographic information such as number of patients, mean age, body mass index, and sex ratio. The primary outcome of interest is symptom scores. Secondary outcomes include ECG effective rate, improvement of blood lipid index, and adverse events. The Cochrane Bias Risk Tool is used independently by 2 reviewers to assess the risk of bias in included randomized controlled trials. The quality of retrospective studies will be assessed using the Newcastle-Ottawa scale. CONCLUSIONS: The results of our review will be reported strictly following the PRISMA criteria and the review will add to the existing literature by showing compelling evidence and improved guidance in clinic settings.

Leaching behavior of polycyclic aromatic hydrocarbons (PAHs) from oil-based residues of shale gas drill cuttings.

Cuttings are the main solid residues which are generated from drilling operations. Due to the presence of heavy and radioactive elements, the environment risk posed by cuttings has attracted increasing attention. In this work, a short-term static immersion experiment was carried out to investigate the leaching of polycyclic aromatic hydrocarbons (PAHs) from oil-based residues of shale gas drilling cuttings. Furthermore, the effects of some relevant environmental factors controlling the leaching behavior were evaluated, including the different particle sizes, pH, extraction time, solid-to-liquid (S/L) ratio and dissolved organic matter (DOM) concentration. The results showed that (1) the concentrations of leached PAHs gradually increased with prolonged leaching time, but the cumulative amount of PAHs released during leaching was less than 3% of the total. (2) The Elovich, parabolic diffusion and power function models were found to fit the experimental data better than the first-order kinetic equation, indicating that the leaching of PAHs was controlled by the coupling of diffusion and chemical reactions at the source surface. (3) Different environmental factors had different impacts on the leaching of PAHs: the shaking time and presence of DOM increased leachability, the particle size and S/L ratio decreased leachability, and the pH did not affect the leachability of PAHs. Therefore, PAHs leaching was a complex process, and it is of scientific and environmental interest to conduct the leaching tests under the simulated environmental conditions.

Cardiac abnormalities after induction of endoplasmic reticulum stress are associated with mitochondrial dysfunction and connexin43 expression.

The endoplasmic reticulum (ER) is responsible for protein synthesis and calcium storage. ER stress, reflected by protein unfolding and calcium handling abnormalities, has been studied as a pathogenic factor in cardiovascular diseases. The aim of this study is to examine the effects of ER stress on mechanical and electrophysiological functions in the heart and explore the underlying molecular mechanisms. A total of 30 rats were randomly divided into control, ER stress inducer (tunicamycin[TN]) and ER stress inhibitor (tunicamycin+4-phenylbutyric acid [4-PBA]) groups. ER stress induction led to significantly systolic and diastolic dysfunction as reflected by maximal increasing/decreasing rate of left intraventricular pressure (±dp/dt), left ventricular peaksystolic pressure(LVSP) and LV end-diastolic pressure(LVEDP). Epicardial mapping performed in vivo revealed reduced conduction velocity and increased conduction heterogeneity associated with the development of spontaneous ventricular tachycardia. Masson's trichrome staining revealed marked fibrosis in the myocardial interstitial and sub-pericardial regions, and thickened epicardium. Western blot analysis revealed increased pro-fibrotic factor transforming growth factor-ß1 (TGF-ß1), decreased mitochondrial biogenesis protein peroxlsome proliferator-activated receptor-γ coactlvator-1α （PGC-1a）, and decreased mitochondrial fusion protein mitofusin-2 (MFN2). These changes were associated with mitochondria dysfunction and connexin 43(CX43)translocation to mitochondria. These abnormalities can be partially prevented by the ER stress inhibitor 4-PBA. Our study shows that ER stress induction can produce cardiac electrical and mechanism dysfunction as well as structural remodelling. Mitochondrial function alterations are contributed by CX43 transposition to mitochondria. These abnormalities can be partially prevented by the ER stress inhibitor 4-PBA.

Down-regulation of SORL1 is associated with Alzheimer's disease through activating ABC transporter pathway.

Alzheimer's disease (AD) is a common neurodegenerative disease with high morbidity among elderly people. A genetic attribution has been extensively proved. Here, we propose to further prioritize genes that harbor single nucleotide variation (SNV) or structural variation (SV) for AD and explore the underlying potential mechanisms through exploiting their expression and methylation spectra. A high-confidence AD-associated candidate gene list was obtained from the ClinVar and Human Gene Mutation Database (HGMD). Genome-wide methylation and expression profiles of AD and normal subjects were downloaded from the Gene Expression Omnibus (GEO). Through comprehensive comparison of expression and methylation levels between AD and normal samples, as well as different stages of AD samples, SORL1 was identified as the most plausible gene for AD incidence and progression. Gene Set Enrichment Analysis (GSEA) revealed significant activation of the ABC (ATP binding cassette) transporter with the aberrant up-regulation of SORL1 within AD samples. This study unfolds the expression and methylation spectra of previously probed genes with SNV or SV in AD for the first time, and reports an aberrant activation of the ABC transporter pathway that might contribute to AD progression. This should shed some light on AD diagnosis and precision treatment.

Activation of NADPH oxidase mediates mitochondrial oxidative stress and atrial remodeling in diabetic rabbits.

AIMS: The mechanisms of atrial fibrillation (AF) in diabetes mellitus (DM) involve a complex interplay between increased oxidative stress, mitochondrial dysfunction and atrial remodeling. In this study, we examined the effects of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation on mitochondrial oxidative stress and atrial remodeling in a rabbit model of diabetes mellitus (DM). MAIN METHODS: Healthy rabbits were selected and randomly divided into control, diabetic and apocynin administration group. Parameters of echocardiography, atrial electrophysiology, oxidative stress and mitochondrial function were compared between the different groups. KEY FINDINGS: Compared to the control group, the DM group showed higher activity of NADPH oxidase, increased oxidative stress, larger left atrial diameter, a reduction in atrial mean conduction velocity. These findings were associated with increased interstitial fibrosis of the atria and higher atrial fibrillation (AF) inducibility. Moreover, atrial ultrastructure and mitochondrial function such as the mitochondrial respiratory control rate (RCR) were impaired. NADPH oxidase inhibition using the pharmacological agent apocynin improved these changes. SIGNIFICANCE: NADPH oxidase activity plays an important role in mitochondrial oxidative stress, which is associated with AF inducibility by promoting adverse atrial remodeling. The NADPH oxidase inhibitor apocynin can prevent these pathological changes and may be a potential drug for AF treatment.

Bioinformatics method combined with logistic regression analysis reveal potentially important miRNAs in ischemic stroke.

PURPOSE: The present study aimed to investigate the comprehensive differential expression profile of microRNAs (miRNAs) by screening for miRNA expression in ischemic stroke and normal samples. METHODS: Differentially expressed miRNA (DEM) analysis was conducted using limma R Bioconductor package. Target genes of DEMs were identified from TargetScanHuman and miRTarBase databases. Functional enrichment analysis of the target genes was performed using clusterProfiler R Bioconductor package. The miRNA-based ischemic stroke diagnostic signature was constructed via logistic regression analysis. RESULTS: Compared with the normal cohort, a total of 14 DEMs, including 5 up-regulated miRNAs and 9 down-regulated miRNAs, were identified in ischemic stroke patients. These DEMs have 1600 regulatory targets. Using a logistic regression model, the top five miRNAs were screened for constructing an miRNA-based ischemic stroke diagnostic signature. Using the miRNA-mRNA interaction pairs, two target genes (specificity protein 1 (SP1) and Argonaute 1 (AGO1)) were speculated to be the primary genes of ischemic stroke. DISCUSSION AND CONCLUSION: Here, several potential miRNAs biomarkers were identified and an miRNA-based diagnostic signature for ischemic stroke was established, which can be a valuable reference for future clinical researches.

Adsorption of Phenol on Commercial Activated Carbons: Modelling and Interpretation.

Adsorption by activated carbons (AC) is an effective option for phenolic wastewater treatment. Three commercial AC, including coal-derived granular activated carbons (GAC950), coal-derived powdered activated carbons (PAC800), and coconut shell-derived powdered activated carbons (PAC1000), were utilized as adsorbent to study its viability and efficiency for phenol removal from wastewater. Pseudo-first order, pseudo-second order, and the Weber-Morris kinetic models were used to find out the kinetic parameters and mechanism of adsorption process. Further, to describe the equilibrium isotherms, the experimental data were analyzed by the Langmuir and Freundlich isotherm models. According to the experimental results, AC presented a micro/mesoporous structure, and the removal of phenol by AC was affected by initial phenol concentration, contact time, pH, temperature, and humic acid (HA) concentration. The pseudo-second order kinetic and Langmuir models were found to fit the experimental data very well, and the maximum adsorption capacity was 169.91, 176.58, and 212.96 mg/g for GAC950, PAC800, and PAC1000, respectively, which was attributed to differences in their precursors and physical appearance. Finally, it was hard for phenol to be desorbed in a natural environment, which confirmed that commercial AC are effective adsorbents for phenol removal from effluent wastewater.