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Abstract Background Numerous reports indicate that both obesity and type 2 diabetes mellitus (T2DM) are factors associated with cognitive impairment (CI). The objective was to assess the relationship between abdominal obesity as measured by waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and CI in middle-aged and elderly patients with T2DM. Methods A cross-sectional study was conducted, in which a total of 1154 patients with T2DM aged ≥ 40 years were included. WHRadjBMI was calculated based on anthropometric measurements and CI was assessed utilizing the Montreal Cognitive Assessment (MoCA). Participants were divided into CI group (n = 509) and normal cognition group (n = 645). Correlation analysis and binary logistic regression were used to explore the relationship between obesity-related indicators including WHRadjBMI, BMI as well as waist circumference (WC) and CI. Meanwhile, the predictive power of these indicators for CI was estimated by receiver operating characteristic (ROC) curves. Results WHRadjBMI was positively correlated with MoCA scores, independent of sex. The Area Under the Curve (AUC) for WHRadjBMI, BMI and WC were 0.639, 0.521 and 0.533 respectively, and WHRadjBMI had the highest predictive power for CI. Whether or not covariates were adjusted, one-SD increase in WHRadjBMI was significantly related to an increased risk of CI with an adjusted OR of 1.451 (95% CI: 1.261–1.671). After multivariate adjustment, the risk of CI increased with rising WHRadjBMI quartiles (Q4 vs. Q1 OR: 2.980, 95%CI: 2.032–4.371, P for trend

Objectives: 'Super-agers,' individuals over 80 with memory abilities comparable to those 20–30 years younger. The relationship between super-agers and dietary acid load (DAL) is an area that warrants further investigation. We aim to examine the link between DAL and super-agers and assess DAL's effects on cognitive functions across different age groups and cognitive domains. Design: Employing a cross-sectional analysis of the 2011–2014 National Health and Nutrition Examination Survey (NHANES) data, we utilized propensity score analysis and multivariate-adjusted regression to mitigate confounding factors. Setting: Older adults aged 60 and above in the United States. Participants: Our primary analysis encompassed 985 older adults, supplemented by a sensitivity analysis with 2,522 participants. Measurements: DAL was assessed through potential renal acid load (PRAL), estimated net acid excretion (NAEes), and net endogenous acid production (NEAP) indices. Results: Super-agers demonstrate a preference for alkaline diets, shown by their lower DAL indices. After inverse probability of treatment weighting (IPTW), multivariate-adjusted logistic regression reveals that each unit reduction in NAEes and PRAL increases the chances of being a super-ager by 3.9% and 3.0%, respectively. The DAL's impact on cognitive function becomes more pronounced with age. Lower PRAL and NAEes scores are significantly linked to higher situational memory and overall cognitive performance scores in those over 70, with these effects being even more pronounced in participants over 80. Conclusion: This research pioneers in demonstrating that super-agers prefer an alkaline diet, highlighting the potential role of alkaline diet in countering cognitive decline associated with aging.

Abstract In the framework of nonrelativistic QCD, the excited doubly heavy baryons are thoroughly studied via the channel $$e^{+} e^{-}\rightarrow \langle QQ^{\prime }\rangle [n] \rightarrow \Xi _{QQ^{\prime }} +\bar{Q^{\prime }} +{\bar{Q}}$$ e + e - → ⟨ Q Q ′ ⟩ [ n ] → Ξ Q Q ′ + Q ′ ¯ + Q ¯ , which takes place at the collision energy Z-pole. $$Q^{(\prime )}$$ Q ( ′ ) represents b or c quark for the production of $$\Xi _{cc}$$ Ξ cc , $$\Xi _{bc}$$ Ξ bc , and $$\Xi _{bb}$$ Ξ bb , respectively. All of the intermediate diquark states $$\langle QQ'\rangle [n]$$ ⟨ Q Q ′ ⟩ [ n ] in P-wave, $$\langle cc\rangle [^{1}P_{1}]_{{\bar{\textbf{3}}}}$$ ⟨ c c ⟩ [ 1 P 1 ] 3 ¯ , $$\langle cc\rangle [^{3}P_{J}]_{{\textbf{6}}}$$ ⟨ c c ⟩ [ 3 P J ] 6 , $$\langle bc\rangle [^{1}P_{1}]_{{\bar{\textbf{3}}}/ {\textbf{6}}}$$ ⟨ b c ⟩ [ 1 P 1 ] 3 ¯ / 6 , $$\langle bc\rangle [^{3}P_{J}]_{{\bar{\textbf{3}}}/ {\textbf{6}}}$$ ⟨ b c ⟩ [ 3 P J ] 3 ¯ / 6 , $$\langle bb \rangle [^{1}P_{1}]_{{\bar{\textbf{3}}}}$$ ⟨ b b ⟩ [ 1 P 1 ] 3 ¯ , and $$\langle bb\rangle [^{3}P_{J}]_{{\textbf{6}}}$$ ⟨ b b ⟩ [ 3 P J ] 6 with $$J=0$$ J = 0 , 1, or 2, are taken into account. The cross sections and differential distributions, including the transverse momentum, rapidity, angular, and invariant mass, are discussed for the excited baryons production. We find that the contributions of $$\langle cc \rangle $$ ⟨ c c ⟩ , $$\langle bc \rangle $$ ⟨ b c ⟩ , and $$\langle bb \rangle $$ ⟨ b b ⟩ in P-wave are found to be 3.97 $$\%$$ % , 5.08 $$\%$$ % , and 5.89 $$\%$$ % , respectively, compared to S-wave. Supposing that all excited states can decay into the ground state 100%, the total events $$N_{\Xi _{cc}}=8.48 \times 10^{4-6}$$ N Ξ cc = 8.48 × 10 4 - 6 , $$N_{\Xi _{bc}}=2.26\times 10^{5-7}$$ N Ξ bc = 2.26 × 10 5 - 7 , and $$N_{\Xi _{bb}}=4.12 \times 10^{3-5}$$ N Ξ bb = 4.12 × 10 3 - 5 would be produced at the Super-Z Factory with a high luminosity up to $${{\mathcal {L}}} \simeq 10^{34-36}\textrm{cm}^{-2} \textrm{s}^{-1}$$ L ≃ 10 34 - 36 cm - 2 s - 1 .

Abstract Background The purpose of the study was to compare the efficacy of two novel obesity indices, lipid accumulation product (LAP) and visceral adiposity index (VAI), with traditional obesity indices in predicting early-onset type 2 diabetes (T2DM). Methods In this cross-sectional study, a total of 744 participants, including 605 patients newly diagnosed with T2DM and 139 non-diabetic control subjects, were enrolled from a tertiary care hospital in Tianjin, China. Participants with T2DM were divided into two groups based on their age at diagnosis, namely early-onset T2DM (age less than 40 years, n = 154) and late-onset T2DM (age 40 years or older, n = 451). The predictive power of each obesity index was evaluated using receiver operating characteristic (ROC) curve analysis. Furthermore, binary logistic regression analysis was conducted to examine the independent relationship between LAP and VAI with early-onset T2DM risk. The relationship between novel obesity indices and the age of T2DM onset was also evaluated through correlation and multiple linear regression analysis. Results In males, LAP had the highest predictive power for early-onset T2DM with an area under the ROC curve (AUC) of 0.742 (95% CI 0.684–0.799, P

BackgroundThe results of current studies on metabolic-dysfunction associated steatotic liver disease (MASLD)-related diseases, cognition and dementia are inconsistent. This study aimed to elucidate the effects of MASLD-related diseases on cognition and dementia.MethodsBy using single-nucleotide polymorphisms (SNPs) associated with different traits of NAFLD (chronically elevated serum alanine aminotransferase levels [cALT], imaging-accessed and biopsy-proven NAFLD), metabolic dysfunction-associated steatohepatitis, and liver fibrosis and cirrhosis, we employed three methods of mendelian randomization (MR) analysis (inverse-variance weighted [IVW], weighted median, and MR-Egger) to determine the causal relationships between MASLD-related diseases and cognition and dementia. We used Cochran's Q test to examine the heterogeneity, and MR-PRESSO was used to identify outliers (NbDistribution = 10000). The horizontal pleiotropy was evaluated using the MR-Egger intercept test. A leave-one-out analysis was used to assess the impact of individual SNP on the overall MR results. We also repeated the MR analysis after excluding SNPs associated with confounding factors.ResultsThe results of MR analysis suggested positive causal associations between MASLD confirmed by liver biopsy (p of IVW = 0.020, OR = 1.660, 95%CI = 1.082-2.546) and liver fibrosis and cirrhosis (p of IVW = 0.009, OR = 1.849, 95%CI = 1.169-2.922) with vascular dementia (VD). However, there was no evidence of a causal link between MASLD-related diseases and cognitive performance and other types of dementia (any dementia, Alzheimer's disease, dementia with lewy bodies, and frontotemporal dementia). Sensitivity tests supported the robustness of the results.ConclusionsThis two-sample MR analysis suggests that genetically predicted MASLD and liver fibrosis and cirrhosis may increase the VD risk. Nonetheless, the causal effects of NAFLD-related diseases on VD need more in-depth research.

Objective The aim of this study was to investigate risk factors for cognitive impairment (CI) and explore the relationship between obesity and cognition in hospitalised middle-aged patients with type 2 diabetes (T2DM).Methods Subjects were divided into normal cognitive function (NCF) (n=320) and CI (n=204) groups based on the results of the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE). The risk factors for CI were determined by logistic regression analysis and generalised linear modelling. The associations between obesity parameters (body mass index (BMI) and waist circumference (WC)) and cognitive ability were studied with the use of linear regression analysis, piecewise regression modelling and interaction analysis. The receiver operating characteristic curve analysis was used to examine the diagnostic value of influencing factors for ccResults The prevalence of CI was 38.9% in hospitalised middle-aged T2DM patients (median age, 58 years). Age, WC, hypoglycaemic episode within past 3 months and cerebrovascular disease (CVD) were identified as independent risk factors for CI, while the independent protective factors were education, diabetic dietary pattern, overweight and obesity. BMI was a protective factor for the MoCA score within a certain range, whereas WC was a risk factor for the MMSE and MoCA scores. The area under the curve for the combination of BMI and WC was 0.754 (p

Abstract Background Chronic inflammatory disorders in atrial fibrillation (AF) contribute to the onset of ischemic stroke. Systemic immune inflammation index (SIII) and system inflammation response index (SIRI) are the two novel and convenient measurements that are positively associated with body inflammation. However, little is known regarding the association between SIII/SIRI with the presence of AF among the patients with ischemic stroke. Methods A total of 526 ischemic stroke patients (173 with AF and 353 without AF) were consecutively enrolled in our study from January 2017 to June 2019. SIII and SIRI were measured in both groups. Logistic regression analysis was used to analyse the potential association between SIII/SIRI and the presence of AF. Finally, the correlation between hospitalization expenses, changes in the National Institutes of Health Stroke Scale (NIHSS) scores and SIII/SIRI values were measured. Results In patients with ischemic stroke, SIII and SIRI values were significantly higher in AF patients than in non-AF patients (all p

AIM: To observe the effect of intravitreal injection of ranibizumab in the treatment of retinal vein occlusion macular edema(RVO-ME), and to apply Logistic regression analysis to screen the factors that affect the vision recovery of patients. METHODS: A total of 106 patients(106 eyes)with retinal vein occlusion and macular edema who were treated in the ophthalmology clinic of our hospital from January 2018 to June 2019 were selected for the study. The clinical data of the patients were retrospectively analyzed and all were given 0.05mL ranibizumab. The monoclonal antibody was injected into the vitreous cavity of the affected eye, and the patients were followed up to observe the treatment effect. The patients were divided into good group and poor group according to the degree of vision recovery after 3mo of treatment, and the two-class Logistic regression analysis was used to screen the factors that affect the vision recovery of patients.RESULTS: The Logarithm of the minimum angle of resolution(LogMAR)of the affected eye at 1d, 1wk, 1, and 3mo after treatment was significantly lower than before treatment, and the macular foveal retinal thickness(CRT)was significantly lower than before treatment. The difference was statistically significant(all P0.05). During and after the treatment, the patient did not develop complications such as endophthalmitis, increased intraocular pressure, lens opacity, and retinal detachment. Logistic regression analysis showed that there was no capillary perfusion in the foveal area of the macula and the center of the macula before treatment. Incomplete outer membrane and incomplete inner plexiform layer structure in the concave area are risk factors that affect the efficacy of ranibizumab injection. CONCLUSION: Intravitreal injection of ranibizumab in the treatment of retinal vein occlusion combined with macular edema is effective and safe in the short term. It can effectively reduce macular edema of the affected eye, improve vision, and normal intraocular pressure after treatment, and it is easy to operate and effective. It has the advantages of repeating, little damage to tissues, no obvious adverse reactions, less pain for patients, economical and practical. In addition, the lack of capillary perfusion in the foveal area of the macula before treatment, the incomplete outer membrane of the foveal area, and the incomplete structure of the inner plexiform layer are risk factors that affect the efficacy of ranibizumab in the treatment of retinal vein occlusion and macular edema.

Abstract Background The associations between serum free triiodothyronine (FT3) and diabetic peripheral neuropatprohy (DPN)/carotid atherosclerotic lesions in euthyroid patients with type 2 diabetes are still unclear. The purpose of our study was to explore the relations of FT3 to DPN and carotid atherosclerotic lesions in Chinese type 2 diabetes inpatients with euthyroid function. Methods 2477 euthyroid inpatients with type 2 diabetes were recruited and they were stratified into quartiles by FT3 levels in this cross-sectional study. Peripheral neuropathy was assessed by neurological symptoms and signs as well as nerve conduction velocity tests. Carotid atherosclerotic lesions, including carotid intima-media thickness, plaque and stenosis, were evaluated by Doppler ultrasound. Results The prevalence of DPN in type 2 diabetic patients exhibited the significant decrease across the FT3 quartiles (23.5%, 20.9%, 18.8%, and 11.2%, respectively, p

AimsWe aimed to examine the association of serum unconjugated bilirubin (UCB) within normal limits with carotid atherosclerosis in Chinese patients with type 2 diabetes mellitus (T2DM).MethodsThis cross-sectional, real-world study was performed in 8,006 hospitalized T2DM patients including 4,153 men and 3,853 women with normal UCB. The subjects were stratified into quintiles based on serum UCB levels (10.9 μmol/l, respectively). Carotid atherosclerotic lesions detected by ultrasonography, including carotid intima-media thickness (CIMT), carotid plaque, and stenosis, were compared among the five groups. The associations of serum UCB levels and quintiles with carotid atherosclerotic lesions were also determined by multiple logistic regression.ResultsThe prevalence of carotid plaque (55.3%, 49.5%, 47.4%, 43.8%, and 37.5%, respectively; p < 0.001 for trend) and stenosis (15.2%, 12.2%, 9.1%, 7.7%, and 5.4%, respectively; p < 0.001 for trend) was progressively lower across the UCB quintiles even after adjusting for age, sex, and duration of diabetes. Results of a fully adjusted multiple logistic regression analysis revealed that serum UCB levels and quintiles were significantly associated with carotid plaque and stenosis. Compared with the subjects in the lowest UCB quintile, the risk of carotid plaque decreased by 25.5%, 28.7%, 33.5%, and 42.8%, and that of carotid stenosis by 24.6%, 37.4%, 44.9%, and 47.3%, respectively, in those from the second to highest UCB quintiles. High serum UCB within the normal range was a protective factor against carotid plaque [odds ratio (OR) 0.810, 95% confidence interval (CI) 0.747–0.878; p < 0.001] and stenosis [OR 0.722, 95% CI 0.647–0.805; p < 0.001]. However, no significant association was observed between serum UCB and CIMT in T2DM patients. Furthermore, C-reactive protein (CRP) levels were significantly higher in the subjects with carotid atherosclerosis than in those without carotid atherosclerosis and clearly decreased across the UCB quintiles.ConclusionsSerum UCB within normal limits is inversely associated with late carotid atherosclerotic lesions including carotid plaque and stenosis but not CIMT, an early carotid atherosclerotic lesion in T2DM patients. High-normal UCB may be protective against carotid atherosclerosis by its anti-inflammation effect, which was indicated by significantly decreased CRP levels from the lowest to highest UCB quintiles.

AimsThyroid hormones widely affect the cardiovascular system, but the effects of mild thyroid dysfunction on the clinical prognosis of patients with acute ST segment elevation myocardial infarction (STEMI) remains unclear. Our aims were to analyze the relations between mild thyroid dysfunction at admission and clinical outcomes in Chinese patients with STEMI.MethodsA total of 1,176 STEMI patients with the available data of thyroid function and follow-up were analyzed, including 348 patients with mild thyroid dysfunction [subclinical hypothyroidism (n=81), hyperthyroidism (SHyper) (n=51), and low triiodothyronine syndrome (LT3S) (n=216)] and 828 patients with euthyroid function. During a median 4.4-year follow-up, in-hospital mortality, cardiac and all-cause mortalities were subsequently compared among the four groups.ResultsCompared with the euthyroid group, STEMI patients in the SHyper and LT3S groups faced obviously increased risks of in-hospital death [odds ratio (OR): 5.007, 95% confidence interval (CI): 1.246–20.124, p = 0.023 and OR: 2.491, 95% CI: 1.054–5.887, p = 0.037, respectively) even after adjustment for various confounding factors. During a median 4.4-year follow-up, STEMI patients with LT3S at baseline had higher cardiovascular mortality [hazard ratio (HR): 1.880, 95% CI: 1.178–2.998, p = 0.008] and all-cause mortality HR: 1.647, 95% CI: 1.072–2.531, p = 0.023] than those with euthyroid at baseline, whereas no significantly increased mortality was found for STEMI patients with SCH and SHyper at baseline.ConclusionsSTEMI patients with SHyper at admission had increased risk of in-hospital mortality, and STEMI patients with LT3S at baseline had worse prognosis and higher incidences of in-hospital mortality and cardiovascular and all-cause deaths compared with euthyroid patients.

AimsOur aim was to evaluate the separate and combined effects of maternal pre-pregnancy obesity and gestational abnormal glucose metabolism (GAGM) on adverse perinatal outcomes.MethodsA total of 2,796 Chinese pregnant women with singleton delivery were studied, including 257 women with pre-pregnancy obesity alone, 604 with GAGM alone, 190 with both two conditions, and 1,745 with neither pre-pregnancy obesity nor GAGM as control group. The prevalence and risks of adverse pregnancy outcomes were compared among the four groups.ResultsCompared with the normal group, pregnant women with maternal pre-pregnancy obesity alone, GAGM alone, and both two conditions faced significantly increased risks of pregnancy-induced hypertension (PIH) (odds ratio (OR) 4.045, [95% confidence interval (CI) 2.286–7.156]; 1.993 [1.171–3.393]; 8.495 [4.982–14.485]), preeclampsia (2.649 [1.224–5.735]; 2.129 [1.128–4.017]; 4.643 [2.217–9.727]), cesarean delivery (1.589 [1.212–2.083]; 1.328 [1.095–1.611]; 2.627 [1.908–3.617]), preterm delivery (1.899 [1.205–2.993]; 1.358 [0.937–1.968]; 2.301 [1.423–3.720]), macrosomia (2.449 [1.517–3.954]; 1.966 [1.356–2.851]; 4.576 [2.895–7.233]), and total adverse maternal outcomes (1.762 [1.331–2.332]; 1.365 [1.122–1.659]; 3.228 [2.272–4.587]) and neonatal outcomes (1.951 [1.361–2.798]; 1.547 [1.170–2.046]; 3.557 [2.471–5.122]). Most importantly, there were no obvious risk differences in adverse pregnancy outcomes between maternal pre-pregnancy obesity and GAGM group except PIH, but pregnant women with both obesity and GAGM exhibited dramatically higher risks of adverse pregnancy outcomes than those with each condition alone.ConclusionsMaternal pre-pregnancy obesity and GAGM were independently associated with increased risks of adverse pregnancy outcomes. The combination of pre-pregnancy obesity and GAGM further worsens adverse pregnancy outcomes compared with each condition alone.

The Cambrian Series 2–Miaolingian transition is a pivotal period during Earth history, which witnessed the decline of biodiversity and the reduction in biomass, i.e., the redlichiid–olenellid trilobite extinction. The notable δ13C excursion (RECE) near the Cambrian Series 2–Miaolingian boundary in east Gondwana and China apparently corresponds with the redlichiid trilobite extinction. To better understand the causal mechanism of this biotic crisis, we report the carbon isotope stratigraphy and facies changes from Cambrian Series 2–Miaolingian transition of the Mantou Formation on the southern North China Craton. The carbon isotope excursions at the Cambrian Series 2–Miaolingian transition in the study area are 0.7‰ in the Chishanhe section and −0.2‰ in the Luoquan section, respectively, showing a weak negative excursion or even no negative excursion. The sedimentary environments in the study area gradually changed through time from a clastic tidal flat to a carbonate platform across the transition, which indicated a gradual rise in sea level, with anoxic conditions occurring predominantly before the RECE δ13C excursion. Microbially induced sedimentary structures and oncoids occurred widely at the top of Cambrian Series 2. Abundant metazoan trace fossils were preserved in the Miaolingian Series of the study area. The evolution of biogenic structures across the Cambrian Series 2–Miaolingian transition indicates the emergence of harsh environments associated with the proliferation of MISS and oncoids at the RECE horizon and the recovery of benthic metazoan fauna after the RECE biotic crisis.

Characterized by lack of evidence of structural heart disease or any secondary causes of atrial fibrillation (AF), “lone AF” is used to represent a unique subtype of AF among young individuals aged less than 60 years. Although the longstanding definition has been proposed for years, the diagnostic criteria for “lone AF” remain ambiguous. As more contributing factors causing AF are recognized gradually, the validity of the term “lone AF” is in question. Despite advances in the past few decades, the mechanism of AF remains poorly understood, particularly in the absence of other structural changes. It is generally accepted that three essential electrophysiological elements (trigger, substrate, and modulators) contribute to the initiation and maintenance of lone AF. In addition, the role of microRNAs and genomic variations in the pathogenesis of lone AF has been also gaining attention. Some changes in relevant biomarker levels have also been proven to correlate with lone AF. Accumulating insights into the pathogenesis of lone AF strongly suggest coexistent disorders in patients with lone AF. Consequently, the growing evidence of these numerous and diverse pathogenic mechanisms and factors related to lone AF inevitably raises the question of whether the term “lone AF” is a meaningful category. The classification of lone AF as a separate identity has not lead to any unique clinical management. In this review, we update knowledge of definition, mechanisms, genetics, biomarkers, and clinical management of “lone AF.” With this comprehensive review, we suggest that the term “lone AF” should be abandoned for its futility. Key Words: lone atrial fibrillation, mechanism, genetics, biomarker, clinical management

Background Capn4 and ZEB1 play important roles in the metastasis of several types of cancer. However, the roles and relationship of Capn4 and ZEB1 in esophageal squamous cell carcinoma (ESCC) remain unclear. Methods ESCC tumor tissues and corresponding normal esophageal epithelial tissues were obtained from 86 patients undergoing resection surgery at the Department of General Surgery, First Affiliated Hospital of Chinese PLA General Hospital from 2012 to 2017. Cell migration and invasion were examined via quantitative real‐time PCR and Western blot assay. Results Our results indicate that both Capn4 and ZEB1 are significantly upregulated in ESCC tissues compared to corresponding adjacent tissues, and a positive correlation between expression and associated malignant characteristics was found. Silencing of Capn4 expression markedly inhibited ESCC invasion and metastasis in vitro and in vivo, and was accompanied by decreased ZEB1 expression. Furthermore, the anti‐metastasis role of Capn4 silencing was reversed by ZEB1 overexpression, whereas knockdown of ZEB1 decreased ESCC metastasis driven by the upregulation of Capn4. Mechanistically, Capn4 regulated ZEB1 expression via activation of the Wnt/β‐catenin signaling pathway in ESCC cells. Conclusion Overall, our results show that enhanced Capn4 expression activates the Wnt/β‐catenin signaling pathway, resulting in increased ZEB1 expression and the promotion of ESCC cell metastasis.

Background: Atrial fibrillation (AF) is increasingly considered an age-related degenerative disease, whose process is associated with the development of impaired left atrial (LA) performance. However, the subtle dynamic changes of LA performance in AF during aging have yet to be fully elucidated. Atrial fibrosis is a key substrate for the development of AF, but the progression of fibrosis during aging and its relationship with LA dysfunction need to be further explored.Methods: A total of 132 control individuals and 117 persistent AF patients were prospectively studied. Subjects were further stratified into three age groups (age group 1: younger than 65 years, age group 2: between 65 and 79 years old, and age group 3: older than 80 years). The two-dimensional speckle tracking imaging was carried out for analyzing the alterations in LA function underlying LA remodeling, whereas electroanatomic mapping was performed to investigate LA fibrosis burden. In animal study, aged mice and young mice served as research subjects. Echocardiography and histological staining were used to assess LA performance and fibrosis burden, respectively.Results: Echocardiography showed progressive increases in LA dimension and LA stiffness index, and progressive decreases in LA global longitudinal strain and LA strain rates with advancing age in both AF and control cohorts, which was more prominent in AF cohort. Electroanatomic mapping showed progressive decrease in mean LA voltage and progressive increases in LA surface area, low-voltage area %, and LA volume with advancing age, whereas more significant alterations were observed in AF patients. Moreover, left atrial global longitudinal strain was positively correlated with mean LA voltage, whereas LA stiffness index was negatively related to mean LA voltage. In animal experiment, increased LA size and pulmonary artery dimension as well as longer P-wave duration and more prominent LA fibrosis were found in aged mice.Conclusions: This study provides new evidence of subtle changes in structure and performance of left atrium and their association with atrial fibrosis in both AF and non-AF subjects during physiological aging. In addition, our study also provides normal values for LA structure and performance in both AF and non-AF conditions during aging. These measurements may provide an early marker for onset of AF and LA adverse remodeling.

Abstract Bi4Ti3O12 is an important lead-free ferroelectric material. Doping modification of Bi4Ti3O12 has attracted great attention to improving its performances. In this work, the effect of Sr dopants on the microstructure, dielectric, and conductivity of Bi4Ti3O12 ceramic was investigated by XRD, SEM, and AC impedance spectroscopy. Substitution of 1 at% Sr for Bi decreased the grain size, suppressed the dielectric dispersion of Bi4Ti3O12 ceramic at room temperature, and resulted in different effects on the conductivity of grains and grain boundaries. The conductivity of grains in Bi4Ti3O12 ceramic was increased by the small amount of Sr dopants in the whole experimental temperature range. While the grain boundaries of 1 at% Sr-doped Bi4Ti3O12 exhibited lower conductivity than pure Bi4Ti3O12 below ~380 °C and higher conductivity above ~380 °C. The experimental phenomena were interpreted in term of compensating defects for Sr dopants.

FeCrNi/CBN cored wire is prepared by use of the pull-type flux cored wire machine (FCWM50 type), FeCrNi/CBN composite coating is made by high velocity arc spraying. The special properties of the composite coating can be improved by adding Cr, Ni and small amounts of rare earth elements to adjust the coating composition. The Tribological properties of FeCrNi/CBN composite coating with high velocity arc spraying is studied. Images and components and cross-section microstructure of coatings are analyzed by means of SEM, and EDS, etc. This research indicated that FeCrNi/CBN composite coatings have typical layered structure feature and high bond strength and hardness. Friction of coatings at near room temperature or higher has “Run-up” period. With the increase of temperature, friction coefficient of coatings becomes low and wearing capacity of coatings high. The adding of CBN powder highly improved the wearing capacity of coatings. Keywords: FeCrNi/CBN, Tribological properties, Structure feature, Wearing capacity

Cholangiocarcinoma (CCA) is one of the most common hepatic and biliary malignancies, accounting for about 3% of all gastrointestinal tumors. GATA5 is a transcription factor capable of suppressing the development of various human cancer types. Transcriptional inactivation and CpG island (CGI) methylation of GATA3 and GATA5, two members of the GATA family of transcription factors, have been observed in some human cancers. But whether high-density CGI methylation of GATA5 is associated with the clinical course of CCA patients has not been clarified. Herein, we observed reduced expression of GATA5 in CCA tissues compared with noncancerous tissues. Treatment with the demethylating agent 5-aza-2'-deoxycytidine restored GATA5 expression in CCA cell lines. Furthermore, GATA5 expression was downregulated after treatment with IL-6 in human intrahepatic biliary epithelial cells. Upregulated GATA5 inhibited CCA cell growth and metastasis. Mechanistically, GATA5 suppressed CCA cell growth and metastasis via Wnt/β-catenin pathway. Specific β-catenin inhibitor or siRNA abolished the discrepancy of the proliferation and metastasis capacity between GATA5-overexpression CCA cells and their control cells, which further confirmed that Wnt/β-catenin was required in GATA5-inhibited CCA cell growth and metastasis.

Background/Aims: Increased endoplasmic reticulum (ER) stress contributes to development of cardiorenal syndrome (CRS), and Silent Information Regulator 1 (SIRT1), a class III histone deacetylase, may have protective effects on heart and renal disease, by reducing ER stress. We aimed to determine if SIRT1 alleviates CRS through ER stress reduction. Methods: Wild type mice (n=37), mice with cardiac-specific SIRT1 knockout (n=29), or overexpression (n=29), and corresponding controls, were randomized into four groups: sham MI (myocardial infarction) +sham STNx (subtotal nephrectomy); MI+sham STNx; sham MI+STNx; and MI+STNx. To establish the CRS model, subtotal nephrectomy (5/6 nephrectomy, SNTx) and myocardial infarction (MI) (induced by ligation of the left anterior descending (LAD) coronary artery) were performed successively to establish CRS model. At week 8, the mice were sacrificed after sequential echocardiographic and hemodynamic studies, and then pathology and Western-blot analysis were performed. Results: Neither MI nor STNx alone significantly influenced the other healthy organ. However, in MI groups, STNx led to more severe cardiac structural and functional deterioration, with increased remodeling, increased BNP levels, and decreased EF, Max +dp/dt, and Max -dp/dt values than in sham MI +STNx groups. Conversely, in STNx groups, MI led to renal structural and functional deterioration, with more severe morphologic changes, augmented desmin and decreased nephrin expression, and increased BUN, SCr and UCAR levels. In MI+STNx groups, SIRT1 knockout led to more severe cardiac structural and functional deterioration, with higher Masson-staining score and BNP levels, and lower EF, FS, Max +dp/dt, and Max -dp/dt values; while SIRT1 overexpression had the opposite attenuating effects. In kidney, SIRT1 knockout resulted in greater structural and functional deterioration, as evidenced by more severe morphologic changes, higher levels of UACR, BUN and SCr, and increased desmin and TGF-β expression, while SIRT1 overexpression resulted in less severe morphologic changes and increased nephrin expression without significant influence on BUN or SCr levels. The SIRT1 knockout but not overexpression resulted in increased myocardial expression of CHOP and GRP78. Cardiac-specific SIRT1 knockout or overexpression resulted in increased or decreased renal expression of CHOP, Bax, and p53 respectively. Conclusions: Myocardial SIRT1 activation appears protective to both heart and kidney in CRS models, probably through modulation of ER stress.

Recent studies indicated that Gene Associated with Retinoid-IFN-Induced Mortality 19 (GRIM-19), a newly discovered mitochondria-related protein, can regulate mitochondrial function and modulate cell viability possibly via interacting with STAT3 signal. In the present study we sought to test: 1) whether GRIM-19 is involved in high glucose (HG) induced altered cell metabolism in both cancer and cardiac cells, 2) whether GRIM-19/STAT3 signaling pathway plays a role in HG induced biological effects, especially whether AMPK activity could be involved. Our data showed that HG enhanced cell proliferation of both HeLa and H9C2 cells, which was closely associated with down-regulated GRIM-19 expression and increased phosphorylated STAT3 level. We showed that GRIM-19 knock-down alone in normal glucose cultured cells can also result in an increase in phosphorylated STAT3 level and enhanced proliferation capability, whereas GRIM-19 over-expression can abolished HG induced STAT3 activation and enhanced cell proliferation. Importantly, both down-regulated or over-expression of GRIM-19 increased lactate production in both HeLa and H9C2 cells. The activated STAT3 was responsible for increased cell proliferation as either AG-490, an inhibitor of JAK2, or siRNA targeting STAT3 can attenuate cell proliferation increased by HG. In addition, HG increased lactate acid levels in HeLa cells, which was also observed when GRIM-19 was genetically manipulated. However, HG did not affect the lactate levels in H9C2 cells. Of note, over-expression of GRIM-19 and silencing of STAT3 both increased lactate production in H9C2 cells. As expected, HG resulted in significant decreases in phosphorylated AMPKα levels in H9C2 cells, but not in HeLa cells. Interestingy, activation of AMPKα by metformin was associated with a reversal of the suppressed GRIM-19 expression in H9C2 cells, the fold of changes in GRIM-19 expression by metformin were much less in HeLa cells. Metformin did not affect the phosphorylated STAT3 lelvels, however, decreased its levels in H9C2, especially in the setting of HG culture. Not like HG alone which resulted in no changes in lactate acid in H9C2 cells, metformin can increase lactate acid levels in H9C2 cells. Increased lactate induced by metformin was also observed in HeLa cells.

Understanding the connectivity of the brain neural network and its evolution in epileptiform discharges is meaningful in the epilepsy researches and treatments. In the present study, epileptiform discharges were induced in rat hippocampal slices perfused with Mg2+-free artificial cerebrospinal fluid. The effective connectivity of the hippocampal neural network was studied by comparing the normal and epileptiform discharges recorded by a microelectrode array. The neural network connectivity was constructed by using partial directed coherence and analyzed by graph theory. The transition of the hippocampal network topology from control to epileptiform discharges was demonstrated. Firstly, differences existed in both the averaged in- and out-degree between nodes in the pyramidal cell layer and the granule cell layer, which indicated an information flow from the pyramidal cell layer to the granule cell layer during epileptiform discharges, whereas no consistent information flow was observed in control. Secondly, the neural network showed different small-worldness in the early, middle and late stages of the epileptiform discharges, whereas the control network did not show the small-world property. Thirdly, the network connectivity began to change earlier than the appearance of epileptiform discharges and lasted several seconds after the epileptiform discharges disappeared. These results revealed the important network bases underlying the transition from normal to epileptiform discharges in hippocampal slices. Additionally, this work indicated that the network analysis might provide a useful tool to evaluate the neural network and help to improve the prediction of seizures.

BACKGROUND: The presence of food-specific IgG antibodies in human serum may be useful for diagnosis of adverse food reactions. However, the clinical utility of testing for such antibodies remains very controversial. The aim of this study was to evaluate the serum levels and population distribution of food-specific IgGs and their association with chronic symptoms in a large-scale Chinese population. METHODOLOGY/PRINCIPAL FINDINGS: A total of 21305 adult participants from different regions of China had 14 type of food-specific serum IgG antibodies that were measured by enzyme-linked immunosorbent assay. Among these, 5,394 participants were randomly chosen to complete follow-up questionnaire surveys on their dietary characteristics and chronic symptoms. The concentrations of food-specific IgGs against 14 foods ranged from a median (interquartile range) of 7.3 (3.8, 12.6) U/mL of pork-specific IgG to 42.3 (28.8, 60.2) U/mL of crab-specific IgG. The concentration of food-specific IgGs was closely related to gender; after adjustment for region and age, women had higher concentrations of food-specific IgGs against all of the 14 foods except chicken (regression coefficient (95% CI): 0.01 (-0.003, 0.023); P = 0.129) and corn (0.002 (-0.013, 0.016); P = 0.825). Similar results were also found in the relationship of geographic region to the food-specific IgG concentrations for the 14 foods. Chronic symptoms were negatively associated with the concentrations of a few food-specific IgGs, and were positively associated with the concentrations of other food-specific IgGs. CONCLUSIONS: The levels of food-specific IgGs were variable both in healthy and in symptomatic Chinese adults. These findings raise awareness that demographic factors, the type of food and specific chronic symptoms should be considered before food elimination treatment based on IgG testing in patients with chronic symptoms is used in clinical practice.

The purpose of this study was to determine the anticancer potential of Ifloga spicata (I. spicata) against HepG-2 cell line. To assess I. spicata cytoxicity, brine shrimp lethality and MTT assays were performed. In the brine shrimp bioassay, the ethyl acetate fraction had a significant impact with an IC50 of 10 µg/ml. The ethyl acetate and chloroform fractions inhibited HepG-2 cell line effectively (IC50 values 5.54 and 6.52 µg/ml, respectively). The isolated compound, heptadecyl benzoate inhibited growth significantly (IC50, 8.92 µg/ml) while methyl dihydroxybenzoate had modest activity (25.66 µg/ml) against the cell line. Both compounds displayed acceptable pharmacokinetic parameters in the ADME study. In the docking study, the methyl dihydroxybenzoate was involved in two hydrogen bonds with two different residues Thr830 and Asp831. The heptadecyl benzoate carbonyl oxygen exhibited a single hydrogen bond with Lys692. Both showed good interactions with the active site of the (EGFR) tyrosine kinase. Our findings suggest that I. spicata might be a viable source of anticancer natural agents. This discovery raises the prospect of the future development of a new medication for the treatment of liver cancer. [ABSTRACT FROM AUTHOR]

Dielectric relaxation behaviors of Aurivillius Bi5Ti3FeO15 ceramics were investigated in a wide range of frequency and temperature via dielectric and impedance spectroscopies. We distinguished two dielectric relaxations using the combination of impedance and modulus analysis. Resistance of the grain boundary was found to be much larger than grains, whereas capacitance was at the same level. The kinetic analysis of dielectric data was carried out to evaluate the contributions of microstructure and defects to the relaxation and conduction. The possible relaxation-conduction mechanism in the ceramics was discussed. The results enable deep understanding of microstructure-defect-relaxation behaviors in Bi5Ti3FeO15 ceramics. [ABSTRACT FROM AUTHOR]