Risk of incident type 2 diabetes in male NAFLD and NAFLD-free smokers: a 7-year post-cessation study.

BACKGROUND: We aimed to investigate the post-cessation T2DM risk in male NAFLD and NAFLD-free smokers in a 7-year cohort study. METHODS: The study population was male adults who underwent annual health checkups in a 7-year cohort study. Recent quitters were categorized into four groups based on their weight gain during follow-up: < 0 kg, 0-1.9 kg, 2.0-3.9 kg, and ≥ 4.0 kg. Cox proportional hazard models, adjusted for various variables, were used to estimate hazard ratios (HRs) for the association between post-cessation weight gain and incident T2DM in NAFLD and NAFLD-free individuals. RESULTS: At baseline, we included 1,409 NAFLD and 5150 NAFLD-free individuals. During a total of 39,259 person-years of follow-up, 222 (15.8%) NAFLD patients and 621 (12.1%) NAFLD-free participants quit smoking, with the corresponding means (standard deviations) of post-cessation weight gain being 2.24 (3.26) kg and 1.15 (3.51) kg, respectively. Among NAFLD individuals, compared to current smokers, the fully adjusted HRs (95% CI) for incident T2DM were 0.41 (0.06-3.01), 2.39 (1.21-4.70), 4.48 (2.63-7.63), and 6.42 (3.68-11.23) for quitters with weight gains < 0 kg, 0.0-1.9 kg, 2.0-3.9 kg, and ≥ 4.0 kg, respectively. For NAFLD-free individuals, we only observed a significant association between post-cessation weight gain ≥ 4.0 kg and the risk of incident T2DM (P < 0.001). Further analysis revealed that the impact of post-cessation weight gain on T2DM risk was not affected by alcohol consumption or obesity status at baseline. CONCLUSIONS: Mild post-cessation weight gain significantly increased the risk of T2DM in male NAFLD patients but not in male NAFLD-free individuals. Therefore, it is recommended that individuals with NAFLD manage their weight after quitting smoking.

Clinical outcome of non-alcoholic fatty liver disease: an 11-year follow-up study.

OBJECTIVES: To clarify non-alcoholic fatty liver disease (NAFLD) prevalence, risk factors and clinical outcome in an exemplary Chinese population, a cohort of company employees was followed up for 11 years. DESIGN: Retrospective cohort study. SETTING: Between 2006 and 2016 in Ning bo, China. PARTICIPANTS: 13 032 company employees. RESULTS: Over 11 years, the prevalence of NAFLD increased from 17.2% to 32.4% (men 20.5%-37% vs women 9.8%-22.2%). Male peak prevalence was between 40 and 60 years of age, whereas highest prevalence in women was at an age of 60 years and older. Logistic and Cox regression revealed 16 risk factors, including body mass index (BMI), albumin, white blood cell, triglycerides (TG), high-density lipoprotein, glutamyl transpeptidase, alanine transaminase, creatinine, urea acid, glucose, systolic blood pressure, diastolic blood pressure, blood sedimentation, haemoglobin, platelet and apolipoprotein B2 (p<0.05 for all factors). The area under the curve of these variables for NAFLD is 0.88. However, cause-effect analyses showed that only BMI, gender and TG directly contributed to NAFLD development. Over an 11-year follow-up period, 12.6%, 37.7% and 14.2% of male patients with NAFLD and 11.6%, 44.7% and 22.6% of female patients with NAFLD developed diabetes, hypertension and hyperuricaemia, respectively. Except one male patient who developed cirrhosis, no patients with NAFLD progressed into severe liver disease. CONCLUSION: Diabetes, hypertension and hyperuricaemia are the main clinical outcomes of NAFLD. Eleven years of NAFLD are not sufficient to cause severe liver disease. Age and obesity are direct risk factors for NAFLD. BMI, gender and TG are three parameters directly reflecting the occurrence of NAFLD.

Fine-grained assessment of greenspace satisfaction at regional scale using content analysis of social media and machine learning.

Assessing perceptions of green spaces is of considerable interest to developers aiming for sustainable urbanization. However, there are numerous challenges facing the development of a rapid, effective, and fine-grained method to assess large-scale greenspace perception. Survey-based studies of perception yielded detailed assessments of green spaces but lacked regional comparisons. The few big-data-based studies of greenspace perception lacked fine-grained explorations. Therefore, we used content analysis to interpret perception in two ways: perceived frequency and perceived satisfaction, including overall park satisfaction and satisfaction with individual landscape features. We analyzed social media posts about urban parks in Beijing, China. A structured lexicon was developed to capture detailed landscape features, and machine learning was employed to assess satisfaction levels. Both of these techniques performed well in interpreting greenspace satisfaction from volunteered textual comments. A detailed study of 50 parks demonstrated that overall park satisfaction was positive. Additionally, individual landscape features were more influential than frequency of landscape features in affecting satisfaction. Our framework confirmed the potential of online comments as complementary to traditional surveys in assessing greenspace perception, while enhancing our understanding of this perception on a regional scale. Practically, this study can facilitate sustainable policy-making regarding urban green spaces, specifically through offering a structured landscape-feature lexicon, rapid regional comparison of various parks, and an emphasis on quality rather than quantity of landscape features.

Light-to-Moderate Alcohol Consumption Is Associated With Increased Risk of Type 2 Diabetes in Individuals With Nonalcoholic Fatty Liver Disease: A Nine-Year Cohort Study.

OBJECTIVE: This study explored the association between light-to-moderate alcohol consumption (LMAC) and risk of type 2 diabetes mellitus (T2DM) in individuals with nonalcoholic fatty liver disease (NAFLD). METHODS: A 9-year cohort study was performed among Chinese men who underwent their annual health checkups between 2009 and 2018. NAFLD was diagnosed based on abdominal ultrasound with exclusion of excess alcohol intake and other causes of liver disease. Logistic regression and Cox proportional regression analyses were applied to identify the risk of prevalent and incident T2DM. RESULTS: Of the 7,079 participants enrolled, 243 had T2DM at baseline and 630 developed T2DM during the 45,456 person-years follow-up. Both at the baseline and by the end of the follow-up, LMAC was associated with a decreased risk of prevalent T2DM in NAFLD-free participants but with a significantly increased risk in patients with NAFLD. LMAC was also associated with a decreased risk of incident T2DM in NAFLD-free participants. The adjusted hazard ratios (95% confidence interval) of incident T2DM were 0.224 (0.115-0.437) and 0.464 (0.303-0.710) for NAFLD-free light drinkers and NAFLD-free moderate drinkers, respectively. Nondrinking, light-drinking, and moderate-drinking patients with NAFLD all showed significantly increased risks of incident T2DM. Compared with NAFLD-free nondrinkers, the adjusted hazard ratios (95% confidence interval) of incident T2DM were 1.672 (1.336-2.092), 2.642 (1.958-3.565), and 2.687 (2.106-3.427) for nondrinking, light-drinking, and moderate-drinking patients with NAFLD, respectively. DISCUSSION: LMAC decreased the risks of prevalent and incident T2DM in NAFLD-free participants. LMAC, however, was associated with an increased risk of T2DM in patients with NAFLD (ClinicalTrials.gov number: NCT03847116).

HbA1c may contribute to the development of non-alcoholic fatty liver disease even at normal-range levels.

Previous clinical studies highlighted nonalcoholic fatty liver disease (NAFLD) as a hepatic facet of metabolic syndrome, which progresses toward Type 2 diabetes along with an elevation of HbA1c in the blood. Longitudinal observations were performed in a cohort of 2811 participants with no liver disease at inception. The rate of the conversion into NAFLD was 15.7% (440/2811), with a steady increase in prevalence observed in sub-cohorts with increasing HbA1c levels. Moreover, regression analysis indicated that HbA1c levels serve as the risk factors for NAFLD after multiple adjustments (odds ratio: 1.58, P-value < 0.004). When HbA1c-related molecular networks were investigated using natural language programming algorithms, multiple genetic/small molecular (SM) pathways were highlighted as connectors between the HbA1c levels and the development of NAFLD, including ones for nitric oxide, hypoxia and receptor for advanced glycation end products (RAGE). Our results suggest that increased levels of HbA1c may contribute to the progression of NAFLD either directly, by stimulating RAGE or indirectly, through the promotion of hypoxia and suppression of the release of NO. Further studies are needed to test the impact of HbA1c on the development of the chronic liver disease.

Evaluation of platelet distribution width in hypertension with hyperhomocysteinemia.

An increased platelet distribution width (PDW) value has been found in various cardiovascular diseases. The objective of this study was to evaluate the association between the PDW and hypertension with hyperhomocysteinemia in an elderly cohort. We performed a cross-sectional analysis among 2,685 elderly individuals who underwent hematological testing and blood pressure assessment. Individuals were divided according to the PDW quartiles. An unconditional multiple logistic regression analysis was used to determine the association between PDW and hypertension with hyperhomocysteinemia, after adjustments for gender, age, drinking status, creatinine levels, glucose levels, uric acid levels, triglyceride levels, platelet counts and body mass index. Homocysteine was observed to steadily and remarkably increase in the PDW quartiles. The PDW values of the hypertension with hyperhomocysteinemia group were significantly greater than the PDW values in the hypertension without hyperhomocysteinemia group or the normotension group. The PDW levels were associated with hypertension and hyperhomocysteinemia independently of the previously mentioned risk factors, and the odds ratio of the hypertension with hyperhomocysteinemia group was steadily and remarkably increased, by as much as two-fold, in the fourth quartile vs. the first quartile. In this elderly population-based cohort, elevated PDW levels were independently associated with hypertension and hyperhomocysteinemia, which may indicate that hypertension and hyperhomocysteinemia can induce platelet activation.

Long Noncoding RNA GM16343 Promotes IL-36ß to Regulate Tumor Microenvironment by CD8+T cells.

OBJECTIVE: To investigate the effect of long noncoding RNA GM16343 on interleukin 36ß promotion of CD8+T cells in tumor microenvironment regulation. METHODS: The differentially expressed long noncoding RNA in interleukin 36ß-stimulated mouse CD8+T cells was screened by gene chip technology, and the significant differentially expressed long noncoding RNAs were verified by real-time polymerase chain reaction. The lentiviral vector that overexpresses or knockdown GM16343 was constructed, transfected into CD8+T cells, and stimulated with interleukin 36ß, and the amount of interferon γ secreted was detected by enzyme-linked immunosorbent assay. A mouse subcutaneous xenograft model that stably express interleukin 36ß was established, and the tumor size and mouse survival time were observed by stimulation with CD8+T cells overexpression or knockdown of GM16343. RESULTS: A total of 12 long noncoding RNAs with significant differences were screened by gene chip analysis. Real-time polymerase chain reaction showed that the difference in GM16343 was larger, and the difference between the groups was observed to be the most significant. Compared to control group, CD8+T cells overexpressing GM16343 increased the secretion of interferon γ, and the tumor diameter of the mice after stimulation showed significant reduction, and the survival time showed significant prolongation. Compared to control group, the CD8+T cells after GM16343 were knocked down. The interferon γ secretion was decreased, and no significant change in tumor diameter and survival time was observed. CONCLUSION: Interleukin 36ß may enhance antitumor immune response of CD8+T cells by regulating GM16343.

Stable Subloop Behavior in Ferroelectric Si-Doped HfO2.

The recent demand for analogue devices for neuromorphic applications requires modulation of multiple nonvolatile states. Ferroelectricity with multiple polarization states enables neuromorphic applications with various architectures. However, deterministic control of ferroelectric polarization states with conventional ferroelectric materials has been met with accessibility issues. Here, we report unprecedented stable accessibility with robust stability of multiple polarization states in ferroelectric HfO2. Through the combination of conventional voltage measurements, hysteresis temperature dependence analysis, piezoelectric force microscopy, first-principles calculations, and Monte Carlo simulations, we suggest that the unprecedented stability of intermediate states in ferroelectric HfO2 is due to the small critical volume size for nucleation and the large activation energy for ferroelectric dipole flipping. This work demonstrates the potential of ferroelectric HfO2 for analogue device applications enabling neuromorphic computing.

Acid-Catalyzed Versus Thermally Induced C1-C1' Bond Cleavage in 1,1'-Bi-2-naphthol: An Experimental and Theoretical Study.

Experiments show that 1,1'-bi-2-naphthol (BINOL) undergoes facile C1-C1' bond cleavage under action of triflic acid at temperatures above 0 °C to give mainly 2-naphthol along with oligomeric material. CASSCF and MRMP//CASSCF computations have demonstrated unambiguously that this unusual mode of scission of the biaryl bond can occur in the C1,C1'-diprotonated form of BINOL via a mechanism involving homolytic cleavage prompted by the intramolecular electrostatic repulsion. These findings also provide insights into the mechanism of a comparatively easy thermal cleavage of BINOL, implying the intermediacy of its neutral diketo form.

Mechanistic investigation of superelectrophilic activation of 1,1'-bi-2-naphthols in the presence of aluminum halides.

7,7'-Dihydroxy-1,1'-bi-2-naphthol, as a result of superelectrophilic activation in the presence of an excess of aluminum halides, reacts with cyclohexane and benzene to yield 5,6,7,8,5',6',7',8'-octahydro-7,7'-dioxo-bi-2-naphthol and its 5,5'-diphenyl derivative, respectively. In contrast, isomeric 6,6'-dihydroxy-1,1'-bi-2-naphthol does not react at all under the same reaction conditions, while the parent 1,1'-bi-2-naphthol (BINOL) reveals an alternative mode of behavior. The mechanistic aspects of these intriguing results are discussed on the basis of experimental and theoretical (DFT) study of the protonation and complexation properties of the starting BINOLs.

High expression of TRIM36 is associated with radiosensitivity in gastric cancer.

Radiotherapy is one of the main adjuvant treatments for gastric cancer (GC) that can effectively reduce local recurrence and improve survival rates. However, radiotherapy may result in cytotoxicity and not benefit all patients. This highlights the requirement for identifying potential radiosensitivity genes in GC. The current study investigated the association between tripartite motif containing 36 (TRIM36) status and the prognosis of patients with GC receiving radiotherapy. A total of 371 patients with GC were selected from The Cancer Genome Atlas and randomly divided into test and the validation groups. The results revealed that TRIM36 expression was not associated with the overall survival (OS) rate. Patients who received radiotherapy with high TRIM36 expression had an improved OS rate compared with patients who did not receive radiotherapy in the test group, as demonstrated by univariate analysis [hazard ratio (HR), 0.062; 95% confidence interval (CI), 0.008-0.462; P=0.007] and multivariate analysis (HR, 0.095; 95% CI, 0.012-0.748; P=0.025). In the validation group, patients with high TRIM36 expression had decreased mortality risk when they received radiotherapy compared with patients who did not receive radiotherapy, as determined by univariate analysis (HR, 0.190; 95% CI, 0.067-0.540; P=0.002) and multivariate analysis (HR, 0.075; 95% CI, 0.020-0.276; P<0.001). However, for patients with low expression, no significant difference was identified in the overall survival rates between the radiotherapy and non-radiotherapy groups. Chi-squared analysis revealed that the expression status of TRIM36 was an independent factor and was not associated with clinicopathological factors. The results indicated that patients with high TRIM36 expression receiving radiotherapy exhibited an improved OS rate. TRIM36 may therefore be an important factor affecting the clinical prognosis of patients with GC receiving radiotherapy and may be considered as a potential radiosensitivity gene signature.

Helicobacter pylori infection associated with an increased risk of colorectal adenomatous polyps in the Chinese population.

BACKGROUND: Gastric Helicobacter pylori (H. pylori) is linked with chronic gastritis, peptic ulcer disease, and gastric malignancy. This study aims to investigate the association of gastric H. pylori with colorectal adenomatous polyps (CAP) in the Chinese population. METHODS: One thousand three hundred seventy five workers of China Petroleum and Chemical Corporation Sinopec Zhenhai Refining & Chemical Branch were recruited. Carbon-13 urea breathes test, and colorectal biopsies were utilized to detect H. pylori and CAP. The correlation between the number and distribution of CAP with H. pylori infection (HPI) was determined. Logistic regression models were applied to calculate the effect of H. pylori on the risk of CAP and pathway studio was used to attribute the cellular processes linking HPI and adenomatous polyps. RESULTS: One hundred Eighty participants were diagnosed as CAP, and 1195 participants were classified as healthy control. The prevalence of HPI in the CAP group was significantly higher than that in the healthy control group (57.8% verse 40.1%) (p<0.001). It was the number not the distribution of CAP corrected with H. pylori status. An increased risk of CAP was found to be associated with H. pylori (OR = 3.237; 95.0% CI 2.184-4.798, p = 0.00) even after multiple parameters adjustment. Pathway studio analysis demonstrated that HPI connected with CAP at multi-level. CONCLUSIONS: HPI is associated with an increased risk of CAP in the Chinese population.

Ferroelectric Polarization-Switching Dynamics and Wake-Up Effect in Si-Doped HfO2.

The ferroelectricity in ultrathin HfO2 offers a viable alternative to ferroelectric memory. A reliable switching behavior is required for commercial applications; however, many intriguing features of this material have not been resolved. Herein, we report an increase in the remnant polarization after electric field cycling, known as the "wake-up" effect, in terms of the change in the polarization-switching dynamics of a Si-doped HfO2 thin film. Compared with a pristine specimen, the Si-doped HfO2 thin film exhibited a partial increase in polarization after a finite number of ferroelectric switching behaviors. The polarization-switching behavior was analyzed using the nucleation-limited switching model characterized by a Lorentzian distribution of logarithmic domain-switching times. The polarization switching was simulated using the Monte Carlo method with respect to the effect of defects. Comparing the experimental results with the simulations revealed that the wake-up effect in the HfO2 thin film is accompanied by the suppression of disorder.

Superelectrophilic activation of 1-nitronaphthalene in the presence of aluminum chloride. Reactions with benzene and cyclohexane.

1-Nitronaphthalene smoothly reacts with benzene and undergoes selective reduction with cyclohexane in the presence of aluminum chloride to give 2,4,4-triphenyl-3,4-dihydronaphthalen-1(2H)-one oxime and 5,6,7,8-tetrahydro-1-naphthylamine, respectively. The mechanistic aspects of these and related reactions are discussed on the basis of DFT, providing insight into the protonation behavior of 1-nitronaphthalene coordinated to AlCl3.

Nonalcoholic Fatty Liver Disease Is Associated with Increased Atrial Fibrillation Risk in an Elderly Chinese Population: A Cross-Sectional Study.

BACKGROUND: Atrial fibrillation and nonalcoholic fatty liver disease are two pathological conditions that are highly prevalent worldwide and share multiple CVD risk factors. There are rare researches performed among elderly adults. AIMS: We conducted this cross-sectional analysis of elderly adults (≥65 years) to investigate the association between atrial fibrillation and nonalcoholic fatty liver disease. METHODS: We analyzed clinical data of the elderly adults (≥ 65 years) who had health examination in Zhenhai Lianhua Hospital, Ningbo, China, in 2014. RESULTS: 522 of the 1688 participants were diagnosed with nonalcoholic fatty liver disease, and 39 participants were diagnosed as having atrial fibrillation. Nonalcoholic fatty liver disease was associated with risk factors for AF in the elderly Chinese population (OR 1.95, 95% CI 1.03-3.69). Adjustments for age, gender, systolic blood pressure, fasting plasma glucose, γ-glutamyl transpeptidase, high-density lipoprotein, triglycerides, total cholesterol and albumin, nonalcoholic fatty liver disease, and prevalent atrial fibrillation remained statistically significant (OR 2.76, 95% CI 1.32-5.77). CONCLUSIONS: Our results show that nonalcoholic fatty liver disease is associated with an increased risk of atrial fibrillation in an elderly Chinese population.

Possible association between Helicobacter pylori infection and nonalcoholic fatty liver disease.

Possible association between Helicobacter pylori infection (HPI) and nonalcoholic fatty liver disease (NAFLD) has been proposed by several studies with inconsistent conclusions. Here, we studied the association between HPI and NAFLD at 3 levels: (i) genetic level; (ii) small molecular level; and (iii) clinical level. Relation data between diseases, genes, and small molecules were acquired from Pathway Studio ResNet Mammalian database. Clinical data were acquired from 2263 elderly South Chinese subjects, including 603 NAFLD patients and 1660 subjects without NAFLD. Results showed that HPI and NAFLD present significantly shared genetic bases (95 genes, p value = 2.5E-72), demonstrating multiple common genetic pathways (enrichment p value ≤ 4.38E-20 for the top 10 pathways). Genetic network analysis suggested that mutual regulation may exist between HPI and NAFLD through 21 out of 95 genes. Furthermore, 85 out of the 95 genes manifested strong interaction with 12 small molecules/drugs that demonstrate effectiveness in treating both diseases. Clinical results showed that HPI rate in the NAFLD group was significantly higher than that in the group without NAFLD (51.9% vs. 43.6%; p value = 4.9E-4). Multivariate logistic regression results supported the observations and suggested that HPI served as a risk factor for NAFLD in the experiment data studied (odds ratio: 1.387, p value = 0.018). Results from this study support the hypothesis that complex biological association may exist between HPI and NAFLD, which partially explains the significant clinical co-incidence in the elderly population of south China.

Protonation Behavior of 1,1'-Bi-2-naphthol and Insights into Its Acid-Catalyzed Atropisomerization.

The behavior of 1,1'-bi-2-naphthol (BINOL) in variety of (super)acid media has been studied by NMR. The results are combined with the theoretical (DFT) study of the role of mono- and diprotonated forms of BINOL in the acid-catalyzed atropisomerization of this compound. It is demonstrated that the process of enantiomeric configuration exchange proceeds mainly via internal rotation around the C1(sp3)-C1'(sp3) bond in intermediates such as C1-monoprotonated keto or C1,C1'-diprotonated forms of BINOL, depending on the acidity level.

Highly crystalline multimetallic nanoframes with three-dimensional electrocatalytic surfaces.

Control of structure at the atomic level can precisely and effectively tune catalytic properties of materials, enabling enhancement in both activity and durability. We synthesized a highly active and durable class of electrocatalysts by exploiting the structural evolution of platinum-nickel (Pt-Ni) bimetallic nanocrystals. The starting material, crystalline PtNi3 polyhedra, transforms in solution by interior erosion into Pt3Ni nanoframes with surfaces that offer three-dimensional molecular accessibility. The edges of the Pt-rich PtNi3 polyhedra are maintained in the final Pt3Ni nanoframes. Both the interior and exterior catalytic surfaces of this open-framework structure are composed of the nanosegregated Pt-skin structure, which exhibits enhanced oxygen reduction reaction (ORR) activity. The Pt3Ni nanoframe catalysts achieved a factor of 36 enhancement in mass activity and a factor of 22 enhancement in specific activity, respectively, for this reaction (relative to state-of-the-art platinum-carbon catalysts) during prolonged exposure to reaction conditions.

Influence of Step Geometry on the Reconstruction of Stepped Platinum Surfaces under Coadsorption of Ethylene and CO.

We demonstrate the critical role of the specific atomic arrangement at step sites in the restructuring processes of low-coordinated surface atoms at high adsorbate coverage. By using high-pressure scanning tunneling microscopy (HP-STM) and ambient-pressure X-ray photoelectron spectroscopy (AP-XPS), we have investigated the reconstruction of Pt(332) (with (111)-oriented triangular steps) and Pt(557) surfaces (with (100)-oriented square steps) in the mixture of CO and C2H4 in the Torr pressure range at room temperature. CO creates Pt clusters at the step edges on both surfaces, although the clusters have different shapes and densities. A subsequent exposure to a similar partial pressure of C2H4 partially reverts the clusters on Pt(332). In contrast, the cluster structure is barely changed on Pt(557). These different reconstruction phenomena are attributed to the fact that the 3-fold (111)-step sites on Pt(332) allows for adsorption of ethylidyne-a strong adsorbate formed from ethylene-that does not form on the 4-fold (100)-step sites on Pt(557).

Structure and chemical state of the Pt(557) surface during hydrogen oxidation reaction studied by in situ scanning tunneling microscopy and X-ray photoelectron spectroscopy.

The surface structure of Pt(557) during the catalytic oxidation of hydrogen was studied with in situ scanning tunneling microscopy and X-ray photoelectron spectroscopy. At 298 K, the surface Pt oxide formed after exposing Pt(557) to approximately 1 Torr of O2 can be readily removed by H2, at H2 partial pressures below 50 mTorr. Water is detected as the product in the gas phase, which also coadsorbs with hydroxyl groups on the Pt(557) surface.