Mild and Catalytic Synthesis of Pyrroles from Vinyl Ethynylethylene Carbonates.

A tandem remote propargylic amination/ring closure/aromatization reaction of vinyl ethynylethylene carbonates and amines has been developed, successfully constructing pyrrole derivatives. The reaction features mild conditions, high regioselectivity, high yields, and good functional group tolerance, making it an efficient method for pyrrole synthesis. Importantly, a variety of substrates containing natural product skeletons could also be compatibly and efficiently converted into pyrroles under the reaction conditions.

miRNA-338-3p/CAMK IIα signaling pathway prevents acetaminophen-induced acute liver inflammation in vivo.

INTRODUCTION AND OBJECTIVES: N-acetyl-p-aminophenol (APAP)-induced liver injury is a major clinical challenge worldwide. The present study investigated the molecular role of microRNA (miR)-338-3p in the development of APAP-induced acute liver injury. MATERIALS AND METHODS: B6 mice were treated with an miR-338-3p agomir, antagomir, and intraperitoneally injected with APAP 24h later to induce acute liver injury. Histological analysis was performed to evaluate the degree of liver injury. The gene expression of miR-338-3p and its downstream regulators was measured by reverse transcription-quantitative PCR and western blot. The miR target was validated using a luciferase reporter assay. RESULTS: The results revealed that miR-338-3p was significantly upregulated following the intraperitoneal administration of APAP. Augmenting miR-338-3p alleviated acute liver injury caused by APAP overdose, while silencing of miR-338-3p exhibited a detrimental effect. Moreover, miR-338-3p inhibited the expression of pro-inflammatory cytokines by preventing the aberrant activation of inflammatory signaling pathways, including the nuclear factor kappa-B (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathway. Furthermore, calcium/calmodulin-dependent protein kinase IIα (CAMK IIα) was identified as a direct target of miR-338-3p. CONCLUSION: The present study demonstrated that miR-338-3p inhibited inflammation in APAP-induced acute liver injury.

ß-arrestin-2 is involved in irisin induced glucose metabolism in type 2 diabetes via p38 MAPK signaling.

Type 2 diabetes mellitus (T2DM) is a common metabolic disease worldwide. It has been reported that irisin play regulatory role in glucose metabolism in T2DM. However, the underlying mechanism involved in that is not completely known. Herein, we determined the novel role of ß-arrestin-2 in irisin-induced glucose utilization in diabetes. Effects of irisin and ß-arrestin-2 on glucose utilization were investigated in a rat model of diabetes and in diabetic C2C12 cells in vitro. Results showed that irisin had positive role in glucose metabolism via regulating glucose tolerance as well as uptake in cardiac and skeletal muscle tissues, as evidenced by IPGTT, 2-deoxyglucose uptake and plasma membrane GLUT-4 assay. ß-arrestin-2 also improved glucose utilization in diabetes by increasing the glucose uptake and insulin sensitivity, as shown in mice overexpressing ß-arrestin-2. In diabetic C2C12 myocytes, irisin-induced GLUT4 and glucose uptake were restrained by ß-arrestin-2 inhibition, but was enhanced by ß-arrestin-2 overexpression. Additionally, irisin and ß-arrestin-2 increased the activation of p38 MAPK in diabetic C2C12 cells, and the repression of p38 MAPK activation decreased the glucose uptake and plasma membrane GLUT-4 was enhanced by irisin and ß-arrestin-2 overexpression in diabetic C2C12 cells. In conclusion, we demonstrated that ß-arrestin-2 has a crucial role in irisin induced glucose metabolism in T2DM by regulating the p38 MAPK signaling. This might present a novel therapeutic target of treatment for human diabetes.

Association of dietary inflammatory index, composite dietary antioxidant index, and frailty in elderly adults with diabetes.

BACKGROUND: We aimed to examine the relationship of 2 dietary scores [dietary inflammatory index (DII) and composite dietary antioxidant index (CDAI)] with frailty in elderly adults with diabetes. METHODS: Data were gathered from the National Health and Nutrition Examination Survey (NHANES) between 2007 and 2018. The frailty index was calculated using 49 deficits across various systems to define frailty. To examine the relationship of 2 dietary scores (DII and CDAI) with frailty in elderly adults with diabetes, multiple logistic regression analyses were performed. In logistic regression model, DII and CDAI were calculated as both continuous and tertiles. Subgroup analyses were performed to demonstrate stability of results. Restricted cubic splines were utilized to examine the non-linear correlations. RESULTS: A total of 2,795 elderly adults with diabetes were included in this study. In the multivariate logistic regression model, the odds ratio (OR) of DII for risk of frailty was 1.08 (95% CI 1.02-1.15) and the OR of CDAI for risk of frailty was 0.96 (95% CI 0.93-0.99). The ORs of DII for risk of frailty were 1.36 (95% CI 1.09-1.70) and 1.33 (95% CI 1.04-1.70) for tertiles 2 and 3, respectively (p for trend 0.027). The ORs of CDAI for risk of frailty were 0.94 (95% CI 0.75-1.17) and 0.75 (95% CI 0.58-0.98) for tertiles 2 and 3, respectively (p for trend 0.036). The subgroup analysis demonstrated reliable and enduring connections between 2 dietary scores and frailty (all p for interaction > 0.05). In the restricted cubic spline analyses, we discovered the non-linear relationship between DII and frailty (P for nonlinearity = 0.045) and linear relationship between CDAI and frailty (P for nonlinearity = 0.769). CONCLUSION: The research showed connections between 2 dietary scores (DII and CDAI) and frailty as measured by frailty index in elderly adults with diabetes.

Microwave heating concentration of raspberry pulp: Evaluation of processing variables on concentration characteristics and quality attributes.

Concentration of fruit pulp is an important unit operation in food processing and has a wide range of applications. In this study, the microwave heating concentration (MHC) of raspberry pulp at different microwave powers, heating times and sample masses were investigated considering concentration characteristics and quality attributes. The results showed that increasing microwave power/heating time or decreasing sample mass significantly decreased the moisture content but had no significant effect on the temperature of raspberry pulp, while these conditions resulted in loss of total anthocyanin content and deterioration of total color difference. LF-NMR and SEM results revealed that the changes in temperature and moisture content caused by MHC significantly affected the total anthocyanin content and total color difference of the final product. Microwave power of 800 W, heating time of 3 min and sample mass of 90 g are selected as suitable parameters for MHC of raspberry pulp. This study may provide guidance for the development of appropriate technology for MHC of berry pulp.

Impact of Model Spatial Resolution on Global Geophysical Satellite-Derived Fine Particulate Matter.

Global geophysical satellite-derived ambient fine particulate matter (PM2.5) inference relies upon a geophysical relationship (η) from a chemical transport model to relate satellite retrievals of aerosol optical depth (AOD) to surface PM2.5. The resolution dependence of simulated η warrants further investigation. In this study, we calculate geophysical PM2.5 with simulated η from the GEOS-Chem model in its high-performance configuration (GCHP) at cubed-sphere resolutions of C360 (∼25 km) and C48 (∼200 km) and satellite AOD at 0.01° (∼1 km). Annual geophysical PM2.5 concentrations inferred from satellite AOD and GCHP simulations at ∼25 km and ∼200 km resolutions exhibit remarkable similarity (R 2 = 0.96, slope = 1.03). This similarity in part reflects opposite resolution responses across components with population-weighted normalized mean difference (PW-NMD) increasing by 5% to 11% for primary species while decreasing by -30% to -5% for secondary species at finer resolution. Despite global similarity, our results also identify larger resolution sensitivities of η over isolated pollution sources and mountainous regions, where spatial contrast of aerosol concentration and composition is better represented at fine resolution. Our results highlight the resolution dependence of representing near-surface concentrations and the vertical distribution of chemically different species with implications for inferring ground-level PM2.5 from columnar AOD.

Optimization of Processing Parameters for Continuous Microwave Drying of Crab Apple Slices via Response Surface Methodology.

To improve product quality and obtain suitable processing parameters for crab apple slices (CASs) produced by continuous microwave drying (CMD), the effects of processing parameters, including slice thickness, microwave power, air velocity, and conveyor belt speed, on the evaluation indexes in terms of temperature, moisture content, color (L*, a*, b*), hardness, brittleness, and total phenolic content of CASs were investigated via the response surface method. The results indicated that microwave power has the greatest effect on the evaluation indexes applied to the CASs under CMD, followed by air velocity, slice thickness, and conveyor belt speed. To produce the desired product quality, the appropriate parameters for CMD of CASs were optimized as 1.25 mm slice thickness, 14,630 W microwave power, 0.50 m·s-1 air velocity, and 0.33 m·min-1 conveyor belt speed. Following that, the moisture content under CMD was found to be 13.53%, the desired color, hardness 0.79 g, brittleness 12.97 (number of peaks), and the total phenolic content 5.48 mg·g-1. This research provides a theoretical framework for optimizing the processing parameters of CASs using the response surface method.

Elemental Characterization of Ambient Particulate Matter for a Globally Distributed Monitoring Network: Methodology and Implications.

Global ground-level measurements of elements in ambient particulate matter (PM) can provide valuable information to understand the distribution of dust and trace elements, assess health impacts, and investigate emission sources. We use X-ray fluorescence spectroscopy to characterize the elemental composition of PM samples collected from 27 globally distributed sites in the Surface PARTiculate mAtter Network (SPARTAN) over 2019-2023. Consistent protocols are applied to collect all samples and analyze them at one central laboratory, which facilitates comparison across different sites. Multiple quality assurance measures are performed, including applying reference materials that resemble typical PM samples, acceptance testing, and routine quality control. Method detection limits and uncertainties are estimated. Concentrations of dust and trace element oxides (TEO) are determined from the elemental dataset. In addition to sites in arid regions, a moderately high mean dust concentration (6 µg/m3) in PM2.5 is also found in Dhaka (Bangladesh) along with a high average TEO level (6 µg/m3). High carcinogenic risk (>1 cancer case per 100000 adults) from airborne arsenic is observed in Dhaka (Bangladesh), Kanpur (India), and Hanoi (Vietnam). Industries of informal lead-acid battery and e-waste recycling as well as coal-fired brick kilns likely contribute to the elevated trace element concentrations found in Dhaka.

Forming Limit Analysis of Thin-Walled Extruded Aluminum Alloy Tubes under Nonlinear Loading Paths Using an Improved M-K Model.

To meet the requirement of lighter weight and better performance in tube hydroforming, one of the most important tasks is to accurately predict the forming limit of thin-walled tubes under nonlinear loading paths. This work established the M-K+DF2012 model, a combination of the M-K model and the DF2012 ductile fracture criterion, for the forming limit prediction of thin-walled tubes under nonlinear loading paths. In this model, the failure of the groove is determined by the DF2012 criterion, and the corresponding strains in the uniform region are the limit strains. The limit strains of an AA6061 aluminum alloy tube under a set of linear loading paths and two typical nonlinear loading paths were tested. Parameter values of the M-K+DF2012 model for the tube were determined based on the experimental limit strains under linear loading paths, and the limit strains under the two nonlinear loading paths were predicted. Then the strain-based forming limit diagram (ε-FLD) and the polar effective plastic strain FLD (PEPS-FLD) of the tube under different pre-strains were predicted and discussed. The results show that the limit strains of the tube are obviously path-dependent, and the M-K+DF2012 model can reasonably capture the limit strains of the tube under both linear and nonlinear loading paths. The predicted ε-FLD shows a strong dependence on the pre-strain, while the predicted PEPS-FLD is weakly strain path-dependent and almost path-independent on the right-hand side for the AA6061 tube.

A Homogeneous Anisotropic Hardening Model in Plane Stress State for Sheet Metal under Nonlinear Loading Paths.

In sheet metal forming, the material is usually subjected to a complex nonlinear loading process, and the anisotropic hardening behavior of the material must be considered in order to accurately predict the deformation of the sheet. In recent years, the homogeneous anisotropic hardening (HAH) model has been applied in the simulation of sheet metal forming. However, the existing HAH model is established in the second-order stress deviator space, which makes the calculation complicated and costly, especially for a plane stress problem such as sheet metal forming. In an attempt to reduce the computational cost, an HAH model in plane stress state is proposed, and called the HAH-2d model in this paper. In the HAH-2d model, both the stress vector and microstructure vector contain only three in-plane components, so the calculation is significantly simplified. The characteristics of the model under typical nonlinear loading paths are analyzed. Additionally, the feasibility of the model is verified by the stress-strain responses of DP780 and EDDQ steel sheets under different two-step uniaxial tension tests. The results show that the HAH-2d model can reasonably reflect the Bauschinger effect and the permanent softening effect in reverse loading, and the latent hardening effect in cross loading, while the predictive accuracy for cross-loading softening remains to be improved. In the future, the HAH-2d model can be further modified to describe more anisotropic hardening behaviors and applied to numerical simulations.

Frailty Index was Associated With Adverse Outcomes in Admitted Elderly Patients With Type 2 Diabetes Mellitus.

We aimed to investigate the role of the laboratory frailty index (LFI) in diabetic complications and incident disability in admitted older patients with type 2 diabetes mellitus (T2DM). We retrospectively collected the clinical data of older patients with T2DM from December 2018 to May 2020. Frailty was quantified using the LFI, which considers the accumulation of 27 items of abnormal laboratory outcomes. Univariate and multivariate analyses were performed to evaluate the relationship between LFI and diabetes-related adverse outcomes. In total, 293 consecutive older patients with T2DM were recruited for this study. According to the predefined LFI criteria, 110 (37.5%) participants were non-frail, 131 (44.7%) were prefrail, and 52 (17.8%) were frail. Univariate and multivariate analysis revealed that LFI was associated with the diabetic microangiopathy complications (odds ratio for prefrail [ORprefrail] 1.760, 95% confidence interval for prefrail [CIprefrail] 1.019-3.041, P = .043; ORfrail 4.667, 95% CIfrail 2.012-10.826, P < .001) and activities of daily living (ADL) disability (ORprefrail 2.323, 95% CIprefrail 1.209-4.463, P = .011; ORfrail 9.367, 95% CIfrail 4.030-21.775, P < .001), but not with the diabetic macroangiopathy complications and diabetic peripheral neuropathy. Frailty, as determined by the LFI, was proven to be an effective tool for the prediction of diabetic microangiopathy complications and ADL disability.

Effect of Heating on Hot Deformation and Microstructural Evolution of Ti-6Al-4V Titanium Alloy.

This paper presents a systematic study of heating effects on the hot deformation and microstructure of dual-phase titanium alloy Ti-6Al-4V (TC4) under hot forming conditions. Firstly, hot flow behaviors of TC4 were characterized by conducting tensile tests at different heating temperatures ranging from 850 °C to 950 °C and heating rates ranging from 1 to 100 °C/s. Microstructure analysis, including phase and grain size, was carried out under the different heating conditions using SEM and EBSD. The results showed that when the heating temperature was lower than 900 °C, a lower heating rate could promote a larger degree of phase transformation from α to ß, thus reducing the flow stress and improving the ductility. When the temperature reached 950 °C, a large heating rate effectively inhibited the grain growth and enhanced the formability. Subsequently, according to the mechanism of phase transformation during heating, a phenomenological phase model was established to predict the evolution of the phase volume fraction at different heating parameters with an error of 5.17%. Finally, a specific resistance heating device incorporated with an air-cooling set-up was designed and manufactured to deform TC4 at different heating parameters to determine its post-form strength. Particularly, the yield strength at the temperature range from 800 °C to 900 °C and the heating rate range from 30 to 100 °C/s were obtained. The results showed that the yield strength generally increased with the increase of heating temperature and the decrease of heating rate, which was believed to be dominated by the phase transformation.

Copper-Catalyzed Enantioselective Formal [4 + 1] and [3 + 3] Cycloaddition of Ethynylethylene Carbonates.

Herein we employed ethynylethylene carbonates (EECs) to achieve formal [4 + 1] and [3 + 3] cycloaddition with cyclic 1,3-dicarbonyl compounds. On one hand, EECs with styryl substitution could undergo a remotely controlled enantioselective [4 + 1] cycloaddition reaction. This reaction exhibits good chemoselectivity, regioselectivity, and enantioselectivity. In addition, a [3 + 3] cycloaddition reaction of EECs with cyclic 1,3-dicarbonyl compounds was also achieved, leading to a series of 4H-pyrans with impressive chemoselectivity and enantioselectivity.

Clinical Outcome After Left Ventricular Thrombus Resolution: Who Needs Long-Term or Lifetime Use of Anticoagulants?

Background Patients with left ventricular thrombus (LVT) resolution can have LVT recurrence and risk for thromboembolism. However, these outcomes after LVT resolution are not well known. We aimed to assess the prevalence, risk factors, and clinical outcomes for LVT recurrence in patients with LVT resolution to inform follow-up and treatment. Methods and Results Patients with LVT resolution were identified retrospectively from a large echocardiography database between January 2009 and May 2022. Participants had echocardiograms at 3 time points, including baseline at LVT diagnosis, at LVT resolution, and a follow-up for identification of LVT recurrence. The cumulative LVT recurrence rate was estimated by the Kaplan-Meier method, and predictors of LVT recurrence were evaluated using Cox regression analysis. Among 115 patients with LVT resolution, 28 (24.3%) had LVT recurrence at a median follow-up of 1.2 (0.5-2.8) years. LV aneurysm (hazard ratio [HR], 2.59 [95% CI, 1.20-5.58], P=0.015) and anticoagulant use (HR, 0.12 [95% CI, 0.04-0.41], P=0.001) were predictors of LVT recurrence on multivariable analysis. Patients with an LV aneurysm who did not receive any anticoagulation demonstrated an LVT recurrence rate of 69.5%, whereas those without an LV aneurysm who received anticoagulation had a recurrence rate of 0%. Patients with LVT recurrence had a higher incidence of an embolic event (10.7% versus 1.1%, P=0.016). Conclusions LVT recurrence after LVT resolution is common, especially in those with an LV aneurysm, and is associated with a higher embolic risk. Continued anticoagulation is protective against LVT recurrence, although bleeding risk needs to be considered. These findings can inform follow-up and treatment of patients with documented LVT resolution.

[Daphnetin alleviates myocardial ischemia injury in rats through mediating oxidative stress and inhibiting JNK/NF-κB pathway].

Objective To study the protective effect and mechanism of daphnetin (DAP) against myocardial ischemia-reperfusion injury in rats. Methods Seventy-five SD rats were randomly divided into five groups: control group, model group, (30, 60, 90) mg/kg DAP-treated groups. The model of myocardial ischemia in rats was established by isoproterenol (85 mg/kg) through subcutaneous injection for 2 consecutive days. DAP was administered by gavage for 7 consecutive days to observe the protective effect of DAP on the injury of rat myocardium. The electrocardiographic changes of each group of experimental rats were measured with electrocardiographic measuring device. The activities of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and malondialdehyde (MDA) in the sera were detected with spectrophotometry. The serum levels of creatine kinase isoenzyme, muscle b (CK-MB), lactate dehydrogenase (LDH) and creatine phosphokinase (CPK), and the content of interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), IL-6 in the homogenate of myocardial tissue were measured by ELISA. The injury and fibrosis of cardiomyocytes were observed by HE staining and Masson staining, the mRNA levels of JNK and NF-κB were detected by real-time quantitative PCR, and the phosphorylation of JNK and NF-κB were determined by Western blot analysis. Results DAP increased the activities of SOD, CAT, GSH-Px, decreased MDA, inhibited the levels of CK-MB, LDH, CPK, TNF-α and IL-ß in the sera, decreased myocardial fibrosis, depressed the expression and phosphorylation of JNK and NF-κBp65. Conclusion DAP can inhibit the activation of JNK/NF-κB signal pathway and myocardial apoptosis and fibrosis induced by myocardial ischemia-reperfusion.

ClO2 pre-oxidation changes the yields and formation pathways of chloroform and chloral hydrate from phenolic precursors during chlorination.

Phenolic moieties in natural organic matter (NOM) are important precursors of disinfection by-products (DBPs). In this study, the formation of chloral hydrate from chlorination of seventeen phenolic compounds, including mono-, di- and tri-hydroxybenzenes, were evaluated and the role of chlorine dioxide (ClO2) pre-oxidation on its formation pathways was explored. Chloroform, was also evaluated for comparison. Chlorination of resorcinol exhibited the highest chloral hydrate yield (2.83 ±â€¯0.13%) followed by chlorination of 2,4,6-trichlorophenol (0.61 ±â€¯0.03%). The median of chloral hydrate yields from the tested phenolic compounds was 0.22%. ClO2 pre-oxidation reduced the yields of chloroform from phenol derivatives by 37-97%, except 4-methoxyphenol, catechol and 2,3-dihydroxyphenol. On the contrary, ClO2 pre-oxidation of di- and tri-hydroxybenzenes tended to increase chloral hydrate yields in post-chlorination. Mixed results (both increases and decreases) were observed in chloral hydrate formation from chlorination of mono-hydroxybenzenes after ClO2 pre-oxidation. The changes of their formation were dependent on ClO2 pre-oxidation time and dosages. Identification of transformation products suggested that phenolic compounds were mainly converted to unsaturated carbonyl structures by ClO2. Chlorine substituted benzoquinones and cyclopent-4-ene-1,3-diones were important transformation products after a series of ring open, decarboxylation, hydrolysis and chlorine substitution reactions. The changes in the formation yields of chloral hydrate and chloroform were governed by the difference in initial phenolic precursors and the transformation products after ClO2 pre-oxidation. ClO2 pre-oxidation in water treatment can effectively reduce chloroform formation but may have a risk of increasing chloral hydrate formation.

Occurrence of nitrogenous and carbonaceous disinfection byproducts in drinking water distributed in Shenzhen, China.

A 12-month sampling program was conducted throughout a drinking water distribution system in Shenzhen and the data from 251 samples provide a comprehensive picture of the spatial and seasonal variability of 17 species disinfection by-products (DBPs) in a city with subtropical monsoon climate. The carbonaceous disinfection by-product (C-DBPs) included four trihalomethanes (THMs), three trihaloacetaldehydes (THAs) and two haloketones (HKs). Their median concentrations over the entire period were 19.9 µg/L, 3.4 µg/L and 1.4 µg/L, respectively. The nitrogenous DBPs (N-DBPs) monitored were four haloacetonitriles (HANs) and four haloacetamides (HAcAms). Their median levels were 2.0 µg/L and 1.5 µg/L, respectively. Low levels of brominated DBP species (bromine substitution factors ≤ 0.5) were observed. The BSF of each DBP class followed the trend: THMs ≈ DHAcAms > DHANs > THAs. All the DBP concentrations showed clear seasonal variations with the highest average concentrations in spring. Correlation analyses showed that the THMs and CH levels in Shenzhen drinking water could be used as statistical indicators of the levels of unregulated N-DBPs (0.4 < r < 0.7, p < 0.5). The results supplement the database of DBP occurrence in drinking water in China, and provide an important reference data set for DBP occurrence in cities with a subtropical monsoon climate around the world.