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Reliable and accurate full-field deformation measurements at elevated temperatures using digital image correlation (DIC) require stable and high-contrast high-temperature speckle patterns to be prepared on the sample surface. However, conventional high-temperature speckle patterns fabricated by the existing methods possess several limitations, e.g., easily fail to preserve original pattern features due to the harsh environment and heavily dependent on the operator's experience. In this study, we propose a reliable and reproducible high-temperature speckle fabrication method based on air plasma spraying (APS) and flexible speckle templates. This method involves covering the sample surface with pre-designed speckle templates and then spraying the melted speckle powders onto the specimen surface using an air plasma spray technique to obtain customized speckle patterns. The validity of the proposed method was verified by the speckle fabrication on both planar and curved samples and heating tests with these samples. Experimental results demonstrate that the speckle patterns made by the proposed method adhere well to the sample surface, remain stable during the heating process, and exhibit excellent agreement with the reference values in terms of the thermal expansion coefficients. The proposed method provides a reliable and efficient way to create customized and stable speckle patterns for accurate high-temperature DIC measurements. [ABSTRACT FROM AUTHOR]

An automated camera exposure control method, which allows a two-camera stereo-digital image correlation (stereo-DIC) system to capture high-quality speckle image pairs, is presented for accuracy-enhanced stereo-DIC measurement. By using this method, the two synchronized cameras can automatically determine the optimal camera exposure and ideal average grayscale for capturing the optimal reference image pair in the reference state. Furthermore, high-quality deformed image pairs can be recorded during the test by adaptively adjusting the camera exposure in case of serious ambient light variations. Validation tests, including varying illumination tests and translation tests, were performed to verify the effectiveness and robustness of this method. Experimental results indicate that the proposed method overperforms the existing stereo-DIC technique with empirically determined fixed camera exposure time. The practicality of the proposed automated camera exposure control method was verified using real high-temperature experiments. [ABSTRACT FROM AUTHOR]

Potato is an important food crop. After harvest, these tubers will undergo a period of dormancy. Brassinosteroids (BRs) are a new class of plant hormones that regulate plant growth and seed germination. In this study, 500 nM of BR was able to break the dormancy of tubers. Additionally, exogenous BR also upregulated BR signal transduction genes, except for StBIN2. StBIN2 is a negative regulator of BR, but its specific role in tuber dormancy remains unclear. Transgenic methods were used to regulate the expression level of StBIN2 in tubers. It was demonstrated that the overexpression of StBIN2 significantly prolonged tuber dormancy while silencing StBIN2 led to premature sprouting. To further investigate the effect of StBIN2 on tuber dormancy, RNA-Seq was used to analyze the differentially expressed genes in OE-StBIN2, RNAi-StBIN2, and WT tubers. The results showed that StBIN2 upregulated the expression of ABA signal transduction genes but inhibited the expression of lignin synthesis key genes. Meanwhile, it was also found that StBIN2 physically interacted with StSnRK2.2 and StCCJ9. These results indicate that StBIN2 maintains tuber dormancy by mediating ABA signal transduction and lignin synthesis. The findings of this study will help us better understand the molecular mechanisms underlying potato tuber dormancy and provide theoretical support for the development of new varieties using related genes. [ABSTRACT FROM AUTHOR]

The stereo-digital image correlation technique using two synchronized industrial-grade cameras has been extensively used for full-field 3D shape, displacement and deformation measurements. However, its use in resource-limited institutions and field settings is inhibited by the need for relatively expensive, bulky and complicated experimental set-ups. To mitigate this problem, we established a cost-effective and ultra-portable smartphone-based stereo-digital image correlation system, which only uses a smartphone and an optical attachment. This optical attachment is composed of four planar mirrors and a 3D-printed mirror support, and can split the incoming scene into two sub-images, simulating a stereovision system using two virtual smartphones. Although such a mirror-based system has already been used for stereo-image correlation, this is the first time it has been combined with a commercial smartphone. This publication explores the potential and limitations of such a configuration. We first verified the effectiveness and accuracy of this system in 3D shape and displacement measurement through shape measurement and in-plane and out-of-plane translation tests. Severe thermal-induced virtual strains (up to 15,000 με) were found in the measured results due to the smartphone heating. The mechanism for the generation of the temperature-dependent errors in this system was clearly and reasonably explained. After a simple preheating process, the smartphone-based system was demonstrated to be accurate in measuring the strain on the surface of a loaded composite specimen, with comparable accuracy to a strain gauge. Measurements of 3D deformation are illustrated by tracking the deformation on the surface of a deflating ball. This cost-effective and ultra-portable smartphone-based system not only greatly decreases the hardware investment in the system construction, but also increases convenience and efficiency of 3D deformation measurements, thus demonstrating a large potential in resource-limited and field settings. [ABSTRACT FROM AUTHOR]

Simple Summary: Barley is the fourth largest cereal crop in the world. Fusarium head blight (FHB) is one of the diseases in barley producing mycotoxins, such as deoxynivalenol (DON), that could affect grain quality as well as human and animal health worldwide. Due to limited reliable biomarkers to identify and develop FHB-resistant cultivars in barley, we investigated the composition of phenolic compounds in ten barley cultivars under clean and FHB-infected conditions. We analyzed free and bound forms of phenolic compounds and identified differences among tested cultivars. Analysis of mycotoxin DON content showed that resistant cultivars produced less compared to susceptible cultivars. In addition, the resistant cultivars showed higher amounts of major phenolic compounds compared to the known susceptible cultivar. The results of this study suggest that phenolic compounds in barley could have a role as potential biomarkers to identify and develop FHB-resistant barley cultivars. Barley (Hordeum vulgare L.) is the fourth largest cereal crop in the world. One of the most devastating diseases in barley worldwide is Fusarium head blight (FHB) caused by Fusarium graminearum Schwabe. Several mycotoxins are produced by FHB infection, and deoxynivalenol (DON) is one of them responsible for the deterioration of grain quality. The current limited number of reliable molecular markers makes the development of FHB-resistant cultivars rather difficult and laborious. Moreover, there is a limited number of designed specific biomarkers that could distinguish the FHB resistance and mycotoxin accumulation in barley cultivars. This study investigated the phenolic compounds of ten different Canadian barley cultivars, grown in artificially FHB-infected and non-infected field trials. The enzyme-linked immunosorbent assay (ELISA) was used to assess the presence of DON in the harvested infected grains of each tested variety. High-performance liquid chromatography (HPLC) analysis was performed using both infected and non-infected samples. We identified differences among cultivars tested in non-infected samples through quantitative analysis of free and bound phenolic compounds. The resistant cultivars showed higher amounts of major bound phenolic compounds compared to the susceptible check CDC Bold. Additionally, the FHB-infected cultivars produced significantly higher amounts of sinapic acid (SIN) () and catechin (CAT) in the soluble free form of phenolics in barley compared to the non-infected subjects. This study suggests that phenolic compounds in barley could allow barley breeders to precisely identify and develop FHB-resistant barley germplasm and cultivars. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is a chronic autoimmune disease that attacks the insulin-producing b cells of the pancreatic islets. Autoantibodies to b cell proteins typically appear in the circulation years before disease onset, and serve as the most accurate biomarkers of T1D risk. Our laboratory has recently discovered novel b cell proteins comprising hybrid proinsulin:islet amyloid polypeptide peptides (IAPP). T cells from a diabetic mouse model and T1D patients are activated by these hybrid peptides. In this study, we asked whether these hybrid molecules could serve as antigens for autoantibodies in T1D and prediabetic patients. We analyzed sera from T1D patients, prediabetics and healthy age-matched donors. Using a highly sensitive electrochemiluminescence assay, sera were screened for binding to recombinant proinsulin:IAPP probes or truncated derivatives. Our results show that sera from T1D patients contain antibodies that bind larger hybrid proinsulin:IAPP probes, but not proinsulin or insulin, at significantly increased frequencies compared to normal donors. Examination of sera from prediabetic patients confirms titers of antibodies to these hybrid probes in more than 80% of individuals, often before seroconversion. These results suggest that hybrid insulin peptides are common autoantigens in T1D and prediabetic patients, and that antibodies to these peptides may serve as valuable early biomarkers of the disease. [ABSTRACT FROM AUTHOR]

This study investigates the role and mechanisms by which the myokine musclin promotes exercise-induced cardiac conditioning. Exercise is one of the most powerful triggers of cardiac conditioning with proven benefits for healthy and diseased hearts. There is an emerging understanding that muscles produce and secrete myokines, which mediate local and systemic "crosstalk" to promote exercise tolerance and overall health, including cardiac conditioning. The myokine musclin, highly conserved across animal species, has been shown to be upregulated in response to physical activity. However, musclin effects on exercise-induced cardiac conditioning are not established. Following completion of a treadmill exercise protocol, wild type (WT) mice and mice with disruption of the musclin-encoding gene, Ostn, had their hearts extracted and exposed to an ex vivo ischemia-reperfusion protocol or biochemical studies. Disruption of musclin signaling abolished the ability of exercise to mitigate cardiac ischemic injury. This impaired cardioprotection was associated with reduced mitochondrial content and function linked to blunted cyclic guanosine monophosphate (cGMP) signaling. Genetic deletion of musclin reduced the nuclear abundance of protein kinase G (PKGI) and cyclic adenosine monophosphate (cAMP) response element binding (CREB), resulting in suppression of the master regulator of mitochondrial biogenesis, peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α), and its downstream targets in response to physical activity. Synthetic musclin peptide pharmacokinetic parameters were defined and used to calculate the infusion rate necessary to maintain its plasma level comparable to that observed after exercise. This infusion was found to reproduce the cardioprotective benefits of exercise in sedentary WT and Ostn-KO mice. Musclin is essential for exercise-induced cardiac protection. Boosting musclin signaling might serve as a novel therapeutic strategy for cardioprotection. [ABSTRACT FROM AUTHOR]

Pyxinol skeleton is a promising framework of anti-inflammatory agents formed in the human liver from 20S-protopanaxadiol, the main active aglycone of ginsenosides. In the present study, a new series of amino acid-containing derivatives were produced from 12-dehydropyxinol, a pyxinol oxidation metabolite, and its anti-inflammatory activity was assessed using an NO inhibition assay. Interestingly, the dehydrogenation at C-12 of pyxinol derivatives improved their potency greatly. Furthermore, half of the derivatives exhibited better NO inhibitory activity than hydrocortisone sodium succinate, a glucocorticoid drug. The structure–activity relationship analysis indicated that the kinds of amino acid residues and their hydrophilicity influenced the activity to a great extent, as did R/S stereochemistry at C-24. Of the various derivatives, 5c with an N-Boc-protected phenylalanine residue showed the highest NO inhibitory activity and relatively low cytotoxicity. Moreover, derivative 5c could dose-dependently suppress iNOS, IL-1β, and TNF-α via the MAPK and NF-κB pathways, but not the GR pathway. Overall, pyxinol derivatives hold potential for application as anti-inflammatory agents. [ABSTRACT FROM AUTHOR]

Barley (Hordeum vulgare L.) grain is rich in fiber and antioxidant phytochemicals, including fatty acids, proteins, phenolic compounds, vitamins, and minerals, that offer various health benefits. Research on identifying different barley genotypes based on their health attributes is very limited. In this study, we performed an analysis of fatty acids, proteins, ascorbic acid, phenolic compounds, and antioxidant activity of several Canadian barley cultivars and elite breeding lines. Linoleic acid (C18:2) was the predominant fatty acid present in the tested barley cultivars. The cultivar CDC Bold contained the highest amount of ascorbic acid, while the highest protein content was in CDC Mindon. An assessment of the free and bound phenolic compounds of barley grains showed quantitative changes among different genotypes of Canadian barley. Catechin is the most abundant molecule in free phenolics, while ferulic acid and para-coumeric acid are the most abundant in bound phenolics. Ferulic acid and vanillic acid were molecules detected in the soluble free fraction of all genotypes. Para-coumeric acid was detected only in genotypes such as CDC Copeland, CDC Bold, Lowe, and elite breeding Line 5 of both free and bound fractions of barley. Breeding Line 5 had the lowest antioxidant activity. An analysis of the above molecules and parameters of Canadian barley would help to uncover potential biomarkers in order to distinguish individual barley genotypes. [ABSTRACT FROM AUTHOR]

Bamboo fibers are considered as a more attractive option for the reinforcement of wood plastic composites as compared to wood fiber due to its fast growth rate and good toughness. Heat treatment is an environment-friendly method of improving the integrated performance of bamboo materials. This paper highlights the heat treatment of bamboo fiber for suitable properties as reinforcements in bamboo plastic composites. The effects of vacuum heat treatment on the surface characteristics of bamboo fibers and the properties of bamboo plastic composites were analyzed by studying the chemical composition, surface elements and polarity of bamboo fiber before and after treatment, and the physical and mechanical properties of bamboo plastic composite. The results showed that after vacuum heat treatment, the bamboo fibers became darker and experienced a transition from green to red. Moreover, FTIR, XPS and contact angle analysis indicated that the hemicellulose content, the oxygen/carbon ratio and the polar component of the bamboo fiber had a decreasing trend as the treatment temperature increased. In addition, the 24 h water absorption and the 24 h thickness expansion rate of the water absorption showed a trend of first decreasing and then increasing as the treatment temperature increased, while the bending performance of bamboo plastic composite showed a trend of increasing first and then decreasing as a result of increased treatment temperature. Therefore, a combined process of vacuum heat treatment and the addition of MAPE could improve the physical and mechanical properties of bamboo plastic composites to a certain extent. [ABSTRACT FROM AUTHOR]

Background: Obsessive-compulsive disorder (OCD) and tic disorders (TDs) are closely related and considered to etiologically overlap. Both disorders are characterized by repetitive behaviors. TD and OCD often co-occur. The high comorbidity between OCD and TD individuals suggests that we also need to pay more attention to the homogeneity and heterogeneity between TS and OCD. To date, there has been no systematic nationwide epidemiological survey of the mental health (including tic disorders and obsessive-compulsive disorder) of children and adolescents in China. Methods: A two-stage epidemiological study of psychiatric point prevalence was conducted. We used the multistage cluster stratified random sampling strategy to assess five provinces of China. The Child Behavior Checklist was used to identify behavioral problems among the enrolled students in the first stage. The results from the Mini-International Neuropsychiatric Interview for Children and Adolescents and evaluations from two psychiatrists based on the Diagnostic and Statistical Manual-IV were used to make a diagnosis. Point weighted prevalence for TD and OCD was estimated. We adjusted prevalence estimates with the product of sampling weights and poststratification weights. Standard error values and 95% confidential intervals were generated with Taylor series linearization. Rao–Scott adjusted chi-square (χ2) tests were employed to compare the prevalence estimates of different age and sex groups. Results: In the first stage, 73,992 participants aged 6–16 years old were selected. The prevalence rates of OCD and TDs were 1.37% (95% CI: 1.28–1.45) and 2.46% (95% CI: 2.35–2.57), respectively. The prevalence of OCD was found to be higher in girls (p < 0.001) and higher in boys with transient tic disorder (TTD) (p < 0.001) and Tourette's syndrome (TS) (p < 0.001). The most common comorbidity of TS was OCD (40.73%), and for OCD, it was TS (11.36%). Conclusions: Our study is the first nationwide survey on the prevalence of TD (2.46%) and OCD (1.37%) in school students aged 6–16 years old in China. The high comorbidity between OCD and TD individuals suggested overlap based on the prevalence dimensions, which might be influenced by age and sex. This result suggested that we also need to pay more attention to the homogeneity and heterogeneity between TS and OCD. [ABSTRACT FROM AUTHOR]

The cardioprotective effects of ginseng root extracts have been reported. However, nothing is known about the myocardial actions of the phenolic compounds enriched in ginseng berry. Therefore, this study was undertaken to investigate the effects of American ginseng berry extract (GBE) in an experimental model of myocardial infarction (MI). Coronary artery ligation was performed on Sprague–Dawley male rats to induce MI after which animals were randomized into groups receiving either distilled water or GBE intragastrically for 8 weeks. Echocardiography and assays for malondialdehyde (MDA) and TNF-α were conducted. Flow cytometry was used to test the effects of GBE on T cell phenotypes and cytokine production. Although GBE did not improve the cardiac functional parameters, it significantly attenuated oxidative stress in post-MI rat hearts. GBE treatment also resulted in lower than control levels of TNF-α in post-MI rat hearts indicating a strong neutralizing effect of GBE on this cytokine. However, there was no effect of GBE on the proportion of different T cell subsets or ex-vivo cytokine production. Taken together, the present study demonstrates GBE reduces oxidative stress, however no effect on cardiac structure and function in post-MI rats. Moreover, reduction of TNF-α levels below baseline raises concern regarding its use as prophylactic or preventive adjunct therapy in cardiovascular disease. [ABSTRACT FROM AUTHOR]

Grapes (Vitis vinifera L.) are rich in bioactive molecules contributing to health benefits. Consumption of grapes is linked to reduced incidence of cardiovascular diseases. Studies on table grape cultivars are limited although much attention in research was focused on the wine industry. Bioactive effects of grapes as anti-inflammatory, anticarcinogenic, cardioprotective, vasorelaxant, phytoestrogenic and neuroprotective have also been reported. For example, resveratrol is a natural food ingredient present in grapes, with high antioxidant potential. Here we conducted an exploratory study to investigate bioactive molecules, antioxidant activity and the association between constitutive stilbene synthase (STS) gene expression and the resveratrol biosynthesis in selected table grape varieties in North America. The phenolic compounds, fatty acid composition and antioxidant activity of four grape varieties were compared. Red Globe variety was rich in unsaturated fatty acids as well as phenolic compounds such as caffeic acid, quercetin and resveratrol. Meanwhile, the constitutive expression of grape stilbene synthase gene was higher in Flame and Autumn Royal where resveratrol content of these cultivars was relatively low compared to the Red Globe variety. This study shows the potential links in grape antioxidant activity and resveratrol production, but more studies are necessary to show the association. [ABSTRACT FROM AUTHOR]

The development of fluorescence sensing platforms with excellent photoluminescence capabilities is of great importance for their further application. In this work, a photonic crystal structure was successfully applied to enhance the luminescence performance of fluorescent hydrogel, and the application of the obtained hydrogel as a fluorescence sensor was explored. A polystyrene photonic crystal template was constructed via vertical deposition self-assembly; then, the precursor solution containing polyethylenimine-capped CdS quantum dots (PEI-CdS QDs) and monomers filled in the gap of the template. After the polymerization process, the desired hydrogel was obtained. PEI-CdS QDs endowed the hydrogel with its fluorescence property, while interestingly, the photonic crystal structure showed a significant enhancement effect on the fluorescence-emission capability. The mechanism of this phenomenon was revealed. Moreover, this hydrogel could be used as a reusable fluorescence sensor for the detection of nitrite in water with good selectivity. The limit of detection was determined to be 0.25 μmol/L, which is much lower than the maximum limit for nitrite in drinking water. [ABSTRACT FROM AUTHOR]

The development and progression of heart failure (HF) due to myocardial infarction (MI) is a major concern even with current optimal therapy. Resveratrol is a plant polyphenol with cardioprotective properties. Sacubitril/valsartan is known to be beneficial in chronic HF patients. In this study, we investigated the comparative and combinatorial benefits of resveratrol with sacubitril/valsartan alongside an active comparator valsartan in MI-induced male Sprague Dawley rats. MI-induced and sham-operated animals received vehicle, resveratrol, sacubitril/valsartan, valsartan alone or sacubitril/valsartan + resveratrol for 8 weeks. Echocardiography was performed at the endpoint to assess cardiac structure and function. Cardiac oxidative stress, inflammation, fibrosis, brain natriuretic peptide (BNP), creatinine and neutrophil gelatinase associated lipocalin were measured. Treatment with resveratrol, sacubitril/valsartan, valsartan and sacubitril/valsartan + resveratrol significantly prevented left ventricular (LV) dilatation and improved LV ejection fraction in MI-induced rats. All treatments also significantly reduced myocardial tissue oxidative stress, inflammation and fibrosis, as well as BNP. Treatment with the combination of sacubitril/valsartan and resveratrol did not show additive effects. In conclusion, resveratrol, sacubitril/valsartan, and valsartan significantly prevented cardiac remodeling and dysfunction in MI-induced rats. The reduction in cardiac remodeling and dysfunction in MI-induced rats was mediated by a reduction in cardiac oxidative stress, inflammation and fibrosis. [ABSTRACT FROM AUTHOR]

Potato tuber dormancy is critical for the post-harvest quality. Snakin/Gibberellic Acid Stimulated in Arabidopsis (GASA) family genes are involved in the plants' defense against pathogens and in growth and development, but the effect of Snakin-2 (SN2) on tuber dormancy and sprouting is largely unknown. In this study, a transgenic approach was applied to manipulate the expression level of SN2 in tubers, and it demonstrated that StSN2 significantly controlled tuber sprouting, and silencing StSN2 resulted in a release of dormancy and overexpressing tubers showed a longer dormant period than that of the control. Further analyses revealed that the decrease expression level accelerated skin cracking and water loss. Metabolite analyses revealed that StSN2 significantly down-regulated the accumulation of lignin precursors in the periderm, and the change of lignin content was documented, a finding which was consistent with the precursors' level. Subsequently, proteomics found that cinnamyl alcohol dehydrogenase (CAD), caffeic acid O-methyltransferase (COMT) and peroxidase (Prx), the key proteins for lignin synthesis, were significantly up-regulated in silencing lines, and gene expression and enzyme activity analyses also supported this effect. Interestingly, we found that StSN2 physically interacts with three peroxidases catalyzing the oxidation and polymerization of lignin. In addition, SN2 altered the hydrogen peroxide (H2O2) content and the activities of superoxide dismutase (SOD) and catalase (CAT). These results suggest that StSN2 negatively regulates lignin biosynthesis and H2O2 accumulation, and ultimately inhibits the sprouting of potato tubers. [ABSTRACT FROM AUTHOR]

Gastric cancer is the most common malignant tumor of the digestive tract and is great challenge in clinical treatment. N6-(2-Hydroxyethyl)-adenosine (HEA), widely present in various fungi, is a natural adenosine derivative with many biological and pharmacological activities. Here, we assessed the antineoplastic effect of HEA on gastric carcinoma. HEA exerted cytotoxic effects against gastric carcinoma cells (SGC-7901 and AGS) in a dose and time-dependent manner. Additionally, we found that HEA induced reactive oxygen species production and mitochondrial membrane potential depolarization. Moreover, it could trigger caspase-dependent apoptosis, promoting intracellular Ca2+-related endoplasmic reticulum (ER) stress and autophagy. On the other hand, HEA could significantly inhibit the growth of transplanted tumors in nude mice and induce apoptosis of tumor tissues cells in vivo. In conclusion, HEA induced apoptosis of gastric carcinoma cells in vitro and in vivo, demonstrating that HEA is a potential chemotherapeutic agent for gastric carcinoma. [ABSTRACT FROM AUTHOR]

Soybean protein hydrolysate, melamine, urea, and concentrated formaldehyde were used to synthesize an environmentally friendly soybean protein-melamine-urea-formaldehyde (SMUF) co-condensation resin. (NH4)2SO4, (NH4)2HPO4, (NH4)2HPO4 + (NH4)2SO4, (NH4)2HPO4 + (NH4)2S2O8, and (NH4)2HPO4 + (NH4)2SO4 + (NH4)2S2O8 were employed as curing agents for SMUF resin. The curing and thermal behaviors of the SMUF resin were investigated using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and scanning electron microscopy (SEM). The results revealed the following: (1) (NH4)2SO4 alone could not cure the SMUF resin completely; thus, the final shear strength accomplished plywood with the resin was low, and its water resistance was poor, while the adhesive section was loose and porous/brittle after curing. (2) (NH4)2HPO4 could be hydrolyzed to generate H+ and promote SMUF curing, but it could also form polyphosphoric acids, resulting in crosslinking reactions with SMUF in parallel; thereby, the curing properties were improved. (3) When (NH4)2HPO4 + (NH4)2SO4 + (NH4)2S2O8 were engaged collectively as curing agent, the shear strength, water resistance, and heat resistance of SMUF attained were the best possible whereas the curing temperature was decreased and the heat released by curing was elevated substantially, which signifies maximized extent of crosslinking was achieved. Further, the adhesive section exhibited mostly a crosslinking intertexture as demonstrated by means of SEM. Accordingly, this study may serve as a guide for the curing of amino resins, with low-molar ratio of formaldehyde to amine in adhesives, which are applied to plywood production. [ABSTRACT FROM AUTHOR]

Islet autoantibody (iAb)-positive individuals have a high risk of progression to type 1 diabetes (T1D), although the rate of progression is highly variable and factors involved in the rate of progression are largely unknown. The ratio of unmethylated/methylated insulin DNA levels (unmethylated INS ratio) has been shown to be higher in participants at high risk of T1D compared to healthy controls. We aimed to evaluate whether an unmethylated INS ratio may be a useful biomarker of beta cell death and rate of progression to T1D. In TrialNet participants who were followed in the Pathway to Prevention Study and progressed to diabetes (n = 57, median age of onset 15.3 years), we measured unmethylated INS ratio and autoantibodies by electrochemiluminescence (ECL) assays (ECL-IAA, ECL-GADA, and ECL-IA2) and radioimmunoassays (RIA) (mIAA, GADA, IA2A, and ZnT8A) longitudinally for 24 months prior to diagnosis. Linear models were used to test the association between unmethylated INS ratio and the age at T1D diagnosis and unmethylated INS ratio and iAb over time. Close to diabetes onset, the unmethylated INS ratio was associated with mIAA (p = 0.003), ECL-IAA (p = 0.002), and IA2A (p = 0.01) levels, but not with GADA, ECL-GADA, ECL-IA2, or ZnT8A levels. No significant associations were found at baseline (24 months prior to T1D diagnosis). Only mIAA levels were significantly associated with an unmethylated INS ratio over time, with a 0.24 change in the ratio for each 0.1 change in mIAA z-score (p = 0.02). Adjusting for a baseline unmethylated INS ratio, an increased rate of change in unmethylated INS ratio from baseline to diabetes onset was associated with a five-year decrease in age at T1D diagnosis (p = 0.04). [ABSTRACT FROM AUTHOR]

In this study, we tested the potential cardioprotective effects of the phytoalexin resveratrol (Rsv) on primary adult rat cardiac fibroblasts (CF), myofibroblasts (MF) and cardiomyocytes. Adult rat CF and cardiomyocytes were isolated from male 10-week old Sprague–Dawley rats, cultured for either 24 h (cardiomyocytes) or 48 h (CF) before treatments. To isolate MF, CF were trypsinized after 48 h in culture, seeded in fresh plates and cultured for 24 h prior to treatment. All three cells were then treated for a further 24 h with a range of Rsv doses. In CF and MF, cell proliferation, viability, apoptosis assays were performed with or without Rsv treatment for 24 h. In cardiomyocytes, cell viability and apoptosis assay were performed 24 h after treatment. In separate experiments, CF was pre-incubated with estrogen, tamoxifen and fulvestrant for 30 min prior to Rsv treatment. Rsv treatment decreased proliferation of both fibroblasts and myofibroblasts. Rsv treatment also increased the proportion of dead CF and MF in a dose dependent manner. However, treatment with Rsv did not induce cell death in adult cardiomyocytes. There was an increase in the percentage of cells with condensed nuclei with Rsv treatment in both CF and MF, but not in cardiomyocytes. Treatment with estrogen, tamoxifen and fulvestrant alone or in combination with Rsv did not have any additional effects on CF survival. Our results demonstrate that treatment with Rsv can inhibit cell proliferation and induce cell death in rat CF and MF, while not affecting cardiomyocyte survival. We also demonstrated that the induction of cell death in CF with Rsv treatment was independent of estrogen receptor alpha (ERα) signaling. [ABSTRACT FROM AUTHOR]