Effects of advanced glycation end-products (AGEs) on skin keratinocytes by nuclear factor-kappa B (NF-κB) activation

Advance glycation end-products (AGEs) are produced in patients with long-term hyperglycemia metabolic disorder and responsible for multiple symptoms including impaired wound healing. This study was designed to reveal the roles and possible mechanism of AGE in diabetic wound healing. Sixteen Sprague-Dawley (SD) rats were divided into two groups randomly; the streptozotocin (STZ) induced diabetic group and the normal group. Eight weeks later, epidermal growth factor (EGF) and AGE levels, nuclear factor-kappa B (NF-κB) localization and cell viability were measured in vivo. Keratinocytes from normal skin were cultured in AGE-enriched conditional media, and the cell viability, apoptosis, adhesion and migration were detected in order to find the directed evidence between AGE and keratinocytes. AGE content was higher and NF-κB expression was more localized in the nuclear of keratinocytes in diabetic skins. AGE could inhibit normal cell growth by inducing apoptosis and arresting cell division cycle, inhibiting cell adhesion and promoting migration which might be mediated by NF-κB in vitro. Blocking NF-κB activity could reverse effects of AGE on cell proliferation and migration, but not adhesion. Therefore, AGE could damage the skin keratinocytes function in vivo and in vitro, and the activation of NF-κB is involved in this process.Key words: AGE, NF-kappaB, keratinocytes, diabetes, wound healing

Change Profiles and Functional Targets of MicroRNAs in Type 2 Diabetes Mellitus Patients with Obesity

Background MicroRNAs (miRNAs) exert an essential contribution to obesity and type 2 diabetes mellitus (T2DM). This study aimed to investigate the differences of miRNAs in the presence and absence of T2DM in patients with obesity, as well as before and after bariatric surgery in T2DM patients with obesity. Characterization of the common changes in both was further analyzed. Methods We enrolled 15 patients with obesity but without T2DM and 15 patients with both obesity and T2DM. Their preoperative clinical data and serum samples were collected, as well as 1 month after bariatric surgery. The serum samples were analyzed by miRNA sequencing, and the miRNAs profiles and target genes characteristics were compared. Results Patients with T2DM had 16 up-regulated and 32 down-regulated miRNAs compared to patients without T2DM. Improvement in metabolic metrics after bariatric surgery of T2DM patients with obesity was correlated with changes in miRNAs, as evidenced by the upregulation of 20 miRNAs and the downregulation of 30 miRNAs. Analysis of the two miRNAs profiles identified seven intersecting miRNAs that showed opposite changes. The target genes of these seven miRNAs were substantially enriched in terms or pathways associated with T2DM. Conclusion We determined the expression profiles of miRNAs in the obese population, with and without diabetes, before and after bariatric surgery. The miRNAs that intersected in the two comparisons were discovered. Both the miRNAs discovered and their target genes were closely associated with T2DM, demonstrating that they might be potential targets for the regulation of T2DM

Geochronology, geochemistry, and tectonic significance of the Shirenshan gneiss in the southern margin of the North China Block

The Shirenshan Block is a complex geological body located in the southern margin of the North China Block (NCB). From south to north, it can be divided into the Taihua Group migmatite, and the Shirenshan gneiss and magmatic rocks. The petrographic features, tectonic setting, provenance, and geological age of the Shirenshan gneiss using comprehensive field investigations, microstructural analysis, zircon U-Pb radioactive dating, and geochemical analyses were investigated for this study. The petrology, geochemistry, and geochronology of the Shirenshan gneiss suggests that it is mainly a felsic rock and its protolith was a high-K calc-alkaline series A-type granite. The protolith is high in SiO2, Al2O3, K2O, Na2O, and low in CaO and MgO. Overall, the Sr-Nd isotope composition of the samples showed no significant difference, indicating that the Taihua Group migmatite and the Shirenshan gneiss have the same source material. The Shirenshan block may be partially melted from the Taihua group and formed during activity of the Luo-Luan Fault. By the method of zircon dating analysis, the protolith age of the Shirenshan block was determined as 1559±16Ma (Early Proterozoic). Then, the crystallization age of the syntectonic migmatite is 439.2±7.6Ma, which was formed by subduction of the Taihua Group. During the early Cretaceous (119.5±1.3Ma), the Shirenshan gneiss may have experienced regional migmatization and formed the zircon rims age of the Yanshanian period. Litho-geochemical features of the Shirenshan block are similar to A1-type granites indicating that they are post-orogenic. Therefore, the metamorphic deformation of the Shirenshan gneiss reflects the tectonics in the southern margin of the NCB.</p

Systematic Comparison of Power Corridor Classification Methods from ALS Point Clouds

Study examines factors that affect power corridor classification using LiDAR (light detection and ranging) point clouds, including the class distribution, feature selection, classifier type and neighborhood radius for classification feature extraction

Prevalence of Metabolic Syndrome Among the Adult Population in Western China and the Association With Socioeconomic and Individual Factors: Four Cross-Sectional Studies

Objectives: This study explored the prevalence of and individual influencing factors for metabolic syndrome (MS) as well as associated socioeconomic factors and regional aggregation. Design: Four cross-sectional surveys were analysed for trends in MS and associations with socioeconomic and individual factors through multilevel logistic regression analyses. The risk associated with nutrient intake was also assessed through a dietary survey in 2015. Setting: From 2010 to 2018, 8-15 counties/districts of West China were included. Participants: A total of 28 274 adults were included in the prevalence analysis. A total of 23 708 adults were used to analyse the related factors. Results: The overall prevalence of MS ranged from 21.4% to 27.8% over the 8 years, remaining basically stable within the 95% CI. Our study found that the urbanisation rate and hospital beds per 1000 people were positively associated with MS, and the number of doctors in healthcare institutions per 1000 persons was negatively associated with MS. The ORs for females, people with college education and higher and unmarried or single people were 1.49, 0.67 and 0.51, respectively (p\u3c0.05). The ORs of people who smoked at least 20 cigarettes/day, ate more than 100 g of red meat/day, consumed fruit or vegetable juice and drank carbonated soft drinks less than weekly were 1.10, 1.16, 1.19-1.27 and 0.81-0.84, respectively. The ORs rose with increasing sedentary time and decreased with higher physical activity. Conclusion: The high burden of MS, unreasonable proportions of energy and micronutrient intake and low percentage of high levels of physical activity were the major challenges to public health in western China. Improving the human resources component of medical services, such as the number of doctors, increasing the availability of public sports facilities and E-health tools and improving individual dietary quality and education might help prevent MS

Irisin attenuates angiotensin II-induced atrial fibrillation and atrial fibrosis via LOXL2 and TGFβ1/Smad2/3 signaling pathways

Objective(s): Irisin was reported as a cardioprotective and anti-oxidative effector, while the effect on atrial fibrosis is unknown. The current research examined irisin’s function in atrial fibrillation (AF); atrial fibrosis brought on by Ang II can be suppressed, thus lessening the risk of developing AF. Materials and Methods: 246 individuals were enrolled in the present case-control study. Chinese AF patients (n=126), 83 of whom were paroxysmal AF (PAF), 43 patients with persistent AF (PeAF), and 120 healthy controls. Saline or Ang II (2.0 mg/kg/day) was subcutaneously injected into healthy male C57BL/6 mice for four weeks. Once daily for four weeks, intraperitoneal injections of exogenous irisin (500 g/kg/day) were administered. Results: In comparison to PAF patients and healthy controls (all P<0.05), PeAF patients had significantly higher rates of heart failure (HF), large left atrial size (LAD), hypertrophic protein B-type natriuretic peptide (BNP), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), C-terminal telopeptide of type I collagen (CTX-I), and transforming growth factor beta-1 (TGF-β1), while superoxide dismutase (SOD) level was low. Expression of irisin was decreased in AF patients’ serum and Ang II-infused mice. Exogenous irisin dramatically reduced apoptosis, atrial fibrosis, atrial inflammation, and the susceptibility to AF caused by Ang II. In the atrial tissue, irisin inhibited Ang II-induced fibroblast transdifferentiation, LOXL2, TGF-β1, collagen production, and phosphorylation of Smad2/3. Conclusion: The study results speculated that irisin could be a potential AF target, and it inhibited atrial fibrosis and significantly impaired increased AF susceptibility through inactivation of LOXL2 and the TGF-β/Smad pathway

Revealing internal flow behaviour in arc welding and additive manufacturing of metals

Internal flow behaviour during melt-pool-based metal manufacturing remains unclear and hinders progression to process optimisation. In this contribution, we present direct time-resolved imaging of melt pool flow dynamics from a high-energy synchrotron radiation experiment. We track internal flow streams during arc welding of steel and measure instantaneous flow velocities ranging from 0.1 m s−1 to 0.5 m s−1. When the temperature-dependent surface tension coefficient is negative, bulk turbulence is the main flow mechanism and the critical velocity for surface turbulence is below the limits identified in previous theoretical studies. When the alloy exhibits a positive temperature-dependent surface tension coefficient, surface turbulence occurs and derisory oxides can be entrapped within the subsequent solid as result of higher flow velocities. The widely used arc welding and the emerging arc additive manufacturing routes can be optimised by controlling internal melt flow through adjusting surface active elements

Overexpression of MsSAG113 gene promotes leaf senescence in alfalfa via participating in the hormone regulatory network

IntroductionAlfalfa (Medicago sativa) is a kind of high quality leguminous forage species, which was widely cultivated in the world. Leaf senescence is an essential process in plant development and life cycle. Here, we reported the isolation and functional analysis of an alfalfa SENESCENCE-ASSOCIATED GENE113 (MsSAG113), which belongs to the PP2C family and mainly plays a role in promoting plant senescence.MethodsIn the study, Agrobacterium-mediated, gene expression analysis, next generation sequencing, DNA pull-down, yeast single hybridization and transient expression were used to identify the function of MsSAG113 gene.ResultsThe MsSAG113 gene was isolated from alfalfa, and the transgenic plants were obtained by Agrobacterium-mediated method. Compared with the wildtype, transgenic plants showed premature senescence in leaves, especially when cultivated under dark conditions. Meanwhile, application of exogenous hormones ABA, SA, MeJA, obviously acclerated leaf senescence of transgenic plants. Furthermore, the detached leaves from transgenic plants turned yellow earlier with lower chlorophyll content. Transcriptome analysis identified a total of 1,392 differentially expressed genes (DEGs), involving 13 transcription factor families. Of which, 234 genes were related to phytohormone synthesis, metabolism and transduction. Pull-down assay and yeast one-hybrid assay confirmed that alfalfa zinc finger CCCH domain-containing protein 39 (MsC3H-39) could directly bind the upstream of MsSAG113 gene. In conclusion, the MsSAG113 gene plays a crucial role in promoting leaf senescence in alfalfa via participating in the hormone regulatory network.DiscussionThis provides an essential basis for further analysis on the regulatory network involving senescence-associated genes in alfalfa