Epigenetic and genetic dissections of UV-induced global gene dysregulation in skin cells through multi-omics analyses

To elucidate the complex molecular mechanisms underlying the adverse effects UV radiation (UVR) on skin homeostasis, we performed multi-omics studies to characterize UV-induced genetic and epigenetic changes. Human keratinocytes from a single donor treated with or without UVR were analyzed by RNA-seq, exome-seq, and H3K27ac ChIP-seq at 4 h and 72 h following UVR. Compared to the relatively moderate mutagenic effects of UVR, acute UV exposure induced substantial epigenomic and transcriptomic alterations, illuminating a previously underappreciated role of epigenomic and transcriptomic instability in skin pathogenesis. Integration of the multi-omics data revealed that UVR-induced transcriptional dysregulation of a subset of genes was attributable to either genetic mutations or global redistribution of H3K27ac. H3K27ac redistribution further led to the formation of distinctive super enhancers in UV-irradiated cells. Our analysis also identified several new UV target genes, including CYP24A1, GJA5, SLAMF7 and ETV1, which were frequently dysregulated in human squamous cell carcinomas, highlighting their potential as new molecular targets for prevention or treatment of UVR-induced skin cancers. Taken together, our concurrent multi-omics analyses provide new mechanistic insights into the complex molecular networks underlying UV photobiological effects, which have important implications in understanding its impact on skin homeostasis and pathogenesis

Effects of two Lactobacillus strains on lipid metabolism and intestinal microflora in rats fed a high-cholesterol diet

<p>Abstract</p> <p>Background</p> <p>The hypocholesterolemic effects of lactic acid bacteria (LAB) have now become an area of great interest and controversy for many scientists. In this study, we evaluated the effects of <it>Lactobacillus plantarum </it>9-41-A and <it>Lactobacillus fermentum </it>M1-16 on body weight, lipid metabolism and intestinal microflora of rats fed a high-cholesterol diet.</p> <p>Methods</p> <p>Forty rats were assigned to four groups and fed either a normal or a high-cholesterol diet. The LAB-treated groups received the high-cholesterol diet supplemented with <it>Lactobacillus plantarum </it>9-41-A or <it>Lactobacillus fermentum </it>M1-16. The rats were sacrificed after a 6-week feeding period. Body weights, visceral organ and fat pad weights, serum and liver cholesterol and lipid levels, and fecal cholesterol and bile acid concentrations were measured. Liver lipid deposition and adipocyte size were evaluated histologically.</p> <p>Results</p> <p>Compared with rats fed a high-cholesterol diet but without LAB supplementation, serum total cholesterol, low-density lipoprotein cholesterol and triglycerides levels were significantly decreased in LAB-treated rats (p < 0.05), with no significant change in high-density lipoprotein cholesterol levels. Hepatic cholesterol and triglyceride levels and liver lipid deposition were significantly decreased in the LAB-treated groups (p < 0.05). Accordingly, both fecal cholesterol and bile acids levels were significantly increased after LAB administration (p < 0.05). Intestinal <it>Lactobacillus </it>and <it>Bifidobacterium </it>colonies were increased while <it>Escherichia coli </it>colonies were decreased in the LAB-treated groups. Fecal water content was higher in the LAB-treated groups. Compared with rats fed a high-cholesterol diet, administration of <it>Lactobacillus plantarum </it>9-41-A resulted in decreases in the body weight gain, liver and fat pad weight, and adipocytes size (p < 0.05).</p> <p>Conclusions</p> <p>This study suggests that LAB supplementation has hypocholesterolemic effects in rats fed a high-cholesterol diet. The ability to lower serum cholesterol varies among LAB strains. Our strains might be able to improve the intestinal microbial balance and potentially improve intestinal transit time. Although the mechanism is largely unknown, <it>L. plantarum </it>9-41-A may play a role in fat metabolism.</p

Interpretable Machine Learning for COVID-19:An Empirical Study on Severity Prediction Task

The black-box nature of machine learning models hinders the deployment of some high-accuracy models in medical diagnosis. It is risky to put one's life in the hands of models that medical researchers do not fully understand. However, through model interpretation, black-box models can promptly reveal significant biomarkers that medical practitioners may have overlooked due to the surge of infected patients in the COVID-19 pandemic. This research leverages a database of 92 patients with confirmed SARS-CoV-2 laboratory tests between 18th Jan. 2020 and 5th Mar. 2020, in Zhuhai, China, to identify biomarkers indicative of severity prediction. Through the interpretation of four machine learning models, decision tree, random forests, gradient boosted trees, and neural networks using permutation feature importance, Partial Dependence Plot (PDP), Individual Conditional Expectation (ICE), Accumulated Local Effects (ALE), Local Interpretable Model-agnostic Explanations (LIME), and Shapley Additive Explanation (SHAP), we identify an increase in N-Terminal pro-Brain Natriuretic Peptide (NTproBNP), C-Reaction Protein (CRP), and lactic dehydrogenase (LDH), a decrease in lymphocyte (LYM) is associated with severe infection and an increased risk of death, which is consistent with recent medical research on COVID-19 and other research using dedicated models. We further validate our methods on a large open dataset with 5644 confirmed patients from the Hospital Israelita Albert Einstein, at S\~ao Paulo, Brazil from Kaggle, and unveil leukocytes, eosinophils, and platelets as three indicative biomarkers for COVID-19.Comment: 14 pages, 10 figure

Eocene magmatic processes and crustal thickening in southern Tibet : insights from strongly fractionated ca. 43 Ma granites in the western Gangdese Batholith

This research was financially co-supported by the Strategic Priority Research Program (B) of the Chinese Academy of Sciences (XDB03010301), the National Key Project for Basic Research of China (Project 2015CB452604), the Chinese National Natural Science Foundation (41225006, 41472061, and 40973026), the MOST Special Fund from the State Key Laboratory of Geological Processes and Mineral Resources (China University of Geosciences). The first author thanks the China Scholarship Council (201306400021).This study reports zircon U-Pb age and Hf isotope, whole-rock major and trace element, and Sr-Nd-Pb-Hf isotope data for the Dajia pluton, western Gangdese Batholith, in southern Tibet. These data indicate that the pluton consists of moderately (Group 1) and strongly (Group 2) fractionated granites that were emplaced synchronously at ca. 43 Ma. The Group 1 samples have SiO2 contents of 69−72 wt.% and vary in terms of the differentiation index (DI = 84−93). These rocks are depleted in Ba, Nb, Sr, P, and Ti, with moderate negative Eu anomalies, and display low heavy rare earth elements (HREEs) and Y abundances. The Group 2 samples are characterized by high SiO2 (75−78 wt.%) and DI (95−97); significantly negative Eu anomalies; marked concave-upward middle REE (Gd-Ho) patterns; and Ba, Sr, P, and Ti anomalies that are significantly more negative than those of the Group 1 samples. The Group 1 samples have whole-rock εNd(t) (-5.9 to -6.0), εHf(t) (-4.0 to -4.5), and zircon εHf(t) (-6.0 to + 5.8) values identical to those of the Group 2 samples [εNd(t) = -5.7 to -6.7, εHf(t) = -3.5 to -2.9, and zircon εHf(t) = -2.0 to + 4.2], as well as similar initial Pb isotopic compositions. These data indicate that the two groups were derived from a common source region with garnet as a residual mineral phase. The Group 1 samples were most likely derived from partial melting of garnet-bearing amphibolite (rather than eclogite) within the juvenile southern Lhasa crust and mixed with the enriched components from the subducting ancient Indian continental crust and/or the ancient central Lhasa basement. The Group 2 samples are interpreted as the products of extensive fractional crystallization (plagioclase, K-feldspar, biotite, apatite, allanite, titanite, monazite, and ilmenite) of the melts represented by the Group 1 samples. Low HREEs and Y abundances of the Dajia pluton, together with the presence of strongly fractionated granites (Group 2) identified for the first time in the Gangdese Batholith, indicate that the crust beneath the Dajia region had already been thickened by ca. 43 Ma. High whole-rock zircon saturation temperatures (815°C−869°C) of the Group 1 samples and the other ca. 43 Ma coeval magmatism documented both in the Gangdese Batholith and in the Tethyan Himalaya can be best interpreted as the final consequences of the magmatic responses to the Neo-Tethyan oceanic slab breakoff.PostprintPeer reviewe

Effect of Corilagin on the Proliferation and NF- κ

Background. This study is to explore the effect of corilagin on the proliferation and NF-κB signaling pathway in U251 glioblastoma cells and U251 glioblastoma stem-like cells. Methods. CD133 positive U251 glioblastoma cells were separated by immunomagnetic beads to isolate glioblastoma stem-like cells. U251 cells and stem-like cells were intervened by different corilagin concentrations (0, 25, 50, and 100 μg/mL) for 48 h, respectively. Cell morphology, cell counting kit-8 assay, flow cytometry, dual luciferase reporter assay, and a western blot were used to detect and analyze the cell proliferation and cell cycle and investigate the expression of IKBα protein in cytoplasm and NF-κB/p65 in nucleus. Results. Corilagin inhibited the cell proliferation of U251 cells and their stem-like cells and the inhibition role was stronger in U251 stem-like cells (P<0.05). The cell cycle was arrested at G2/M phase in the U251 cells following corilagin intervention; the proportion of cells in G2/M phase increased as the concentration of corilagin increased (P<0.05). The U251 stem-like cells were arrested at the S phase following treatment with corilagin; the proportion of cells in the S phase increased as the concentration of corilagin increased (P<0.05). The ratio of dual luciferase activities of U251 stem-like cells was lower than that of U251 cells in the same corilagin concentration. With increasing concentrations of corilagin, the IKBα expression in cytoplasm of U251 cells and U251 stem-like cells was increased, but the p65 expression in nucleus of U251 cells and U251 stem-like cells was decreased (P<0.05). Conclusion. Corilagin can inhibit the proliferation of glioblastoma cells and glioblastoma stem-like cells; the inhibition on glioblastoma stem-like cell proliferation is stronger than glioblastoma cells. This different result indicates that the effect of corilagin on U251 cells and U251 stem-like cells may have close relationships with mechanism of cell cycle and NF-κB signaling pathway; however, the real antitumor mechanism of corilagin is not yet clear and requires further study

Biomimetic synthesis technology for preparation of Fe3O4-encapsulated biochar using in highly efficient peroxodisulfate activation

The background value of iron in red soil is superior, primarily absorbed and homogeneously encapsulated in harvested biomass. However, this property on the high-value utilization of bionic iron-encapsulated biomass remains unknown. In this study, special biochar (Fe@BC) was obtained from this kind of biomass by one-step pyrolysis method, which was further used to activate peroxydisulfate (PDS) and degrade 2,4-dichlorophenol (2,4-DCP). The results showed that Fe3O4 was formed and homogeneously embedded in biochar at 500oC. Comparing to catalysts prepared by impregnation pyrolysis (Fe/BC), Fe@BC exhibited excellent degradation performance (90.9%, k = 0.0037 min−1) for 2,4-DCP. According to the free radicals quenching studies, hydroxyl radicals (·OH) and superoxide radicals (·O2−) were the dominant reactive oxygen species (ROS) in Fe@BC/PDS system. Importantly, a PDS adsorption model was established, and the electron transport and PDS activation in the core-shell structure were demonstrated by DFT calculations. Therefore, this study could supply a high-performance catalyst and significant implications for high-value biomass utilization in red soil

Surfactant Supplementation to Enhance the Production of Vitamin K2 Metabolites in Shake Flask Cultures Using Escherichia sp. Mutant FM3-1709

Ispitan je utjecaj dodatka različitih surfaktanata na rast stanica i proizvodnju metabolita vitamina K2, poput unutarstaničnih i izvanstaničnih menakinona MK-4 i MK-6, pri submerznom uzgoju bakterije Escherichia sp. Svi su surfaktanti produljili eksponencijalnu fazu rasta bakterije. Betain, polioksietilen oleil eter i Tween-80 povoljno su djelovali na rast stanica mutanta bakterije Escherichia sp. FM3-1709. Najveći je rast stanica bio Xmax=(12,6±0,2) g/L, najveća stopa proizvodnje biomase Qx=(0,21±0,01) g/(L·h), a najveći prinos biomase YX/S=(2,42±0,02) g/g. Rezultati pokazuju da se dodatkom surfaktanata smanjila proizvodnja unutarstaničnog MK-4, dok se proizvodnja izvanstaničnog MK-4 bitno povećala. Od pet ispitanih surfaktanata, najbolji su rezultati postignuti dodatkom neionskog surfaktanta polioksietilen oleil etera (1,0 g/L), pri čemu je koncentracija izvanstaničnog MK-4 bila (33,6±0,4) mg/L, a izvanstaničnog MK-6 (2,56±0,07) mg/L, dok je ukupni prinos MK-4 bio (47,6±0,4) mg/L, a MK-6 (6,0±0,1) mg/L. Dodatak je polioksilen oleil etera djelovao puno povoljnije na lučenje MK-4, nego na lučenje MK-6.The effects of the addition of various surfactants on the cell growth and production of vitamin K2 metabolites, such as intracellular menaquinone-4 (MK-4), extracellular MK-4, intracellular MK-6 and extracellular MK-6, were studied in the submerged culture of Escherichia sp. All of the added surfactants caused the extension of the exponential phase. Betaine, polyoxyethylene oleyl ether and Tween-80 were favourable to the cell growth of Escherichia sp. mutant strain FM3-1709. The highest cell growth (Xmax), biomass production rate (Qx) and biomass yield (Yx/s) were (12.6±0.2) g/L, (0.21±0.01) g/(L·h) and (2.42± 0.02) g/g, respectively. The results show that the addition of all surfactants led to a lower production of intracellular MK-4, whereas the production of extracellular MK-4 increased remarkably. Among the five investigated surfactants, the addition of the nonionic surfactant polyoxyethylene oleyl ether (1.0 g/L) led to the highest production of extracellular MK-4 ((33.6±0.4) mg/L), MK-6 ((2.56±0.07) mg/L) and the highest yield of total MK-4 ((47.6±0.4) mg/L) and MK-6 ((6.0±0.1) mg/L). The addition of polyoxyethylene oleyl ether proved to be more beneficial for the secretion of MK-4 than MK-6

Effects of Tai Chi versus Proprioception Exercise Program on Neuromuscular Function of the Ankle in Elderly People: A Randomized Controlled Trial

Background. Tai Chi is a traditional Chinese medicine exercise used for improving neuromuscular function. This study aimed to investigate the effects of Tai Chi versus proprioception exercise program on neuromuscular function of the ankle in elderly people. Methods. Sixty elderly subjects were randomly allocated into three groups of 20 subjects per group. For 16 consecutive weeks, subjects participated in Tai Chi, proprioception exercise, or no structured exercise. Primary outcome measures included joint position sense and muscle strength of ankle. Subjects completed a satisfaction questionnaire upon study completion in Tai Chi and proprioception groups. Results. (1) Both Tai Chi group and proprioception exercise group were significantly better than control group in joint position sense of ankle, and there were no significant differences in joint position sense of ankle between TC group and PE group. (2) There were no significant differences in muscle strength of ankle among groups. (3) Subjects expressed more satisfaction with Tai Chi than with proprioception exercise program. Conclusions. None of the outcome measures on neuromuscular function at the ankle showed significant change posttraining in the two structured exercise groups. However, the subjects expressed more interest in and satisfaction with Tai Chi than proprioception exercise

The LAMOST Survey of Background Quasars in the Vicinity of the Andromeda and Triangulum Galaxies -- II. Results from the Commissioning Observations and the Pilot Surveys

We present new quasars discovered in the vicinity of the Andromeda and Triangulum galaxies with the LAMOST during the 2010 and 2011 observational seasons. Quasar candidates are selected based on the available SDSS, KPNO 4 m telescope, XSTPS optical, and WISE near infrared photometric data. We present 509 new quasars discovered in a stripe of ~135 sq. deg from M31 to M33 along the Giant Stellar Stream in the 2011 pilot survey datasets, and also 17 new quasars discovered in an area of ~100 sq. deg that covers the central region and the southeastern halo of M31 in the 2010 commissioning datasets. These 526 new quasars have i magnitudes ranging from 15.5 to 20.0, redshifts from 0.1 to 3.2. They represent a significant increase of the number of identified quasars in the vicinity of M31 and M33. There are now 26, 62 and 139 known quasars in this region of the sky with i magnitudes brighter than 17.0, 17.5 and 18.0 respectively, of which 5, 20 and 75 are newly-discovered. These bright quasars provide an invaluable collection with which to probe the kinematics and chemistry of the ISM/IGM in the Local Group of galaxies. A total of 93 quasars are now known with locations within 2.5 deg of M31, of which 73 are newly discovered. Tens of quasars are now known to be located behind the Giant Stellar Stream, and hundreds behind the extended halo and its associated substructures of M31. The much enlarged sample of known quasars in the vicinity of M31 and M33 can potentially be utilized to construct a perfect astrometric reference frame to measure the minute PMs of M31 and M33, along with the PMs of substructures associated with the Local Group of galaxies. Those PMs are some of the most fundamental properties of the Local Group.Comment: 26 pages, 6 figures, AJ accepte