Integrated spatial genomics reveals global architecture of single nuclei

Identifying the relationships between chromosome structures, nuclear bodies, chromatin states and gene expression is an overarching goal of nuclear-organization studies. Because individual cells appear to be highly variable at all these levels, it is essential to map different modalities in the same cells. Here we report the imaging of 3,660 chromosomal loci in single mouse embryonic stem (ES) cells using DNA seqFISH+, along with 17 chromatin marks and subnuclear structures by sequential immunofluorescence and the expression profile of 70 RNAs. Many loci were invariably associated with immunofluorescence marks in single mouse ES cells. These loci form ‘fixed points’ in the nuclear organizations of single cells and often appear on the surfaces of nuclear bodies and zones defined by combinatorial chromatin marks. Furthermore, highly expressed genes appear to be pre-positioned to active nuclear zones, independent of bursting dynamics in single cells. Our analysis also uncovered several distinct mouse ES cell subpopulations with characteristic combinatorial chromatin states. Using clonal analysis, we show that the global levels of some chromatin marks, such as H3 trimethylation at lysine 27 (H3K27me3) and macroH2A1 (mH2A1), are heritable over at least 3–4 generations, whereas other marks fluctuate on a faster time scale. This seqFISH+-based spatial multimodal approach can be used to explore nuclear organization and cell states in diverse biological systems

Integrated spatial genomics reveals global architecture of single nuclei

Identifying the relationships between chromosome structures, nuclear bodies, chromatin states and gene expression is an overarching goal of nuclear-organization studies. Because individual cells appear to be highly variable at all these levels, it is essential to map different modalities in the same cells. Here we report the imaging of 3,660 chromosomal loci in single mouse embryonic stem (ES) cells using DNA seqFISH+, along with 17 chromatin marks and subnuclear structures by sequential immunofluorescence and the expression profile of 70 RNAs. Many loci were invariably associated with immunofluorescence marks in single mouse ES cells. These loci form ‘fixed points’ in the nuclear organizations of single cells and often appear on the surfaces of nuclear bodies and zones defined by combinatorial chromatin marks. Furthermore, highly expressed genes appear to be pre-positioned to active nuclear zones, independent of bursting dynamics in single cells. Our analysis also uncovered several distinct mouse ES cell subpopulations with characteristic combinatorial chromatin states. Using clonal analysis, we show that the global levels of some chromatin marks, such as H3 trimethylation at lysine 27 (H3K27me3) and macroH2A1 (mH2A1), are heritable over at least 3–4 generations, whereas other marks fluctuate on a faster time scale. This seqFISH+-based spatial multimodal approach can be used to explore nuclear organization and cell states in diverse biological systems

Thermochemical sulfate reduction in fossil Ordovician deposits of the Majiang area: Evidence from a molecular-marker investigation

The main reservoirs of Majiang fossil deposits consist of the Silurian Wengxiang group, dominantly sandstones, and the Ordovician Honghuayuan formation, dominantly carbonate rocks, and the Lower Cambrian Niutitang Formation mudstones serve as the major source rocks. Thermochemical sulfate reduction (TSR) might have taken place in the Paleozoic marine carbonate oil pools, as indicated by high concentrations of dibenzothiophenes in the extracts (MDBT=0.27-4.32 µg/g extract, and MDBT/MPH= 0.71-1.38). Hydrocarbons in the Pojiaozhai Ordovician carbonate reservoirs have undergone severe TSR and are characterized by higher quantities of diamondoids and MDBT and heavier isotopic values (δ13C=-28.4‰). The very large amounts of dibenzothiophenes might be products of reactions between biphenyls and sulfur species associated with TSR

Chinese Sumac Fruits (<i>Rhus chinesis</i> Mill.) Alleviate Type 2 Diabetes in C57BL/6 Mice through Repairing Islet Cell Functions, Regulating IRS-1/PI3K/AKT Pathways and Promoting the Entry of Nrf2 into the Nucleus

This research aimed to probe the potential alleviative effects of ethanol extracts of Chinese sumac (Rhus chinesis Mill.) fruits against type 2 diabetes mellitus (T2DM) in C57BL/6 mice induced by high-fat/high-fructose diet (HFFD) and streptozotocin. The results showed that the ethanol extracts could significantly regulate blood glucose levels, glycosylated hemoglobin, blood lipids, insulin, and insulin resistance, while also restoring endogenous oxidative stress. Pathological and immunohistochemical analyses revealed that the extracts partially restored the physiological function of islet cells. Furthermore, Western blotting results suggested that the extracts could regulate the protein expression in IRS-1/PI3K/AKT signaling pathway, and immunofluorescence findings demonstrated their potential to promote the translocation of Nrf2 into the nucleus. This study elucidated a novel finding that ethanol extracts derived from Chinese sumac fruits have the potential to alleviate symptoms of T2DM in mice. Moreover, these findings could offer valuable scientific insights into the potential utilization of R. chinensis fruits as nutritional supplement and/or functional food to prevent or ameliorate diabetes

Investigation on the Effects and Mechanisms of Alkaline Natural Mineral Water and Distilled Water on Ethanol-Induced Gastric Ulcers In Vivo and In Vitro

Studies have proven that alkaline water has a protective effect on gastric diseases. However, the underlying mechanism is not clear. Moreover, in some countries, especially in China, purified water (distilled water) is also an important form of drinking water, while its protective effect on gastric diseases is still unknown. This study aimed to compare the effects of distilled water (pH = 5.6 &plusmn; 0.3) and alkaline natural mineral water (pH = 9.3 &plusmn; 0.6) on ethanol-induced gastric ulcers in mice and to further clarify the underlying mechanisms. Pepsin activity, prostaglandin E-2 (PGE2) and heat shock protein 70 (HSP70), superoxide dismutase (SOD), reduced glutathione (GSH), and malondialdehyde (MDA), as well as the oxidative stress pathway related proteins such as nuclear factor erythroid-2 related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NADH quinone oxidoreductase 1 (NQO1) were measured. After alkaline natural mineral water treatment, the levels of PGE2 and HSP70 were significantly increased (p &lt; 0.05). Antioxidant indexes (SOD, GSH, and MDA) and Western blot results (Nrf2, HO-1, and NQO1) showed that alkaline natural mineral water did not alleviate gastric ulcers by improving oxidative stress. Pepsin activity assay displayed that the pepsin activity was significantly declined after alkaline natural mineral water treatment compared with the distilled water treatment (p &lt; 0.05). This study indicated that alkaline natural mineral water may alleviate the ethanol-induced gastric ulcers in mice by inhibiting the pepsin activity and increasing the levels of PGE2 and HSP70

Effects and Mechanisms of Rhus chinensis Mill. Fruits on Suppressing RANKL-Induced Osteoclastogenesis by Network Pharmacology and Validation in RAW264.7 Cells

Rhus chinensis Mill. fruits are a kind of widely distributed edible seasoning, which have been documented to possess a variety of biological activities. However, its inhibitory effect on osteoclast formation has not been determined. The objective of this study was to evaluate the effect of the fruits on osteoclast differentiation of RAW264.7 cells, induced by receptor activator of nuclear factor-&kappa;B ligand (RANKL) and to illuminate the potential mechanisms using network pharmacology and western blots. Results showed that the extract containing two organic acids and twelve phenolic substances could effectively inhibit osteoclast differentiation in RANKL-induced RAW264.7 cells. Network pharmacology examination and western blot investigation showed that the concentrate essentially decreased the expression levels of osteoclast-specific proteins, chiefly through nuclear factor kappa-B, protein kinase B, and mitogen-activated protein kinase signaling pathways, particularly protein kinase B &alpha; and mitogen-activated protein kinase 1 targets. Moreover, the extract likewise directly down regulated the expression of cellular oncogene Fos and nuclear factor of activated T-cells cytoplasmic 1 proteins. Citric acid, quercetin, myricetin-3-O-galactoside, and quercetin-3-O-rhamnoside were considered as the predominant bioactive ingredients. Results of this work may provide a scientific basis for the development and utilization of R. chinensis fruits as a natural edible material to prevent and/or alleviate osteoporosis-related diseases

Different Phenolic Extracts of Oil Palm Fruits and Caffeic Acid Prevent Palmitic Acid-Induced Lipotoxicity in HepG2 Cells via Improving Mitochondrial Function

Oil palm (Elaeis guineensis Jacq.) fruits are rich in antioxidative phenolic compounds, which exert various health improving effects. This study aimed to comparatively study the protective effects of different phenolic fractions from the fruits treated with or without ultrahigh pressure (UHP) and their most abundant phenolic substance, caffeic acid, against the palmitic acid-induced lipotoxicity in HepG2 cells and to clarify the potential mechanisms. Results showed that the TG accumulation, intracellular reactive oxygen species content, cell apoptosis, and mitochondrial membrane potential depolarization were relieved by the administration of those phenolic fractions and caffeic acid. The protection of insoluble-bound (IB) phenolic fraction was the best, and UHP treatment significantly enhanced its protective effect on lipotoxicity. The lipotoxicity preventive effect may be achieved by alleviating intracellular oxidative stress, downregulating the expression of P-P38, COX-2, and iNOS to relieve inflammation, and downregulating Bax and cytochrome C and upregulating Bcl-2 to suppress the mitochondrial-mediated apoptosis. Therefore, the oil palm fruits phenolic fractions, especially the IB phenolic fraction, might be utilized as dietary antioxidants to relieve the adverse effects of a high-fat diet on the body, and UHP treatment is a potential method to increase this bioactivity

The profiles of free, esterified and insoluble-bound phenolics in peach juice after high pressure homogenization and evaluation of their antioxidant capacities, cytoprotective effect, and inhibitory effects on α-glucosidase and dipeptidyl peptidase-Ⅳ

The phenolic profiles, antioxidant capacities, cytoprotective effect, and α-glucosidase and DPP-IV inhibitory capacity of free (FP), esterified (EP) and insoluble-bound (IBP) phenolic fractions in ‘Lijiang snow’ peach juice after high pressure homogenization (HPH) were investigated, and the molecular docking was used to explore the enzyme inhibition mechanism. HPH increased total phenolic and total flavonoid contents in three fractions without changing compositions. The IC50 of radicals scavenged by three fractions were all reduced by HPH. The best inhibition on intracellular ROS production were found for phenolic fractions after HPH at 300 MPa, with ROS levels ranged within 95.26–119.16 %. HPH at 300 MPa reduced the apoptosis rates of FP and EP by 16.52 % and 9.33 %, respectively. All phenolic fractions showed effective inhibition on α-glucosidase and DPP-IV by formation of hydrogen bonding and van der Waals forces. This study explored the feasibility of HPH to enhance the phenolics and bioactivity of peach juice