Stepwise exhumation of the Triassic Lanling high-pressure metamorphic belt in Central Qiangtang, Tibet: Insights from a coupled study of metamorphism, deformation, and geochronology

The E-W trending Central Qiangtang metamorphic belt (CQMB) is correlated to the Triassic orogeny of the Paleo-Tethys Ocean prior to Cenozoic growth of the Tibetan Plateau. The well-exposed Lanling high-pressure, low-temperature (HP-LT) metamorphic complex was chosen to decipher the process by which it was exhumed, which thereby provides insights into the origin of the CQMB and Qiangtang terrane. After a detailed petrological and structural mapping, three distinct N-S-trending metamorphic domains were distinguished. Microscopic observations show that core domain garnet (Grt)-bearing blueschist was exhumed in a heating plus depressurization trajectory after peak eclogitic conditions, which is more evident in syntectonic vein form porphyroblastic garnets with zoning typical of a prograde path. Grt-free blueschist of the mantle domain probably underwent an exhumation path of temperature increasing and dehydration, as evidenced by pervasive epidote veins. The compilation of radiometric results of high-pressure mineral separates in Lanling and Central Qiantang, and reassessments on the published phengite data sets of Lanling using Arrhenius plots allow a two-step exhumation model to be formulated. It is suggested that core domain eclogitic rocks were brought onto mantle domain blueschist facies level starting at 244-230 Ma, with exhumation continuing to 227-223.4 Ma, and subsequently were exhumed together starting at 223-220 Ma, reaching lower greenschist facies conditions generally after 222-217 Ma. These new observations indicate that the CQMB formed as a Triassic autochthonous accretionary complex resulting from the northward subdcution of the Paleo-Tethys Ocean and that HP-LT rocks therein were very probably exhumed in an extensional regime.This work was jointly funded by the Young Scientist Fund of the National Natural Science Foundation of China (grant 41402177) and the Fundamental Research Funds for the Central Universities (2652014004). Our field work was supported by a project issued by the China Geological Survey (CGS): The integrated geological survey on the west part and central uplift of Qiangtang Block (grant 12120115026901)

Genome-Wide Expression Analysis Reveals Diverse Effects of Acute Nicotine Exposure on Neuronal Function-Related Genes and Pathways

Previous human and animal studies demonstrate that acute nicotine exposure has complicated influences on the function of the nervous system, which may lead to long-lasting effects on the behavior and physiology of the subject. To determine the genes and pathways that might account for long-term changes after acute nicotine exposure, a pathway-focused oligoarray specifically designed for drug addiction research was used to assess acute nicotine effect on gene expression in the neuron-like SH-SY5Y cells. Our results showed that 295 genes involved in various biological functions were differentially regulated by 1 h of nicotine treatment. Among these genes, the expression changes of 221 were blocked by mecamylamine, indicating that the majority of nicotine-modulated genes were altered through the nicotinic acetylcholine receptors (nAChRs)-mediated signaling process. We further identified 14 biochemical pathways enriched among the nicotine-modulated genes, among which were those involved in neural development/synaptic plasticity, neuronal survival/death, immune response, or cellular metabolism. In the genes significantly regulated by nicotine but blocked by mecamylamine, 13 enriched pathways were detected. Nine of these pathways were shared with those enriched in the genes regulated by nicotine, including neuronal function-related pathways such as glucocorticoid receptor signaling, p38 MAPK signaling, PI3K/AKT signaling, and PTEN signaling, implying that nAChRs play important roles in the regulation of these biological processes. Together, our results not only provide insights into the mechanism underlying the acute response of neuronal cells to nicotine but also provide clues to how acute nicotine exposure exerts long-term effects on the nervous system

CD8(+) T Cells Involved in Metabolic Inflammation in Visceral Adipose Tissue and Liver of Transgenic Pigs

Anti-inflammatory therapies have the potential to become an effective treatment for obesity-related diseases. However, the huge gap of immune system between human and rodent leads to limitations of drug discovery. This work aims at constructing a transgenic pig model with higher risk of metabolic diseases and outlining the immune responses at the early stage of metaflammation by transcriptomic strategy. We used CRISPR/Cas9 techniques to targeted knock-in three humanized disease risk genes, GIPR(dn) , hIAPP and PNPLA3(I148M) . Transgenic effect increased the risk of metabolic disorders. Triple-transgenic pigs with short-term diet intervention showed early symptoms of type 2 diabetes, including glucose intolerance, pancreatic lipid infiltration, islet hypertrophy, hepatic lobular inflammation and adipose tissue inflammation. Molecular pathways related to CD8(+) T cell function were significantly activated in the liver and visceral adipose samples from triple-transgenic pigs, including antigen processing and presentation, T-cell receptor signaling, co-stimulation, cytotoxicity, and cytokine and chemokine secretion. The similar pro-inflammatory signaling in liver and visceral adipose tissue indicated that there might be a potential immune crosstalk between the two tissues. Moreover, genes that functionally related to liver antioxidant activity, mitochondrial function and extracellular matrix showed distinct expression between the two groups, indicating metabolic stress in transgenic pigs' liver samples. We confirmed that triple-transgenic pigs had high coincidence with human metabolic diseases, especially in the scope of inflammatory signaling at early stage metaflammation. Taken together, this study provides a valuable large animal model for the clinical study of metaflammation and metabolic diseases.Peer reviewe

Characterization of Insufficiency Fracture and Bone Metastasis After Radiotherapy in Patients With Cervical Cancer Detected by Bone Scan: Role of Magnetic Resonance Imaging

Background: Insufficiency fracture (IF) can show increased uptake on a bone scan (BS). IFs are often misinterpreted as bone metastases if the characteristic “Honda sign” (H-sign) is invisible. The purpose of the present study was to evaluate the utility of magnetic resonance imaging (MRI) alone for the characterization of IF and bone metastasis after radiotherapy in patients with cervical cancer detected by BS.Materials and Methods: Our study included 40 patients with cervical cancer after radiotherapy that showed pelvic emerging increased uptake on a BS during follow-up. Then further MRI examination was performed in all patients. Two radiologists independently reviewed the MR images, and the sensitivity, specificity and accuracy were calculated based on the mean scores. Diagnostic validity of the inter-observer was calculated by using kappa statistics. The gold standard was based on radiologic findings, clinical data and follow-up at least 12 months.Results: A total of 57 emerging bone lesions detected at BS were identified in the reference standard, including 43 IFs and 14 bone metastases. Only 20 patients showed a “H-sign” on the BS images. Using MRI analysis, all lesions detected by BS were found in MRI by both radiologists. On average, the sensitivity, specificity, and accuracy for distinguishing IFs from bone metastases were 95.3% (41/43), 92.8% (13/14), and 94.7% (54/57), respectively. The inter-observer variability was determined to be very good (kappa value = 0.962).Conclusions: MRI is a reliable diagnostic technique for the further characterization of emerging lesions detected by BS, MRI shows great diagnostic efficiency in the differentiation of IF and bone metastasis

Effects of long term tai chi practice and jogging exercise on muscle strength and endurance in older people

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miR-96 exerts carcinogenic effect by activating AKT/GSK-3β/β-catenin signaling pathway through targeting inhibition of FOXO1 in hepatocellular carcinoma

Abstract Background The aim of this research was to investigate the mechanism of miR-96 affecting hepatocellular carcinoma (HCC). Methods mRNA and protein expression was detected by qRT-PCR and Western blot, respectively. HepG2 cells were transfected and grouped as follows: miR-NC group, miR-mimics group, NC + Vector group, mimics + Vector group, mimics + FOXO1 group. Luciferase reporter assay was performed. MTT and Transwell assay was conducted. In vivo studies by nude mice were performed. Immunohistochemistry and immunofluorescence was executed. Results Up-regulated miR-96 and down-regulated FOXO1 was found in tumor tissues and HepG2 cells (P < 0.01). FOXO1 was directly suppressed by miR-96. Compared with NC + Vector group, mimics + Vector group has higher OD495 value (P < 0.05), higher migration and invasion cells (P < 0.01), larger transplanted tumor volume (P < 0.01), lower FOXO1 positive cell numbers (P < 0.01), higher p-AKT and p-GSK-3β expression (P < 0.01), lower p-β-catenin expression (P < 0.01), more β-catenin expression in the nucleus (P < 0.01). Compared with mimics + Vector group, mimics + FOXO1 group has lower OD495 value (P < 0.05), lower migration and invasion cells (P < 0.01), smaller transplanted tumor volume (P < 0.01), higher FOXO1 positive cells (P < 0.01), lower p-AKT and p-GSK-3β expression (P < 0.01), higher p-β-catenin expression (P < 0.01), less β-catenin expression in the nucleus (P < 0.01). Conclusion miR-96 exerts carcinogenic effect by activating AKT/GSK-3β/β-catenin signaling pathway through targeting inhibition of FOXO1 in HCC