A saúde mental é o fator mais importante que influencia a qualidade de vida de idosos deixados para trás quando as famílias emigram da China rural

OBJECTIVES: to investigate the quality of life and the associated factors on left behind elderly in rural China. METHOD: the research was conducted cluster sampling to select 456 elderly left behind when family members migrated out of rural China to participate in a cross-sectional study by completing a general data questionnaire and Quality of Life questionnaire. RESULTS: 91.5% of the elderly requested psychological counseling and education. For the elderly, scores for mental health (39.56±13.73) were significantly lower compared with Chinese standard data (61.6±13.7) (POBJETIVOS: investigar la calidad de vida y los factores asociados a los adultos mayores que se quedan en las zonas rurales de China. MÉTODO: la investigación se realizó por medio de muestreo por conglomerados para seleccionar 456 adultos mayores que se quedaron cuando los miembros de la familia emigraron de zonas rurales de China, para participar en un estudio de corte transversal, completando un cuestionario de datos generales y cuestionario de calidad de vida. RESULTADOS: el 91.5% de los adultos mayores solicitó asistencia psicológica y educación. Para los adultos mayores, las puntuaciones de salud mental (39.56±13.73) fueron significativamente más bajos en comparación con los datos estándar de China (61.6±13.7) (pOBJETIVOS: investigar a qualidade de vida e fatores associados de idosos deixados para trás na China rural. MÉTODO: foi realizada amostragem por conglomerado para selecionar 456 idosos deixados para trás quando os membros da família emigram da China rural. Este é um estudo transversal com preenchimento de um questionário de dados gerais e de qualidade de vida. RESULTADOS: 91,5% dos idosos convidados solicitaram aconselhamento e educação psicológicos. Para os idosos, os escores de saúde mental (39,56±13,73) foram significativamente menores em comparação aos dados padrões chineses (61,6±13,7) (

Nuclear spin pair coherence in diamond for atomic scale magnetometry

The nitrogen-vacancy (NV) centre, as a promising candidate solid state system of quantum information processing, its electron spin coherence is influenced by the magnetic field fluctuations due to the local environment. In pure diamonds, the environment consists of hundreds of C-13 nuclear spins randomly spreading in several nanometers range forming a spin bath. Controlling and prolonging the electron spin coherence under the influence of spin bath are challenging tasks for the quantum information processing. On the other hand, for a given bath distribution, many of its characters are encoded in the electron spin coherence. So it is natural to ask the question: is it possible to 'decode' the electron spin coherence, and extract the information about the bath structures? Here we show that, among hundreds of C-13 bath spins, there exist strong coupling clusters, which give rise to the millisecond oscillations of the electron spin coherence. By analyzing these oscillation features, the key properties of the coherent nuclear spin clusters, such as positions, orientations, and coupling strengths, could be uniquely identified. This addressability of the few-nuclear-spin cluster extends the feasibility of using the nuclear spins in diamond as qubits in quantum computing. Furthermore, it provides a novel prototype of single-electron spin based, high-resolution and ultra-sensitive detector for the chemical and biological applications.Comment: 15 pages, 4 figures, Nature Nanotechnology (2011

DPHL: A DIA Pan-human Protein Mass Spectrometry Library for Robust Biomarker Discovery

To address the increasing need for detecting and validating protein biomarkers in clinical specimens, mass spectrometry (MS)-based targeted proteomic techniques, including the selected reaction monitoring (SRM), parallel reaction monitoring (PRM), and massively parallel data-independent acquisition (DIA), have been developed. For optimal performance, they require the fragment ion spectra of targeted peptides as prior knowledge. In this report, we describe a MS pipeline and spectral resource to support targeted proteomics studies for human tissue samples. To build the spectral resource, we integrated common open-source MS computational tools to assemble a freely accessible computational workflow based on Docker. We then applied the workflow to generate DPHL, a comprehensive DIA pan-human library, from 1096 data-dependent acquisition (DDA) MS raw files for 16 types of cancer samples. This extensive spectral resource was then applied to a proteomic study of 17 prostate cancer (PCa) patients. Thereafter, PRM validation was applied to a larger study of 57 PCa patients and the differential expression of three proteins in prostate tumor was validated. As a second application, the DPHL spectral resource was applied to a study consisting of plasma samples from 19 diffuse large B cell lymphoma (DLBCL) patients and 18 healthy control subjects. Differentially expressed proteins between DLBCL patients and healthy control subjects were detected by DIA-MS and confirmed by PRM. These data demonstrate that the DPHL supports DIA and PRM MS pipelines for robust protein biomarker discovery. DPHL is freely accessible at https://www.iprox.org/page/project.html?id=IPX0001400000

A transcriptomic study of probenecid on injured spinal cords in mice

Background Recent studies have found that probenecid has neuroprotective and reparative effects on central nervous system injuries. However, its effect on genome-wide transcription in acute spinal cord injury (SCI) remains unknown. In the present study, RNA sequencing (RNA-Seq) is used to analyze the effect of probenecid on the local expression of gene transcription 8 h after spinal injury. Methods An Infinite Horizon impactor was used to perform contusive SCI in mice. The SCI model was made by using a rod (1.3 mm diameter) with a force of 50 Kdynes. Sham-operated mice only received a laminectomy without contusive injury. The injured mice were randomly assigned into either the control (SCI_C) or probenecid injection (SCI_P) group. In the latter group, the probenecid drug was intraperitoneally injected (0.5 mg/kg) immediately following injury. Eight hours after the injury or laminectomy, the spinal cords were removed from the mice in both groups. The total RNAs were extracted and purified for library preparation and transcriptome sequencing. Differential gene expressions (DEGs) of the three groups—sham, SCI_C and SCI_P—were analyzed using a DESeq software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of DEGs were performed using a GOseq R package and KOBAS software. Real-time quantitative reverse-transcriptase polymerase chain reaction was used to validate RNA-Seq results. Results RNA-Seq showed that, compared to the SCI_C group, the number of DEGs was 641 in the SCI_P group (286 upregulated and 355 downregulated). According to GO analysis, DEGs were most enriched in extracellular matrix (ECM), collagen trimer, protein bounding and sequence specific DNA binding. KEGG analysis showed that the most enriched pathways included: cell adhesion molecules, Leukocyte transendothelial migration, ECM-receptor interactions, PI3K-Akt signaling pathways, hematopoietic cell lineages, focal adhesions, the Rap1 signaling pathway, etc. The sequence data have been deposited into the Sequence Read Archive (https://www.ncbi.nlm.nih.gov/sra/PRJNA554464)

Yap promotes hepatocellular carcinoma metastasis and mobilization via governing cofilin/F-actin/lamellipodium axis by regulation of JNK/Bnip3/SERCA/CaMKII pathways

Despite the increasingly important role of Hippo-Yap in hepatocellular carcinoma (HCC) development and progression, little insight is available at the time regarding the specifics interaction of Yap and cancer cells migration. Here, we identified the mechanism by which tumor-intrinsic Yap deletion resulted in HCC migratory inhibition. Yap was greatly upregulated in HCC and its expression promoted the cells migration. Functional studies found that knockdown of Yap induced JNK phosphorylation which closely bound to the Bnip3 promoter and contributed to Bnip3 expression. Higher Bnip3 employed excessive mitophagy leading to mitochondrial dysfunction and ATP shortage. The insufficient ATP inactivated SERCA and consequently triggered intracellular calcium overload. As the consequence of calcium oscillation, Ca/calmodulin-dependent protein kinases II (CaMKII) was signaled and subsequently inhibited cofilin activity via phosphorylated modification. The phosphorylated cofilin failed to manipulate F-actin polymerization and lamellipodium formation, resulting into the impairment of lamellipodium-based migration. Collectively, our results identified Hippo-Yap as the tumor promoter in hepatocellular carcinoma that mediated via activation of cofilin/F-actin/lamellipodium axis by limiting JNK-Bnip3-SERCA-CaMKII pathways, with potential application to HCC therapy involving cancer metastasis. Keywords: Yap, JNK, Bnip3, SERCA, CaMKII, F-actin, Cofilin, Lamellipodium, Migratio

DUSP1 alleviates cardiac ischemia/reperfusion injury by suppressing the Mff-required mitochondrial fission and Bnip3-related mitophagy via the JNK pathways

Mitochondrial fission and selective mitochondrial autophagy (mitophagy) form an essential axis of mitochondrial quality control that plays a critical role in the development of cardiac ischemia-reperfusion (IR) injury. However, the precise upstream molecular mechanism of fission/mitophagy remains unclear. Dual-specificity protein phosphatase1 (DUSP1) regulates cardiac metabolism, but its physiological contribution in the reperfused heart, particularly its influence on mitochondrial homeostasis, is unknown. Here, we demonstrated that cardiac DUSP1 was downregulated following acute cardiac IR injury. In vivo, compared to wild-type mice, DUSP1 transgenic mice (DUSP1TG mice) demonstrated a smaller infarcted area and the improved myocardial function. In vitro, the IR-induced DUSP1 deficiency promoted the activation of JNK which upregulated the expression of the mitochondrial fission factor (Mff). A higher expression level of Mff was associated with elevated mitochondrial fission and mitochondrial apoptosis. Additionally, the loss of DUSP1 also amplified the Bnip3 phosphorylated activation via JNK, leading to the activation of mitophagy. Increased mitophagy overtly consumed mitochondrial mass resulting into the mitochondrial metabolism disorder. However, the reintroduction of DUSP1 blunted Mff/Bnip3 activation and therefore alleviated the fatal mitochondrial fission/mitophagy by inactivating the JNK pathway, providing a survival advantage to myocardial tissue following IR stress. The results of our study suggest that DUSP1 and its downstream JNK pathway are therapeutic targets for conferring protection against IR injury by repressing Mff-mediated mitochondrial fission and Bnip3-required mitophagy. Keywords: Cardiac IR injury, Mitochondrial fission, Mitophagy, Mff, Bnip3, DUSP1, JN

MiR-133a Is Functionally Involved in Doxorubicin-Resistance in Breast Cancer Cells MCF-7 via Its Regulation of the Expression of Uncoupling Protein 2

<div><p>The development of novel targeted therapies holds promise for conquering chemotherapy resistance, which is one of the major hurdles in current breast cancer treatment. Previous studies indicate that mitochondria uncoupling protein 2 (UCP-2) is involved in the development of chemotherapy resistance in colon cancer and lung cancer cells. In the present study we found that lower level of miR133a is accompanied by increased expression of UCP-2 in Doxorubicin-resistant breast cancer cell cline MCF-7/Dox as compared with its parental cell line MCF-7. We postulated that miR133a might play a functional role in the development of Doxorubicin-resistant in breast cancer cells. In this study we showed that: 1) exogenous expression of miR133a in MCF-7/Dox cells can sensitize their reaction to the treatment of Doxorubicin, which is coincided with reduced expression of UCP-2; 2) knockdown of UCP-2 in MCF-7/Dox cells can also sensitize their reaction to the treatment of Doxorubicin; 3) intratumoral delivering of miR133a can restore Doxorubicin treatment response in Doxorubicin-resistant xenografts <i>in vivo</i>, which is concomitant with the decreased expression of UCP-2. These findings provided direct evidences that the miR133a/UCP-2 axis might play an essential role in the development of Doxorubicin-resistance in breast cancer cells, suggesting that the miR133a/UCP-2 signaling cohort could be served as a novel therapeutic target for the treatment of chemotherapy resistant in breast cancer.</p></div

Knockdown of UCP-2 in MCF-7/DOX restores its Doxorubicin sensitivity.

<p>(A) The mRNA and protein expression levels of UCP-2in MCF-7/Dox cells infected with lentivirus expressing eithershUCP-2 or scramble shRNA for 72 h were measured by real-time PCR (Left) and western blot analysis (Right) respectively. (B) Cell growth curve plotted with total cell amount of MCF-7/Dox cells infected with lentivirus expressingscramble shRNA and shUCP-2by cell counting in connective 8 days treated with 0.4 nM Doxorubicin (Left).Cells were seeded in amount according to their doubling time to ensure comparable amount in the starting day of treatment. Right, cell viability under the treatment of Doxorubicin was shown as folds change of cell viability normalized to that of the cells treated with saline. Each bar represents the mean ± SEM. The results shown were repeated in three independent experiments. *, P < 0.05; **, P<0.01 and***, P < 0.001 significantly different from the respective control group.</p

MiR133a helps to increase Doxorubicin treatment response inDoxorubicin-resistant in vivo via its decreasing the expression of UCP-2.

<p>(A) Tumor growth curve in the nude mice treated with Doxorubicin intraperitoneally (<i>i</i>.<i>p</i>.) (4 mg/kg, twice per week) combined with intratumoral injection of pre-miR133a, scramble or saline for four weeks. (B) Expressions levels of miR-133a were detected by real-time PCR analysis in tumor tissues. (C) Expression levels of UCP-2 in tumor tissues were determined by real-time PCR (Left) and Western blot analysis (Right), respectively. Each bar represents the mean ± SEM. All the results shown were repeated in three independent experiments. **, P < 0.01; and***, P < 0.001 significantly different from the respective control group.</p