Construction of a cross-species cell landscape at single-cell level.

Individual cells are basic units of life. Despite extensive efforts to characterize the cellular heterogeneity of different organisms, cross-species comparisons of landscape dynamics have not been achieved. Here, we applied single-cell RNA sequencing (scRNA-seq) to map organism-level cell landscapes at multiple life stages for mice, zebrafish and Drosophila. By integrating the comprehensive dataset of > 2.6 million single cells, we constructed a cross-species cell landscape and identified signatures and common pathways that changed throughout the life span. We identified structural inflammation and mitochondrial dysfunction as the most common hallmarks of organism aging, and found that pharmacological activation of mitochondrial metabolism alleviated aging phenotypes in mice. The cross-species cell landscape with other published datasets were stored in an integrated online portal-Cell Landscape. Our work provides a valuable resource for studying lineage development, maturation and aging

Exploring association between certified EHRs adoption and patient experience in U.S. psychiatric hospitals.

ObjectiveCertified Electronic Health Records (EHR) have been shown to improve the health service quality in some health settings, but there is scant evidence related to its adoption in psychiatric hospitals. This paper aimed to examine the relationship between certified EHR adoption and patient experience across psychiatric hospitals in the United States.MethodsA cross-sectional study design compared the difference in patient experience measures between psychiatric hospitals with and without certified EHR. Data were drawn from the American Hospital Association (AHA) Annual Survey Database and Hospital Compare datasets. Eleven publicly reported measures for patient experience from the Consumer Assessment of Healthcare Providers and Systems Hospital Survey (HCAHPS) were applied for analysis. Independent relationship of certified EHR adoption and patient experience was explored with multiple linear regression models adjusted for hospital organizational characteristics.ResultsPositive associations were identified between certified EHR adoption and five patient perception measures-"recommend hospital" (β = 0.66, 95% CI = [0.16,1.16]; t = 2.68, p = 0.010), "overall hospital rating" (β = 0.39, 95% CI = [0.03,0.75]; t = 2.11, p = 0.035), "discharge information" (β = 0.45, 95% CI = [0.03,0.86]; t = 2.09, p = 0.037), "care transition" (β = 0.44, 95% CI = [0.14, 0.75]; t = 2.84, p = 0.005), and "responsiveness of hospital staff" (β = 0.47, 95% CI = [0.04, 0.90]; t = 2.13, p = 0.033).ConclusionOur results suggest the positive association between certified EHR adoption and patient experience. More studies are needed to explore impacts of certified EHR adoption and potential improvement in patient experience to quality of care

Reservoir quality prediction of deeply buried tight sandstones in extensively faulted region: A case from the middle-Upper Jurassic Shishugou Group in central Junggar Basin, NW China

The reservoir quality of tight sandstones is generally determined by the depositional environment, burial depth and diagenesis. However, the relationship between reservoir quality of tight sandstones and the controlling factors are very complicated. Deeply buried Middle-Upper Jurassic Shishugou Group sandstones are important tight oil sandstone reservoirs in the central Junggar Basin of NW china. The individual sandstones are thin (2–20m, av.7.8m), overlain by an unconformity and directly connected to the source rock by a well-developed fault system. The diagenetic system and reservoir quality of the Shishugou Group sandstones in the Central Junggar Basin was investigated using petrology, mineralogy, pore characteristics, sedimentary facies, burial and thermal history, knowledge of hydrocarbon charging, fault/fracture system, diagenetic reactions and sequence, controlling factors of reservoir quality, paleo-porosity reconstruction and formation mechanism of high-quality reservoir. The thin-section observation, scanning electron microscope (SEM and BSD), granularity analysis, Xray diffraction (XRD) and fluorescence microscope, 3D seismic and well logging analysis were used in this research. The top unconformity and faults system were the pathways for water and hydrocarbon migration. Organic acids and meteoric water with high concentrations of CO2 were the main fluids that caused dissolution of volcanic rock fragments, feldspar, analcime cement and early calcite cement. The paleo-porosity variation of Shishugou Group sandstones was analyzed quantitatively by the inversion and back stripping with the constrain of diagenetic evolution history and theoretical compaction models. The comprehensive researches including the origin of pore waters, origin of acidic fluids, fault/fracture system and hydrocarbon charging history, show that near-surface or meteoric diagenetic reactions of Shishugou Group sandstones closely beneath top unconformities were in open (geochemical) diagenetic systems, and that diagenetic (geochemical) systems were relatively open, especially in the faults-developed zone during burial process. The central sandstone body of the point bar, underwater distributary channel and distributary channel, which were cut through by the oil source fault, retained high-quality reservoir. The reservoir quality can be mostly predicted as a function of sedimentary environment (sedimentary facies and provenance), diagenetic reactions and burial history with the constrain of source rocks, diagenetic system and fault system

Autophagy inhibitor chloroquine increases sensitivity to cisplatin in QBC939 cholangiocarcinoma cells by mitochondrial ROS.

The tumor cells have some metabolic characteristics of the original tissues, and the metabolism of the tumor cells is closely related to autophagy. However, the mechanism of autophagy and metabolism in chemotherapeutic drug resistance is still poorly understood. In this study, we investigated the role and mechanism of autophagy and glucose metabolism in chemotherapeutic drug resistance by using cholangiocarcinoma QBC939 cells with primary cisplatin resistance and hepatocellular carcinoma HepG2 cells. We found that QBC939 cells with cisplatin resistance had a higher capacity for glucose uptake, consumption, and lactic acid generation, and higher activity of the pentose phosphate pathway compared with HepG2 cells, and the activity of PPP was further increased after cisplatin treatment in QBC939 cells. It is suggested that there are some differences in the metabolism of glucose in hepatocellular carcinoma and cholangiocarcinoma cells, and the activation of PPP pathway may be related to the drug resistance. Through the detection of autophagy substrates p62 and LC3, found that QBC939 cells have a higher flow of autophagy, autophagy inhibitor chloroquine can significantly increase the sensitivity of cisplatin in cholangiocarcinoma cells compared with hepatocellular carcinoma HepG2 cells. The mechanism may be related to the inhibition of QBC939 cells with higher activity of the PPP, the key enzyme G6PDH, which reduces the antioxidant capacity of cells and increases intracellular ROS, especially mitochondrial ROS. Therefore, we hypothesized that autophagy and the oxidative stress resistance mediated by glucose metabolism may be one of the causes of cisplatin resistance in cholangiocarcinoma cells. It is suggested that according to the metabolism characteristics of tumor cells, inhibition of autophagy lysosome pathway with chloroquine may be a new route for therapeutic agents against cholangiocarcinoma

Time-dependent proteomics and drug response in expanding cancer cells

Cancer cell line is commonly used for discovery and development of anti-cancer drugs. It is generally considered that drug response remains constant for a certain cell line due to the identity of genetics thus protein patterns. Here, we demonstrated that cancer cells continued dividing even after reaching confluence, in that the proteomics was changed continuously and dramatically with strong relevance to cell division, cell adhesion and cell metabolism, indicating time-dependent intrinsically reprogramming of cells during expansion. Of note, the inhibition effect of most anti-cancer drugs was strikingly attenuated in culture cells along with cell expansion, with the strongest change at the third day when cells were still expanding. Profiling of an FDA-approved drug library revealed that attenuation of response with cell expansion is common for most drugs, an exception was TAK165 that was a selective inhibitor of mitochondrial respiratory chain complex I. Finally, we screened a panel of natural products and identified four pentacyclic triterpenes as selective inhibitors of cancer cells under prolonged growth. Taken together, our findings underscore that caution should be taken in evaluation of anti-cancer drugs using culture cells, and provide agents selectively targeting overgrowth cancer cells

Dalbergioidin Ameliorates Doxorubicin-Induced Renal Fibrosis by Suppressing the TGF-β Signal Pathway

We investigated the effect of Dalbergioidin (DAL), a well-known natural product extracted from Uraria crinita, on doxorubicin- (DXR-) induced renal fibrosis in mice. The mice were pretreated for 7 days with DAL followed by a single injection of DXR (10 mg/kg) via the tail vein. Renal function was analyzed 5 weeks after DXR treatment. DXR caused nephrotoxicity. The symptoms of nephrotic syndrome were greatly improved after DAL treatment. The indices of renal fibrosis, the phosphorylation of Smad3, and the expression of alpha-smooth muscle actin (α-SMA), fibronectin, collagen III (Col III), E-cadherin, TGF-β, and Smad7 in response to DXR were all similarly modified by DAL. The present findings suggest that DAL improved the markers for kidney damage investigated in this model of DXR-induced experimental nephrotoxicity

The application of BMRT-HPV viral load to secondary screening strategies for cervical cancer.

OBJECTIVE:Evaluate the significance of BMRT HPV assay viral load and its performance for secondary screening. METHODS:BMRT-HPV reports type-specific viral loads/10,000 cells. We tested 1,495 physician collected, stored specimens from Chinese Multiple-center Screening Trial (CHIMUST), that were positive by Cobas, SeqHPV, and/or Cytology (≥LSIL); and 2,990 age matched, negatives in a nested case control study. We explored the relationship between BMRT HR-HPV viral load and cervical lesions, determined alternative CIN2+ cut-points by ROC curve, and evaluated BMRT HR-HPV for primary / secondary cervical cancer screening. RESULTS:The viral loads of HPV16/18, 12 other subtypes HR-HPV and 14 HR-HPV were statistically different in all grades of cervical lesions (P0.05), specificity was higher than Cobas (84.8% vs 83.3%, 83.5% vs 82.0%, P0.05). However, the BMRT HR-HPV viral load combined with subtypes did not require cytology. CONCLUSION:BMRT is as sensitive as Cobas4800 for primary cervical cancer screening. BMRT HR-HPV viral load combined with subtypes can be used as a secondary strategy for cervical cancer screening, especially for areas with insufficient cytological resources

QBC939 cells are resistant to cisplatin.

<p>QBC939 and HepG2 cells were treated with cisplatin for 12 or 24 h, and then cell viability, apoptosis and cell death rates, and mtROS were measured. (A) Cells were treated with cisplatin (1.25–80 μg/ml) for 24 h and then cell viability was determined by MTT assays. (B) Cells were treated with cisplatin (10 or 20 μg/ml) for 12 h and then the apoptotic rate was measured by flow cytometry (fluorescence intensity: x axis, Annexin V-FITC; y axis, PI). (C) Quantitation of the apoptosis rate (including early and late apoptosis) under the same treatment conditions as in (B). (D) Quantitation of the cell death rate by trypan blue staining under the same treatment conditions as in (B). (E) Cells were treated with cisplatin (20 μg/ml) for 24 h followed by 5 μm mitoSOX for 10 min, and then fluorescence intensity was observed by fluorescence microscopy (×200). (F) Quantitation of the cell average fluorescence intensity under the same treatment conditions as in (E). All values are the mean±SE. *<i>p</i><0.05 between QBC939 cells group and HepG2 cells group.</p