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Supplementary Fig. S4 shows the effects of USP36 on DGCR8 ubiquitination and that USP36 SUMOylation of DGCR8 does not depend on its DUB activity.

miRNA biogenesis is a cellular process that produces mature miRNAs from their primary transcripts, pri-miRNAs, via two RNAse III enzyme complexes: the Drosha-DGCR8 microprocessor complex in the nucleus and the Dicer-TRBP complex in the cytoplasm. Emerging evidence suggests that miRNA biogenesis is tightly regulated by posttranscriptional and posttranslational modifications and aberrant miRNA biogenesis is associated with various human diseases including cancer. DGCR8 has been shown to be modified by SUMOylation. Yet, the SUMO ligase mediating DGCR8 SUMOylation is currently unknown. Here, we report that USP36, a nucleolar ubiquitin-specific protease essential for ribosome biogenesis, is a novel regulator of DGCR8. USP36 interacts with the microprocessor complex and promotes DGCR8 SUMOylation, specifically modified by SUMO2. USP36-mediated SUMOylation does not affect the levels of DGCR8 and the formation of the Drosha-DGCR8 complex, but promotes the binding of DGCR8 to pri-miRNAs. Consistently, abolishing DGCR8 SUMOylation significantly attenuates its binding to pri-miRNAs and knockdown of USP36 attenuates pri-miRNA processing, resulting in marked reduction of tested mature miRNAs. Induced expression of a SUMOylation-defective mutant of DGCR8 inhibits cell proliferation. Together, these results suggest that USP36 plays an important role in regulating miRNA biogenesis by SUMOylating DGCR8.Significance:This study identifies that USP36 mediates DGCR8 SUMOylation by SUMO2 and is critical for miRNA biogenesis. As USP36 is frequently overexpressed in various human cancers, our study suggests that deregulated USP36-miRNA biogenesis pathway may contribute to tumorigenesis.

Potential features in the primordial power spectrum have been searched for in galaxy surveys in recent years since these features can assist in understanding the nature of inflation. The null detection to date suggests that any such features should be fairly weak, and next-generation galaxy surveys, with their unprecedented sizes and precisions, are in a position to place stronger constraints than before. However, even if such primordial features once existed in the early Universe, they would have been significantly damped in the non-linear regime at low redshift due to structure formation, which makes them difficult to be directly detected in real observations. A potential way to tackle this challenge for probing the features is to undo the cosmological evolution, i.e. using reconstruction to obtain an approximate linear density field. By employing a set of N-body simulations, here we show that a recently proposed non-linear reconstruction algorithm can effectively retrieve damped oscillatory features from halo catalogues and improve the accuracy of the measurement of feature parameters (assuming that such primordial features do exist). We do a Fisher analysis to forecast how non-linear reconstruction affects the constraining power, and find that it can lead to significantly more robust constraints on the feature amplitude for a DESI-like survey. Comparing non-linear reconstruction with other ways of improving constraints, such as increasing the survey volume and range of scales, this shows that it is possible to achieve what the latter do, but at a lower cost.

Fast Radio Bursts (FRBs) are bright millisecond-duration radio transients that appear about 1,000 times per day, all-sky, for a fluence threshold 5 Jy ms at 600 MHz. The FRB radio-emission physics and the compact objects involved in these events are subjects of intense active debate. To better constrain source models, the Bustling Universe Radio Survey Telescope in Taiwan (BURSTT) is optimized to discover and localize a large sample of rare, high-fluence, nearby FRBs. This is the population most amenable to multi-messenger, multi-wavelength follow-up, allowing deeper understanding of source mechanisms. BURSTT will provide horizon-to-horizon sky coverage with a half power field-of-view (FoV) of $\sim$10$^{4}$ deg$^{2}$, a 400 MHz effective bandwidth between 300-800 MHz, and sub-arcsecond localization, made possible using outrigger stations hundreds to thousands of km from the main array. Initially, BURSTT will employ 256 antennas. After tests of various antenna designs and optimization of system performance we plan to expand to 2048 antennas. We estimate that BURSTT-256 will detect and localize $\sim$100 bright ($\geq$100 Jy ms) FRBs per year. Another advantage of BURSTT's large FoV and continuous operation will be greatly enhanced monitoring of FRBs for repetition. The current lack of sensitive all-sky observations likely means that many repeating FRBs are currently cataloged as single-event FRBs., Published version

BACKGROUND Constipation is one of the most important nonmotor symptoms in Parkinson's disease (PD) patients, and constipation of different severities is closely related to the pathogenesis of PD. PD with constipation (PDC) is considered a unique type of constipation, but its mechanism of formation and factors affecting its severity have been less reported. Understanding the gastrointestinal motility characteristics and constipation classification of PDC patients is essential to guide the treatment of PDC. In this study, the colonic transit test and high-resolution anorectal manometry were used to identify the intestinal motility of PDC to provide a basis for the treatment of PDC. AIM To investigate the clinical classification of PDC, to clarify its characteristics of colonic motility and rectal anal canal pressure, and to provide a basis for further research on the pathogenesis of PDC. METHODS Twenty PDC patients and 20 patients with functional constipation (FC) who were treated at Xuanwu Hospital of Capital Medical University from August 6, 2018 to December 2, 2019 were included. A colonic transit test and high-resolution anorectal manometry were performed to compare the differences in colonic transit time, rectal anal canal pressure, and constipation classification between the two groups. RESULTS There were no statistically significant differences in sex, age, body mass index, or duration of constipation between the two groups. It was found that more patients in the PDC group exhibited difficulty in defecating than in the FC group, and the difference was statistically significant. The rectal resting pressure, anal sphincter resting pressure, intrarectal pressure, and anal relaxation rate in the PDC group were significantly lower than those in the FC group. The proportion of paradoxical contractions in the PDC group was significantly higher than that in the FC group. There was a statistically significant difference in the type composition ratio of defecatory disorders between the two groups (P < 0.05). The left colonic transit time, rectosigmoid colonic transit time (RSCTT), and total colonic transit time were prolonged in PDC and FC patients compared to normal values. The patients with FC had a significantly longer right colonic transit time and a significantly shorter RSCTT than patients with PDC (P < 0.05). Mixed constipation predominated in PDC patients and FC patients, and no significant difference was observed. CONCLUSION Patients with PDC and FC have severe functional dysmotility of the colon and rectum, but there are certain differences in segmental colonic transit time and rectal anal canal pressure between the two groups.

Background The coronavirus disease 2019 (COVID-19) outbreak has brought great challenges to public health. Aggravation of COVID-19 is closely related to the secondary systemic inflammatory response. Glucocorticoids are used to control severe diseases caused by the cytokine storm, owing to their anti-inflammatory effects. However, glucocorticoids are a double-edged sword, as the use of large doses has the potential risk of secondary infection and long-term serious complications, and may prolong virus clearance time. Nonetheless, the risks and benefits of glucocorticoid adjuvant therapy for COVID-19 are inconclusive. Aim To determine the effect of methylprednisolone in severe and critically ill patients with COVID-19. Methods This single-center retrospective study included 102 adult COVID-19 patients admitted to a ward of a designated hospital in Wuhan, Hubei Province from January to March 2020. All patients received general symptomatic treatment and organ function support, and were given different respiratory support measures according to their conditions. In case of deterioration, considering the hyperinflammatory state of the patients, methylprednisolone was intravenously administered at 0.75-1.5 mg/kg/d, usually for less than 14 d. Patient vital signs and oxygenation were closely monitored, in combination with imaging and routine blood tests such as C-reactive protein, biochemical indicators (liver and kidney function, myocardial enzymes, electrolytes, etc.), and coagulation function. Patient clinical outcomes were discharge or death. Results A total of 102 severe and critically ill COVID-19 patients were included in this study. They were divided into treatment (69, 67.6%) and control groups (33, 32.4%) according to methylprednisolone use. Comparison of baseline data between the two groups showed that the treatment group patients had higher aspartic acid aminotransferase, globulin, hydroxybutyrate dehydrogenase, and lactate dehydrogenase. There was no significant difference in other baseline data between the two groups. With regard to prognosis, 29 (78.4%) patients in the treatment group died as opposed to 40 (61.5%) in the control group. The mortality was higher in the treatment group than in the control group; however, according to the log-rank test and the Kaplan-Meier survival curve, the difference in mortality between both groups was insignificant (P = 0.655). The COX regression equation was used to correct the variables with differences, and the results showed that methylprednisolone treatment did not improve prognosis. Conclusion Methylprednisolone treatment does not improve prognosis in severe and critical COVID-19 patients.

BACKGROUND: The Helicobacter pylori (H. pylori) infection rate in China is approximately 50%. H. pylori is a pathogenic factor of peptic ulcer and chronic gastritis. In addition, H. pylori infection may also be associated with a variety of cardiovascular diseases in elderly people, such as arteriosclerosis, coronary heart disease, and cerebral infarction, having deleterious effect on their health. With the aging of the population, the disease characteristics of the elderly population have been increasingly valued by the whole society. We conducted an epidemiological survey of H. pylori infection among elderly people in Beijing to provide a basis for health management of H. pylori infection. AIM: To understand the epidemiological characteristics of H. pylori infection in elderly people in Beijing. METHODS: A total of 1090 elderly people aged more than 60 years from different parts of Beijing (urban and rural areas) were selected using the random cluster sampling method. Structured questionnaires were completed during home visits and the (13)C-urea breath test was conducted for H. pylori detection. RESULTS: The prevalence of H. pylori infection was 46.5% (507/1090). The infection rate in men was 51.8%, which was significantly higher than that in women (42.5%; P < 0.05). The H. pylori infection rate in illiterate people was significantly higher than that in literate persons (53.5% vs 44.8%, P < 0.05). The total infection rate of H. pylori gradually increased with age and the difference was statistically significant (P < 0.01). The H. pylori infection rate in smokers was significantly higher than that in non-smokers and those who had quit smoking (P < 0.05). CONCLUSION: The prevalence of H. pylori infection among elderly people is 46.5% and the infection rate gradually increases with age. Sex, education level, age, and smoking were determined to be H. pylori infection risk factors. The relationship of H. pylori infection with region, occupation, drinking, and diet structure needs to be further studied.

Moderately severe acute pancreatitis (MSAP) and severe acute pancreatitis (SAP) are associated with organ failure (OF), which can be lethal. This study determined the factors that predict the severity of AP at admission in elderly patients. In this retrospective study, the data from elderly patients (> 60 years of age) admitted within 72 h of onset of symptoms without OF were collected. These data at admission were analyzed and correlated with the severity of AP. To identify the factors associated with more serious AP (i.e. MSAP and SAP), patients were divided into mild acute pancreatitis (MAP) and MSAP + SAP groups. A total of 198 patients [MAP group (n = 135) and MSAP + SAP group (n = 63)] were included. Biliary disease was the most common etiology. Respiratory failure was the most common OF. Logistic regression analyses indicated that idiopathic etiology (odds ratio [OR]: 3.029, 95% confidence interval [CI]: 1.017–9.022, p = 0.047), pre-existing pulmonary disease (OR: 7.104, CI 1.750–28.84, p = 0.006), increased hematocrit level (OR: 3.717, 95%CI 1.372–10.070, p = 0.010), serum calcium (OR: 0.023, 95%CI 0.001–0.371, p = 0.008), serum glucose (OR: 1.157, 95%CI 1.031–1.299, p = 0.013), arterial partial pressure of oxygen (PaO2) (OR: 0.914, 95%CI 0.874–0.956, p

The angular momentum of galaxies (galaxy spin) contains rich information about the initial condition of the Universe, yet it is challenging to efficiently measure the spin direction for the tremendous amount of galaxies that are being mapped by the ongoing and forthcoming cosmological surveys. We present a machine learning based classifier for the Z-wise vs S-wise spirals, which can help to break the degeneracy in the galaxy spin direction measurement. The proposed Chirality Equivariant Residual Network (CE-ResNet) is manifestly equivariant under a reflection of the input image, which guarantees that there is no inherent asymmetry between the Z-wise and S-wise probability estimators. We train the model with Sloan Digital Sky Survey (SDSS) images, with the training labels given by the Galaxy Zoo 1 (GZ1) project. A combination of data augmentation tricks are used during the training, making the model more robust to be applied to other surveys. We find a $\sim\!30\%$ increase of both types of spirals when Dark Energy Spectroscopic Instrument (DESI) images are used for classification, due to the better imaging quality of DESI. We verify that the $\sim\!7\sigma$ difference between the numbers of Z-wise and S-wise spirals is due to human bias, since the discrepancy drops to $, Comment: 13+4 pages, 11 figures, 2 tables, accepted by ApJ

SUMOylation plays a crucial role in regulating diverse cellular processes including ribosome biogenesis. Proteomic analyses and experimental evidence showed that a number of nucleolar proteins involved in ribosome biogenesis are modified by SUMO. However, how these proteins are SUMOylated in cells is less understood. Here, we report that USP36, a nucleolar deubiquitinating enzyme (DUB), promotes nucleolar SUMOylation. Overexpression of USP36 enhances nucleolar SUMOylation, whereas its knockdown or genetic deletion reduces the levels of SUMOylation. USP36 interacts with SUMO2 and Ubc9 and directly mediates SUMOylation in cells and in vitro. We show that USP36 promotes the SUMOylation of the small nucleolar ribonucleoprotein (snoRNP) components Nop58 and Nhp2 in cells and in vitro and their binding to snoRNAs. It also promotes the SUMOylation of snoRNP components Nop56 and DKC1. Functionally, we show that knockdown of USP36 markedly impairs rRNA processing and translation. Thus, USP36 promotes snoRNP group SUMOylation and is critical for ribosome biogenesis and protein translation.

As all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are widely accepted in treating acute promyelocytic leukemia (APL), deescalating toxicity becomes a research hotspot. Here, we evaluated whether chemotherapy could be replaced or reduced by ATO in APL patients at different risks. After achieving complete remission with ATRA-ATO–based induction therapy, patients were randomized (1:1) into ATO and non-ATO groups for consolidation: ATRA-ATO versus ATRA–anthracycline for low-/intermediate-risk patients, or ATRA-ATO–anthracycline versus ATRA–anthracycline–cytarabine for high-risk patients. The primary end point was to assess disease-free survival (DFS) at 3 y by a noninferiority margin of –5%; 855 patients were enrolled with a median follow-up of 54.9 mo, and 658 of 755 patients could be evaluated at 3 y. In the ATO group, 96.1% (319/332) achieved 3-y DFS, compared to 92.6% (302/326) in the non-ATO group. The difference was 3.45% (95% CI –0.07 to 6.97), confirming noninferiority (P < 0.001). Using the Kaplan–Meier method, the estimated 7-y DFS was 95.7% (95% CI 93.6 to 97.9) in ATO and 92.6% (95% CI 89.8 to 95.4) in non-ATO groups (P = 0.066). Concerning secondary end points, the 7-y cumulative incidence of relapse (CIR) was significantly lower in ATO (2.2% [95% CI 1.1 to 4.2]) than in non-ATO group (6.1% [95% CI 3.9 to 9.5], P = 0.011). In addition, grade 3 to 4 hematological toxicities were significantly reduced in the ATO group during consolidation. Hence, ATRA-ATO in both chemotherapy-replacing and -reducing settings in consolidation is not inferior to ATRA–chemotherapy (https://www.clinicaltrials.gov/, NCT01987297).

The gravitational coupling between large-scale perturbations and small-scale perturbations leads to anisotropic distortions of the small-scale matter distribution. The measured local small-scale power spectrum can thus be used to infer the large-scale matter distribution. In this paper, we present a new tidal reconstruction algorithm for reconstructing large-scale modes using the full three-dimensional tidal shear information. We apply it to simulated dark matter halo fields and the reconstructed large-scale density field correlates well with the original matter density field on large scales, improving upon the previous tidal reconstruction method which only uses two transverse shear fields. This has profound implications for recovering lost 21~cm radial modes due to foreground subtraction and constraining primordial non-Gaussianity using the multi-tracer method with future cosmological surveys., Comment: 10 pages, 5 figures

BACKGROUND The outbreak of coronavirus disease 2019 (COVID-19) has rapidly evolved into a global pandemic. COVID-19 is clinically categorized into mild, moderate, severe, and critical illness. Acute kidney injury is an independent risk factor for poor prognosis in patients with. Serum cystatin C (sCys C) is considered a more sensitive biomarker for early renal insufficiency than conventional indicators of renal function. Early detection of risk factors that affect the prognosis of severe and critically ill patients while using active and effective treatment measures is very important and can effectively reduce the potential mortality rate. AIM To determine the predictive value of sCys C for the prognosis of patients with COVID-19. METHODS The clinical data of 101 severe and critically ill patients with COVID-19 at a designated hospital in Wuhan, Hubei Province, China were analyzed retrospectively. According to the clinical outcome, the patients were divided into a discharge group (64 cases) and a death group (37 cases). The general information, underlying diseases, and laboratory examination indexes of the two groups were compared. Multivariate Cox regression was used to explore the relationship between sCys C and prognosis. The receiver operating characteristic (ROC) curve was used to demonstrate the sensitivity and specificity of sCys C and its optimal cut-off value for predicting death. RESULTS There were significant differences in age, sCys C, creatinine, C-reactive protein, serum albumin, creatine kinase-MB, alkaline phosphatase, lactate dehydrogenase, neutrophil count, and lymphocyte count between the two groups (P < 0.001). Multivariate logistic regression analysis showed that sCys C was an independent risk factor for death in patients with COVID-19 (Odds ratio = 1.812, 95% confidence interval [CI]: 1.300-2.527, P < 0.001). The area under the ROC curve was 0.755 (95%CI: 1.300-2.527), the cut-off value was 0.80, the specificity was 0.562, and the sensitivity was 0.865. CONCLUSION sCys C is an independent risk factor for death in patients with COVID-19. Patients with a sCys C level of 0.80 mg/L or greater are at a high risk of death.

Galaxy-galaxy strong gravitational lenses have become a popular probe of dark matter (DM) by providing a window into structure formation on the smallest scales. In particular, the convergence power spectrum of subhalos within lensing galaxies has been suggested as a promising observable to study DM. However, the distances involved in strong-lensing systems are vast, and we expect the relevant volume to contain line-of-sight (LOS) halos that are not associated with the main lens. We develop a formalism to calculate the effect of LOS halos as an effective convergence power spectrum. The multi-lens plane equation couples the angular deflections of consecutive lens planes, but by assuming that the perturbations due to the LOS halos are small, we show that they can be projected onto the main-lens plane as effective subhalos. We test our formalism by simulating lensing systems using the full multi-plane lens equation and find excellent agreement. We show how the relative contribution of LOS halos and subhalos depends on the source and lens redshift, as well as the assumed halo and subhalo mass functions. For a fiducial system with fraction of DM halo mass in substructure $f_{\rm sub}=0.4\%$ for subhalo masses $[10^5-10^8]\rm{M}_{\odot}$, the interloper contribution to the power spectrum is at least several times greater than that of subhalos for source redshifts $z_s\gtrsim0.5$. Furthermore, it is likely that for the SLACS and BELLS lenses the interloper contribution dominates: $f_{\rm sub}\gtrsim2\%$ ($4\%$) is needed for subhalos to dominate in SLACS (BELLS), which is higher than current upper bounds on $f_{\rm sub}$ for our mass range. Since the halo mass function is better understood from first principles, the dominance of interlopers in galaxy-galaxy lenses with high-quality imaging can be seen as a significant advantage when translating this observable into a constraint on DM., Comment: 24 pages, 8 figures, Matches accepted version, v3: Fixed a typo in Eq. C4 in the appendix. No changes in the derivations

AIM To elucidate the effects of small intestinal bacterial overgrowth (SIBO) on the severity and complications of acute pancreatitis (AP). METHODS In total, 208 patients with AP as defined by the revised Atlanta classification were admitted to Xuanwu Hospital of Capital Medical University from 2013 to 2016. All patients were admitted within 72 h of AP onset. The hydrogen breath test was performed 7 d after AP onset to detect hydrogen production and evaluate the development of SIBO. The incidence of SIBO was analyzed in patients with AP of three different severity grades. The association between SIBO and complications of AP was also assessed. RESULTS Of the 27 patients with severe AP (SAP), seven (25.92%) developed SIBO. Of the 86 patients with moderately severe AP (MSAP), 22 (25.58%) developed SIBO. Of the 95 patients with mild AP (MAP), eight (8.42%) developed SIBO. There were significant differences in the rates of SIBO among patients with AP of different severities. Additionally, more severe AP was associated with higher rates of SIBO positivity (P < 0.05). SIBO in patients with AP mainly occurred within 72 h of the onset of AP. The incidence of organ failure was significantly higher in patients with SIBO than in those without (P < 0.05). CONCLUSION SIBO occurs more frequently in patients with MSAP or SAP than in those with MAP, usually ≤ 72 h after AP onset. Additionally, SIBO is associated with organ failure.

Reconstruction is becoming a crucial procedure of galaxy clustering analysis for future spectroscopic redshift surveys to obtain subpercent level measurement of the baryon acoustic oscillation scale. Most reconstruction algorithms rely on an estimation of the displacement field from the observed galaxy distribution. However, the displacement reconstruction degrades near the survey boundary due to incomplete data and the boundary effects extend to $\sim100\,\mathrm{Mpc}/h$ within the interior of the survey volume. We study the possibility of using radial velocities measured from the cosmic microwave background observation through the kinematic Sunyaev-Zel'dovich effect to improve performance near the boundary. We find that the boundary effect can be reduced to $\sim30-40\,\mathrm{Mpc}/h$ with the velocity information from Simons Observatory. This is especially helpful for dense low redshift surveys where the volume is relatively small and a large fraction of total volume is affected by the boundary., 12 pages, 14 figures, in press

We discuss the possibility of studying diffuse baryon distributions with kinematic Sunyaev-Zel'dovich (kSZ) effect by correlating cosmic microwave background (CMB) temperature fluctuations with density fluctuations from 21\,cm intensity mapping (IM). The biggest challenge for the cross-correlation is the loss of large-scale information in IM, due to foregrounds and the zero spacing problem of interferometers. We apply the tidal reconstruction algorithm to restore the lost large-scale modes, which increases the correlation by more than a factor of three. With the predicted foreground level, we expect a $\sim20\,\sigma$ detection of kSZ signal for $0.8\lesssim z\lesssim2.5$ with CHIME and Planck, and a $\sim40\, \sigma$ detection with HIRAX and Planck. The significance can be greatly increased with next-generation facilities of higher spatial resolutions.

We present a new method to measure neutrino masses using the dark matter-neutrino relative velocity. The relative motion between dark matter and neutrinos results in a parity-odd bispectrum which can be measured from cross-correlation of different cosmic fields. This new method is not affected by most systematics which are parity even and not limited by the knowledge of optical depth to the cosmic microwave background. We estimate the detectability of the relative velocity effect and find that the minimal sum of neutrino masses could be detected at high significance with upcoming surveys., 6 pages, 2 figures, 1 table, published version

Nasopharyngeal carcinoma (NPC) is one of the most common malignancies in the head and neck. The aim of the current study was to identify the key pathways and genes involved in NPC through bioinformatics analysis and to identify potential molecular mechanisms underlying NPC proliferation and progression. Three gene expression profiles (GSE12452, GSE34573 and GSE64634) were downloaded from the Gene Expression Omnibus database. A total of 76 samples were analyzed, of which 59 were NPC samples and 17 were normal samples. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were subsequently conducted. The protein-protein interaction (PPI) network of the differentially expressed genes (DEGs) was constructed using Cytoscape software. Analysis of GSE12452, GSE34573 and GSE64634 datasets identified 1,301 (553 upregulated and 748 downregulated), 1,232 (348 upregulated and 884 downregulated) and 1,218 (555 upregulated and 663 downregulated) DEGs, respectively. Using Venn diagram analysis, 268 DEGs (59 upregulated and 209 downregulated) that intersected all three datasets, were selected for further analysis. The results of GO analysis revealed that upregulated DEGs were significantly enriched in biological processes, including 'cell adhesion', 'cell division', 'mitosis' and 'mitotic cell cycle'. The downregulated DEGs were mainly enriched in 'microtubule-based movement', 'cilium movement', 'cilium axoneme assembly' and 'epithelial cell differentiation'. The KEGG pathway analysis results revealed that the upregulated DEGs were highly associated with several pathways, including 'extracellular matrix-receptor interaction', 'human papillomavirus infection', 'arrhythmogenic right ventricular cardiomyopathy' and 'focal adhesion', whereas the downregulated DEGs were enriched in 'metabolic pathways', 'Huntington's disease', 'fluid shear stress and atherosclerosis' and 'chemical carcinogenesis'. On the basis of the PPI network of the DEGs, the following top 10 hub genes were identified: Dynein axonemal light intermediate chain 1, dynein axonemal intermediate chain 2, calmodulin 1, coiled-coil domain containing 114, dynein axonemal heavy chain 5, radial spoke head 9 homolog, radial spoke head component 4A, NDC80 kinetochore complex component, thymidylate synthetase and coiled-coil domain containing 39. In conclusion, by performing a comprehensive bioinformatics analysis of DEGs, putative targets that could be used to elucidate the molecular mechanisms underlying NPC were identified.

Microwave digestion was performed to study the pretreatment methods of aluminum-plastic packaging materials (APPMs). Five different digestion reagent combinations and proportions were thoroughly considered. Digestion results indicated that the most suitable reagent combination was sulfuric and nitric acids with the optimal proportion of 1∶7 after the orthogonal experiment. Moreover, the possible reasons of the experimental phenomenon were analyzed. The contents of Pb, Cr, Cd, and As in APPMs were subsequently determined via inductively coupled plasma-mass spectrometry (ICP-MS). The satisfactory linearity of calibration curves was obtained with the linear correlation coefficients above 0.999 5, and the instrument detection limits of Pb, Cr, Cd, and As for the current method were 0.215, 0.067, 0.006 and 0.020 ng·mL-1, respectively. Furthermore, the recoveries of standard addition ranged from 83.8% to 111.6%, and the relative standard deviations ranged from 0.5% to 7.4%. Two independent parallel determination results of Pb, Cr, Cd, and As in APPMs were approaching, and the student’s t-test (confidence level, α=0.05) showed that the determination results had no significant differences. In conclusion, the present method exhibited fine linearity, low detection limit, high recovery, and good precision, which can accurately be utilized to analyze Pb, Cr, Cd, and As elements in APPMs or other similar materials.

Efficacy of thromboelastography (TEG)-derived parameters for the prediction of acute thromboembolism (AT) in patients with non-steroidal anti-inflammatory drug (NSAID)-induced gastrointestinal bleeding (GIB) remains to be determined. A retrospective propensity score matching (PSM) study was performed to evaluate this efficacy. Patients with NSAID-induced GIB (98 with AT; 830 without AT) were matched for age, sex and history of cardiovascular and cerebrovascular diseases using PSM. Multivariate logistic regression was used to determine the efficacy of TEG-derived predictors of AT. Mean Decrease Gini (MDG) coefficients were used to rank the importance of the variables from random forest algorithm results. Univariate analysis indicated that the following indexes were significantly different between the two groups: Reaction time (R value), coagulation forming time, solidification angle, maximum amplitude (MA), coagulation index (CI), hemoglobin levels, D-dimer levels, platelet aggregation test (pAgt) results, fibrinogen levels and Acute Physiology and Chronic Health Evaluation II score (all P

The present study aims to investigate the radiosensitization effect of the migration and invasion inhibitory protein (MIIP) gene on nasopharyngeal carcinoma (NPC) cells. The MIIP gene was transfected into NPC 5-8F and CNE2 cells. The level of MIIP was analyzed by quantitative reverse transcription-polymerase chain reaction analysis and western blot. The changes in radiosensitivity of the cells were analyzed by colony formation assay. The changes in cell apoptosis and cycle distribution following irradiation were detected by flow cytometry. The expression of BCL2 associated X, apoptosis regulator/B-cell lymphoma 2 was evaluated using western blot. DNA damage was analyzed by counting γ-H2AX foci. The expression levels of γ-H2AX were evaluated by immunofluorescence and western blot. In a previous study by the authors, the results indicated that the expression of MIIP gene evidently increased in MIIP-transfected 5-8F (5–8F OE) and MIIP-transfected CNE2 (CNE2 OE) cells compared with the parental or negative control cells. In the present study, the survival rate of 5-8F OE and CNE2 OE cells markedly decreased following irradiation (0, 2, 4, 6 and 8 Gy) compared with the negative control (5–8F NC and CNE2 NC) and the untreated (5–8F and CNE2) groups. The expression of MIIP was able to increase apoptosis, which resulted in G2/M cell cycle arrest and DNA damage repair was attenuated in 5-8F and CNE2 cells following irradiation as measured by the accumulation of γ-H2AX. It was indicated that MIIP expression is associated with the radiosensitivity of NPC cells and has a significant role in regulating cell radiosensitivity.

We apply nonlinear reconstruction to the dark matter density field in redshift space and solve for the nonlinear mapping from the initial Lagrangian position to the final redshift space position. The reconstructed anisotropic field inferred from the nonlinear displacement correlates with the linear initial conditions to much smaller scales than the redshift space density field. The number of linear modes in the density field is improved by a factor of 30-40 after reconstruction. We thus expect this reconstruction approach to substantially expand the cosmological information including baryon acoustic oscillations and redshift space distortions for dense low-redshift large scale structure surveys including for example SDSS main sample, DESI BGS, and 21 cm intensity mapping surveys., Comment: 18 pages, 21 figures, published version. The nonlinear reconstruction code is available at https://github.com/ColdThunder/NR-code

AIM To investigate correlations between diet and prevalence of constipation among elderly people in Beijing. METHODS A total of 2776 (≥ 60 years) were selected in Beijing region for investigation. Data regarding constipation and diet habits was collected via hierarchical status, segmentation and random cluster sampling. Investigation included constipation-related demographic indicators and diet habits. Door-to-door questionnaires and surveys included daily staple food intakes, frequency of fish, egg, fruits and vegetables consumption. Constipation was defined according to the China Chronic Constipation Diagnosis and Treatment Guideline (2013), with the following constipation judgment indicators: decreased defecation frequency, dry and hard stool, and difficulty in defecation. RESULTS The prevalence of constipation among elderly people in Beijing region was 13%. There was a positive correlation between prevalence of constipation and age, but negative correlations between prevalence of constipation and staple food, fish and dietary fibres (fruits and vegetables) intakes. These differences were all statistically significant. CONCLUSION The prevalence of elderly constipation in Beijing region is closely related to diet habits, and is significantly decreased by high staple foods intake, fish eating and high dietary fibres (fruits and vegetables) consumption.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are the popular seed cells for regenerative medicine, and there has been a rapid increase in the number of BM-MSC-based clinical trials. However, the safety of these cells should also be closely studied. In this study, spontaneous calcification of BM-MSCs from rats was evaluated in normoxia (20% O(2)) without osteogenic medium after continuous culture for 21 days; obvious mineralized nodules were observed, which were positive for Alizarin Red, collagen-I (Col-I), osteocalcin (OC) and alkaline phosphatase (ALP), and mainly consisted of C, O and Ca elements. Interestingly, hypoxia (2% O(2)) significantly inhibited this spontaneous calcification. In addition, the ALP and calcium content of rBM-MSCs were sharply reduced. Based on RT-PCR results, the expression of osteogenic genes (Cbfa1/Runx2, Col-I, ALP, and OC) was reduced compared to that in normoxia. These results demonstrate a natural and unique characterization of rat BM-MSCs in normoxia after continuous culture and highlight the inhibiting effects of hypoxia. Finally, this study contributes to the information regarding the application of BM-MSCs in the regeneration of various tissues.

Traditional Herbal Medicine (THM) has many advantages that make it a promising choice for the treatment of ischemic heart disease (IHD). To study the mechanism of IHDs or pharmacological actions of THM, many hypoxia-induced cardiomyocyte injury models have been established. Radix Salvia miltorrhiza (Danshen) was used as a representative of THM. Danshen is a famous medicinal herb widely applied in Asia to relieve ischemic cardiovascular diseases.To investigate the effects of various hypoxic conditions and discuss a suitable hypoxia model, cell viability, apoptosis, release of myocardial injury markers, and mRNA levels of target genes were tested for the first time.Radix Salvia miltorrhiza (Danshen) was purchased from a GMP-compliant producer and both its preparation method and quality control were standardized. Cellular status, such as cell viability, apoptosis, releases of myocardial injury markers, and the mRNA level of target gene were tested by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) method, biochemical analyzer, flow cytometry, Hoechst 33258 staining, and real-time PCR, respectively.Based on our data, we found a treppe response of cardiomyocyte in the hypoxic condition and suggested that 8 h in 2% O2 might be a suitable condition for in vitro pharmacological study of cardiomyocytes.Our findings outlined more extended and in-depth capability of cardiomyocyte suffering from hypoxia, and might be of particular interest due to the high prevalence of THM pharmacological study.

Supplemental Digital Content is available in the text, Gastrointestinal (GI) bleeding is an unwanted side effect common to all chemical types of nonsteroidal anti-inflammatory drugs (NSAIDs), particularly in elderly people. However, the risk factors of GI bleeding associated with NSAIDs for elderly people remain unknown. This study aims to evaluate the risks of GI bleeding associated with NSAIDs in 4728 elderly people over 60 years old based on database from a hospital in Beijing. This retrospective hospital-based study included 4728 patients over 60 years old prescribed with NSAIDs, of which 928 patients had GI bleeding and 3800 did not have. Odds ratios (OR) for the risk of GI bleeding associated with NSAIDs were determined by logistic regression analysis. Mean Decrease Gini (MDG) involved in random forest algorithm was used to rank the associated factors with GI bleeding. In multivariate analysis, family history of GI bleeding (OR, 3.348; P = .000), history of peptic ulcers (OR, 4.068; P = .000), history of cardiovascular and cerebrovascular disease (OR, 1.476; P = .001), diabetes mellitus (OR, 1.408; P = .000), antiplatelet drugs (OR, 3.106; P = .000), Helicobacter pylori infection (OR, 1.312; P = .001), cholesterol level (OR, 0.516; P = .000), upper abdominal discomfort (OR, 3.467; P = .000), anorexia (OR, 2.038; P = .000), and NSAIDs used for 0.5 to 3 months (OR, 0.780; P = .000) were associated with GI bleeding. After ranked the MDG of each factor, the top 5 ranked factors associated with GI bleeding were melena, hematemesis, antiplatelet drugs, cholesterol level, and upper abdominal discomfort. We found that family history of GI bleeding, history of peptic ulcers, history of cardiovascular and cerebrovascular disease, diabetes mellitus, antiplatelet drugs, Helicobacter pylori infection, hypocholesterolemia, and NSAIDs used for 0.5 to 3 months were independent risk factors for GI bleeding on people over 60 years old. Meanwhile, upper abdominal discomfort might be the predictor of GI bleeding associated with NSAIDs elderly users.

Interaction between steel cables and concrete is complicated in prestressed concrete bridges, especially in curved prestressed concrete bridges. The most significant behavior of curved beam bridges under the loads is that, at the same time of vertical flexure, torsion occurs on the cross section, which complicates the mechanical analysis to curved beam bridges. Based on coordinating relations of steel cables and concrete (CRSC), the grillage structure finite-element method was adopted to analyze the spatial effect of curved beam bridges. This way, the effect of all prestressing procedures can be simulated properly, including the prestressing loss due to concrete shrinkage and creep, batch prestressing of the cables, etc. Furthermore, it is effective to analyze the integrated behavior of the combined steel cables space out and concrete. The efficiency and reliability of the CRSC method is demonstrated by our analysis system WXQ2.0 developed for curved-skew bridges.

AIM: To investigate the present situation of elderly constipation in urban and rural areas of the Beijing region. METHODS: A total of 1942 cases (≥ 60 years) were selected in the Beijing region for investigation. Constipation-related data collection was carried out via hierarchical status, segmentation, and random cluster sampling. Patient data concerning constipation-related demographic indicators, education level, occupation, economic status, and history of gastrointestinal disease was obtained via questionnaires and surveys. Constipation was defined according to the Rome III criteria, with the following constipation judgment indicators: defecation less than 3 times per week, stool weight less than 35 g/d, dry and hard stool, and difficulty in defecating during more than 25% of evacuation attempts. RESULTS: Of the 1942 cases, 634 were diagnosed with constipation, and the total prevalence rate was 32.6%, which increased with age. There was a statistically insignificantly higher prevalence of constipation in females (compared to males) and urban areas (compared to rural areas). There was a statistically insignificantly higher prevalence in the illiterate group compared to the literacy group. Those engaged in mental work suffered from statistically significantly higher constipation prevalence than those engaged in physical labor. A total of 1847 cases did not suffer from gastritis, of which 595 cases were constipated; although the prevalence rate was 32.2%, showing a higher incidence of constipation in patients with gastritis, no significant statistical difference between the two groups was found. A total of 59 cases with a past history of biliary tract disease were found, of which 26 had constipation; constipation prevalence was 44.1% (far higher than other groups), which was a statistically significant difference. CONCLUSION: The prevalence of elderly constipation in the Beijing region closely resembles Western countries, and is significantly affected by region, age, and past history of other related illnesses.

To investigate seroepidemiology of cagA(+) and vacA(+) strains of Helicobacter pylori (H. pylori) in an elderly population in Beijing and to determine risk factors for seropositivity.A total of 2006 elderly persons (60 years) were selected using a random cluster sampling method in different parts of the Beijing area (urban, suburban and mountainous districts). Structured questionnaires were completed during home visits, including history of H. pylori infection, history of gastrointestinal diseases, diet types, hygiene habits, occupation and economic status. Blood samples (2 mL) were collected from each participant, and serum IgG antibodies to cagA, vacA and H. pylori urease antigens were measured by immunodetection.The prevalence of H. pylori infection in elderly subjects was 83.4% and the type I H. pylori strain infection rate was 56%. The seroprevalence for type I H. pylori strain infection in urban and suburban districts was higher than that in the mountainous areas (P0.001). Elderly subjects who had previously performed manual labor or were in the young-old age group (age75 years) had a higher seroprevalence of H. pylori infection than those who had previously performed mental labor or were in the oldest-old age group (age ≥ 75 year) (P0.05). The type I H. pylori strain infection rate in the elderly with vegetarian diets was higher than in those eating high-protein foods (P0.001). There was no significant difference in the prevalence of H. pylori strains between male and female elderly participants (P0.05).Type I H. pylori seroprevalence is higher in elderly people. The distribution of strains of H. pylori is significantly affected by age, area and dietary habits.

MSCs (mesenchymal stem cells) may be promising seed cells for tissue regeneration because of their self-renewal and multi-differentiation potential. Shh (sonic hedgehog) is involved in the skeletal formation during embryo development and skeletal regeneration. However, how Shh regulates the biological characteristics of BM-MSCs (bone marrow-derived MSCs) is poorly understood. We have investigated the effect of rShh-N (recombinant N-terminal Shh) on the proliferation and osteogenic differentiation of rBM-MSCs (rat BM-MSCs) in vitro. rBM-MSCs were treated with rShh-N at concentrations up to 200 ng/ml. Proliferation and colony-forming ability of rBM-MSCs were increased in a dose-dependent manner. rShh-N increased the ratio of cells in S and G2/M phase, as well as the number of Ki-67+ cells. In addition, ALP (alkaline phosphatase) activity and matrix mineralization were enhanced by 200 ng/ml rShh-N. Real-time PCR showed that rShh-N (200 ng/ml) up-regulated the expression of genes encoding Cbfa-1 (core-binding factor α1), osteocalcin, ALP and collagen type I in rBM-MSCs. This information reveals some potential of rShh-N in the therapeutics of bone-related diseases.