Search

Abstract Emotions shared by posters on social media can have a profound impact on individuals and society. This was particularly evident during the COVID-19 pandemic. To examine the types, trends, and dynamics of emotions communicated by the public, government, and media, this study collected 67,689 public posts, 36,740 government posts, and 126,988 media posts on Sina Weibo during the first 6 months of the COVID-19 pandemic. The vector autoregression model and Granger causality analysis were used to measure affective agenda networks and examine affective agenda dynamics. The findings show that the public, government, and media predominantly expressed positive emotions on Sina Weibo. The findings also reveal the significant influence of government emotions on media emotions, which subsequently affects public emotions. This study extends agenda-setting theory by integrating the dimension of emotional contagion. It underscores the potential for government and media to shape public emotions during health crises in order to maintain social order and increase compliance with emergency policies.

A k-edge coloring φ of a graph G is injective if φ (e 1) ≠ φ (e 3) for any three consecutive edges e 1 , e 2 and e 3 of a path or a triangle. The injective chromatic index χ i ′ (G) of G is the smallest k such that G admits an injective k-edge coloring. By discharging method, we demonstrate that any graph with maximum degree Δ ≤ 5 has χ i ′ (G) ≤ 12 (resp. 13) if its maximum average degree is less than 20 7 (resp. 3), which improves the results of Zhu (2023). [ABSTRACT FROM AUTHOR]

Background: Pediatric antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is a life-threatening systemic vasculitis featured by liability to renal involvement. However, there are few studies on the risk factors and predictive models for renal outcomes of AAV in children. Methods: Data from 179 AAV children in multiple centers between January 2012 and March 2020 were collected retrospectively. The risk factors and predictive model of end-stage renal disease (ESRD) in AAV were explored. Results: Renal involvement was the most typical manifestation (95.5%), and the crescent was the predominant pathological lesion (84.9%). The estimated glomerular filtration rate (eGFR) was evaluated in 114 patients, of whom 59.6% developed ESRD, and the median time to ESRD was 3.20 months. The eGFR [P = 0.006, odds ratio (OR) = 0.955, 95% confidence interval (CI) = 0.924–0.987] and the percentages of global glomerulosclerosis (pGGS; P = 0.018, OR = 1.060, 95% CI = 1.010–1.112) were independent risk factors for ESRD of renal biopsy. Based on the pGGS and eGFR at renal biopsy, we developed three risk grades of ESRD and one predictive model. The Kaplan‒Meier curve indicated that renal outcomes were significantly different in different risk grades (P < 0.001). Compared with serum creatinine at baseline, the predictive model had higher accuracy (0.86 versus 0.58, P < 0.001) and a lower coefficient of variation (0.07 versus 0.92) in external validation. Conclusions: Renal involvement is the most common manifestation of pediatric AAV in China, of which more than half deteriorates into ESRD. The predictive model based on eGFR at renal biopsy and the pGGS may be stable and accurate in speculating the risk of ESRD in AAV children. 342BNb9AdCycy4MnMisg3F Supplementary file 2 (MP4 18937 KB) [ABSTRACT FROM AUTHOR]

Pevonedistat (TAK924) is a Nedd8-activating enzyme inhibitor with preclinical activity in non-Hodgkin lymphoma (NHL). This open-label, Phase I, multicenter, investigator-sponsored study enrolled patients with relapsed/refractory (R/R) NHL and chronic lymphocytic leukemia (CLL). The primary objective was safety. Pevonedistat was given intravenously on days 1, 3, 5 of a 21-day cycle for 8 cycles at five dose levels (15 to 50 mg/m2); ibrutinib was administered at 420 or 560 mg orally daily continuously. Eighteen patients with NHL were enrolled, including 8 patients with mantle cell lymphoma (MCL) and 4 patients with CLL. One dose-limiting toxicity (mediastinal hemorrhage) occurred at 50 mg/m2 of pevonedistat which is the estimated maximum tolerated dose. Bruising and diarrhea were the most common adverse events (56% and 44%). Atrial fibrillation occurred in 3 patients (17%). Grade ≥3 toxicities included arthralgia, atrial fibrillation, bone pain, diarrhea, hypertension, and mediastinal hemorrhage (one patient each). The overall response rate (ORR) was 65% (100% ORR in MCL). Pevonedistat disposition was not modified by ibrutinib. scRNA-Seq analysis showed that pevonedistat downregulated NFκB signaling in malignant B-cells in vivo. Thus, pevonedistat combined with ibrutinib demonstrated safety and promising early efficacy in NHL and CLL. NAE inhibition downregulated NFκB signaling in vivo. [ABSTRACT FROM AUTHOR]

Immune checkpoint blockade has revolutionized the field of oncology, inducing durable anti-tumour immunity in solid tumours. In patients with advanced prostate cancer, immunotherapy treatments have largely failed1–5. Androgen deprivation therapy is classically administered in these patients to inhibit tumour cell growth, and we postulated that this therapy also affects tumour-associated T cells. Here we demonstrate that androgen receptor (AR) blockade sensitizes tumour-bearing hosts to effective checkpoint blockade by directly enhancing CD8 T cell function. Inhibition of AR activity in CD8 T cells prevented T cell exhaustion and improved responsiveness to PD-1 targeted therapy via increased IFNγ expression. AR bound directly to Ifng and eviction of AR with a small molecule significantly increased cytokine production in CD8 T cells. Together, our findings establish that T cell intrinsic AR activity represses IFNγ expression and represents a novel mechanism of immunotherapy resistance.. Androgen-receptor blockade can overcome immunotherapy resistance in prostate cancer by intrinsically enhancing T cell function and IFNγ responses. [ABSTRACT FROM AUTHOR]

Bulk and single cell measurements are integrated to identify phenotype-associated subpopulations of cells. Single-cell RNA sequencing (scRNA-seq) distinguishes cell types, states and lineages within the context of heterogeneous tissues. However, current single-cell data cannot directly link cell clusters with specific phenotypes. Here we present Scissor, a method that identifies cell subpopulations from single-cell data that are associated with a given phenotype. Scissor integrates phenotype-associated bulk expression data and single-cell data by first quantifying the similarity between each single cell and each bulk sample. It then optimizes a regression model on the correlation matrix with the sample phenotype to identify relevant subpopulations. Applied to a lung cancer scRNA-seq dataset, Scissor identified subsets of cells associated with worse survival and with TP53 mutations. In melanoma, Scissor discerned a T cell subpopulation with low PDCD1/CTLA4 and high TCF7 expression associated with an immunotherapy response. Beyond cancer, Scissor was effective in interpreting facioscapulohumeral muscular dystrophy and Alzheimer's disease datasets. Scissor identifies biologically and clinically relevant cell subpopulations from single-cell assays by leveraging phenotype and bulk-omics datasets. [ABSTRACT FROM AUTHOR]

Young women's breast cancer (YWBC) has poor prognosis and known interactions with parity. Women diagnosed within 5–10 years of childbirth, defined as postpartum breast cancer (PPBC), have poorer prognosis compared to age, stage, and biologic subtype-matched nulliparous patients. Genomic differences that explain this poor prognosis remain unknown. In this study, using RNA expression data from clinically matched estrogen receptor positive (ER+) cases (n = 16), we observe that ER+ YWBC can be differentiated based on a postpartum or nulliparous diagnosis. The gene expression signatures of PPBC are consistent with increased cell cycle, T-cell activation and reduced estrogen receptor and TP53 signaling. When applied to a large YWBC cohort, these signatures for ER+ PPBC associate with significantly reduced 15-year survival rates in high compared to low expressing cases. Cumulatively these results provide evidence that PPBC is a unique entity within YWBC with poor prognostic phenotypes. The molecular differences between postpartum (PPBC) and nulliparous (NPBC) young women breast cancer (YWBC) patients remain unknown. Here the authors perform RNA sequencing and multiplex immunohistochemistry on an FFPE breast cancer cohort and suggest that PPBC is a unique entity within YWBC with poor prognosis. [ABSTRACT FROM AUTHOR]

Aims: Diabetic cardiomyopathy (DCM) is a specific myocardial alteration in patients with diabetics. LncRNA KCNQ1OT1 has been previously demonstrated to be involved in various diabetic complications. Our aims are to further investigate the underlying regulatory mechanisms/pathways of KCNQ1OT1 in DCM. Methods: In vitro and in vivo models of DCM were established in high glucose (HG)-treated human cardiomyocytes and in streptozotocin (STZ)-induced diabetic mice, respectively. Gene and protein expressions were examined by qPCR, western blotting and ELISA. Cell proliferation and apoptosis were determined by CCK8 assay, flow cytometry and TUNEL staining. The association between KCNQ1OT1 and miR-181a-5p, miR-181a-5p and PDCD4 was predicted using bioinformatics methods and subsequently confirmed by dual luciferase reporter and RNA immunoprecipitation assays. Mouse cardiac tissues were collected and analysed using HE staining, Masson's staining and immunohistochemical analysis. Results: KCNQ1OT1 and PDCD4 were upregulated in HG-treated human cardiomyocytes, while miR-181a-5p was downregulated. In addition, KCNQ1OT1 could negatively regulate miR-181a-5p expression; meanwhile, miR-181a-5p also negatively regulated PDCD4 expression. KCNQ1OT1 silencing suppressed the expression of inflammatory cytokines and cell apoptosis in vitro, whereas inhibition of miR-181a-5p abrogated those effects of KCNQ1OT1 knockdown. Moreover, overexpressed PDCD4 abolished the inhibition on inflammation and apoptosis caused by miR-181a-5p overexpression. Finally, KCNQ1OT1 knockdown reduced the expression of PDCD4 via regulating miR-181a-5p and inhibited myocardial inflammation and cardiomyocyte apoptosis in the in vivo DCM model. Conclusions: Our findings suggest that KCNQ1OT1 and its target gene miR-181a-5p regulate myocardial inflammation and cardiomyocyte apoptosis by modulating PDCD4 in DCM. [ABSTRACT FROM AUTHOR]

Tritium with different chemical forms have different effects on the human body. In tritium migration and conversion, soil plays a significant role. In this study, our samples are from the surrounding environment of the Qinshan Nuclear Power Plant, in addition, Qinshan Phase III Nuclear Power Plant is the only heavy water reactor nuclear power plant (CANDU type, 700 MWe) in China. Both tritiated water (HTO) and non-exchangeable organically bound tritium (NE-OBT) were measured at the surface soil (0–2 cm) at 8 sampling sites and their depth profiles in the subsurface 30 cm of soil in two sampling sites around Qinshan Nuclear Power Plant in 2015, 2016 and 2018. The distribution analysis showed the further away from the nuclear power plant, the lower activity concentration of HTO at the surface soil. Also, in the depth profile, the HTO activity concentration decreased as the depth increase. Through soil analysis at different depths of sampling points A and D, it is concluded that the activity concentration of NE-OBT is the largest in the surface soil of the selected sampling points, which is similar to the HTO of most sampling points. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the novel molecular mechanisms of the antioxidant and anti-inflammatory properties of S-allylmercaptocysteine (SAMC) based on a transcriptomic study in a nonalcoholic steatohepatitis (NASH) rat model Methods: NASH was induced in Sprague–Dawley rats by feeding with a high fat diet (HFD) for 12 weeks. 200 mg/kg SAMC was fed by oral gavage for 4 weeks from 9 to 12 week. Results: SAMC co-administration attenuated HFD-induced liver injury, including the increased serum ALT, hepatic oxidative stress and inflammation. Transcriptomic analysis revealed that SAMC dramatically induced the XRE- and ARE-driven drug metabolising enzymes (DMEs) including Akr7a3, Akr1b8, and Nqo1. The nuclear translocation of the upstream regulator of xenobiotics metabolism, AHR, and regulator of antioxidant responses, NRF2, were significantly increased by SAMC treatment. Furthermore, SAMC counteracted the effects of HFD on NF-κB/IκB and NLRP3/6 pathways with decreasing protein levels of ASC, cleaved caspase-1, IL-18, and IL-1β. These results were further verified in another mice NASH model induced by an MCD diet with SAMC co-administration. Conclusion: We propose that SAMC triggers AHR/NRF2-mediated antioxidant responses which may further suppress the NLRP3/6 inflammasome pathway and NF-κB activation, contributing to the improvement of NASH. [ABSTRACT FROM AUTHOR]

Empirical-likelihood-based inference for parameters defined by the general estimating equations of Qin and Lawless (1994) remains an active research topic. When the response is missing at random (MAR) and the dimension of covariate is not low, the authors propose a two-stage estimation procedure by using the dimension-reduced kernel estimators in conjunction with an unbiased estimating function based on augmented inverse probability weighting and multiple imputation (AIPW-MI) methods. The authors show that the resulting estimator achieves consistency and asymptotic normality. In addition, the corresponding empirical likelihood ratio statistics asymptotically follow central chi-square distributions when evaluated at the true parameter. The finite-sample performance of the proposed estimator is studied through simulation, and an application to HIV-CD4 data set is also presented. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Zhejiang University: Science A is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Mizoribine (MZR) is an immunosuppressant used to treat adult nephropathy. There is little experience with the drug in treating Chinese children with frequently relapsing nephrotic syndrome (FRNS). We investigated the efficacy and safety for treating MZR with FRNS. Furthermore, the relationship between efficacy and serum concentration was investigated. Methods: A prospective multicenter observational 12-month study was performed for evaluating the usefulness of MZR with FRNS. Serum MZR concentration was measured, and the relationships between pharmacokinetic parameters (Cmax, AUC), number of relapses, and urinary protein were evaluated. Results: Eighty-two pediatric patients from four hospitals were treated with MZR and prednisone. MZR treatment significantly reduced the number of relapses and steroid doses. A correlation between pharmacokinetic parameters and relapses was observed, which fits well with the sigmoidal Emax model. Even in the relationship between pharmacokinetic parameters and urinary proteins, it was recognized that there was a threshold in the pharmacokinetic parameters for the therapeutic effect similar to the results obtained with the sigmoidal Emax model. Eleven patients (13.4%) experienced mild adverse events. Conclusions: MZR therapy was effective in reducing the number of relapses and steroid doses. No severe adverse reactions were observed. Therapeutically effective serum concentrations were estimated to be Cmax ≥ about 2 μg/mL or AUC ≥ about 10 μg h/mL. MZR and steroid treatment were effective and safe for pediatric FRNS. [ABSTRACT FROM AUTHOR]

Sponsored search auction has been recently studied and auctioneer's revenue is an important consideration in probabilistic single-item second-price auctions. Some papers have analyzed the revenue maximization problem on different methods to bundle contexts. In this paper, we propose a more flexible and natural method which is called the bracketing method.We prove that finding a bracketing scheme that maximizes the auctioneer's revenue is strongly NP-hard. Then, a heuristic algorithm is given. Experiments on three test cases show that the revenue of the optimal bracketing scheme is very close to the optimal revenue without any bundling constraint, and the heuristic algorithm performs very well. Finally, we consider a simpler model that for each row in the valuation matrix, the non-zero cells have the same value. We prove that the revenue maximization problem with K-anonymous signaling scheme and cardinality constrained signaling scheme in this simpler model are both NP-hard. [ABSTRACT FROM AUTHOR]

As the core component of transmission systems, converters are very prone to failure. To improve the accuracy of fault diagnosis for wind power converters, a fault feature extraction method combined with a wavelet transform and compressed sensing theory is proposed. In addition, an improved AdaBoost-SVM is used to diagnose wind power converters. The three-phase output current signal is selected as the research object and is processed by the wavelet transform to reduce the signal noise. The wavelet approximation coefficients are dimensionality reduced to obtain measurement signals based on the theory of compressive sensing. A sparse vector is obtained by the orthogonal matching pursuit algorithm, and then the fault feature vector is extracted. The fault feature vectors are input to the improved AdaBoost-SVM classifier to realize fault diagnosis. Simulation results show that this method can effectively realize the fault diagnosis of the power transistors in converters and improve the precision of fault diagnosis. [ABSTRACT FROM AUTHOR]

We present a highly scalable assay for whole-genome methylation profiling of single cells. We use our approach, single-cell combinatorial indexing for methylation analysis (sci-MET), to produce 3,282 single-cell bisulfite sequencing libraries and achieve read alignment rates of 68 ± 8%. We apply sci-MET to discriminate the cellular identity of a mixture of three human cell lines and to identify excitatory and inhibitory neuronal populations from mouse cortical tissue. [ABSTRACT FROM AUTHOR]

Marine sponges are ancient and simple multicellular filter-feeding invertebrates attached to solid substrates in benthic habitats and host a variety of fungi both inside and on their surface because of its unique ingestion and digest system. Investigation on marine sponge-associated fungi mainly focused on the small molecular metabolites, yet little attention had been paid to the extracellular polysaccharides. In this study, a homogeneous extracellular polysaccharide AS2-1 was obtained from the fermented broth of the marine sponge endogenous fungus Alternaria sp. SP-32 using ethanol precipitation, anion-exchange, and size-exclusion chromatography. Results of chemical and spectroscopic analyses showed that AS2-1 was composed of mannose, glucose, and galactose with a molar ratio of 1.00:0.67:0.35, and its molecular weight was 27.4 kDa. AS2-1 consists of a mannan core and a galactoglucan chain. The mannan core is composed of (1→6)-α-Man p substituted at C-2 by (1→2)-α-Man p with different degrees of polymerization. The galactoglucan chain consists of (1→6)-α-Glc p residues with (1→6)-β-Gal f residues attached to the last glucopyranose residue at C-6. (1→6)-β-Gal f residues have additional branches at C-2 consisting of disaccharide units of (1→2)-β-Gal f and (1→2)-α-Glc p residues. The glucopyranose residue of the galactoglucan chain is linked to the mannan core. AS2-1 possessed a high antioxidant activity as evaluated by scavenging of 1,1-diphenyl-2-picrylhydrazyl and hydroxyl radicals in vitro. AS2-1 was also evaluated for cytotoxic activity on Hela, HL-60, and K562 cell lines by the MTT and SRB methods. The investigation demonstrated that AS2-1 was a novel extracellular polysaccharide with different characterization from extracellular polysaccharides produced by other marine microorganisms. [ABSTRACT FROM AUTHOR]

Tumor suppressors are mostly defined by inactivating mutations in tumors, yet little is known about their epigenetic features in normal cells. Through integrative analysis of 1,134 genome-wide epigenetic profiles, mutations from >8,200 tumor-normal pairs and our experimental data from clinical samples, we discovered broad peaks for trimethylation of histone H3 at lysine 4 (H3K4me3; wider than 4 kb) as the first epigenetic signature for tumor suppressors in normal cells. Broad H3K4me3 is associated with increased transcription elongation and enhancer activity, which together lead to exceptionally high gene expression, and is distinct from other broad epigenetic features, such as super-enhancers. Genes with broad H3K4me3 peaks conserved across normal cells may represent pan-cancer tumor suppressors, such as TP53 and PTEN, whereas genes with cell type-specific broad H3K4me3 peaks may represent cell identity genes and cell type-specific tumor suppressors. Furthermore, widespread shortening of broad H3K4me3 peaks in cancers is associated with repression of tumor suppressors. Thus, the broad H3K4me3 epigenetic signature provides mutation-independent information for the discovery and characterization of new tumor suppressors. [ABSTRACT FROM AUTHOR]

The global shortening of messenger RNAs through alternative polyadenylation (APA) that occurs during enhanced cellular proliferation represents an important, yet poorly understood mechanism of regulated gene expression. The 3? untranslated region (UTR) truncation of growth-promoting mRNA transcripts that relieves intrinsic microRNA- and AU-rich-element-mediated repression has been observed to correlate with cellular transformation; however, the importance to tumorigenicity of RNA 3?-end-processing factors that potentially govern APA is unknown. Here we identify CFIm25 as a broad repressor of proximal poly(A) site usage that, when depleted, increases cell proliferation. Applying a regression model on standard RNA-sequencing data for novel APA events, we identified at least 1,450 genes with shortened 3??UTRs after CFIm25 knockdown, representing 11% of significantly expressed mRNAs in human cells. Marked increases in the expression of several known oncogenes, including cyclin D1, are observed as a consequence of CFIm25 depletion. Importantly, we identified a subset of CFIm25-regulated APA genes with shortened 3??UTRs in glioblastoma tumours that have reduced CFIm25 expression. Downregulation of CFIm25 expression in glioblastoma cells enhances their tumorigenic properties and increases tumour size, whereas CFIm25 overexpression reduces these properties and inhibits tumour growth. These findings identify a pivotal role of CFIm25 in governing APA and reveal a previously unknown connection between CFIm25 and glioblastoma tumorigenicity. [ABSTRACT FROM AUTHOR]

The biological role of interleukin-37 (IL-37) in cancer is large unknown. Through immunohistochemical detection using 163 primary hepatocellular carcinoma (HCC) clinical specimens, we found the expression of IL-37 was decreased in tumor tissues, and the expression level was negatively correlated with tumor size. High expression of IL-37 in HCC tumor tissues was associated with better overall survival (OS) and disease-free survival (DFS). IL-37 expression in tumor tissues was positively associated with the density of tumor-infiltrating CD571natural killer (NK) cells, but not with the CD31and CD81T cells. Consistently, in vitro chemotaxis analysis showed that IL-37- overexpressing HCC cells could recruit more NK cells. The in vivo mouse model experiments also revealed that overexpression IL-37 in HCC cells significantly delayed tumor growth and recruited more NK cells into tumors tissues. Our finding suggested that IL-37 might play an important role for the prognosis of HCC patients via regulating innate immune-action. [ABSTRACT FROM AUTHOR]

Recognition of modified histones by 'reader' proteins plays a critical role in the regulation of chromatin. H3K36 trimethylation (H3K36me3) is deposited onto the nucleosomes in the transcribed regions after RNA polymerase II elongation. In yeast, this mark in turn recruits epigenetic regulators to reset the chromatin to a relatively repressive state, thus suppressing cryptic transcription. However, much less is known about the role of H3K36me3 in transcription regulation in mammals. This is further complicated by the transcription-coupled incorporation of the histone variant H3.3 in gene bodies. Here we show that the candidate tumour suppressor ZMYND11 specifically recognizes H3K36me3 on H3.3 (H3.3K36me3) and regulates RNA polymerase II elongation. Structural studies show that in addition to the trimethyl-lysine binding by an aromatic cage within the PWWP domain, the H3.3-dependent recognition is mediated by the encapsulation of the H3.3-specific 'Ser 31' residue in a composite pocket formed by the tandem bromo-PWWP domains of ZMYND11. Chromatin immunoprecipitation followed by sequencing shows a genome-wide co-localization of ZMYND11 with H3K36me3 and H3.3 in gene bodies, and its occupancy requires the pre-deposition of H3.3K36me3. Although ZMYND11 is associated with highly expressed genes, it functions as an unconventional transcription co-repressor by modulating RNA polymerase II at the elongation stage. ZMYND11 is critical for the repression of a transcriptional program that is essential for tumour cell growth; low expression levels of ZMYND11 in breast cancer patients correlate with worse prognosis. Consistently, overexpression of ZMYND11 suppresses cancer cell growth in vitro and tumour formation in mice. Together, this study identifies ZMYND11 as an H3.3-specific reader of H3K36me3 that links the histone-variant-mediated transcription elongation control to tumour suppression. [ABSTRACT FROM AUTHOR]

Six lanthanide compounds [Ln(HO)]( m-BDTH)·9(HO) where Ln = La ( 1), and [Ln(HO)]( m-BDTH)·9(HO) ( m-BDTH = 1,3-benzeneditetrazol-5-yl) where Ln = Lu ( 2), Yb ( 3), Er ( 4), Ho ( 5) and Y ( 6) were hydrothermally synthesized and characterized by elemental analyses, infrared spectra, powder X-ray diffraction (PXRD) and X-ray single crystal diffraction. PXRD indicates that 2- 6 are isomorphous. Structural analyses reveal that 1 is coordinated by nine water molecules forming a capped-square antiprism, while 2- 6 are coordinated by eight water molecules forming a simple square antiprismatic geometry. Effects of water molecules on thermal stability were also discussed by thermogravimetric (TG), DSC, and PXRD under different temperatures. TG analyses suggest that 1 loses lattice and coordinated water molecules with no diacritical boundary, and 6 removes lattice water molecules first and then coordinated water molecules. DSC and PXRD further confirm the consequence. [ABSTRACT FROM AUTHOR]

Various antidepressants, mainly tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs), have exhibited potent anticancer properties in different cancer cell types. In the present study, desipramine (DMI), a representative of TCAs, was examined with respect to its apoptosis-inducing activity in rat C6 glioma cells and the underlying mechanism of action. DMI induced typical apoptotic morphology of chromatin condensation in rat glioma C6 cells and activated intracellular caspase 9 and caspase 3 with no change in mitochondrial membrane potential. Simultaneously, DMI significantly elevated expression of endoplasmic reticulum stress regulator CHOP/GADD153 and its targeting molecule GADD34. However, knockdown of CHOP by CHOP-specific short interfering RNA (siRNA) could decrease the activity of intracellular caspase 3 and the cytotoxicity of DMI to C6 cells. These results revealed that the CHOP-dependent endoplasmic reticulum (ER) stress pathway is responsible for DMI-induced apoptosis in C6 cells. [ABSTRACT FROM AUTHOR]

Life cycle assessment (LCA) was applied to analyze a food-processing wastewater treatment plant and investigate the economic and environmental effects of the plant. With the long-term operational data of this plant, an inventory of relative inputs, e.g., flow rate, chemical oxygen demand (COD), and suspended solids, etc., and outputs of the plant, e.g., effluent COD and suspended solids, methane production, etc., was compiled. The potential environmental effects associated with those inputs and outputs were evaluated, and the results of the inventory analysis and impact assessment phases of the plant were interpreted. One feature of this study was the assessment of the treatment plant based on both energy and material flows. Another feature was the establishment of an assessment model with an integration of plant operating parameters, system recognition and grey relation. The analytical results are helpful for the design and operation of wastewater treatment plants. [ABSTRACT FROM AUTHOR]

n ultra-low carbon acicular ferrite steel heavy plate was obtained with an advanced thermo-mechanical control process-relaxed precipitation controlled transformation (TMCP-RPC) at Xiangtan Steel, Valin Group. The heavy plate has a tensile strength of approximately 600 MPa with a lower yield ratio. The impact toughness of the heavy plate achieves 280 J at −40°C. The fine-grained mixed microstructures of the heavy plate mainly consist of acicular ferrite, granular bainite, and polygonal ferrite. The high strength and excellent toughness of the heavy plate are attributed to the formation of acicular ferrite microstructure. The prevention of blocks of martensite/retained austenite (M/A) and the higher cleanness are also responsible for the superior toughness. [ABSTRACT FROM AUTHOR]

Modeling of network traffic is a fundamental building block of computer science. Measurements of network traffic demonstrate that self-similarity is one of the basic properties of the network traffic possess at large time-scale. This paper investigates the change of non-stationary self-similarity of network traffic over time, and proposes a method of combining the discrete wavelet transform (DWT) and Schwarz information criterion (SIC) to detect change points of self-similarity in network traffic. The traffic is segmented into pieces around changing points with homogenous characteristics for the Hurst parameter, named local Hurst parameter, and then each piece of network traffic is modeled using fractional Gaussian noise (FGN) model with the local Hurst parameter. The presented experimental performance on data set from the Internet Traffic Archive (ITA) demonstrates that the method is more accurate in describing the non-stationary self-similarity of network traffic. [ABSTRACT FROM AUTHOR]

We report our investigation on electroosmotic flow (EOF) in a wavy channel between a plane wall and a sinusoidal wall. An exact solution is obtained by using complex function formulation and boundary integral method. The effects of the channel width and wave amplitude on the electric field, streamline pattern, and flow field are studied. When a pressure gradient of sufficient strength in the opposite direction is added to an EOF in the wavy channel, various patterns of recirculation regions are observed. Experimental results are presented to validate qualitatively the theoretical description. The solution is further exploited to determine the onset condition of flow recirculation and the size of the recirculation region. It is found that they are dependent on one dimensionless parameter related to forces ( K, the ratio of the pressure force to the electrokinetic force) and two dimensionless parameters related to the channel geometry (α, the ratio of the wave amplitude to the wavelength, and h, the ratio of the channel width to the wavelength). [ABSTRACT FROM AUTHOR]

Abstract  Over the past 6 years, we have generated about 50,000 individual transgenic rice plants by an Agrobacterium-mediated transformation approach with the pER38 activation tagging vector. The vector contains tandemly arranged double 35S enhancers next to the right border of T-DNA. Expression analysis by reverse transcription-PCR indicates that the activation efficiency is high if the genes are located within 7 kb of the inserted double 35S enhancers. Comparative field phenotyping of part of the activation tagging and enhancer trapping populations in two generations (6,000 and 6,400 lines, respectively, in the T0 generation, and 36,000 and 32,000 lines, respectively, in the T1 generation) identified about four hundred dominant mutants. Characterization of a dominant mutant with a large leaf angle (M107) suggests that this mutant phenotype is caused by enhanced expression of CYP724B1/D11. The activation tagging pool described in this paper is a valuable alternative tool for functional analysis of the rice genome. [ABSTRACT FROM AUTHOR]

Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, has long been thought to exert its benefits by reducing cholesterol synthesis, and has been shown to significantly reduce cardiovascular events and mortality in patients with or without coronary artery disease. However, it is still unknown whether acute administration of simvastatin beneficially affects the cardiac function prior or during ischemia–reperfusion. The aim of this study is to evaluate the cardioprotective effect of acute simvastatin treatment on isolated rat hearts or isolated ischemia–reperfusion hearts. Hearts were isolated from male Sprague–Dawley rats and attached to a Langendorff apparatus. The isolated hearts with or without ischemia (15 min) and reperfusion (60 min) were perfused with different concentrations of simvastatin. The parameters of cardiac function (such as left ventricular developed pressure [LVDP], +d p/d t max, and −d p/d t max), heart rate, and coronary flow were recorded. Simvastatin (3–30 µmol/l) significantly increased LVDP, +d p/d t max, and −d p/d t max in isolated rat hearts perfused for 60 min. Heart rate was depressed by 30 µmol/l simvastatin and the coronary flow was increased by 10 and 30 µmol/l simvastatin. At a concentration of 100 µmol/l simvastatin, worsening of heart function and subsequent cardiac arrest occurred. Administration of simvastatin (3–30 µmol/l) significantly preserved cardiac function detected by LVDP, +d p/d t max, and −d p/d t max in the isolated ischemia/reperfused (15/60 min) rat hearts. Simvastatin also significantly decreased heart rate at 30 µmol/l, and increased coronary flow at 10 and 30 µmol/l in these rat hearts. However, the protective effect of simvastatin reverted to increased damage at 100 µmol/l. Only 3 µmol/l simvastatin pretreatment before 15/60 min ischemia–reperfusion altered LVDP, +d p/d t max, and −d p/d t max. Both heart rate and coronary flow were unaltered after simvastatin pretreatment. Since simvastatin at a concentration lower than 100 µmol/l exerted beneficial effects on cardiac function in isolated perfused rat hearts, it could be applied just after myocardial ischemia and reperfusion. [ABSTRACT FROM AUTHOR]

To investigate the effect of simvastatin on the cardiac contractile function and the alteration of gene and protein expression of the sarcoplasmic calcium regulatory proteins, including sarcoplasmic reticulum Ca2+-ATPase (SERCA), phospholamban (PLB), and ryanodine receptor 2 (RyR2) in rat hearts. Langendorff-perfused rat hearts were subjected to 60-min perfusion with different concentrations of simvastatin (1, 3, 10, 30, or 100 μmol/L), and the parameters of cardiac function such as left ventricular developed pressure (LVDP), + dp/dtmax, and -dp/dtmax were determined. The cultured neonatal rat ventricular cardiomyocytes were incubated with simvastatin (1,3,10,30, and 100 μmol/L) for 1 h or 24 h. The levels of SERCA, PLB, and RyR2 expression were measured by reverse transcription-polymerase chain reaction and Western blot. Cytotoxic effect of simvastatin on ventricular cardiomyocytes was assessed by the MTT colorimetric assay. LVDP, + dp/dtmax, and -dp/dtmax of hearts were increased significantly after treatment with simvastatin 3, 10, and 30 μmol/L. In simvastatin-treated isolated hearts, the levels of mRNA expression of SERCA and RyR2 were elevated compared with the control (P<0.05), while the mRNA expression of PLB did not change. After the cultured neonatal rat ventricular cardiomyocytes were incubated with 3,10,30, and 100 μmol/L simvastatin for 1 h, SERCA and RyR2 mRNA expressions of cardiomyocytes rose, but there was no alteration in protein expressions. However, with the elongation of simvastatin treatment to 24 h, the protein expression of SERCA and RyR2 were also elevated. Additionally, simvastatin (1-30 μmol/L) had no influence on cell viability of cultured cardiac myocytes, but simvastatin 100 μmol/L inhibited the cell viability. Simvastatin improved cardiac performance accompanied by the elevation of SERCA and RyR2 gene and protein expression. [ABSTRACT FROM AUTHOR]

To construct a recombinant adeno-associated virus (rAAV) vector containing gene encoding phospholamban antisense RNA (asPLB), and analyse its effect on expression of PLB, expression and activity of sarco-endoplasmic reticulum Ca2+-ATPase (SERCA), and the change of intracellular free Ca2+ concentration ([Ca2+]i) in rat cardiomyocytes.The target gene encoding PLB antisense RNA was inserted inversely into the adeno-associated virus plasmid pAAV-MCS digested by corresponding restricted endonuclease enzyme. The recombinant plasmid and pAAV-RC and pHelper were co-transfected into 293 cell. At the same time, a viral production positive control (rAAV-LacZ) and negative control were performed. The recombinant viruses were used to transfect the cultured rat cardiomyocytes. Siteβ-Galactosidase staining were performed to observe the transfer efficiency. Reverse transcription-PCR and Western blot were used to determine the mRNA and protein expression of PLB and SERCA. The activity of SERCA and the [Ca2+]i were measured.The rAAV vectors were constructed successfully and were transfected into rat cardiomyocytes effectively. The PLB mRNA and protein expression were reduced in rat cardiomyocytes transfected by rAAV-asPLB compared with controls. The activity of SERCA was increased. In rest state, the level of [Ca2+]i in the rAAV-asPLB transfected group decreased. The level of [Ca2+]i increased when induced by isoproterenol.AAV-asPLB vector was constructed successfully, which disrupted the expression of PLB, enhanced the activity of SERCA, reduced the resting [Ca2+]i, and improved the cardiac function. [ABSTRACT FROM AUTHOR]

Poly ethylene oxide (PEO)x−V2O5−V2O5−MoO3 (x=0, 0.5, 1) films were prepared by the sol-gel method. The synthesis and structure of the films were investigated by XRD, TG-DTA, FTIR, etc. The results show that V2O5−MoO3 xerogel has a layered structure and its interlayer space increased from 1.3181 nm at x=0 to 1. 7898 nm at x=1 after the nanocomposite films were dried, and PEO in the interlayer changes the interface structure by forming hydrogen bonds with V=0 bands. CV measurement indicates that the intercalation of PEO improves insertion/extration properties of Li+ ions in the interlayer. [ABSTRACT FROM AUTHOR]

Pb (Mn1/3Sb2/3) x (Zn1/3Nb2/3) y (Zr0.535Ti0.465)1-x-yO3 (PMZN) piezoelectric ceramics were fabricated. The effects of sintering temperature and heat-treatment time on properties were discussed, the optimum preparation technology parameters were obtained. In this case, the ceramics have the highest electromechanical coupling coefficients and mechanical quality factor and the least dielectric loss. It is revealed that the PMZN piezoceramics material can be utilized for high-power ultrasound transducers. [ABSTRACT FROM AUTHOR]

Some profile of a rock section and some isopleth of a fractured surface of the rock were divided each into three parts. Then three parts were measured by dividers method and lattice method. It was discovered that the fractal dimensions of the three parts were remarkably different, so the fractured surface of rock was not simple fractal but multi-range fractals. [ABSTRACT FROM AUTHOR]

Two successive magnetocaloric effects consisting of inverse magnetocaloric effect around martensitic transition and negative magnetocaloric effect around magnetic transition of austenitic phase have been observed in Ni50Mn34In15Al alloy. Large inverse magnetic entropy change ΔSm ( ~ 21.3 J kg−1 K−1), small thermal and magnetic hysteresis of martensitic transition give rise of large net refrigerant capacity ( ~ 152.3 J kg−1) under a magnetic field of 50 kOe, which is comparable with that ( ~ 157.9 J kg−1) of second-order transition. The large combined magnetocaloric effects make the Ni50Mn34In15Al alloy as a promising candidate material for room temperature magnetic refrigeration. [ABSTRACT FROM AUTHOR]

The scale and severity of soil erosion within the headwaters of the Yangtze River in Yunnan Province are discussed. The Yangtze River rises in the western uplands of the Qinghai-Tibet Plateau and traverses 6380 km through southern and central China. The headwaters are in tectonically active and geologically unstable uplands. The basin is alsogenerally under intensive agricultural use, mainly for rice cultivation. Hence, erosion rates are high and of increasing concern, especially considering the construction of the Three Gorges (Sanxia) Dam in the middle section. Sedimentation within the proposed reservoir couldimpair its efficiency and therefore soil conservation must be an integral component of basin management. Soil conservation efforts in Yunnan are reviewed and the local-scale planned approach to soil conservation is illustrated, using Dongchuan and Xundian as case studies. Anongoing runoff plot study at Yunnan Agricultural University (Kunming) is used to evaluate the effectiveness of various soil conservation measures. Maize (Zea mays) cropping treatments, typically employed inlocal agronomic practices, are applied to 30 erosion plots at 3 different slope angles, cultivated both parallel and perpendicular to thecontour, thus, simulating a range of agricultural conditions on arable slopes. Plot data from 1993-1996 suggest several suitable soil conservation measures. Erosion rates were generally lower on plots wherecontour cultivation was used. The mean contour cultivation erosion rate was 0.69 of the mean downslope orientated cultivation rate. Strawmulch and contour cultivation seem particularly suitable soil conservation measures." [ABSTRACT FROM AUTHOR]