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Hotspot driver mutations presented by human leukocyte antigens might be recognized by anti-tumor T cells. Based on their advantages of tumor-specificity and immunogenicity, neoantigens derived from hotspot mutations, such as PIK3CAH1047L, may serve as emerging targets for cancer immunotherapies. NetMHCpan V4.1 was utilized for predicting neoepitopes of PIK3CA hotspot mutation. Using in vitro stimulation, antigen-specific T cells targeting the HLA-A*11:01-restricted PIK3CA mutation were isolated from healthy donor-derived peripheral blood mononuclear cells. T cell receptors (TCRs) were cloned using single-cell PCR and sequencing. Their functionality was assessed through T cell activation markers, cytokine production and cytotoxic response to cancer cell lines pulsed with peptides or transduced genes of mutant PIK3CA. Immunogenic mutant antigens from PIK3CA and their corresponding CD8+ T cells were identified. These PIK3CA mutation-specific CD8+ T cells were subsequently enriched, and their TCRs were isolated. The TCR clones exhibited mutation-specific and HLA-restricted reactivity, demonstrating varying degrees of functional avidity. Identified TCR genes were transferred into CD8+ Jurkat cells and primary T cells deficient of endogenous TCRs. TCR-expressing cells demonstrated specific recognition and reactivity against the PIK3CAH1047L peptide presented by HLA-A*11:01-expressing K562 cells. Furthermore, mutation-specific TCR-T cells demonstrated an elevation in cytokine production and profound cytotoxic effects against HLA-A*11:01+ malignant cell lines harboring PIK3CAH1047L. Our data demonstrate the immunogenicity of an HLA-A*11:01-restricted PIK3CA hotspot mutation and its targeting therapeutic potential, together with promising candidates of TCR-T cell therapy. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to develop machine learning models for risk prediction of continuous renal replacement therapy (CRRT) following coronary artery bypass grafting (CABG) surgery in intensive care unit (ICU) patients. Methods: We extracted CABG patients from the electronic medical record system of the hospital. The endpoint of this study was the requirement for CRRT after CABG surgery. The Boruta method was used for feature selection. Seven machine learning algorithms were developed to train models and validated using 10 fold cross-validation (CV). Model discrimination and calibration were estimated using the area under the receiver operating characteristic curve (AUC) and calibration plot, respectively. We used the SHapley Additive exPlanations (SHAP) method to illustrate the effects of the features attributed to the model and analyze the effects of individual features on the output of the mode. Results: In this study, 72 (37.89%) patients underwent CRRT, with a higher mortality compared to those patients without CRRT. The Gaussian Naïve Bayes (GNB) model with the highest AUC were considered as the final predictive model and performed best in predicting postoperative CRRT. The analysis of importance revealed that cardiac troponin T, creatine kinase isoenzyme, albumin, low-density lipoprotein cholesterol, NYHA, serum creatinine, and age were the top seven features of the GNB model. The SHAP force analysis illustrated how created model visualized individualized prediction of CRRT. Conclusions: Machine learning models were developed to predict CRRT. This contributes to the identification of risk variables for CRRT following CABG surgery in ICU patients and enables the optimization of perioperative managements for patients. [ABSTRACT FROM AUTHOR]

Simulation models are used to emulate real-world phenomena, and errors are inevitable in the numerical computation process. Owing to that, simulation models need to be verified and validated to ensure the models and their implementations are correct. In this paper, V&V has been done for the micro3d discrete dislocation dynamics (DDD) model by comparing simulation results with corresponding theory, including any analytical solutions, other numerical solutions and experimental data. DDD simulations are a powerful simulation methodology that can help researchers better understand the plastic behavior of crystalline materials. In this study, parametric analyses for DDD simulations parameters have been performed. In addition, simulation results are verified and validated. [ABSTRACT FROM AUTHOR]

IgG4-related disease (IgG4-RD) has complex clinical manifestations ranging from fibrosis and inflammation to deregulated metabolism. The molecular mechanisms underpinning these phenotypes are unclear. In this study, by using IgG4-RD patient peripheral blood mononuclear cells (PBMCs), IgG4-RD cell lines and Usp25 knockout mice, we show that ubiquitin-specific protease 25 (USP25) engages in multiple pathways to regulate fibrotic and inflammatory pathways that are characteristic to IgG4-RD. Reduced USP25 expression in IgG4-RD leads to increased SMAD3 activation, which contributes to fibrosis and induces inflammation through the IL-1β inflammatory axis. Mechanistically, USP25 prevents ubiquitination of RAC1, thus, downregulation of USP25 leads to ubiquitination and degradation of RAC1. Decreased RAC1 levels result in reduced aldolase A release from the actin cytoskeleton, which then lowers glycolysis. The expression of LYN, a component of the B cell receptor signalosome is also reduced in USP25-deficient B cells, which might result in B cell activation deficiency. Altogether, our results indicate a potential anti-inflammatory and anti-fibrotic role for USP25 and make USP25 a promising diagnostic marker and potential therapeutic target in IgG4-RD. [ABSTRACT FROM AUTHOR]

Low-angle grain boundary and twin significantly affect precipitation behavior. Twins were introduced into AZ91 magnesium alloys by pre-rolling. And then, aging treatment was carried out in pre-rolled AZ91 magnesium alloys to investigate the precipitation behavior. The results show that the low-angle grain boundary and the extension twin provide the nucleation position for second phase, while double twin with low-elastic strain energy is not favored for the segregation of Al atom, causing that the precipitate hardly nucleates. Second phase firstly precipitates in the low-angle grain boundary and the twin boundary, followed by precipitating inside the twin. The low-angle grain boundary-induced lath-shaped second phase is attributed to dislocation, while the twin-induced precipitate is mainly affected by dislocation and stacking fault. From thermodynamic perspective, the morphology of twin-induced precipitate firstly displays spherical shape and then grows into lath-like shape. [ABSTRACT FROM AUTHOR]

A cost-effective approach has been developed to synthesize Cu nanoparticles encapsulated into B and N double-doped carbon nanotubes (Cu@BCNNTs) by one-step pyrolysis. According to the specific binding of Cu–Cl and Cu–glutathione (GSH), we employed Cu@BCNNTs to build an electrochemical sensing platform to detect GSH. The unique space-confined structure can prevent Cu nanoparticles from agglomeration. In addition, B and N co-doped porous hollow tubes can improve the electrochemical conductivity, expand the number of active sites, enhance surface adsorption, and shorten the transport path. These favorable characteristics of Cu@BCNNTs make them have excellent electrocatalytic properties. These results display that the prepared sensor can detect GSH from 0.5 to 120 μM with a detection limit of 0.024 μM. The obtained sensors can be successfully applied in the human serum with recovery of GSH ranging from 100.2 to 103.9%. This work provides a new vision to synthesize nanoparticles confined in a hollow tube for the applications in biosensing and medical diagnostics. [ABSTRACT FROM AUTHOR]

Indentation hardness tests are widely used in engineering to test the hardness of a material, which can be performed on a macroscopic scale or microscopic scale. In the present work, copper specimens with different thicknesses were indented with a mechanically-instrumented Rockwell tester. The effects of spacing between indents, indent distance to the edge of the sample, and specimen thickness on the hardness measurement were systematically quantified. Non-linear finite-element modeling was performed, assuming elastic-plastic material response with strain hardening. The two-dimensional numerical modeling of stand-alone and multiple indentations helped to shed more light on the deformation field under indentation, especially the size of the plastic zones and any interaction between them. In addition to the geometric effects, the influence of strain hardening of the test material was also investigated using the finite element analysis. The combined experimental and numerical results provided a range of indent spacings and thicknesses, which yield small to no effect on hardness values. The simulations also quantified the size and shape of the plastic zone under an indent. Lastly, the modeling results showed a competition between the effect of intrinsic material hardening and indent spacing on the value of the measured hardness. [ABSTRACT FROM AUTHOR]

A stable { 1 - 10 } <110> single component sharp texture was obtained during ambient temperature tube High-Pressure Shearing (t-HPS) of 99.999% purity aluminum. It is shown that the grain size and the grain aspect ratio saturate at ~ 8 μm and ~ 1.6, respectively, at an equivalent strain of ~ 30 and the high-angle grain boundary fraction continues to decrease after this saturation even to equivalent strains exceeding ~ 200. The { 1 - 10 } <110> texture emerges at an equivalent strain of ~ 6 to 9 with the completion of recrystallization and develops gradually as a sole component sharp texture with increasing intensity upon further processing. This component is a stable orientation in t-HPS processing although it was not previously observed experimentally as a shear texture. Thus, t-HPS processing provides a new and effective experimental tool for simple shear testing that is distinctly different from earlier shear strain methods such as torsional processing. [ABSTRACT FROM AUTHOR]

Copyright of Rare Metals 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.)

Objectives: Acute respiratory failure (ARF) is a common medical complication in patients with cervical traumatic spinal cord injury (TSCI). To identify independent predictors for ARF onset in patients who underwent cervical TSCI without premorbid respiratory diseases and to apply appropriate medical supports based on accurate prediction, a nomogram relating admission clinical information was developed for predicting ARF during acute care period. Methods: We retrospectively reviewed clinical profiles of patients who suffered cervical TSCI and were emergently admitted to Qingdao Municipal Hospital from 2014 to 2020 as the training cohort. Univariate analysis was performed using admission clinical variables to estimate associated factors and a nomogram for predicting ARF occurrence was generated based on the independent predictors from multivariate logistic regression analysis. This nomogram was assessed by concordance index for discrimination and calibration curve with internal-validated bootstrap strategy. Receiver operating characteristic curve was conducted to compare the predictive accuracy between the nomogram and the traditional gold standard, which combines neuroimaging and neurological measurements by using area under the receiver operating characteristic curve (AUC). An additional 56-patient cohort from another medical center was retrospectively reviewed as the test cohort for external validation of the nomogram. Results: 162 patients were eligible for this study and were included in the training cohort, among which 25 individuals developed ARF and were recorded to endure more complications. Despite the aggressive treatments and prolonged intensive care unit cares, 14 patients insulted with ARF died. Injury level, American Spinal Injury Association Impairment Scale (AIS) grade, admission hemoglobin (Hb), platelet to lymphocyte ratio, and neutrophil percentage to albumin ratio (NPAR) were independently associated with ARF onset. The concordance index of the nomogram incorporating these predictors was 0.933 in the training cohort and 0.955 in the test cohort, although both calibrations were good. The AUC of the nomogram was equal to concordance index, which presented better predictive accuracy compared with previous measurements using neuroimaging and AIS grade (AUC 0.933 versus 0.821, Delong's test p < 0.001). Similar significant results were also found in the test cohort (AUC 0.955 versus 0.765, Delong's test p = 0.034). In addition, this nomogram was translated to a Web-based calculator that could generate individual probability for ARF in a visualized form. Conclusions: The nomogram incorporating the injury level, AIS grade, admission Hb, platelet to lymphocyte ratio, and NPAR is a promising model to predict ARF in patients with cervical TSCI who are absent from previous respiratory dysfunction. This nomogram can be offered to clinicians to stratify patients, strengthen evidence-based decision-making, and apply appropriate individualized treatment in the field of acute clinical care. [ABSTRACT FROM AUTHOR]

Differentiation states of glioma cells correlated with prognosis and tumor-immune microenvironment (TIME) in patients with gliomas. We aimed to identify differentiation related genes (DRGs) for predicting the prognosis and immunotherapy response in patients with gliomas. We identified three differentiation states and the corresponding DRGs in glioma cells through single-cell transcriptomics analysis. Based on the DRGs, we separated glioma patients into three clusters with distinct clinicopathological features in combination with bulk RNA-seq data. Weighted correlation network analysis, univariate cox regression analysis and least absolute shrinkage and selection operator analysis were involved in the construction of the prognostic model based on DRGs. Distinct clinicopathological characteristics, TIME, immunogenomic patterns and immunotherapy responses were identified across three clusters. A DRG signature composing of 12 genes were identified for predicting the survival of glioma patients and nomogram model integrating the risk score and multi-clinicopathological factors were constructed for clinical practice. Patients in high-risk group tended to get shorter overall survival and better response to immune checkpoint blockage therapy. We obtained 9 candidate drugs through comprehensive analysis of the differentially expressed genes between the low and high-risk groups in the model. Our findings indicated that the risk score may not only contribute to the determination of prognosis but also facilitate in the prediction of immunotherapy response in glioma patients. [ABSTRACT FROM AUTHOR]

Because of its convenience and safety, percutaneous balloon compression (PBC) has become a more popular remedy for trigeminal neuralgia (TN) recently. The objective of this study was to establish a nomogram that can be used to preoperatively prognosticate the likelihood of pain-free based on preoperative disease characteristics. Clinical data were collected from those TN cases who had undergone PBC during the period of 2015 and 2020 in Qingdao Municipal Hospital. We excluded the cases caused by space-occupying lesion or had undergone MVD, percutaneous glycerol rhizotomy (PGR), and glycerol rhizotomy (GR). A nomogram was established based on the results of multivariable logistic analysis. A receiver operating characteristic curve (ROC) analysis was applied to evaluate the reliability of models. The plotted decision curves were also used to assess the net benefit of nomogram-assisted decisions. Internal validation was performed using the ROC by bootstrap sampling. Finally, 16 cases and 69 cases were included into the ineffective and effective groups respectively. In the crude, adjust I and adjust II models, response to carbamazepine positively, the grade II or III compression severity score, and classical TN type were all considered to be significant predictors of pain relief (BNI grades I–III) at 3 months' follow-up. The AUC, accuracy, specificity, and sensitivity of the nomogram system were 0.83, 0.85, 0.75, and 0.87 respectively for predicting patient outcomes. The decision curves showed good performance for the nomogram system in terms of clinical application, while more research with validation in multiple, external independent patient populations is needed. [ABSTRACT FROM AUTHOR]

Valvuloplasty for rheumatic aortic valve disease remains controversial. We conducted this study to explore whether aortic valvuloplasty is appropriate for the rheumatic population. A comprehensive search was conducted, and 7 eligible retrospective studies were identified from PubMed, Embase, Medline and Cochrane (up to April 7, 2020) according to the inclusion and exclusion criteria. The data for hospital mortality, 5-year survival, 5-year reoperation, aortic insufficiency grade (AIG) and aortic valve gradient (AVG) were extracted by 2 independent reviewers and were analysed to evaluate the safety and availability of aortic valvuloplasty for rheumatic patients. The heterogeneity of the results was estimated using the Q test and I2 statistics. The fixed pooling model was used when I2 ≤ 50%; otherwise, the random pooling model was selected. 7 articles with 418 patients were included. The pooled hospital mortality, 5-year survival and 5-year reoperation rates were 3.2%, 94.5% and 9.9%, respectively. The heterogeneities of the weighted mean differences (WMD) values of the AIG and AVG between preoperation and postoperation were extremely high (I2 = 81.5%, p < 0.001 in AIG, I2 = 97.6%, p = 0.003 in AVG). Subgroup analysis suggested that the AIG and AVG were improved by 3.03 grades (I2 = 0%, p < 0.001) and 3.16 mmHg (I2 = 0%, p < 0.001) in the European group, respectively. In the Asian group, the AIG and AVG were improved by 2.57 grades (I2 = 0%, p < 0.001) and 34.39 mmHg (I2 = 0%, p < 0.001), respectively. Compared with the values at discharge, the AIG was increased by 0.15 grades (I2 = 0%, p = 0.031) and the AVG was still decreased by 2.07 mmHg (I2 = 0%, p = 0.031) at the time of follow up. Valvuloplasty is safe and effective to treat rheumatic aortic insufficiency and stenosis, and the duration of maintenance required to improve stenosis was longer than that of insufficiency. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Central South University 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.)

Whereas loess-mudstone landslides are widely distributed and frequently occurred at the loess Plateau, this type of landslides is hard to detect due to its particularity, and easily generates serious losses. To clarify the shear characteristics and formation mechanism of loess-mudstone landslides, field investigations, ring shear tests and numerical simulation analyses were performed on the loess specimens collected from the Dingjiagou landslide in Yan'an city, China. The test results showed that both the peak strength and residual strength of slip zone soils have a decreasing tendency with moisture content, while the increasing of normal stress caused an increase in the shear strength. These phenomena indicate that the rise in the moisture content induced by precipitation or the decreasing of normal stress due to excavation activities would result in the weakening of slip zone soils. Numerical simulations of the evolution process of slope failure using the finite element method were conducted based on the Mohr-Coulomb criterion. It was found that the heavy precipitation played a more important role in the slope instability compared with the excavation. In addition, the field investigation showed that loess soils with well-developed cracks and underlying mudstone soils provide material base for the formation of loess-mudstone landslides. Finally, the formation mechanism of this type of landslides was divided into three stages, namely, the local deformation stage, the penetration stage, the creeping — sliding stage. This study may provide a basis for understanding the sliding process of loess-mudstone landslides, as well as guidelines for the prevention and mitigation of loess-mudstone landslides. [ABSTRACT FROM AUTHOR]

The rapid development of nanoparticles (NPs) and their broad applications in medicine caused concerns about biological effects and biosafety. Here, the interaction of silver NPs (Ag NPs) and trypsin is studied with ultravioletvisible spectra, circular dichroism, and fluorescence spectra. Trypsin is exposed to various sizes and concentrations of Ag NPs. The intensities of the trypsin ultraviolet-visible absorption peaks are proportional to the Ag NP concentration and size. In the circular dichroism spectra, there was evidence that Ag NPs affected the secondary structure of trypsin. Fluorescence spectra show that the formation of the protein-nanoparticle complexes alters the protein chromophore chemical environment or structure and quenches its fluorescence. Hence, the extent of Ag NP binding of trypsin depends on both NP concentration and size, and changes the Ag NPs physicochemical properties as well as the trypsin secondary structure. With regard to nanomaterial safety, the interaction of NPs with proteins must be explored further for establishing NP toxicity and design guidance. [ABSTRACT FROM AUTHOR]

Background: The role of HOX transcript antisense RNA (HOTAIR) has been proven to be important in tumorigenesis. However, how this molecule promotes metastasis and invasion in PCa is still unclear.Methods: The relationship between HOTAIR and hepatocellular adhesion molecule (hepaCAM) in PCa was identified by immunohistochemistry, immunofluorescence, plasmid transfection, quantitative real-time PCR and immunoblotting. The regulatory effects of HOTAIR on hepaCAM and MAPK signalling and their key roles in PCa metastasis were investigated in vitro.Results: The expression of HOTAIR was inversely correlated with hepaCAM in the blood and tissue of PCa patients. Here, hepaCAM was identified as a novel target gene of HOTAIR and was critical for the invasiveness of PCa. HOTAIR recruited PRC2 to the hepaCAM promoter, resulting in high levels of H3K27me3 and the absence of hepaCAM with an abnormally activated MAPK pathway. Both HOTAIR depletion and EZH2 inhibition could induce hepaCAM re-expression with inhibitory MAPK signalling and decrease the invasive and metastatic capabilities of PCa cells.Conclusions: This study demonstrates that HOTAIR promotes invasion and metastasis of PCa by decreasing the inhibitory effect of hepaCAM on MAPK signalling. Therefore, the HOTAIR/hepaCAM/MAPK axis may provide a new avenue towards therapeutic strategies and prognostic indicators for advanced prostate cancer. [ABSTRACT FROM AUTHOR]

The effects of Sr and Y on microstructure, tensile property and free bulge formability of AZ31 alloy sheet produced by twin-roll casting and sequential hot rolling were investigated to improve the mechanical properties and formability of the AZ31 alloy. Sr and Y addition can form Al4Sr, Al2Y and Al3Y phases which can impede dislocation movement and promote dynamic recrystallization during the rolling deformation and decrease the lattice resistance to dislocation motion by decreasing Al solubility in the alloy, resulting in finer grains, lower dislocation density and no twinning generating in the twin-roll casting and sequential hot rolling (TRC-HR) AZ31–1.3Sr–1.0Y alloy. The maximum stress and elongation of the alloy increase significantly after adding Sr and Y. The average cavity and grain sizes of the TRC-HR AZ31–1.3Sr–1.0Y alloy are smaller, resulting in higher elongation in the alloy. The addition of Y and Sr can effectively improve the free bulge formability and the thickness uniform of the alloy. The Al4Sr, Al2Y and Al3Y phases can inhibit the grain growth by obstructing dislocation motion or grain boundary slip, resulting in smaller grain size of AZ31–1.3Sr–1.0Y alloy bulge parts. [ABSTRACT FROM AUTHOR]

The development of massively parallel sequencing (MPS) has quickly changed forensic short tandem repeat (STR) genotyping. By providing detailed sequence information, MPS technology may be used as an alternative or additional method to overcome the limitations of capillary electrophoresis-based STR profiling. Most current NGS processes are labour-intensive with regard to library preparation and require high-quality DNA template. In this study, a 16-plex STR typing system (SeqType®R16) was used to achieve direct library preparation without DNA extraction and adaptor ligation. The efficiency of this system was tested in 601 individuals, including 593 old blood samples from the Chinese Han population and eight positive controls. It took approximately 4 hours for library preparation, including blood direct multiplex PCR (1.5 hours), mixing of the product (15 minutes), single tube purification (2 hours) and quantification (15 minutes). The results showed that MPS presented a broader allele range and higher discrimination power. Except for FGA and D19S433, the allele number almost doubled or more than doubled at all complex STR loci and simple STR loci, including D13S317, D16S539, D5S818, and D7S820. The range of discrimination power increased from 0.8008–0.9572 to 0.8401–0.9753, and the culminated matching probability decreased from 1.7 × 10−15 to 1.1 × 10−17. [ABSTRACT FROM AUTHOR]

Rice blast, caused by Magnaporthe oryzae, is a serious threat to global rice production. In recent years, many pathogenicity genes of M. oryzae have been identified, although most of their functions remain unknown. In this study, we report the synergistic deletion of RGS1 and COS1 that may reduce the pathogenicity of M. oryzae. The investigation involved comparing ΔMorgs1, ΔMocos1, and ΔMorgs1/ΔMocos1 mutants. The ΔMorgs1/ΔMocos1 mutant showed a weak reduction in vegetative growth, and the colonies displayed fewer and smoother aerial hyphae. The ΔMorgs1/ΔMocos1 mutant exhibited delayed appressorium-like structure formation and 'low pathogenicity' on detached rice seedling leaves when compared with ΔMocos1. Moreover, the melanin content of the single and double mutants was remarkably lower than that of the WT type. Thus, our results indicate that the synergy between RGS1 and COS1 may be crucial in the pathogenicity of M. oryzae. [ABSTRACT FROM AUTHOR]

Toxocara canis is a zoonotic parasite with worldwide distribution. ATP-binding cassette (ABC) transporters are integral membrane proteins which involve in a range of biological processes in various organisms. In present study, the full-length coding sequence of abcg-5 gene of T. canis (Tc-abcg-5) was cloned and characterized. A 633 aa polypeptide containing two conserved Walker A and Walker B motifs was predicted from a continuous 1902 nt open reading frame. Quantitative real-time PCR was employed to determine the transcriptional levels of Tc-abcg-5 gene in adult male and female worms, which indicated high mRNA level of Tc-abcg-5 in the reproductive tract of adult female T. canis. Tc-abcg-5 was expressed to produce rabbit polyclonal antiserum against recombinant TcABCG5. Indirect-fluorescence immunohistochemical assays were carried out to detect the tissue distribution of TcABCG5, which showed predominant distribution of TcABCG5 in the uterus (especially in the germ cells) of adult female T. canis. Tissue transcription and expression pattern of Tc-abcg-5 indicated that Tc-abcg-5 might play essential roles in the reproduction of this parasitic nematode. [ABSTRACT FROM AUTHOR]

Dissolved black carbon (DBC) is the largest known slow-cycling organic carbon pool in the world's oceans. Atmospheric deposition could significantly contribute to the oceanic DBC pool, but respective information is lacking. Here we estimate that, during the dust outbreak season, the atmospheric dry deposition of water-soluble black carbon (WSBC) is ~ 40% of the riverine input to the China coastal seas. The molecular composition of atmospheric WSBC determined by ultrahigh-resolution mass spectrometry, reveals similar soil-derived sources as for riverine discharge. WSBC is significantly positively correlated with watersoluble organic carbon (WSOC) in marine aerosols, and water-soluble black carbon contributes on average 2.8 ± 0.65% to the total WSOC. Based on this relationship, the global atmospheric deposition of DBC to the ocean is estimated to be 1.8 ± 0.83 Tg yr-1 Anticipated future changes in biomass burning and dust mobilization might increase these numbers, with consequences for regional ecosystems and global carbon reservoirs. [ABSTRACT FROM AUTHOR]

The study of the effects of exogenous abscisic acid (ABA) addition on cadmium (Cd) accumulation of two ecotypes (mining and farmland) of Solanum photeinocarpum was operated through a pot experiment. The results showed that the biomass and chlorophyll content of the two ecotypes of S. photeinocarpum increased with increasing ABA concentration. Applying exogenous ABA increased Cd content in the two ecotypes of S. photeinocarpum. The maximum Cd contents in shoots of the two ecotypes of S. photeinocarpum were obtained at 20 μmol/L ABA; shoot Cd contents respectively for the mining and farmland ecotypes were 33.92 and 24.71% higher than those for the control. Applying exogenous ABA also increased Cd extraction by the two ecotypes of S. photeinocarpum, and the highest Cd extraction was obtained at 20 μmol/L ABA with 569.42 μg/plant in shoots of the mining ecotype and 520.51 μg/plant in shoots of the farmland ecotype respectively. Therefore, exogenous ABA can be used for enhancing the Cd extraction ability of S. photeinocarpum, and 20 μmol/L ABA was the optimal dose. [ABSTRACT FROM AUTHOR]

Low levels of folate combined with high levels of homocysteine may cause unexplained recurrent pregnancy loss (URPL). However, the relationships between polymorphisms in genes of the folate metabolic pathway and URPL remain controversial. We conducted a case-control study to explore polymorphisms of the major folate pathway genes, including methylenetetrahydrofolate reductase (MTHFR) 677C>T, MTHFR 1298A>C, methionine synthase (MTR) 2756A>G, methionine synthase reductase (MTRR) 66A>G and reduced folate carrier 1 (RFC-1) 80A>G, and their associations with URPL. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the distributions of MTHFR, MTR and RFC-1 polymorphisms, and the results were validated using direct sequencing. The polymorphisms in MTRR were determined using direct sequencing. Haplotypes were analyzed using SHEsis, an online tool for biological analysis. We found that the MTHFR 677T allele and the 677T/1298A/2756A/66A/80G haplotype were risk factors for URPL, while the MTR 2756G allele and the 677C/1298A/2756A/66A/80A haplotype exhibited protective effects on susceptibility to URPL in a Chinese Han population from the Hangzhou area. [ABSTRACT FROM AUTHOR]

Background: Ziziphus jujuba Mill. is nutritious and used as food and medicine for more than two thousand years. It has many pharmacological effects, such as elimination of fatigue, dilation of blood vessels, etc. The polysaccharide in it is one of the bioactive substances. In this paper, the ultrasonic extraction effects on the yield and activity of polysaccharide were studied. Results: The optimum ultrasonic extraction conditions were investigated based on a Box-Behnken statistical experimental design. Response surface methodology (RSM) of three factors (ultrasonic power, extraction time and extraction temperature) and three levels was employed to optimize the yield and the antioxidant activity of the polysaccharides. The experimental data were fitted to quadratic response surface models using multiple regression analysis. The best extraction conditions were 120 W, 15 min. and 55°C for highest yield, and 80 W, 15 min. and 40°C for highest hydroxyl radical scavenging activity. Conclusion: The study showed that high ultrasonic power was good for obtaining high yield but bad for keeping the antioxidant activity of the polysaccharides. [ABSTRACT FROM AUTHOR]

Based on the serial-parallel model of single-layer board and the lamination theory, the forces exerted on different layers of the high-pressure hose and the resulting deformations were analyzed when the hose was radially stretched. An equation was proposed to calculate the anisotropic elastic constant of the composite layer with the wound steel wires. Furthermore, the finite element analysis (FEA) model of the high-pressure hose was established, followed by a simulation of the forces that act on different layers, and their deformations. The simulation results show that the stress imposed on the inner reinforced layer and external reinforced layer of the high-pressure hose are approximately 150 MPa and 115 MPa, respectively, in the presence of inner pressure. The stress of the rubber coating and polyethylene coating is lower. The lowest stress occurs on the inner surface of the high-pressure hose and the rubber coating between the two composite layers. The deformation of the rubber layer in the inner surface of the high-pressure hose decreases gradually along the radial direction from the inner surface to the external surface. The deformation of the reinforced composite layer is less than that of the external surface of the rubber coating. The equivalent stress of the reinforced composite layer is higher than that caused by the inner pressure, due to the presence of both inner pressure and axial tension. [ABSTRACT FROM AUTHOR]

Both matrix metalloproteinase-9 (MMP9) and transforming growth factors-β1 (TGF-β1) are the important factors in the pathogenesis of the aortic aneurysm (AA) and aortic dissection (AD). Recent studies have shown that inhibition of reactive oxygen species (ROS) production, extracellular signal-regulated kinase 1/2(ERK1/2) or NF-κB pathways is able to suppress aneurysm formation. The median layers of arterial walls are mainly the vascular smooth muscle cells (VSMCs), while the pathogenesis of AA and AD is closely related to the changes in the median layer structure. Thus, we investigated the molecular mechanisms underlying TGF-β1-induced MMP-9 expression in VSMC, the involvement of intracellular ROS and signaling molecules, including ERK1/2 and NF-κB. Rat vascular smooth muscle cells (A7r5) were used. MMP-9 expression was analyzed by gelatin zymography, western blot and RT-PCR. The involvement of intracellular ROS and signaling molecules including ERK1/2 and NF-κB in the responses was investigated using reactive oxygen scavenger N-acetylcysteine (NAC) and pharmacological inhibitors (U0126 and BAY11-7082), determined by ROS testing and western blot testing for their corresponding proteins. TGF-β1 induces MMP-9 expression via ROS-dependent signaling pathway. ROS production leads to activation of ERK1/2 and then activation of the NF-κB transcription factor. Activated NF-κB turns on transcription of the MMP-9 gene. The process in which TGF-β1 induces MMP9 expression involves the ROS-dependent ERK-NF-κB signal pathways in VSMC. This discovery raises a new regulation pathway in the VSMC, and it shows the potential to help to find a new solution to treating aortic aneurysm and aortic dissection. [ABSTRACT FROM AUTHOR]

Environmental heterogeneity is universal and occurs at various spatial scales. Many studies have examined effects of environmental heterogeneity on growth of individual species, but few have tested the effects on species composition and biomass of plant communities, especially those consisting of submerged macrophytes. Moreover, no study has tested effects of scale of heterogeneity on plant communities. We constructed communities with four submerged macrophytes (i.e., Ceratophyllum demersum, Hydrilla verticillata, Egeria densa and Myriophyllum verticillatum) and subjected the communities to three homogeneous light treatments (100%, 65% and 30% of full light and coded as high, medium and low light treatment, respectively) and two heterogeneous light treatments differing in patch size (large vs. small patch treatment). The total amount of light received by the whole communities in the two patchy treatments was the same as that in the homogeneous medium light treatment. Under homogeneous treatments, decreasing light intensity significantly decreased total biomass, total number of nodes and total shoot length of the submerged macrophyte communities and of H. verticillata and E. densa, but did not significantly affect growth of M. verticillatum or C. demersum. Light heterogeneity, i.e., light patchiness or patch scale, did not affect these three growth variables of the community as well as those of the individual macrophytes. Therefore, light intensity can affect structure and biomass of submerged macrophyte communities, but light heterogeneity may not. [ABSTRACT FROM AUTHOR]

Background and aims: Caloric restriction (CR) extends mammals' lifespans and suppresses ovary development. Sirtuins are involved in these mechanisms. If, and to what extent CR affects ovarian lifespan and follicle development is largely unknown. We investigated the effects of moderate and severe caloric restriction compared with a high-fat dietary regimen on ovarian follicle reserves in rats. Methods: Female Sprague-Dawley rats (n=48) randomly divided into four groups including normal control (NC), 25% caloric restriction (MCR), 45% CR (SCR) and high-fat diet (HF) were maintained on these regimens for 2 months. Results: Histological analysis showed that both the 25 and 45% CR rats had a significantly higher percentage of primordial follicles and a larger number of healthy follicles than the NC rats, whereas the HF rats did not differ significantly from the NC rats. Immunohistochemical analysis revealed that SIRT1 and SIRT6 proteins were present in the nucleus and cytoplasm of the oocytes. The 25% CR diet increased the expression of both SIRT1 and SIRT6 in the ovary, whereas the 45% CR and HF diets caused a decrease in SIRT1 expression. The level of SIRT6 protein did not change with the 45% CR diet, and it appeared slightly lower in the HF than in the NC groups. Conclusions: Caloric restriction may inhibit the transition from primordial to developing follicles and extend the entire growth phase of a follicle to preserve the reserve of germ cells. SIRT1 and SIRT6 are both associated with these effects. [ABSTRACT FROM AUTHOR]

Rice gene Oryza sativa Drought Stress Response-1 ( OsDSR-1) was one of the genes identified to be responsive to drought stress in the panicle of rice at booting and heading stages by both microarray and quantitative real-time PCR analyses. OsDSR-1 encodes a putative calcium-binding protein, and its overexpression in Arabidopsis rendered transgenic plants to produce much shorter lateral roots (LRs) than wild-type (WT) plants in the medium supplemented with abscisic acid (ABA), suggesting that OsDSR-1 may act as a positive regulator during the process of ABA inhibition of LR development. No significant difference was observed in the total LR length between WT and transgenic plants in the media with the increase of only osmotic stress caused by NaCl, LiCl, and mannitol, while transgenic Arabidopsis seedlings appeared to produce larger root systems with longer total LR lengths under high-potassium conditions than WT seedlings. Further analysis showed that external Ca was required for the production of larger root systems, indicating that the promotion by OsDSR-1 of the LR development of transgenic Arabidopsis seemed to occur in a Ca-dependent manner under high-potassium conditions. We propose that OsDSR-1 may function as a calcium sensor of the signal transduction pathway controlling the LR development under high-potassium conditions. [ABSTRACT FROM AUTHOR]

Rhodamine B can be degraded using Prussian blue as a photo-Fenton like reagent under λ > 420 nm visible irradiation. Kinetic studies show ln( C/ C) is linearly proportional to the reaction time during the photo-degradation process; thus, the degradation reaction obeys a pseudo-first order kinetic law. It is very interesting that the presence of salinity such as 0.1 M KCl can speed up greatly the degradation rate: the time to achieve 90.0% degradation ratio is shortened from 120.0 to 40.0 min under comparable conditions, which is very useful in the treatment of wastewaters with high content of salinity. [ABSTRACT FROM AUTHOR]

Hot compression tests of Mg-3Al-1Zn magnesium alloy were performed at temperatures between 300-500 °C and strain rates between 0.03 and 90 s. Dynamic recrystallization of the alloy is developed by the necklace mechanism. At the temperature of 300 °C, structures are fully dynamic recrystallized except at intermediate strain rates. As temperature rises to 400 °C, structures are fully recrystallized at all strain rates. The abnormal grain size increase at high strain rate is attributed to the temperature rising of the deforming sample. [ABSTRACT FROM AUTHOR]

Mutations in the Parkin, PINK1, and DJ-1 genes can cause autosomal recessive early onset Parkinsonism. We studied three families with the mutations of the Parkin, PINK1 and DJ-1 genes, respectively, with a dopamine transporter ligand [(11)C]-CFT positron emission tomography. A marked bilaterally and dissymmetrically decrement of [(11)C]-CFT uptake was found in all these patients, and putamen as well as caudate nucleus was affected. We also found asymptomatic Parkin and PINK1 heterozygotes showed a mild but significant decrement in [(11)C]-CFT uptake, but this phenomenon was not found in the DJ-1-heterozygotes. Our results suggested the three autosomal recessive forms of early onset are similar to each other on pathophysiological grounds, a sub-clinical disease process in Parkin and PINK1-heterozygotes, but not in DJ-1-heterozygotes. [ABSTRACT FROM AUTHOR]

Mutations in the Parkin, PINK1, and DJ- 1 genes can cause autosomal recessive early onset Parkinsonism. We studied three families with the mutations of the Parkin, PINK1 and DJ- 1 genes, respectively, with a dopamine transporter ligand [C]-CFT positron emission tomography. A marked bilaterally and dissymmetrically decrement of [C]-CFT uptake was found in all these patients, and putamen as well as caudate nucleus was affected. We also found asymptomatic Parkin and PINK1 heterozygotes showed a mild but significant decrement in [C]-CFT uptake, but this phenomenon was not found in the DJ- 1-heterozygotes. Our results suggested the three autosomal recessive forms of early onset are similar to each other on pathophysiological grounds, a sub-clinical disease process in Parkin and PINK1-heterozygotes, but not in DJ- 1-heterozygotes. [ABSTRACT FROM AUTHOR]

We introduce oriented tree diagram Lie algebras which are generalized from Xu's both upward and downward tree diagram Lie algebras, and study certain numerical invariants of these algebras related to abelian ideals. [ABSTRACT FROM AUTHOR]

The application of strain-based design for pipelines requires comprehensive understanding of the postyield mechanical behavior of materials. In this article, the impact of plastic prestrain on near-neutral pH stress corrosion cracking (SCC) susceptibility of welded X70 steel was investigated with a slow strain rate tensile (SSRT) test. Generally, plastic prestrain reduces the SCC resistance in various welded zones. The SCC susceptibility of the test materials can be put in the following order: heat-affected zone (HAZ) > weld metal (WM) > base metal (BM). Fractographic analysis indicates that there are two cracking modes, mode I and mode II, during SSRT tests. Mode I cracks propagate along the direction perpendicular to the maximum tensile stress, and mode II cracks lie in planes roughly parallel to the plane where the maximum shear exists. The SCC of the BM is governed by mode I cracking and fracture of the HAZ, and the WM is dominated by mode II cracking. Damage analysis shows that the detrimental impact of plastic prestrain on the residual SCC resistance cannot be evaluated with the linear superposition model. A plastic prestrain sensitivity, a material constant independent of plastic prestrain, is proposed to characterize the susceptibility of SCC resistance to plastic prestrain, and it increases with the SCC susceptibility of the steels. The enhanced SCC susceptibility caused by plastic prestrain may be related to an increase in yield strength. The correlation of the ratio of the reduction in area in NS4 solution to that in air ( RA/ RA) with the yield strength is microstructure dependent. [ABSTRACT FROM AUTHOR]

Current GWAS have primarily focused on testing association of single SNPs. To only test for association of single SNPs has limited utility and is insufficient to dissect the complex genetic structure of many common diseases. To meet conceptual and technical challenges raised by GWAS, we suggest gene and pathway-based GWAS as complementary to the current single SNP-based GWAS. This publication develops three statistics for testing association of genes and pathways with disease: linear combination test, quadratic test and decorrelation test, which take correlations among SNPs within a gene or genes within a pathway into account. The null distribution of the suggested statistics is examined and the statistics are applied to GWAS of rheumatoid arthritis in the Wellcome Trust Case–Control Consortium and the North American Rheumatoid Arthritis Consortium studies. The preliminary results show that the suggested gene and pathway-based GWAS offer several remarkable features. First, not only can they identify the genes that have large genetic effects, but also they can detect new genes in which each single SNP conferred a small amount of disease risk, and their joint actions can be implicated in the development of diseases. Second, gene and pathway-based analysis can allow the formation of the core of pathway definition of complex diseases and unravel the functional bases of an association finding. Third, replication of association findings at the gene or pathway level is much easier than replication at the individual SNP level. [ABSTRACT FROM AUTHOR]

Early onset parkinsonism (EOP) has been associated with mutations in the Parkin, PINK1, and DJ- 1 genes. We studied the prevalence of mutations in all three genes in 127 unrelated Chinese patients with apparently sporadic EOP using direct sequencing analysis and real-time quantitative PCR analysis assay. There are 16 patients (12.6%) with mutations of Parkin gene, four patients (3.1%) with mutations of PINK1 gene, and three patients (2.4%) with mutation of DJ- 1 gene. In conclusion, Parkin gene mutation is the most common pathogenic factor in Chinese patients with sporadic EOP. Mutations of DJ- 1 and PINK1 gene are also found in Chinese patients with sporadic EOP. [ABSTRACT FROM AUTHOR]

Prostate cancer (CaP) progresses from prostatic intraepithelial neoplasia through locally invasive adenocarcinoma to castration-resistant metastatic carcinoma. Although radical prostatectomy, radiation and androgen ablation are effective therapies for androgen-dependent CaP, metastatic castration-resistant CaP is a major complication with high mortality. Androgens stimulate growth and survival of prostate epithelium and early CaP. Although most patients initially respond to androgen ablation, many develop castration-resistant CaP within 12–18 months. Despite extensive studies, the mechanisms underlying the emergence of castration-resistant CaP remain poorly understood and their elucidation is critical for developing improved therapies. Curiously, castration-resistant CaP remains androgen-receptor dependent, and potent androgen-receptor antagonists induce tumour regression in castrated mice. The role of inflammation in castration-resistant CaP has not been addressed, although it was reported that intrinsic NF-κB activation supports its growth. Inflammation is a localized protective reaction to injury or infection, but it also has a pathogenic role in many diseases, including cancer. Whereas acute inflammation is critical for host defence, chronic inflammation contributes to tumorigenesis and metastatic progression. The inflammation-responsive IκB kinase (IKK)-β and its target NF-κB have important tumour-promoting functions within malignant cells and inflammatory cells. The latter, including macrophages and lymphocytes, are important elements of the tumour microenvironment, but the mechanisms underlying their recruitment remain obscure, although they are thought to depend on chemokine and cytokine production. We found that CaP progression is associated with inflammatory infiltration and activation of IKK-α, which stimulates metastasis by an NF-κB-independent, cell autonomous mechanism. Here we show that androgen ablation causes infiltration of regressing androgen-dependent tumours with leukocytes, including B cells, in which IKK-β activation results in production of cytokines that activate IKK-α and STAT3 in CaP cells to enhance hormone-free survival. [ABSTRACT FROM AUTHOR]

Despite the great success of genome-wide association studies (GWAS) in identification of the common genetic variants associated with complex diseases, the current GWAS have focused on single-SNP analysis. However, single-SNP analysis often identifies only a few of the most significant SNPs that account for a small proportion of the genetic variants and offers only a limited understanding of complex diseases. To overcome these limitations, we propose gene and pathway-based association analysis as a new paradigm for GWAS. As a proof of concept, we performed a comprehensive gene and pathway-based association analysis of 13 published GWAS. Our results showed that the proposed new paradigm for GWAS not only identified the genes that include significant SNPs found by single-SNP analysis, but also detected new genes in which each single SNP conferred a small disease risk; however, their joint actions were implicated in the development of diseases. The results also showed that the new paradigm for GWAS was able to identify biologically meaningful pathways associated with the diseases, which were confirmed by a gene-set-rich analysis using gene expression data. [ABSTRACT FROM AUTHOR]

AbstractAim:It is unclear why α1D-adrenergic receptors (α1D-ARs) play a critical role in the mediation of peripheral vascular resistance and blood pressure in situ but function inefficiently when studied in vitro. The present study examined the causes for these inconsistencies in native α1-adrenergic functional performance between the vascular smooth muscle and myocytes.Methods:The α1-adrenergic mediated contraction, Ca2+ signaling and the subcellular receptor distribution were evaluated using the Fluo-4, BODIPY-FL prazosin and subtype-specific antibodies.Results:Rat aortic rings and freshly dissociated myocytes displayed contractile and increased intracellular Ca2+ responses to stimulation with phenylephrine (PE, 10 μmol), respectively. However, the PE-induced responses disappeared completely in cultured aortic myocytes, whereas PE-enhanced Ca2+ transients were seen in cultured rat cardiac myocytes. Further studies indicated that α1D-ARs, the major receptor subtype responsible for the α1-adrenergic regulation of aortic contraction, were distributed both intracellularly and at the cell membrane in freshly dispersed aortic myocytes, similar to the α1A-AR subcellular localization in the cultured cardiomyocytes. In the cultured aortic myocytes, however, in addition to a marked decrease in their protein expression relative to the aorta, most labeling signals for α1D-ARs were found in the cytoplasm. Importantly, treating the culture medium with charcoal/dextran caused the reappearance of α1D-ARs at the cell surface and a partial restoration of the Ca2+ signal response to PE in approximately 30% of the cultured cells.Conclusion:Reduction in α1D-AR total protein expression and disappearance from the cell surface contribute to the insensitivity of cultured vascular smooth muscle cells to α1-adrenergic receptor activation. [ABSTRACT FROM AUTHOR]

Histone H3 lysine 4 methylation (H3K4me) has been proposed as a critical component in regulating gene expression, epigenetic states, and cellular identities. The biological meaning of H3K4me is interpreted by conserved modules including plant homeodomain (PHD) fingers that recognize varied H3K4me states. The dysregulation of PHD fingers has been implicated in several human diseases, including cancers and immune or neurological disorders. Here we report that fusing an H3K4-trimethylation (H3K4me3)-binding PHD finger, such as the carboxy-terminal PHD finger of PHF23 or JARID1A (also known as KDM5A or RBBP2), to a common fusion partner nucleoporin-98 (NUP98) as identified in human leukaemias, generated potent oncoproteins that arrested haematopoietic differentiation and induced acute myeloid leukaemia in murine models. In these processes, a PHD finger that specifically recognizes H3K4me3/2 marks was essential for leukaemogenesis. Mutations in PHD fingers that abrogated H3K4me3 binding also abolished leukaemic transformation. NUP98–PHD fusion prevented the differentiation-associated removal of H3K4me3 at many loci encoding lineage-specific transcription factors (Hox(s), Gata3, Meis1, Eya1 and Pbx1), and enforced their active gene transcription in murine haematopoietic stem/progenitor cells. Mechanistically, NUP98–PHD fusions act as ‘chromatin boundary factors’, dominating over polycomb-mediated gene silencing to ‘lock’ developmentally critical loci into an active chromatin state (H3K4me3 with induced histone acetylation), a state that defined leukaemia stem cells. Collectively, our studies represent, to our knowledge, the first report that deregulation of the PHD finger, an ‘effector’ of specific histone modification, perturbs the epigenetic dynamics on developmentally critical loci, catastrophizes cellular fate decision-making, and even causes oncogenesis during mammalian development. [ABSTRACT FROM AUTHOR]