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Lung cancer is the world’s highest morbidity and mortality of malignant tumors, with lung adenocarcinoma (LUAD) as a major subtype. The competitive endogenous RNA (ceRNA) regulative network provides opportunities to understand the relationships among different molecules, as well as the regulative mechanisms among them in order to investigate the whole transcriptome landscape in cancer pathology. We designed this work to explore the role of a key oncogene, MYC, in the pathogenesis of LUAD, and this study aims to identify important long noncoding RNA (lncRNA)-microRNA (miRNA)- transcription factor (TF) interactions in non-small cell lung cancer (NSCLC) using a bioinformatics analysis. The Cancer Genome Atlas (TCGA) database, containing mRNA expression data of NSCLC, was used to determine the deferentially expressed genes (DEGs), and the ceRNA network was composed of WT1-AS, miR-206, and nicotinamide phosphoribosyltransferase (NAMPT) bashing on the MYC expression level. The Kaplan–Meier univariate survival analysis showed that these components may be closely related prognostic biomarkers and will become new ideas for NSCLC treatment. Moreover, the high expression of WT1-AS and NAMPT and low expression of miR-206 were associated with a shortened survival in NSCLC patients, which provided a survival advantage. In summary, the current study constructing a ceRNA-based WT1-AS/miR-206/NAMPT axis might be a novel important prognostic factor associated with the diagnosis and prognosis of LUAD.

Predicting Click-Through Rate (CTR) is crucial in product and content recommendation, as it involves estimating the likelihood of a user engaging with a specific advertisement or content link. This task encompasses understanding the complex cognitive processes behind human interactions with recommended content. Learning varied feature embeddings that reflect different cognitive responses in various circumstances is significantly important. However, traditional methods typically learn fixed feature representations, leading to suboptimal performance. Some recent approaches attempt to address this issue by learning bit-wise weights or augmented embeddings for feature representations, but suffer from uninformative or redundant features in the context. To tackle this problem, inspired by the Global Workspace Theory in conscious processing, which posits that only a specific subset of the product features are pertinent while the rest can be noisy and even detrimental to human-click behaviors, we propose a CTR model that enables Dynamic Embedding Learning with Truncated Conscious Attention for CTR prediction, termed DELTA. DELTA contains two key components:(I) conscious truncation module (CTM), which utilizes curriculum learning to apply adaptive truncation on attention weights to select the most critical feature in the context;(II) explicit embedding optimization (EEO), which applies an auxiliary task during training that directly and independently propagates the gradient from the loss layer to the embedding layer, thereby optimizing the embedding explicitly via linear feature crossing. Extensive experiments on five challenging CTR datasets demonstrate that DELTA achieves new state-of-the-art performance among current CTR methods.

In this study, three kinds of CeO2 were synthesized, and supported PdOx (x = 0,1) catalysts were prepared for benzene catalytic combustion. The samples were characterized by XRD, N2 adsorption/desorption, HRTEM, XPS and H2-TPR. The results show that three kinds of CeO2 with different structures can be formed by different preparation methods. This is mainly reflected in the differences in pore structure, particle size and crystal plane. CeO2-DC obtained from directly calcined Ce(NO3)3·6H2O had the largest pore volume and pore diameter and smallest particle size. CeO2-DC was mainly exposed to the (200) plane. Combined with the results of the ability test, it could be concluded that when Pd2+ and Pd0 exist at the same time, the activity increases with an increase in the proportion of Pd2+. Meanwhile, the structure of CeO2 affects the formation of oxygen vacancies, thereby affecting the adsorption and degradation of benzene. This article reveals that the particle size, crystal planes, oxygen vacancies and proportion of Pd2+ have a great impact on the catalytic combustion of benzene and allow a more comprehensive understanding of the structure–activity relationship, which can guide us to design high-efficiency catalysts targeted to obtain suitable CeO2-based catalysts for the catalytic combustion of benzene.

Abstract Background DNMT3A mutations are frequently discovered in acute myeloid leukemia (AML), associated with poor outcome. Recently, a relapse case report of AML extramedullary disease has showed that AML cells harboring DNMT3A variation were detected in the cerebral spinal fluid. However, whether a causal relationship exists between DNMT3A mutation (D3Amut) and extramedullary infiltration (EMI) is unclear. Methods We took advantage of DNMT3A (R882C) mutation-carrying AML cell strain, that is, OCI-AML3, assessing its migration ability in vitro and in vivo. By RNA interfering technology and a xenograft mouse model, we evaluated the effect of DNMT3A mutation on cell mobility and explored the possible mechanism. Results OCI-AML3 displayed extraordinary migration ability in vitro and infiltrated into meninges of NOD/SCID mice after intravenous transfusion. We found that this leukemic migration or infiltration capacity was significantly compromised by the knockdown of DNMT3A mutant. Notably, TWIST1, a critical inducer of epithelial–mesenchymal transition, which underlies the metastasis of carcinomas, was highly expressed in association with R882 mutations. Abrogation of TWIST1 in DNMT3A mutated cells considerably weakened their mobility or infiltration. Conclusions Our results demonstrate that D3Amut in OCI-AML3 strain enhances leukemic aggressiveness by promoting EMI process, which is partially through upregulating TWIST1.

Type 2 immune responses are viewed as opposites of Type 1 and 17 responses. Here the authors show that activation of Type 2 immunity by helminth infection counteracts the development of inflammatory arthritis, a type 17-mediated pathology, via IL-4/IL-13- STAT6 signalling and eosinophil activation.

Genomic landscapes of 92 adult and 111 pediatric patients with B-cell acute lymphoblastic leukemia (B-ALL) were investigated using next-generation sequencing and copy number alteration analysis. Recurrent gene mutations and fusions were tested in an additional 87 adult and 93 pediatric patients. Among the 29 newly identified in-frame gene fusions, those involving MEF2D and ZNF384 were clinically relevant and were demonstrated to perturb B-cell differentiation, with EP300-ZNF384 inducing leukemia in mice. Eight gene expression subgroups associated with characteristic genetic abnormalities were identified, including leukemia with MEF2D and ZNF384 fusions in two distinct clusters. In subgroup G4 which was characterized by ERG deletion, DUX4-IGH fusion was detected in most cases. This comprehensive dataset allowed us to compare the features of molecular pathogenesis between adult and pediatric B-ALL and to identify signatures possibly related to the inferior outcome of adults to that of children. We found that, besides the known discrepancies in frequencies of prognostic markers, adult patients had more cooperative mutations and greater enrichment for alterations of epigenetic modifiers and genes linked to B-cell development, suggesting difference in the target cells of transformation between adult and pediatric patients and may explain in part the disparity in their responses to treatment.

Quercetin (QE) and resveratrol (RSV) are powerful antioxidants with the potential to protect the testes against ischemia/reperfusion (I/R) injury. We compared their effects in testicular torsion/detorsion (T/D) in adult rats. Twenty-four male Wistar rats were divided into four groups: sham (group A), T/D (group B), T/D treated with QE (group C), and T/D treated with RSV (group D). QE (20 mg kg−1 ) and RSV (20 mg kg−1 ) were injected intra-peritoneally at 60 min of torsion. After 90 min of surgically induced torsion, the testicular cord was restored to its anatomical position. Twenty-four hour after torsion, blood and tissue samples were obtained for further examination. Testicular tissue malondialdehyde (MDA) and nitric oxide (NO) levels and serum total oxidant status (TOS) were higher in group B than in group A (P < 0.05). Group A had higher serum total antioxidant status (TAS) than group B. (P < 0.05) QE and RSV significantly lowered MDA, NO, and TOS levels and TAS consumption (P < 0.05). QE reduced the MDA and TOS levels more than RSV (P < 0.05), but their effects on NO reduction and TAS consumption were similar (P > 0.05). Group A had normal testicular architecture (grade 1). Groups C (mean grade 2.60) and D (mean grade 3.00) had lower testicular injury grades than group B (mean grade 3.45) (P < 0.05). Group C had lower testicular injury grade than group D (P < 0.05). Treatment with QE and RSV protects against I/R injury after testicular T/D. QE may exhibit better function than RSV at the doses tested in this study.

Introduction:Amomum villosum Lour., a herbaceous plant in the ginger family, has been proven to be effective in treating gastrointestinal diseases. It has been listed in the Chinese Pharmacopeia as a legal source of Amomi Fructus. In our previous study, we demonstrated that treatment with extracts of A. villosum prevented the development and progression of intestinal mucositis. In the current study, we aimed to verify and explain the potential beneficial effects of A. villosum on inflammatory bowel disease (IBD).Methods: The effect of water extracts (WEAV) and volatile oil of A. villosum (VOAV) were evaluated on the immunological role of T lymphocytes and intestinal microecology in IBD rats induced with 2,4,6-trinitrobenzenesulfonic acid (TNBS). Body weight, food intake, colon length/weight, and disease activity index (DAI) as well as tissue damage scores were evaluated. The inflammatory response to IBD was assessed by measuring the expression of myeloperoxidase, interleukin (IL)-17 (IL-17), interferon-γ (IFN-γ), IL-10, tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β). The percentage of regulatory CD4+ T cells in rat spleen was measured by flow cytometry and effects on the microbial community were evaluated by 16S rDNA gene sequencing.Results: All TNBS-induced rats showed typical clinical manifestations of IBD. IBD rats in the WEAV and VOAV treatment groups were effective in relieving body weight and appetite loss. Middle and high dosage of VOAV and WEAV significantly reduced the DAI, and tissue damage scores, whereas colon weight/length ratio was increase. All rats in the WEAV and VOAV groups showed significantly decreased IFN-γ levels and increased levels of IL-10 and TGF-β. Moreover, we observed that the percentage of regulatory CD4+ T cells was significantly enhanced during treatment with WEAV. In addition, administration of WEAV and VOAV effectively inhibited the release of enterogenic endotoxin, increased short-chain fatty acid-producing bacteria belonging to Firmicutes and Bacteroidetes, and decreased the abundance of Proteobacteria.Conclusion: Treatment with WEAV and VOAV significantly attenuated intestinal inflammation in IBD rats, which was possibly associated with its regulation on inflammatory cytokine and CD4+CD25+FOXP3+ T cells. Moreover, WEAV and VOAV may help maintaining the balance of intestinal microecology.

As a traditional Chinese medicine, Ganoderma lingzhi has attracted increasing attention for both scientific research and medical application. In this work, in order to improve the production of polysaccharides from an original wide-type (WT) strain (named "RWY-0") of Ganoderma lingzhi, we applied atmospheric-pressure dielectric barrier discharge (DBD) nonthermal plasma to the protoplasts of RWY-0 for mutagenesis treatment. Through a randomly amplified polymorphic DNA (RAPD) assay, at least 10 mutagenic strains were confirmed. They also showed different mycelium characteristics in terms of shape, color, size and biomass in liquid fermentation. The mutant strains were examined by infrared spectroscopy, and based on the established near-infrared (NIR) quantification model, the polysaccharide contents in these mutants were quantitatively evaluated. As a result, we found that the Ganoderma polysaccharide contents in some of the mutant strains were significantly changed compared with that of the original WT strain. The polysaccharide content of RWY-1 G. lingzhi was considerably higher than that of the WT strain, with an increase of 25.6%. Thus, this preliminary work demonstrates the extension of the plasma mutagenesis application in acquiring polysaccharide-enhanced Ganoderma lingzhi mutants and shows the usefulness of NIR spectroscopy in the rapid screening of mutagenic strains for other important ingredients.

Background: Acute promyelocytic leukemia (APL) is a model for synergistic target cancer therapy using all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), which yields a very high 5-year overall survival (OS) rate of 85 to 90%. Nevertheless, about 15% of APL patients still get early death or relapse. We performed this study to address the possible impact of additional gene mutations on the outcome of APL. Methods: We included a consecutive series of 266 cases as training group, and then validated the results in a testing group of 269 patients to investigate the potential prognostic gene mutations, including FLT3-ITD or -TKD, N-RAS, C-KIT, NPM1, CEPBA, WT1, ASXL1, DNMT3A, MLL (fusions and PTD), IDH1, IDH2 and TET2. Results: More high-risk patients (50.4%) carried additional mutations, as compared with intermediate- and low-risk ones. The mutations of epigenetic modifier genes were associated with poor prognosis in terms of disease-free survival in both training (HR = 6.761, 95% CI 2.179–20.984; P = 0.001) and validation (HR = 4.026, 95% CI 1.089–14.878; P = 0.037) groups. Sanz risk stratification was associated with CR induction and OS. Conclusion: In an era of ATRA/ATO treatment, both molecular markers and clinical parameter based stratification systems should be used as prognostic factors for APL.

Plasma homocysteine (Hcy) is a modifiable, independent risk factor for cardiovascular disease (CVD) and is affected by both environmental and genetic factors. This study aimed to describe the gender- and age-specific distribution of Hcy concentration for 1117 subjects aged 10–66 years, a subset of a community-based rural Chinese twin cohort. In addition, we examined environmental and genetic contributions to variances in Hcy concentration by gender and age groups. We found that the distribution pattern for Hcy varied by both age and gender. Males had higher Hcy than females across all ages. Elevated Hcy was found in 43% of male adults and 13% of female adults. Moreover, nearly one fifth of children had elevated Hcy. Genetic factors could explain 52%, 36% and 69% of the variation in Hcy concentration among children, male adults and female adults, respectively. The MTHFR C677T variant was significantly associated with Hcy concentrations. Smokers with the TT genotype had the highest Hcy levels. Overall, our results indicate that elevated Hcy is prevalent in the children and adults in this rural Chinese population. The early identification of elevated Hcy will offer a window of opportunity for the primary prevention of CVD and metabolic syndrome.

Setd2 is known as a histone-H3K36-specific methyltransferase. However, its role in physiological function remains unclear. In this study, we show that Setd2 mainly regulates differentiation of murine embryonic stem cells (mESCs) toward primitive endoderm. Furthermore, we show that downregulated endoderm-related genes in Setd2−/− mESCs are associated with an aberrantly low level of Erk activity and that enforced expression of Fgfr3 can rescue the defective Erk pathway in Setd2−/− mESCs. Interestingly, the transcriptional initiation of Fgfr3 is directly regulated through histone H3K36me3 modification in its distal promoter region by Setd2. These results indicate that Setd2 controls the primitive endoderm differentiation of mESCs by regulating the Fgfr3-Erk signaling.

A series of rare earth elements (REEs)-modified and Mobil Composition of Matter (MCM)-22-supported Pd nanocrystal catalysts were synthesized via a high-temperature solution-phase reduction method and tested for toluene complete oxidation. These catalytic materials were systematically characterized by N2 adsorption/desorption, X-ray powder diffraction (XRD), scanning electron microscopy (SEM), high-resolution transmission electron microscopy (HRTEM), energy-dispersive spectroscopy (EDS), inductively coupled plasma atomic emission spectroscopy (ICP-AES), temperature-programmed surface reaction of toluene (toluene-TPSR) and X-ray photoelectron spectroscopic (XPS) techniques in order to investigate the structure−catalytic property relationship. Moreover, catalysts with an appropriate yttrium content greatly improved the catalytic activity of 0.2%Pd/MCM-22. PdOx (x = 0, 1) nanoparticles, ranging from 3.6 to 6.8 nm, which were well distributed on the surface of MCM-22. Efficient electron transfer from the Pd2+/Pd0 redox cycle facilitated the catalytic oxidation process, and the formation of Pd (or Y) −O−Si bonds improved the high dispersion of the PdOx and Y2O3 particles. Toluene−TPSR experiments suggested that the addition of Y2O3 improved the physical/chemical adsorption of 0.2%Pd/MCM-22, thus increasing the toluene adsorption capacity. Then, 0.2%Pd/7.5%Y/MCM-22 exhibited the highest catalytic performance. In addition, this catalyst maintained 95% conversion with high resistance to water and chlorine poisoning, even after toluene oxidation at 210 °C for 100 h, making it more valuable in practical applications.

Abscisic acid (ABA) plays a central role in the plant response to water deficit by inducing stomatal closure to conserve water when the soil dries. Exogenous ABA was applied at 45 days after sowing (DAS) as a soil drench, the physiological and seed yield response of soybean to exogenous ABA were examined as the soil was drying. Three experiments were conducted using the drought-tolerant soybean cultivar Jindou 19, grown in pots at the Yuzhong Experimental Station of Lanzhou University, China. In experiment 1, plants were exposed to progressive soil drying and leaf ABA concentration, leaf photosynthesis rate, leaf relative water content (RWC) and osmotic adjustment (OA) were measured. In experiment 2, plants were under progressive soil drying and lethal leaf water potential was measured. In experiment 3, flower production and abortion, and grain yield were measured in plants under well-watered (WW), moderate (MWD) and severe water deficits (SWD). Exogenous ABA application increased ABA accumulation in leaves and reduced the rate of soil drying. It also increased leaf photosynthetic rate, stomatal conductance and transpiration rate at 7−10 days after withholding water. The intrinsic and instantaneous water use efficiency (WUE) was consistently higher with exogenous ABA than without ABA as the soil dried. Exogenous ABA increased OA when the leaf relative water content (RWC) decreased at eight days after withholding water, lowering the lethal leaf water potential by 0.4 MPa. Exogenous ABA reduced water use, increased WUE for grain yield under WW and MWD, and had no effect on flower number, flower abortion or grain yield in any water treatment. We concluded that (1) exogenous ABA induced OA, improved leaf photosynthetic rate, leaf water relations and desiccant tolerance, but did not benefit grain yield in soybean under water deficits; (2) exogenous ABA improved the WUE at the leaf level as soil drying and WUE for grain yield under moderate water deficit.

The pantograph arcing phenomenon may shorten the service life of a pantograph and even destroy onboard devices and instruments, due to the irregular motions of the train and the intermittent line–pantograph disconnection. This paper points out that abrupt inductive energy from the magnetizing inductance of the traction transformer can lead to an electromagnetic transient process with unexpected overvoltage across it. Further, a supercapacitor-based power electronic system is proposed, which can not only redirect the inductive energy to the supercapacitor pack through bidirectional converters but also mitigate the overvoltage across the main electrical equipment when pantograph arcing occurs. Simulation results show the overvoltage could be reduced and the energy stored in the supercapacitor which could also be used to provide energy for sensors or other devices.

Glucagon-like peptide-1 receptor (GLP-1R) agonists have emerged as treatment options for type 2 diabetes mellitus (T2DM). Here, we designed a high-throughput GLP-1R extracellular domain (ECD)-based system that enabled the screening of high-potency receptor-biased GLP-1R agonists demonstrating new pharmacological virtues. Firstly, six 12-mer peptides (termed PEP01⁻06), screened from a large phage displayed peptide library were fused to the N-terminus of Exendin-4 (29⁻39) to generate PEP07⁻12. By the use of four lysine-altered PEP07 (PEP13⁻16) as the starting point, a series of fatty chain conjugates (PEP17⁻20) were synthesized and evaluated by in vitro GLP-1R-based cell assays. In addition, the acute and long-term in vivo effects on diet-induced obesity (DIO) mice were further evaluated. All four conjugates showed good receptor activation efficacy, and PEP20 was selected to undergo further assessment. Preclinical experiments in DIO mice demonstrated that PEP20 had significant insulinotropic activities and glucose-lowering abilities. Moreover, a prolonged antidiabetic effect of PEP20 was also observed by the hypoglycemic test in DIO mice. Furthermore, long-term treatment with PEP20 achieved beneficial effects on the food intake, weight gain, hemoglobin A1C (HbA1C) lowering activity, and glucose tolerance compared with the control and was similar to the Liraglutide. In conclusion, PEP20, a GLP-1R ECD-biased agonist, may provide a novel therapeutic approach to T2DM.

Since the time of J. H. van’t Hoff [1], it has been known that chemical equilibrium is dynamic, meaning that at equilibrium, chemical reactions do not cease, but instead the forward and backward reaction rates are equal. The constant concentrations at equilibrium preclude the use of concentrations to measure reaction rates at equilibrium. Therefore, with the exception of a few special cases, no reaction rates at equilibrium have been published in the literature of chemistry, physics, or chemical engineering. Here we report dissolution and precipitation rates at equilibrium for quartz and barite with the isotope-doping method. Experimental data show that dissolution and precipitation rates are equal at equilibrium, indicating the principle of detailed balance (PDB) appear to be applicable at these experimental conditions. The PDB has been a cornerstone for irreversible thermodynamics and chemical kinetics for a long time, and its wide application in geochemistry has mostly been implicit and without experimental testing of its applicability. Nevertheless, many extrapolations based on PDB without experimental validation have far reaching impacts on society’s mega environmental enterprises. The isotope doping method appears to able to test its applicability for a variety of minerals at a wide range of conditions.

A UMTS 900 MHz planning resolution based on the feasibility analysis of UMTS 900 MHz implementation was proposed. The deployment of UMTS 900 MHz in Shekou area in Shenzhen，taking the advantage of 1ow-frequency signa1 diffraction capability，expand the depth of the coverage and also provide an expansion of frequency used for UMTS.