Single-Shot Two-Pronged Detector with Rectified IoU Loss

In the CNN based object detectors, feature pyramids are widely exploited to alleviate the problem of scale variation across object instances. These object detectors, which strengthen features via a top-down pathway and lateral connections, are mainly to enrich the semantic information of low-level features, but ignore the enhancement of high-level features. This can lead to an imbalance between different levels of features, in particular a serious lack of detailed information in the high-level features, which makes it difficult to get accurate bounding boxes. In this paper, we introduce a novel two-pronged transductive idea to explore the relationship among different layers in both backward and forward directions, which can enrich the semantic information of low-level features and detailed information of high-level features at the same time. Under the guidance of the two-pronged idea, we propose a Two-Pronged Network (TPNet) to achieve bidirectional transfer between high-level features and low-level features, which is useful for accurately detecting object at different scales. Furthermore, due to the distribution imbalance between the hard and easy samples in single-stage detectors, the gradient of localization loss is always dominated by the hard examples that have poor localization accuracy. This will enable the model to be biased toward the hard samples. So in our TPNet, an adaptive IoU based localization loss, named Rectified IoU (RIoU) loss, is proposed to rectify the gradients of each kind of samples. The Rectified IoU loss increases the gradients of examples with high IoU while suppressing the gradients of examples with low IoU, which can improve the overall localization accuracy of model. Extensive experiments demonstrate the superiority of our TPNet and RIoU loss.Comment: Accepted by ACM MM 202

CDKN1C (p57KIP2) Is a Direct Target of EZH2 and Suppressed by Multiple Epigenetic Mechanisms in Breast Cancer Cells

CDKN1C (encoding tumor suppressor p57KIP2) is a cyclin-dependent kinase (CDK) inhibitor whose family members are often transcriptionally downregulated in human cancer via promoter DNA methylation. In this study, we show that CDKN1C is repressed in breast cancer cells mainly through histone modifications. In particular, we show that CDKN1C is targeted by histone methyltransferase EZH2-mediated histone H3 lysine 27 trimethylation (H3K27me3), and can be strongly activated by inhibition of EZH2 in synergy with histone deacetylase inhibitor. Consistent with the overexpression of EZH2 in a variety of human cancers including breast cancer, CDKN1C in these cancers is downregulated, and breast tumors expressing low levels of CDKN1C are associated with a poor prognosis. We further show that assessing both EZH2 and CDKN1C expression levels as a measurement of EZH2 pathway activity provides a more predictive power of disease outcome than that achieved with EZH2 or CDKN1C alone. Taken together, our study reveals a novel epigenetic mechanism governing CDKN1C repression in breast cancer. Importantly, as a newly identified EZH2 target with prognostic value, it has implications in patient stratification for cancer therapeutic targeting EZH2-mediated gene repression

Efficacy of transcranial direct current stimulation for improving postoperative quality of recovery in elderly patients undergoing lower limb major arthroplasty: a randomized controlled substudy

BackgroundPrevious studies have demonstrated improvements in motor, behavioral, and emotional areas following transcranial direct current stimulation (tDCS), but no published studies have reported the efficacy of tDCS on postoperative recovery quality in patients undergoing lower limb major arthroplasty. We hypothesized that tDCS might improve postoperative recovery quality in elderly patients undergoing lower limb major arthroplasty.MethodsNinety-six patients (≥65 years) undergoing total hip arthroplasty (THA) or total knee arthroplasty (TKA) were randomized to receive 2 mA tDCS for 20 min active-tDCS or sham-tDCS. The primary outcome was the 15-item quality of recovery (QoR-15) score on postoperative day one (Т2). Secondary outcomes included the QoR-15 scores at the 2nd hour (T1), the 1st month (Т3), and the 3rd month (Т4) postoperatively, numeric rating scale scores, and fatigue severity scale scores.ResultsNinety-six elderly patients (mean age, 71 years; 68.7% woman) were analyzed. Higher QoR-15 scores were found in the active-tDCS group at T2 (123.0 [114.3, 127.0] vs. 109.0 [99.3, 115.3]; median difference, 13.0; 95% CI, 8.0 to 17.0; p < 0.001). QoR-15 scores in the active-tDCS group were higher at T1 (p < 0.001), T3 (p = 0.001), and T4 (p = 0.001). The pain scores in the active-tDCS group were lower (p < 0.001 at motion; p < 0.001 at rest). The fatigue degree scores were lower in the active-tDCS group at T1 and T2 (p < 0.001 for each).ConclusiontDCS may help improve the quality of early recovery in elderly patients undergoing lower limb major arthroplasty.Clinical trial registrationThe trial was registered at the China Clinical Trial Center (ChiCTR2200057777, https://www.chictr.org.cn/showproj.html?proj=162744)

Structural Basis and Catalytic Mechanism for the Dual Functional Endo-β-N-Acetylglucosaminidase A

Endo-β-N-acetylglucosaminidases (ENGases) are dual specificity enzymes with an ability to catalyze hydrolysis and transglycosylation reactions. Recently, these enzymes have become the focus of intense research because of their potential for synthesis of glycopeptides. We have determined the 3D structures of an ENGase from Arthrobacter protophormiae (Endo-A) in 3 forms, one in native form, one in complex with Man3GlcNAc-thiazoline and another in complex with GlcNAc-Asn. The carbohydrate moiety sits above the TIM-barrel in a cleft region surrounded by aromatic residues. The conserved essential catalytic residues – E173, N171 and Y205 are within hydrogen bonding distance of the substrate. W216 and W244 regulate access to the active site during transglycosylation by serving as “gate-keepers”. Interestingly, Y299F mutation resulted in a 3 fold increase in the transglycosylation activity. The structure provides insights into the catalytic mechanism of GH85 family of glycoside hydrolases at molecular level and could assist rational engineering of ENGases

The Structural Basis of Gas-Responsive Transcription by the Human Nuclear Hormone Receptor REV-ERBβ

Heme is a ligand for the human nuclear receptors (NR) REV-ERBα and REV-ERBβ, which are transcriptional repressors that play important roles in circadian rhythm, lipid and glucose metabolism, and diseases such as diabetes, atherosclerosis, inflammation, and cancer. Here we show that transcription repression mediated by heme-bound REV-ERBs is reversed by the addition of nitric oxide (NO), and that the heme and NO effects are mediated by the C-terminal ligand-binding domain (LBD). A 1.9 Å crystal structure of the REV-ERBβ LBD, in complex with the oxidized Fe(III) form of heme, shows that heme binds in a prototypical NR ligand-binding pocket, where the heme iron is coordinately bound by histidine 568 and cysteine 384. Under reducing conditions, spectroscopic studies of the heme-REV-ERBβ complex reveal that the Fe(II) form of the LBD transitions between penta-coordinated and hexa-coordinated structural states, neither of which possess the Cys384 bond observed in the oxidized state. In addition, the Fe(II) LBD is also able to bind either NO or CO, revealing a total of at least six structural states of the protein. The binding of known co-repressors is shown to be highly dependent upon these various liganded states. REV-ERBs are thus highly dynamic receptors that are responsive not only to heme, but also to redox and gas. Taken together, these findings suggest new mechanisms for the systemic coordination of molecular clocks and metabolism. They also raise the possibility for gas-based therapies for the many disorders associated with REV-ERB biological functions

Environmental Issues and Challenges of Chinese Abandoned Oil Pipelines

China energy pipeline industry commonly faced with aging and abandonment problem. The research on pipeline abandonment was still in preliminary state, because there are no pipeline abandonment standards and guidelines. The foreign developed countries formulated pipeline abandonment standards, advanced experience and technology of residual cleaning and the crossing section grouting. But it not totally suitable for china because of difference between china and foreign country, such as the pipeline residual has a very high paraffin and resin-asphaltenes content. It is very hard to remove. So china pipeline company faced with many environmental issues and challenges in the pipeline abandonment. Study on abandonment of pipeline was conducted by pipeline company of Petrochina from 2013. A case of Petrochina abandonment pipeline was introduced in the paper, and it showed good effect. Some experience and technology of chemical cleaning were formulated from previous study and several pipeline abandonment projects. The first China industry standard on abandoned pipeline is applying for by pipeline company of Petrochina. This standard will assist pipeline company make pipeline abandonment plan to ensure public safety and environment protection

Cogels of Hyaluronic Acid and Acellular Matrix for Cultivation of Adipose-Derived Stem Cells: Potential Application for Vocal Fold Tissue Engineering

Stem cells based tissue engineering has been one of the potential promising therapies in the research on the repair of tissue diseases including the vocal fold. Decellularized extracellular matrix (DCM) as a promising scaffold has be used widely in tissue engineering; however, it remained to be an important issue in vocal fold regeneration. Here, we applied the hydrogels (hyaluronic acid [HA], HA-collagen [HA-Col], and HA-DCM) to determine the effects of hydrogel on the growth and differentiation of human adipose-derived stem cells (hADSCs) into superficial lamina propria fibroblasts. hADSCs were isolated and characterized by fluorescence-activated cell sorting. The results indicated that HA-DCM hydrogel enhanced cell proliferation and prolonged cell morphology significantly compared to HA and HA-Col hydrogel. Importantly, the differentiation of hADSCs into fibroblasts was also promoted by cogels of HA-Col and HA-DCM significantly. The differentiation of hADSCs towards superficial lamina propria fibroblasts was accelerated by the secretion of HGF, IL-8, and VEGF, the decorin and elastin expression, and the synthesis of chondroitin sulfate significantly. Therefore, the cogel of HA-DCM hydrogel was shown to be outstanding in apparent stimulation of hADSCs proliferation and differentiation to vocal fold fibroblasts through secretion of important growth factors and synthesis of extracellular matrix