Akt finds its new path to regulate cell cycle through modulating Skp2 activity and its destruction by APC/Cdh1

Skp2 over-expression has been observed in many human cancers. However, the mechanisms underlying elevated Skp2 expression have remained elusive. We recently reported that Akt1, but not Akt2, directly controls Skp2 stability by interfering with its association with APC/Cdh1. As a result, Skp2 degradation is protected in cancer cells with elevated Akt activity. This finding expands our knowledge of how specific kinase cascades influence proteolysis governed by APC/Cdh1 complexes. However, it awaits further investigation to elucidate whether the PI3K/Akt circuit affects other APC/Cdh1 substrates. Our results further strengthen the argument that different Akt isoforms might have distinct, even opposing functions in the regulation of cell growth or migration. In addition, we noticed that Ser72 is localized in a putative Nuclear Localization Sequence (NLS), and that phosphorylation of Ser72 disrupts the NLS and thus promotes Skp2 cytoplasmic translocation. This finding links elevated Akt activity with the observed cytoplasmic Skp2 staining in aggressive breast and prostate cancer patients. Furthermore, it provides the rationale for the development of specific Akt1 inhibitors as efficient anti-cancer therapeutic agents

Preparation of supported skeletal Ni catalyst and its catalytic hydrogenation performance of C9 fraction from coking process

Currently, the inferior compressive strength of traditional Raney-Ni catalyst restricts its application in fixed-bed reactor. To approach this problem a series of supported skeletal Ni catalysts were prepared by mixing pseudo boehmite and Ni-Al alloy powder. In the process,the calcination temperature and atmosphere, mass ratio of pseudo boehmite to Ni-Al alloy powder and the sodium hydroxide solution concentration were investigated. The catalysts characterized by intelligent granule intensity tester(IGIT), scanning electron microscopy(SEM), X-ray photoelectron spectroscopy(XPS), X-ray diffraction (XRD),low temperature nitrogen adsorption, temperature programmed reduction of hydrogen (H2-TPR), and thermogravimetric-differential thermal analysis (TG-DTA).The results were shown that the calcination atmosphere had a considerable impact on the compressive strength of the catalyst. Compared with air atmosphere, the compressive strength of the catalyst increased from 12.62 N/mm to 23.96N/mm, obviously, in argon atmosphere, which was almost twice as much as the former.The inherent reason for this was that the argon obviously inhibited the transform of NiAl3 to Ni2Al3 in which the latter was the key factor to improve compressive strength. Additionally, coke-oven C9 hydrogenation was used to evaluate the performance of the catalyst and the results indicated that the conversion of indene, the key component of coke-oven C9, was as high as 90% in 1000h under the optimum reaction conditions:T=220oC, P(H2)=2.5MPa, H2/oil=200(v/v), LHSV=3.0h-1. Our data demonstrated that the supported skeletal Ni catalyst have a good industrial prospect in the fixed-bed reactor in future

RaSa: Relation and Sensitivity Aware Representation Learning for Text-based Person Search

Text-based person search aims to retrieve the specified person images given a textual description. The key to tackling such a challenging task is to learn powerful multi-modal representations. Towards this, we propose a Relation and Sensitivity aware representation learning method (RaSa), including two novel tasks: Relation-Aware learning (RA) and Sensitivity-Aware learning (SA). For one thing, existing methods cluster representations of all positive pairs without distinction and overlook the noise problem caused by the weak positive pairs where the text and the paired image have noise correspondences, thus leading to overfitting learning. RA offsets the overfitting risk by introducing a novel positive relation detection task (i.e., learning to distinguish strong and weak positive pairs). For another thing, learning invariant representation under data augmentation (i.e., being insensitive to some transformations) is a general practice for improving representation's robustness in existing methods. Beyond that, we encourage the representation to perceive the sensitive transformation by SA (i.e., learning to detect the replaced words), thus promoting the representation's robustness. Experiments demonstrate that RaSa outperforms existing state-of-the-art methods by 6.94%, 4.45% and 15.35% in terms of Rank@1 on CUHK-PEDES, ICFG-PEDES and RSTPReid datasets, respectively. Code is available at: https://github.com/Flame-Chasers/RaSa.Comment: Accepted by IJCAI 2023. Code is available at https://github.com/Flame-Chasers/RaS

Mechanically enhanced electrical conductivity of polydimethylsiloxane-based composites by a hot embossing process

Electrically conductive polymer composites are in high demand for modern technologies, however, the intrinsic brittleness of conducting conjugated polymers and the moderate electrical conductivity of engineering polymer/carbon composites have highly constrained their applications. In this work, super high electrical conductive polymer composites were produced by a novel hot embossing design. The polydimethylsiloxane (PDMS) composites containing short carbon fiber (SCF) exhibited an electrical percolation threshold at 0.45 wt % and reached a saturated electrical conductivity of 49 S/m at 8 wt % of SCF. When reducing the sample thickness from 1.0 to 0.1 mm by the hot embossing process, a compression-induced percolation threshold occurred at 0.3 wt %, while the electrical conductivity was further enhanced to 378 S/m at 8 wt % SCF. Furthermore, the addition of a second nanofiller of 1 wt %, such as carbon nanotube or conducting carbon black, further increased the electrical conductivity of the PDMS/SCF (8 wt %) composites to 909 S/m and 657 S/m, respectively. The synergy of the densified conducting filler network by the mechanical compression and the hierarchical micro-/nano-scale filler approach has realized super high electrically conductive, yet mechanically flexible, polymer composites for modern flexible electronics applications

Skp2 is a Promising Therapeutic Target in Breast Cancer

Breast cancer is the most common type of cancer among American women, and remains the second leading cause of cancer-related death for female in the United States. It has been known that several signaling pathways and various factors play critical roles in the development and progression of breast cancer, such as estrogen receptor, Notch, PTEN, human epidermal growth factor receptor 2, PI3K/Akt, BRCA1, and BRCA2. Emerging evidence has shown that the F-box protein S-phase kinase associated protein 2 (Skp2) also plays an important role in the pathogenesis of breast cancer. Therefore, in this brief review, we summarize the novel functions of Skp2 in the pathogenesis of breast cancer. Moreover, we provide further evidence regarding the state of our knowledge toward the development of novel Skp2 inhibitors especially natural “chemopreventive agents” as targeted approach for the prevention and/or treatment of breast cancer

Global Parameters Sensitivity Analysis and Development of a Two-Dimensional Real-Time Model of Proton-Exchange-Membrane Fuel Cells

This paper presents a 2-D real-time modeling approach for a proton-exchange-membrane fuel cell (PEMFC). The proposed model covers multi-physical domains for both fluidic and electrochemical features, which considers in particular the flow field geometric form of fuel cell. The characteristics of reactant gas convection in the serpentine gas pipeline and diffusion phenomenon through the gas diffusion layer (GDL) are thoroughly considered in fluidic domain model. In addition, a three levels iterative solver is developed in order to accurately calculate the implicit spatial physical quantities distribution in electrochemical domain. Moreover, the proposed 2-D real-time modeling approach uses a numerical method to achieve a fast execution time, and can thus be further easily applied to any real-time control implementation or online diagnostic system. After experimental validation under different fuel cell operating conditions, an iterative Least Angle Regression (LAR) method is used to efficiently and accurately perform the global parameters sensitivity analysis based on Sobol definition. The online analysis results give an insight into the influences of modeling parameters on fuel cell performance. The effect of interactions between parameters’ sensitivities is especially investigated, which can provide useful in- formation for degradation understanding, parameters tuning, re-calibration of the parameters and online prognostic.This work is supported by European Commission H2020 grant ESPESA (H2020-TWINN-2015) EU Grant agreement No: 692224

Treatment of multisegmental vertebral compression, burst fractures, and sandwich vertebra with severe osteoporosis using the PKP technique: a case report and literature review

This study aimed to present a special case of treatment of a patient with multisegmental vertebral compression fracture, burst fracture, and sandwich vertebra and to review the literature on this condition. An 85 year-old female presented with severe low back pain but no radiating pain in the lower extremities. The patient was diagnosed with T12 and L5 vertebral compression fractures, fresh vertebral burst fractures in L2 and L3, and osteoporosis. The focus was on formulating a surgical treatment strategy. At the 12 month follow-up, no neurological deficits were observed, and the chosen surgical treatment approach yielded favorable clinical outcomes. A comprehensive literature review indicates that percutaneous kyphoplasty (PKP) can effectively alleviate pain and ensure safety in managing osteoporotic vertebral burst fractures. While complications remain a theoretical risk, they can be mitigated through meticulous assessment, careful surgical procedures, and appropriate preventive measures. PKP is an effective and safe treatment modality for osteoporotic vertebral burst fractures. Conservative management of sandwich vertebrae can yield positive clinical outcomes, but regular anti-osteoporosis treatment is necessary

Survival, Virulent Characteristics, and Transcriptomic Analyses of the Pathogenic Vibrio anguillarum Under Starvation Stress

Many bacteria have developed strategies for metamorphosis into sophisticated survival forms to survive extended periods of environmental stress. As a global causative agent of vibriosis in marine fish farming, Vibrio anguillarum (V. anguillarum) can efficiently grow and proliferate under environmental stress, but the specific mechanism is not clear. In the present study, survival, virulent characteristics, and transcriptomic analysis of the V. anguillarum BH1 were performed under starvation stress. The results demonstrated that V. anguillarum was still culturable and showed rippled surface after 6 months of starvation. Starved cells maintained their infectivity in half-smooth tongue sole (Cynoglossus semilaevi). Detection of virulence factors and virulence-associated genes in starved cells showed that the starved strain still produced β-hemolysis on rabbit blood agar, caseinase, dnase, and gelatinase, and possessed empA, vah1, vah2, vah3, vah4, vah5, rtxA, flaA, flaD, flaE, virC, tonB, mreB, toxR, rpoS, and ftsZ virulence-related genes. In addition, we first reported the RNA-seq study for V. anguillarum with and without starvation treatment for a period of 6 months and emphasized the regulation of gene expression at the whole transcriptional level. It indicated that V. anguillarum expressed 3,089 and 3,072 genes in the control group and starvation stress group, respectively. The differently expressed genes (DEGs) of the starved strain were thereby identified, including 251 up-regulated genes and 272 down-regulated genes in comparison with the non-starved strain. Gene Ontology (GO) analysis and Kyto Encyclopedia Genes and Genomes (KEGG) enrichment analysis of DEGs were also analyzed. GO functional classification revealed that among the significantly regulated genes with known function categories, more genes affiliated with signal transducer activity, molecular transducer activity, and cell communication were significantly up-regulated, and more genes affiliated with cellular macromolecule, cellular component, and structural molecule activity were significantly down-regulated. In addition, the DEGs involved in the pathway of two-component system was significantly up-regulated, and the pathways of ribosome and flagellar assembly were significantly down-regulated. This study provides valuable insight into the survival strategies of V. anguillarum and suggests that a portion of the bacterial populations may remain pathogenic while persisting under starvation stress by up-regulating or down-regulating a series of genes

An anchoring array assembly method for enhancing the electrical conductivity of composites of polypropylene and hybrid fillers

Constructing an interconnected filler-filler network in a polymer matrix is essential for enhancing the electrical conductivity of polymer composites. This work describes an Anchoring Array Assembly method for distribution of copper particles (CP) and carbon fibers (CF) in a polypropylene (PP) matrix. Constrained by a predesigned array anchoring template, the CP distribution achieved a high packing density in the PP matrix during compression molding which is key for filling the gaps between CFs, as well as for forming an interconnected hybrid filler network. Using the fixed array anchoring design, the dispersion and flow behavior of the conductive fillers and the polymer matrix are critical. When the inclination angle between the groove of the anchor mold and the horizontal plane was greater than 11.5 °, the migration of CP in the molten PP when in the anchor mold during the hot embossing process is restricted. The most conductive composites were obtained when the CPs were densely arranged in a triangular format. The conductive filler network was determined by the preset dense triangular "island-bridge" structure of the customized microarray mold. The conductivity of the composites prepared by the anchoring array assembly method reached 137.70 S/m, some 52 times higher than that prepared by traditional hot embossing methods with the same filler loading

Sin1 phosphorylation impairs mTORC2 complex integrity and inhibits downstream Akt signaling to suppress tumorigenesis

The mechanistic target of rapamycin (mTOR) functions as a critical regulator of cellular growth and metabolism by forming multi-component, yet functionally distinct complexes mTORC1 and mTORC2. Although mTORC2 has been implicated in mTORC1 activation, little is known about how mTORC2 is regulated. Here we report that phosphorylation of Sin1 at T86 and T398 suppresses mTORC2 kinase activity by dissociating Sin1 from mTORC2. Importantly, Sin1 phosphorylation, triggered by S6K or Akt, in a cellular context-dependent manner, inhibits not only insulin/IGF-1-mediated, but also PDGF or EGF-induced Akt phosphorylation by mTORC2, demonstrating a negative regulation of mTORC2 independent of IRS-1 and Grb10. Lastly, a cancer patient-derived Sin1-R81T mutation impairs Sin1 phosphorylation, leading to hyper-mTORC2 activation via bypassing this negative regulation. Together, our work reveals a Sin1 phosphorylation-dependent mTORC2 regulation, providing a potential molecular mechanism by which mutations in the mTORC1/S6K/Sin1 signaling axis might cause aberrant hyper-activation of mTORC2/Akt that facilitates tumorigenesis