A regulator of the protein phosphatase 2A (PP2A), α4, has been implicated in a variety of functions that regulate many cellular processes. To explore the role of α4 in human cell transformation and ...tumorigenesis, we show that α4 is highly expressed in human cells transformed by chemical carcinogens including benzo(a)pyrene, aflatoxin B(1), N-methyl-N'-nitro-N-nitrosoguanidine, nickel sulfate and in several hepatic and lung cancer cell lines. In addition, overexpression of α4 was detected in 87.5% (74/80) of primary hepatocellular carcinomas, 84.0% (21/25) of primary lung cancers and 81.8% (9/11) of primary breast cancers, indicating that α4 is ubiquitously highly expressed in human cancer. Functional studies revealed that elevated α4 expression results in an increase in cell proliferation, promotion of cell survival and decreased PP2A-attributable activity. Importantly, ectopic expression of α4 permits non-transformed human embryonic kidney cells (HEKTER) and L02R cells to form tumors in immunodeficient mice. Furthermore, we show that the highly expressed α4 in transformed cells or human tumors is not regulated by DNA hypomethylation. A microRNA, miR-34b, that suppresses the expression of α4 through specific binding to the 3'-untranslated region of α4 is downregulated in transformed or human lung tumors. Taken together, these observations identify that α4 possesses an oncogenic function. Reduction of PP2A activity due to an enhanced α4-PP2A interaction contributes directly to chemical carcinogen-induced tumorigenesis.
Abstract Background Sarcopenia is a syndrome characterized by progressive and generalized loss of skeletal muscle mass and strength. This study aims to explore the prevalence of sarcopenia in ...overweight and obese gastric cancer (GC) patients and figured out the impacts of sarcopenia on the postoperative complication of overweight and obese GC patients. Methods According to the recommended body-mass index (BMI) for Asian populations by WHO, we conducted a prospective study of overweight and obese gastric cancer patients (BMI ≥ 23kg/m2 ) under curative gastrectomy from August 2014 to December 2015. Including lumbar skeletal muscle index, handgrip strength and gait speed as the sarcopenic components were measured before surgery. Patients were followed up after gastrectomy to gain the actual clinical outcomes. Factors contributing to postoperative complications were analyzed by univariate and multivariate analysis. Results Total of 206 overweight or obese patients were enrolled in this study, 14 patients were diagnosed sarcopenia and were demonstrated having significantly association with higher risk of postoperative complications, higher hospital costs, and higher rate of 30-days readmission compared with the non-sarcopenic ones. On the basis of univariate and multivariate analysis, sarcopenia was an independent risk factor for postoperative complication of overweight and obese patients with gastric cancer ( P = 0.002). Conclusion Sarcopenia is an independent predictor of postoperative complications in overweight or obese patients with gastric cancer after radical gastrectomy.
The independent control of two magnetic electrodes and spin-coherent transport in magnetic tunnel junctions are strictly required for tunneling magnetoresistance, while junctions with only one ...ferromagnetic electrode exhibit tunneling anisotropic magnetoresistance dependent on the anisotropic density of states with no room temperature performance so far. Here, we report an alternative approach to obtaining tunneling anisotropic magnetoresistance in α'-FeRh-based junctions driven by the magnetic phase transition of α'-FeRh and resultantly large variation of the density of states in the vicinity of MgO tunneling barrier, referred to as phase transition tunneling anisotropic magnetoresistance. The junctions with only one α'-FeRh magnetic electrode show a magnetoresistance ratio up to 20% at room temperature. Both the polarity and magnitude of the phase transition tunneling anisotropic magnetoresistance can be modulated by interfacial engineering at the α'-FeRh/MgO interface. Besides the fundamental significance, our finding might add a different dimension to magnetic random access memory and antiferromagnet spintronics.Tunneling anisotropic magnetoresistance is promising for next generation memory devices but limited by the low efficiency and functioning temperature. Here the authors achieved 20% tunneling anisotropic magnetoresistance at room temperature in magnetic tunnel junctions with one α'-FeRh magnetic electrode.
Summary
Erector spinae plane block and paravertebral block can provide analgesia for abdominal surgery. It is unclear whether erector spinae block is inferior to paravertebral block. We aimed to ...determine whether sufentanil dose and pain intensity (11‐point scale) to 24 h after erector spinae block exceeded those after paravertebral block by no more than 5 μg and 1 point, respectively. We randomly allocated 166 adults to 0.4 ml.kg−1 ropivacaine 0.375% before scheduled laparoscopic nephroureterectomy, 83 each to erector spinae or paravertebral injection. We measured incision pain and intra‐abdominal pain at rest and on movement 0.5 h, 2 h, 6 h, 18 h, 24 h and 48 h after surgery. Median (IQR range) cumulative sufentanil dose after erector spinae block was 15 (5–30 0–105) μg vs. 20 (10–50 0–145) μg after paravertebral block, median (95%CI) difference 5 μg (0–10), erector spinae non‐inferiority p < 0.001. Median (IQR range) pain were 1.5 (1.0–2.0 0.0–5.3) after erector spinae block vs. 2.0 (1.0–2.5 0.0–6.0) after paravertebral block, median (95% CI) difference 0.3 (0.0–0.5), erector spinae non‐inferiority p < 0.001. Adverse events did not differ between groups. Erector spinae block analgesia was not inferior to paravertebral block analgesia after laparoscopic nephroureterectomy.
Cloud manufacturing (CM) and Internet of things (IoT) are interlinked, yet most works only focused on one of them and take the other as a constituent technology unit. This is practically inadequate, ...especially for a highly service-driven manufacturing execution system which entails systematical CM supports to respond to the real-time dynamics captured from the IoT-enabled execution hierarchy. To deal with the dynamics occurring in production logistics (PL) processes, this paper investigates a dynamic PL synchronization (PLS) of a manufacturer adopting public PL services. Contemporary CM and IoT infrastructures are systematically integrated to enable a smart PLS control mechanism with multi-level dynamic adaptability. The S-CM operation framework, operation logic, and PLS infrastructure are presented with an industrial case, and the effectiveness is also demonstrated and analyzed.
Evasion of immune system is a hallmark of cancer, which enables cancer cells to escape the attack from immune cells. Cancer cells can express many immune inhibitory signalling proteins to cause ...immune cell dysfunction and apoptosis. One of these inhibitory molecules is programmed death-ligand-1 (PD-L1), which binds to programmed death-1 (PD-1) expressed on T-cells, B-cells, dendritic cells and natural killer T-cells to suppress anti-cancer immunity. Therefore, anti-PD-L1 and anti-PD-1 antibodies have been used for the treatment of cancer, showing promising outcomes. However, only a proportion of patients respond to the treatments. Further understanding of the regulation of PD-L1 expression could be helpful for the improvement of anti-PD-L1 and anti-PD-1 treatments. Studies have shown that PD-L1 expression is regulated by signalling pathways, transcriptional factors and epigenetic factors. In this review, we summarise the recent progress of the regulation of PD-L1 expression in cancer cells and propose a regulatory model for unified explanation. Both PI3K and MAPK pathways are involved in PD-L1 regulation but the downstream molecules that control PD-L1 and cell proliferation may differ. Transcriptional factors hypoxia-inducible factor-1α and signal transducer and activation of transcription-3 act on the promoter of PD-L1 to regulate its expression. In addition, microRNAs including miR-570, miR-513, miR-197, miR-34a and miR-200 negatively regulate PD-L1. Clinically, it could increase treatment efficacy of targeted therapy by choosing those molecules that control both PD-L1 expression and cell proliferation.
Toll-like receptor 4 (TLR4)-tumor necrosis factor receptor 6 (TRAF6) signaling is activated in atherosclerosis (AS), inducing inflammatory mediators. Because miR-146a, a TLR4 microRNA (miRNA), can ...regulate TLR4 signaling during inflammatory responses, this study investigated the effects of aerobic exercise on TLR4-targeted miRNAs in AS. Apolipoprotein E-null mice fed a high-fat diet for 12 weeks were separated into 3 groups: (i) no treatment (AS), (ii) statin treatment (AD), or (iii) aerobic exercise (AE). Plaques and foam cells were observed in the untreated control and statin groups, respectively, but not in the AE group. Reduced angiotensin II (Ang II) and endothelin 1 (ET1) levels were observed in the AE group. Both treatment groups significantly altered the expression of inflammatory cytokine expression and reduced vascular TLR4 levels. Increased miR-146a and miR-126 and reduced miR-155 levels were observed in both treatment groups (all, P<0.001). miR-146a interacted with the 3' untranslated region of the TRAF6 gene, reducing its expression. Thus, aerobic exercise and statins may induce miR-146a expression, thereby reducing vascular TRAF and TLR4 signaling and vascular inflammatory injury in AS. Further analysis of this pathway may provide insight into the protective effects of aerobic exercise on vascular disease as well as new therapeutic targets.
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Due to the poor self-regeneration of brain tissue, stem cell transplantation therapy is purported to enable the replacement of lost neurons after traumatic brain injury (TBI). The ...main challenge of brain regeneration is whether the transplanted cells can survive and carry out neuronal functions in the lesion area. The brain is a complex neuronal network consisting of various types of cells that significantly influence on each other, and the survival of the implanted stem cells in brain is critically influenced by the surrounding cells. Although stem cell-based therapy is developing rapidly, most previous studies just focus on apply single type of stem cells as cell source. Here, we found that co-culturing human umbilical cord mesenchymal stem cells (hUC-MSCs) directly with the activated astrocytes benefited to the proliferation and neuron differentiation of hUC-MSCs in vitro. In this study, hUC-MSCs and the activated astrocytes were seeded in RADA16-BDNF peptide scaffold (R-B-SPH scaffold), a specifical self-assembling peptide hydrogel, in which the environment promoted the differentiation of typical neuron-like cells with neurites extending in three-dimensional directions. Moreover, the results showed co-culture of hUC-MSCs and activated astrocytes promoted more BDNF secretion which may benefit to both neural differentiation of ectogenic hUC-MSCs and endogenic neurogenesis. In order to promote migration of the transplanted hUC-MSCs to the host brain, the hUC-MSCs were forced with CXC chemokine receptor 4 (CXCR4). We found that the moderate-sized lesion cavity, but not the large cavity caused by TBI was repaired via the transplantation of hUC-MSCsCXCR4 and activated astrocytes embedded in R-B-SPH scaffolds. The functional neural repair for TBI demonstrated in this study is mainly due to the transplantation system of double cells, hUC-MSCs and activated astrocytes. We believe that this novel cell transplantation system offers a promising treatment option for cell replacement therapy for TBI.
In this reach, we specifically linked RGIDKRHWNSQ, a functional peptide derived from BDNF, to the C-terminal of RADARADARADARADA (RADA16) to structure a functional self-assembling peptide hydrogel scaffold, RADA16-BDNF (R-B-SPH scaffold) for the better transplantation of the double cell unit. Also, the novel scaffold was used as cell-carrier for transplantation double cell unit (hUC-MSCs/astrocyte) for treating traumatic brain injury. The results of this study showing that R-B-SPH scaffold was pliancy and flexibility to fit the brain lesion cavity and promotes the outgrowth of axons and dendrites of the neurons derived from hUC-MSCs in vitro and in vivo, indicating the 3D R-B-SPH scaffold provided a suitable microenvironment for hUC-MSC survival, proliferation and differentiation. Also, our results showing the double-cells transplantation system (hUC-MSCs/astrocyte) may be a novel cell-based therapeutic strategy for neuroregeneration after TBI with potential value for clinical application.
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