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miR-374b and AKT inhibitor V inhibit the AKT phosphorylation and suppress cell growth as well as enhance cell apoptosis

The effect of Replenishment of Wnt16b and AKT1 on cell growth and apoptosis in SUP-T1-374b cells

Supplementary Table 1. RT-PCR primers for Wnt16, AKT1 and GAPDH, and primers for Wnt16 and AKT1 3'-UTR in the luciferase report assay Supplementary Table 2. Differentiated dysregulation of miRNAs in T-LBL Supplementary Table 3. The corresponding cutoff score of miR-374b expression for each clinicapathological feature according to ROC curve analysis Supplementary Table 4. Association of miR-374b downregulation with clinicopathological features of 58 L-TBL patients

Inhibition of PTEN enhanced the activation of AKT and rescued the effect of miR-374b on cell proliferation and cell apoptosis

Depletion of miR-374b promoted cell proliferation and suppressed serum starvation-induced apoptosis in T-LBL cells

The effect of β-catenin on the roles of miR-374b in T-LBL cells

Purpose: Deregulation of microRNA (miRNA) has been extensively investigated in both Hodgkin and non-Hodgkin lymphomas (NHL); however, little is known about the roles of miRNAs in T-cell lymphoblastic lymphoma (T-LBL). The aim of the present study was to investigate the potential roles of miR-374b in the development and treatment of T-LBL.Experimental Design: MiRCURY LNA array was used to generate a miRNA-expressing profile. Real-time quantitative PCR and immunohistochemistry (IHC) were applied to detect the expression of miR-374b, AKT1, and Wnt16 in T-LBL samples. The dual-luciferase reporter assay was conducted to confirm target associations of miR-374b. The tumor-suppressive effect of miR-374b was determined by both in vitro and in vivo studies.Results: The expression of 380 miRNAs was evaluated in five human T-LBL tissues and five infantile thymus samples by microRNA microarrays. Downregulation of miR-374b was frequently detected in primary T-LBL tissues, which was significantly associated with worse overall survival and increased risk of recurrence of the 58 patients enrolled in this study. miR-374b suppressed T-LBL cell proliferation in vitro and in vivo and sensitized cells to serum starvation- and chemotherapeutic agent-induced apoptosis. Furthermore, we characterized two AKT pathway–associated molecules, AKT1 and Wnt16, as direct targets of miR-374b. Consistently, in T-LBL patient tissues, AKT1 and Wnt16 expression was inversely correlated with miR-374b levels, and was an independent predictor of recurrence and survival.Conclusions: Our data highlight the molecular etiology and clinical significance of miR-374b in T-LBL. Targeting miR-374b may represent a new therapeutic strategy to improve therapy and survival for T-LBL patients. Clin Cancer Res; 21(21); 4881–91. ©2015 AACR.

Receiver operation characteristic (ROC) curve analysis was employed to determine the cutoff score for the high expression of miR-374b

Supplementary Figure 1: Receiver operation characteristic (ROC) curve analysis was employed to determine the cutoff score for the high expression of miR-374b. Supplementary Figure 2：Depletion of miR-374b promoted cell proliferation and suppressed serum starvation-induced apoptosis in T-LBL cells. Supplementary Figure 3: The effect of Replenishment of Wnt16b and AKT1 on cell growth and apoptosis in SUP-T1-374b cells. Supplementary Figure 4: miR-374b and AKT inhibitor V inhibit the AKT phosphorylation and suppress cell growth as well as enhance cell apoptosis. Supplementary Figure 5：The effect of β-catenin on the roles of miR-374b in T-LBL cells. Supplementary Figure 6: Inhibition of PTEN enhanced the activation of AKT and rescued the effect of miR-374b on cell proliferation and cell apoptosis.

Industrial Control Systems (ICSs) are the lifeline of a country Therefore, the anomaly detection of ICS traffic is an important endeavor. This paper proposes a model based on a deep residual Convolution Neural Network (CNN) to prevent gradient explosion or gradient disappearance and guarantee accuracy. The developed methodology addresses two limitations: most traditional machine learning methods can only detect known network attacks and deep learning algorithms require a long time to train. The utilization of transfer learning under the modification of the existing residual CNN structure guarantees the detection of unknown attacks. One-dimensional ICS flow data are converted into two-dimensional grayscale images to take full advantage of the features of CNN. Results show that the proposed method achieves a high score and solves the time problem associated with deep learning model training. The model can give reliable predictions for unknown or differently distributed abnormal data through short-term training. Thus, the proposed model ensures the safety of ICSs and verifies the feasibility of transfer learning for ICS anomaly detection.

Multiple surgeries for patients with cleft lip and palate may be required to repair secondary deformities after the completion of cleft repair. This meta-analysis aimed to evaluate the three-dimensional nasal morphology in patients with unilateral cleft palate who underwent cleft lip and palate repair but did not undergo terminal nasal repair. PubMed, Embase, Web of Science, China National Knowledge Infrastructure, Wanfang Data, and SINOMED databases were searched from inception until December 2020. Studies involving patients ages ≥6 years with cleft lip and palate who did not undergo terminal nasal repair were included. Quantitative data were obtained through three-dimensional evaluation. Mean weighted effect sizes with 95% confidence intervals, heterogeneities, and publication biases were assessed using raw data obtained from 13 studies. In general, patients with unilateral cleft lip and palate had a significantly wider nose; shorter bridge length and nasal height; larger forehead-nose angle, nasal tip angle, and alar slope angle; and smaller nasolabial angle. The number of studies that included patients with unilateral cleft lip, unilateral cleft lip and alveolus, and unclassified deformities was limited, and their results were similar to those involving patients with unilateral cleft lip and palate. Patients with unilateral cleft tend to have short, flat, and wide noses. Nasal tip elevation and alar base adduction should be prioritized during terminal nasal repair to achieve more normalized cleft-side nostrils.

With the explosively growth of battery usage from consumer electronics to electric vehicles, and large scale on/off-grid renewable energy storage, a large quantity of spent batteries that once powered those devices has been generated and will accelerate within the next decade and beyond. To avoid tons of spent batteries ending up in landfills, which would be hazardous wastes and could cause severe environmental pollution, we developed a highly cost-effective and energy-efficient technology “Hydro-to-Cathode” to recover the precious elements (Li, Ni, Mn, Co, etc.) from the spent batteries and make them into new cathode materials and batteries to power new devices. Without extracting and separating the elements in the leached solution like the traditional hydrometallurgy approach does, Ascend Elements starts directly with the impurity-removed and adjusted solution to make high quality precursor for cathode materials. By controlling the conditions of precursor reactions and sintering process, we can make cathode materials with a wide range of particle sizes (2~16 µm), single crystal/polycrystalline, porous or dense intraparticle structure, and different compositions, including LiNi1/3Mn1/3Co1/3O2 (NMC 111), LiNi0.5Mn0.3Co0.2O2 (NMC 532), LiNi0.6Mn0.2Co0.2O2 (NMC 622), LiNi0.8Mn0.1Co0.1O2 (NMC 811), LiNi0.83Mn0.06Co0.11O2 (Ni 83), and LiCoO2 (LCO). The recycled cathode materials show as good as, or even better performance than cathode materials made from newly mined salts. Our unique Hydro-to-CathodeTM process significantly reduces the steps and costs to recover and recycle cathode materials from spent batteries.

Genome-wide analysis of miRNA expression has revealed increased levels of miR-144 in the brains of Alzheimer's disease (AD) patients. Nuclear factor erythroid 2-related factor 2 (NRF2), a potential target of miR-144, is a central regulator of antioxidant response, and plays an important role in glutathione (GSH) biosynthesis and recycling. In this study, miR-144 mimic was used to over express miR-144. Aβ (1-42) was used to induce oxidative stress in SH-SY5Y cells. Cell viability and intracellular reactive oxygen species (ROS) were assessed to identify the effects of miR-144 on oxidative stress status. GSH and glutathion peroxidase (GPX) activities were detected to reveal the effect of miR-144 on GSH accumulation. To understand the effects of miR-144 on GSH biosynthesis and recycling, intracellular GPX1, glutamate-cysteine ligase catalytic subunit (GCLC), glutamate-cysteine ligase modifier subunit (GCLM), glutathione reductase (GR), and NRF2 expression were detected by western blot and Real-time PCR. In oxidative stress conditions, miR-144 increased the intracellular accumulation of ROS, reduced cell viability, reduced the activities of GSH and antioxidant enzymes, GPX1, and decreased the expression of GCLC, GCLM, GR and NRF2. In conclusion, miR-144 modulates oxidative stress tolerance by regulating NRF2 expression and GSH generation, which may contribute to the pathogenesis of AD.

Purpose: Deregulation of microRNA (miRNA) has been extensively investigated in both Hodgkin and non-Hodgkin lymphomas (NHL); however, little is known about the roles of miRNAs in T-cell lymphoblastic lymphoma (T-LBL). The aim of the present study was to investigate the potential roles of miR-374b in the development and treatment of T-LBL. Experimental Design: MiRCURY LNA array was used to generate a miRNA-expressing profile. Real-time quantitative PCR and immunohistochemistry (IHC) were applied to detect the expression of miR-374b, AKT1, and Wnt16 in T-LBL samples. The dual-luciferase reporter assay was conducted to confirm target associations of miR-374b. The tumor-suppressive effect of miR-374b was determined by both in vitro and in vivo studies. Results: The expression of 380 miRNAs was evaluated in five human T-LBL tissues and five infantile thymus samples by microRNA microarrays. Downregulation of miR-374b was frequently detected in primary T-LBL tissues, which was significantly associated with worse overall survival and increased risk of recurrence of the 58 patients enrolled in this study. miR-374b suppressed T-LBL cell proliferation in vitro and in vivo and sensitized cells to serum starvation- and chemotherapeutic agent-induced apoptosis. Furthermore, we characterized two AKT pathway–associated molecules, AKT1 and Wnt16, as direct targets of miR-374b. Consistently, in T-LBL patient tissues, AKT1 and Wnt16 expression was inversely correlated with miR-374b levels, and was an independent predictor of recurrence and survival. Conclusions: Our data highlight the molecular etiology and clinical significance of miR-374b in T-LBL. Targeting miR-374b may represent a new therapeutic strategy to improve therapy and survival for T-LBL patients. Clin Cancer Res; 21(21); 4881–91. ©2015 AACR.

Additional file 1: Table S1. Expression of 84 metastasis-related genes in H1993-shAIB1 cells relative to that in H1993-vector cells.

Despite extensive studies on CD4(+)CD25(+) regulatory T cells (Tregs) during the past decade, the progress on their clinical translation remains stagnant. Mounting evidence suggests that naturally occurring CD8(+)CD122(+) T cells are also Tregs with the capacity to inhibit T-cell responses and suppress autoimmunity as well as alloimmunity. In fact, they are memory-like Tregs that resemble a central memory T cell (TCM) phenotype. The mechanisms underlying their suppression are still not well understood, although they may include IL-10 production. We have recently demonstrated that programmed death-1 (PD-1) expression distinguishes between regulatory and memory CD8(+)CD122(+) T cells and that CD8(+)CD122(+) Tregs undergo faster homeostatic proliferation and are more potent in the suppression of allograft rejection than conventional CD4(+)CD25(+) Tregs. These findings may open a new line of investigation for accelerating effective Treg therapies in the clinic. In this review, we summarize the significant progress in this promising field of CD8(+)CD122(+) Treg research and discuss their phenotypes, suppressive roles in autoimmunity and alloimmunity, functional requirements, mechanisms of action and potential applications in the clinic.

Effect of Cu foil substrate surface conditions on the electrochemical performance of Si thin film anode was investigated on four substrate surface conditions, smooth Cu foil, island-shaped s Cu foil, roughened Cu foil with sandpaper, and Cu foil implanted by plasma immersion lanthanum ion implantation (LaPIII). The relationship of effect significant with the thickness of Si was identifiedned. Sample on island-shaped surface and LaPIII treated on one showed better performance. For the thicker Si films, more roughness is better for the substrate. An optimized substrate surface condition according to the film thickness is necessary for the deposition of Si films.

The electrochemical performance of LaNi5−xSnx alloys with x=0, 0.06, 0.12, 0.20, 0.30, 0.36, 0.42, and 0.48 have been investigated by battery testing instruments in alkaline electrolyte. Most of the Sn substituted alloys were found to possess an exceptional electrochemical performance. For a tin content of x=0.42, the electrochemical performance of these alloys is best, even under a large charge–discharge current. It is also found that the electrochemical influence of Sn on LaNi5 alloys is not linear and that the existence of the second phase LaNi4Sn2 harms the improvement of the electrochemical properties of LaNi5−xSnx alloys.

The phase relationships in the La–Ni–Sn ternary system at 673 K have been investigated by means of X-ray powder diffraction (XRD), differential thermal analysis (DTA), scanning electron microscopy (SEM) and electron probe microanalysis (EPMA). Most of this ternary system was studied at 673 K. At this temperature, a new ternary compound whose atomic ratio is close to La/Ni/Sn=1:1:3 has been found. The existences of 15 binary compounds La 7 Ni 3 , LaNi, La 2 Ni 3 , La 7 Ni 16 , LaNi 3 , La 2 Ni 7 , LaNi 5 , Ni 3 Sn, Ni 3 Sn 2 , Ni 3 Sn 4 , La 5 Sn 3 , La 5 Sn 4 , LaSn, La 3 Sn 5 , LaSn 3 and seven other ternary compounds LaNi 5 Sn, LaNi 4 Sn 2 , LaNi 2 Sn 2 , La 3 Ni 2 Sn 6 , La 3 Ni 2 Sn 7 , La 3 Ni 8 Sn 16 , LaNiSn have been confirmed too. There are 31 three-phase regions in the 673 K isothermal section. Due to the lower melting point of Sn (about 504 K), a small part of the ternary system that lies in the Sn-rich part was studied at 483 K.

Transfer hydrogenation of ketones was efficiently carried out with a ruthenium(II) complex bearing the ligand 2,6-bis(3,5-dimethylpyrazol-1-yl)pyridine (Me(4)BPFy), i.e., RuCl2(PPh3)(Me(4)BPFy), in 2-propanol at 82 degrees C. The single-crystal structure of the complex was first characterized by an X-ray crystallographic study, correcting the mistaken structural assignment of the complex in the literature. The results have demonstrated that the new family of ligands of the type Me4BPPy can act as pseudo-N-3 ligands to construct transition-metal catalysts.

The isothermal section of the phase diagram of the ternary system Dy–Mn–Ni system at 803 K was investigated by powder X-ray diffraction (XRD), differential thermal analysis (DTA), optical microanalysis and electron probe microanalysis techniques. It consists of 13 single-phase regions, 22 two-phase regions and 10 three-phase regions. At 803 K, the maximum solid solubilities of Mn in Ni, Dy2Ni17, DyNi5, Dy2Ni7, DyNi3, DyNi, Dy3Ni2 and Dy3Ni are about 31at.% Mn, 6 at.% Mn, 5.5 at.% Mn, 3 at.% Mn, 5 at% Mn, 5 at.% Mn, 3 at.% Mn and 1.5 at.% Mn, respectively. The maximum solid solubilities of Ni in Mn, DyMn12 and Dy6Mn23 are about 2.6 at.% Ni, 2 at.% Ni and 4 at.% Ni, respectively. DyMn2 and DyNi2 form a continous solid solution in this system. The binary compounds DyNi4 and Dy4Ni17 were not observed in this work. The existence of any ternary compound was not observed.

The AKT signaling pathway controls the survival and growth of human cancer cells. The purpose of this study was to investigate the expression dynamics of phosphorylated AKT (pAKT) in peripheral T-cell lymphoma (PTCL) and its clinical significance.Immunohistochemistry was performed to examine the pAKT expression in 106 PTCL cases. pAKT expression and its association with clinicopathologic characteristics of a patient with PTCL were analyzed.A total of 106 samples were tested, and 52 (49.1%) were positive for pAKT. There was significant positive correlation between pAKT expression and higher levels of lactic dehydrogenase (P.05), whereas positive pAKT expression was negatively correlated with patients' overall response rate (P.05). Further multivariate analysis revealed that positive pAKT expression predicted decreased progression-free survival and/or overall survival (P.05).Analysis of our results suggest that pAKT expression, as examined by immunohistochemistry, is an independent prognostic factor for PTCL. The clinical value of pAKT expression analysis in PTCL is worthy of further clinical investigations.

Naspharyngeal carcinoma (NPC) is a common malignant tumor. Radiotherapy is the main treatment for patients with early-stage NPC. Some chemotherapeutic methods have been used to delay the progression of NPC during the later stages. Osteopontin (OPN), a secreted phosphoglycoprotein, has been shown to be involved in cell proliferation, migration and invasion in a variety of tumor models. However, the effect of OPN on the proliferation and migration activity of human NPC cells is still unknown. In this study, we detected the expression of OPN in NPC CNE-2 cells, and investigated the roles of OPN in CNE-2 cells. Our results show that the down-regulation of OPN inhibits the growth and migration of CNE-2 cells. Additionally, our results indicate that the cell number in the G2 phase can be regulated by OPN. We further demonstrate that OPN shRNA down-regulates the expression of MMP-2 and MMP-9, and that OPN overexpression up-regulates the expression of MMP-2 and MMP-9.

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Candidate cathode materials of cobalt-incorporated and lithium-enriched Li{sub (1+x)}Ni{sub 0.25}Co{sub 0.15}Mn{sub 0.6}O{sub (2.175+x/2)} (x=0.225-0.65) have been prepared by a coprecipitation method and a solid-state reaction. We systematically investigated the effect of both cobalt presence and lithium concentration on the structure, physical properties, and electrochemical behavior of the studied samples. The electrochemical performance of the cobalt-containing compounds showed much less dependence on the variation in the lithium amounts compared to the cobalt-free counterpart. The study demonstrated that even with cobalt incorporation, proper lithium content is the key to desirable cathode materials with nanostructured primary particles that are indispensable to achieve high capacity and high rate capability and, therefore, both improved energy and power densities for lithium-ion batteries.

The electrochemical performance of pristine and AlF{sub 3}-coated Li{sub 1.1}Ni{sub 0.15}Co{sub 0.1}Mn{sub 0.55}O{sub 1.95} cathodes is reported for cells cycled at 25 and 55 C. In a half-cell configuration, a nanolayer coating of AlF{sub 3} on the Li{sub 1.1}Ni{sub 0.15}Co{sub 0.1}Mn{sub 0.55}O{sub 1.95} stabilizes the capacity on cycling. However, in cell tests with metallic lithium anodes, the initial coulombic efficiency decreased slightly at both 25 and 55 C for AlF{sub 3}-coated Li{sub 1.1}Ni{sub 0.15}Co{sub 0.1}Mn{sub 0.55}O{sub 1.95} in comparison to the pristine material. For cells constructed with graphite instead of lithium anodes, the capacity stability improved with cycling for the coated cathode materials. Transition-metal dissolution was more pronounced for the AlF{sub 3}-coated sample when stored at 55 C in electrolytes. For both the pristine and AlF{sub 3}-coated samples, there was no extra capacity loss due to the elevated temperature. Around 10% capacity gain of the cathode materials at elevated temperature is assumed to be due to improved thermodynamic activation.

Nanostructured lithium nickel manganese oxides were investigated as advanced positive electrode materials for lithium-ion batteries designated to power plug-in hybrid electric vehicles and all-electric vehicles. The investigation included material characterization and electrochemical testing. In cell tests, the Li{sub 1.375}Ni{sub 0.25}Mn{sub 0.75}O{sub 2.4375} composition achieved high capacity (210 mAh g{sup -1}) at an elevated rate (230 mA g{sup -1}), which makes this material a promising candidate for high energy density Li-ion batteries, as does its being cobalt-free and uncoated. The material has spherical morphology with nanoprimary particles embedded in micrometer-sized secondary particles, possesses a multiphase character (spinel and layered), and exhibits a high packing density (over 2 g cm{sup -3}) that is essential for the design of high energy density positive electrodes. When combined with the Li{sub 4}Ti{sub 5}O{sub 12} stable anode, the cell showed a capacity of 225 mAh g{sup -1} at the C/3 rate (73 mA g{sup -1}) with no capacity fading for 200 cycles. Other chemical compositions, Li{sub (1+x)}Ni{sub 0.25}Mn{sub 0.75}O{sub (2.25+x/2)} (0.32 {le} x {le} 0.65), were also studied, and the relationships among their structural, morphological, and electrochemical properties are reported.

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The electrochemical performance of LiNi{sub 0.5}Mn{sub 1.5}O{sub 4} (LNMO)/Li{sub 4}Ti{sub 5}O{sub 12} (LTO) cells with different designs, positive-electrode-limited, negative-electrode-limited, and positive/negative capacity ratio of {approx} (1) was investigated at different temperatures and current densities. Half-cells based on either LNMO/Li or LTO/Li exhibited an outstanding rate capability. When both electrodes were combined in a full cell configuration, the LNMO/LTO cells showed an excellent rate capability, with 86% discharge capacity retention at the 10C rate. Of the three designs, the negative-limited full cell showed the best cycling performance when discharged at the 2C rate in tests at room temperature: 98% capacity retention after 1000 cycles. The negative-limited full cell also exhibited excellent cycling characteristics in tests at 55 C: 95% discharge capacity retention after 200 cycles. These results clearly demonstrate that the LNMO/LTO system with a negative-limited design is attractive for plug-in hybrid electric vehicles, where a long cycle life and a reasonable power are needed.

Manganese-rich and cobalt-free compounds of LixNi0.25Mn0.75Oy (0.5 ≤ x ≤ 2, 2 ≤ y ≤ 2.75) were investigated as the positive electrode materials for high energy lithium-ion batteries. Compounds with x = 0.5, 1, 1.25, 1.5, and 2 were prepared by a solid-state reaction from the same carbonate precursor, Ni0.25Mn0.75CO3, with an appropriate amount of Li2CO3. The structural and physical characteristics of these phases were determined by X-ray diffraction and scanning electron microscopy. With an increase of the lithium content, the LixNi0.25Mn0.75Oy evolved from a spinel (Fdm) structure (x = 0.5) to a mixed spinel-layered (Fdm and C2/c) structure (x = 1 and 1.25), to a more layered (Rm and C2/c) structure (x = 1.5 and 2). A similar structural trend was found for samples prepared from NiMn2O4–Mn2O3 mixed oxide, itself prepared by thermal decomposition of Ni0.25Mn0.75CO3carbonate precursor, to which appropriate amounts of Li2CO3 were added. An increase of the lithium content also affected the size of the primary particles and the roughness of the secondary particles, without any substantial change of their spherical morphology and packing densities. Further results showed that the electrochemical performance and safety characteristics of the LixNi0.25Mn0.75Oy materials were primarily governed by their structures.

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