Search

Herein, we successfully fabricated an Al-doped α-Ga2O3 nanorod array on FTO using the hydrothermal and post-annealing processes. To the best of our knowledge, it is the first time that an Al-doped α-Ga2O3 nanorod array on FTO has been realized via a much simpler and cheaper way than that based on metal–organic chemical vapor deposition, magnetron sputtering, molecular beam epitaxy, and pulsed laser deposition. And, a self-powered Al-doped α-Ga2O3 nanorod array/FTO photodetector was also realized as a photoanode at 0 V (vs. Ag/AgCl) in a photoelectrochemical (PEC) cell, showing a peak responsivity of 1.46 mA/W at 260 nm. The response speed of the Al-doped device was 0.421 s for rise time, and 0.139 s for decay time under solar-blind UV (260 nm) illumination. Compared with the undoped device, the responsivity of the Al-doped device was ~5.84 times larger, and the response speed was relatively faster. When increasing the biases from 0 V to 1 V, the responsivity, quantum efficiency, and detectivity of the Al-doped device were enhanced from 1.46 mA/W to 2.02 mA/W, from ~0.7% to ~0.96%, and from ~6 × 109 Jones to ~1 × 1010 Jones, respectively, due to the enlarged depletion region. Therefore, Al doping may provide a route to enhance the self-powered photodetection performance of α-Ga2O3 nanorod arrays.

Purpose To take the advantages of terrain-adaptive capability of legged platform and fast-moving ability of wheeled platform, this paper aims to design a leg-wheel mobile platform for obstacle surmounting and analyze the feasibility and locomotivity of different moving modes. Design/methodology/approach The platform consists of six leg-wheel units. Each of the units has a close-chain mechanical leg and an actuated wheel at the end of the leg. The platform moves with two modes: legged mode and leg-wheel composite mode. The legged mode achieves high mobility driven by crank motors, while the leg-wheel composite mode achieves obstacle-surmounting ability actuated by crank motors and pitch link motors and obtains high efficiency with the hub motors. The gait planning in different modes has been carried out and the obstacle-surmounting capacity has been analyzed. Findings Based on the results of kinematic analysis and gait planning of the close-chain leg-wheel platform, the high mobility and efficiency obstacle-surmounting ability are demonstrated with the two movement modes. The feasibility of the design and the performance of the mobile platform is verified with the prototype experiment. The results of this paper show that the platform possesses good obstacle-surmounting capability. Originality/value The work presented in this paper is a novel exploration to design a close-chain leg mechanism and with an actuated wheel in series. The close-chain leg mechanism has the advantages of high leg lift and single degree of freedom characteristics, which makes the platform obtain the ability of obstacle-surmounting.

Shale gas has become an important natural gas resource in recent years as the conventional oil and gas resources are depleting. Shale gas content is one of the most important parameters for reserve calculation and sweet-spot prediction. The traditional core recovery method is widely used to determine gas content. However, the estimation of lost gas content is the main factor of error and difficulty. Large errors and uncertainties occur when using the widely used methods, such as the United States Bureau of Mines (USBM) method. Hence, a more accurate method is required. In this work, a full-process model is developed in COMSOL Multiphysics to describe the lost gas with time during the core recovery process as well as the desorption stage after the core is covered. In this method, by setting the initial gas pressure and flow parameters and matching the desorbed gas volume and considering variable diffusivity with respect to temperature, the initial gas content and the gas lost with respect to time are calculated. Overall, 10 field data are tested using this full-process model, and the USBM method is also applied to compare the results. It is found that if the ratio of lost gas volume estimated using the USBM method to the desorbed gas volume of the field data is lower than 2.0, the USBM method underestimates the lost gas compared to the full-process method; if the ratio is about 2.0, the results from the USBM and the full-process methods are comparable; and if the ratio is close to 3.0, the USBM method tends to overestimate the lost gas. The modeling results indicate that this proposed full-process method is more theoretically sound than the USBM method, which has high uncertainties depending on the number of desorbed gas data points used. Nevertheless, this proposed method requires a large number of parameters, leading to the difficulty in finding true parameters. Therefore, an optimization algorithm is required. In summary, this study provides theoretical support and a mathematical model for the inversion calculation of lost gas during shale core recovery. It is helpful to evaluate the resource potential and development economics of shale gas more accurately.

Abstract Metabolic dysregulations have emerged as a major mediator of cardiovascular disorders and fibrotic diseases. Metabolic reprogramming contributes a lot to cardiac fibroblast activation and cardiac fibrosis post-myocardial infarction (MI), yet the mechanism remains incompletely understood. Our work aimed to determine whether or not glycolytic reprogramming, regulated by phosphofructokinase-2/fructose-2,6-bisphosphatase 3 (PFKFB3), is a therapeutic target for alleviating post-MI cardiac fibrosis. Here, we showed that cardiac fibroblasts displayed cell energy phenotype toward augmented glycolysis in response to transforming growth factor-beta 1 (TGF-β1), evidenced by significant extracellular acidification rate (ECAR) increase and lactate accumulation. The expression of glycolytic enzyme PFKFB3, a master activator of glycolysis, was up-regulated in TGF-β1-treated cardiac fibroblasts and in cardiac fibroblasts of post-MI mice. Pharmacological inhibition of PFKFB3 by 3PO diminished TGF-β1-mediated profibrotic phenotypes, attenuated cardiac fibrosis, and preserved cardiac functions in post-MI mice. Meanwhile, the genetic inhibition of PFKFB3 decreased the cardiac fibroblast activation and reversed the differentiated phenotypes in vitro and in vivo. Mechanistically, we identified deubiquitinase OTUD4 as a new binding protein of PFKFB3, and their interaction blocked PFKFB3 degradation via OTUD4-mediated deubiquitylation. Taken together, this work characterized a key role for PFKFB3 in cardiac fibroblast activation and suggested that inhibiting PFKFB3-involved glycolysis is an alternative way to alleviate post-MI cardiac fibrosis. Key messages PFKFB3, a master activator of glycolysis, was highly expressed in ischemic cardiac fibroblasts to enhance cardiac fibrosis The deubiquitinase OTUD4 was identified as a new binding protein of PFKFB3 TGF-β1 blunted the ubiquitination-mediated degradation of PFKFB3 via OTUD4-mediated deubiquitylation Blockade of PFKFB3 contributed to ameliorating ischemia-induced cardiac fibrosis

The availability of detailed surface runoff and river flow data across large geographic areas is needed for several scientific applications, such as refined freshwater environmental risk assessments. Some limiting factors in developing detailed river flow datasets over large spatial scales have been paucity of detailed input spatial data and challenges in processing of these data. The well-established USDA Curve Number (CN) method was applied for spatially distributed hydrologic processing to estimate surface runoff. Publicly available global datasets for hydrologic soil groups, land cover, and precipitation were spatially processed by applying the CN equations to create a global mean annual surface runoff grid of 50 meters. Runoff was spatially combined with global hydrology of catchments and rivers from publicly available datasets to estimate daily mean annual flow (MAF) across the globe. Estimated daily MAF were compared with measured gauge flow at rivers in several countries which showed good correlation (R2 of 0.76–0.98). These flow estimates can be used for diverse applications at local watersheds to larger regions across the globe. The two spatial data products of this project representing MAF at the global scale are publicly available for download at https://doi.org/10.6084/m9.figshare.22694146 (Heisler, et al., 2023).

Introduction: Anemia is a common manifestation of chronic liver diseases. It is a predictor of severe disease, a high risk of complications, and poor outcomes in various liver diseases. However, it remains unclear whether anemia serves as a similar indicator in patients with Wilson disease (WD). Therefore, this study aimed to investigate the relationship between anemia and severity, hepatic complications, and the progression of WD. Methods: Medical data were collected retrospectively from January 1, 2016, to December 31, 2020. Univariate and multivariate analyses were carried out to investigate the relationship between anemia and liver-associated disease severity, hepatic complications, and the progression of WD. Results: A total of 288 WD patients (48 with and 240 without anemia) were enrolled in the study. Multivariate linear regression revealed that WD patients with anemia had significantly higher levels of bilirubin, alanine transaminase, prothrombin time, international normalized ratio, type Ⅳ collagen, and hyaluronic acid and significantly lower levels of albumin, total cholesterol, and high-density lipoprotein-cholesterol (all P < 0.05). Multivariate logistic regression showed that anemia was a risk factor for gastric varices and ascites (all P < 0.05). Fully adjusted Cox regression revealed that anemia was an independent risk factor for advanced Child–Pugh classification (P = 0.034). Conclusions: Anemia was common in WD patients and was associated with greater disease severity, a higher risk of hepatic complications, and a faster progression.

The potential phosphorylation motifs of human SIRT3 were predicted by searching the data base using the combination of software Netphos2.0 server and Automotif server

Local mice xenograft tumor radiation settings showing the images of xenograft tumors derived from HCT116 cells harboring Thr150/Ser159 mutant or wild type SIRT3

Clonogenic survival ability of HCT116 cells via MnSOD activation

Western blot of mitochondrial acetylated proteins from irradiated MDA-231 or U87 cells harboring wild-type or Thr150/Ser159 mutant SIRT3.

MnSOD activity in MCF10A cells harboring mock, wild type or Thr150/Ser159 mutant SIRT3 following irradiation

Western blot analysis of SIRT3 and acetylated mitochondrial proteins of human breast cancer MDA-231 cells and glioblastoma U87 cells

PDF file - 89K, Enhanced gap filling rates in HER2+ versus HER2- BCSCs

PDF file - 540K, Protein profiling analysis of HER2+ versus HER2- BCSCs

PDF file - 513K, IHS of co-activation of HER2/CD44 cells in tumor tissues

Purpose: To understand the role of HER2-associated signaling network in breast cancer stem cells (BCSC) using radioresistant breast cancer cells and clinical recurrent breast cancers to evaluate HER2-targeted therapy as a tumor eliminating strategy for recurrent HER2−/low breast cancers.Experimental Design: HER2-expressing BCSCs (HER2+/CD44+/CD24−/low) were isolated from radiation-treated breast cancer MCF7 cells and in vivo irradiated MCF7 xenograft tumors. Tumor aggressiveness and radioresistance were analyzed by gap filling, Matrigel invasion, tumor-sphere formation, and clonogenic survival assays. The HER2/CD44 feature was analyzed in 40 primary and recurrent breast cancer specimens. Protein expression profiling in HER2+/CD44+/CD24−/low versus HER2−/CD44+/CD24−/low BCSCs was conducted with two-dimensional difference gel electrophoresis (2-D DIGE) and high-performance liquid chromatography tandem mass spectrometry (HPLC/MS-MS) analysis and HER2-mediated signaling network was generated by MetaCore program.Results: Compared with HER2-negative BCSCs, HER2+/CD44+/CD24−/low cells showed elevated aldehyde dehydrogenase (ALDH) activity and aggressiveness tested by Matrigel invasion, tumor sphere formation, and in vivo tumorigenesis. The enhanced aggressive phenotype and radioresistance of the HER2+/CD44+/CD24−/low cells were markedly reduced by inhibition of HER2 via siRNA or Herceptin treatments. Clinical breast cancer specimens revealed that cells coexpressing HER2 and CD44 were more frequently detected in recurrent (84.6%) than primary tumors (57.1%). In addition, 2-D DIGE and HPLC/MS-MS of HER2+/CD44+/CD24−/low versus HER2−/CD44+/CD24−/low BCSCs reported a unique HER2-associated protein profile including effectors involved in tumor metastasis, apoptosis, mitochondrial function, and DNA repair. A specific feature of HER2–STAT3 network was identified.Conclusion: This study provides the evidence that HER2-mediated prosurvival signaling network is responsible for the aggressive phenotype of BCSCs that could be targeted to control the therapy-resistant HER2−/low breast cancer. Clin Cancer Res; 18(24); 6634–47. ©2012 AACR.

PDF file - 187K, Enhanced aggressiveness of C6 and HER2 cells

PDF file - 112K

PDF file - 79K, Peptide and protein HPLC-MS/MS identification data for all proteins included in Table S1

PDF file - 36K, Mitochondrial membrane potential in HER2 siRNA treated cells

PDF file - 80K, Proteins identified by HPLC-MS/MS analysis are categorized into functional groups

Supplemental Experimental Procedures. The details of plasmid construction and siRNA synthesis

Supplemental Figure 3. Cell viability following MKP1 siRNA treatment

Supplementary Figure S3. DMSO mediated injury after 4OHT injection requires c-Met for sarcoma promotion.

Supplemental Figure 7. Inhibition of mitochondrial localization of MKP1 upon HER2 inhibitor, Lapatinib, treatment in MCF7/C6 cells

Supplemental Figure 2. The inhibition of ERK phosphorylation by U0126

Supplemental Figure 6. Cell viability after HER2 inhibitor, Lapatinib, treatment in MCF7/C6 and SKBR3 cells

Some patients with soft-tissue sarcoma (STS) report a history of injury at the site of their tumor. Although this phenomenon is widely reported, there are relatively few experimental systems that have directly assessed the role of injury in sarcoma formation. We recently described a mouse model of STS whereby p53 is deleted and oncogenic Kras is activated in muscle satellite cells via a Pax7CreER driver following intraperitoneal injection with tamoxifen. Here, we report that after systemic injection of tamoxifen, the vast majority of Pax7-expressing cells remain quiescent despite mutation of p53 and Kras. The fate of these muscle progenitors is dramatically altered by tissue injury, which leads to faster kinetics of sarcoma formation. In adult muscle, quiescent satellite cells will transition into an active state in response to hepatocyte growth factor (HGF). We show that modulating satellite cell quiescence via intramuscular injection of HGF increases the penetrance of sarcoma formation at the site of injection, which is dependent on its cognate receptor c-MET. Unexpectedly, the tumor-promoting effect of tissue injury also requires c-Met. These results reveal a mechanism by which HGF/c-MET signaling promotes tumor formation after tissue injury in a mouse model of primary STS, and they may explain why some patients develop a STS at the site of injury. Cancer Res; 75(3); 605–14. ©2014 AACR.

Supplemental Figure 5. Cell viability following MKP1 inhibitior, Sanguinarine, treatment in MCF7/C6 cells

Supplemental Figure 4. Cell viability following MKP1 inhibitior, Sanguinarine, treatment in SKBR3 cells

Supplemental Figure 1. Mitochondrial membrane potential of MCF7 wt, C6 and HER2 cells

Background Locally advanced non-small cell lung cancer (NSCLC) is a heterogeneous disease with poor long-term survival. This study examined overall survival (OS), progression-free survival (PFS), treatment effectiveness, and toxicity in patients with locally advanced NSCLC treated with definitive radiotherapy. Methods A retrospective analysis of demographic information, clinical characteristics, treatment patterns, and clinical outcomes of 789 patients with locally advanced NSCLC who underwent radical radiotherapy at our center between January 2005 and December 2015 was performed. The Kaplan–Meier method and log-rank test were used for survival comparisons, and Cox regression was used for multivariate analysis. Results There were 328 patients with stage IIIA disease and 461 with stage IIIB disease. By the last follow-up, there were 365 overall deaths and 576 cases of recurrence, metastasis, or death. The median survival time was 31 months. The OS rates at 1-, 2-, 5-, and 10 years were 83.7%, 59.5%, 28.8%, and 18.9%, respectively. PFS rates at 1, 2, 5, and 10 years were 48%, 24.5%, 11.9%, and 5.5%, respectively. Rates of ≥ grade 3 acute radiation pneumonitis or esophagitis were 7.6% and 1.9%, respectively. Rates of ≥ grade 3 chronic radiation pneumonitis and esophagitis were 11% and 0.4%, respectively. Multivariate analysis showed that the Karnofsky Performance Status (KPS) score, smoking status, and combined chemotherapy were independent prognostic factors for OS (P P