Prolactinoma is an estrogen-related tumor and leukemia-related protein 16 （LRP16） is correlated with the progression of estrogen-related tumors, but the regulatory mechanism between LRP16 and ...prolactinoma remain unclear. This study demonstrates a variation in LRP16 with estrogen receptor a （ERa） in prolactinoma models and the up and downregulation effects of LRP16 on prolactin secretion of pituitary adenomas cells （GH3 cells）. In our study, 50 male SD rats （30-day-old） were randomly divided into five groups of 10 rats each. After 120 days of treatment,
Transforming growth factor β (TGF-β)/Smad3 signaling plays a role in tissue fibrosis. We report here that Erbb4-IR is a novel long non-coding RNA (lncRNA) responsible for TGF-β/Smad3-mediated renal ...fibrosis and is a specific therapeutic target for chronic kidney disease. Erbb4-IR was induced by TGF-β1 via a Smad3-dependent mechanism and was highly upregulated in the fibrotic kidney of mouse unilateral ureteral obstructive nephropathy (UUO). Silencing Erbb4-IR blocked TGF-β1-induced collagen I and alpha-smooth muscle actin (α-SMA) expressions in vitro and effectively attenuated renal fibrosis in the UUO kidney by blocking TGF-β/Smad3 signaling. Mechanistic studies revealed that Smad7, a downstream negative regulator of TGF-β/Smad signaling, is a target gene of Erbb4-IR because a binding site of Erbb4-IR was found on the 3′ UTR of Smad7 gene. Mutation of this binding site prevented the suppressive effect of Erbb4-IR on the Smad7 reporter activity; in contrast, overexpression of Erbb4-IR largely inhibited Smad7 but increased collagen I and α-SMA transcriptions. Thus, kidney-specific silencing of Erbb4-IR upregulated renal Smad7 and thus blocked TGF-β/Smad3-mediated renal fibrosis in vivo and in vitro. In conclusion, the present study identified that Erbb4-IR is a novel lncRNA responsible for TGF-β/Smad3-mediated renal fibrosis by downregulating Smad7. Targeting Erbb4-IR may represent a precise therapeutic strategy for progressive renal fibrosis.
Feng et al. characterize a novel Smad3-dependent long non-coding RNA Erbb4-IR and further demonstrate its role in promoting renal fibrosis in a mouse unilateral ureteral obstruction model. Erbb4-IR binds and represses the promoter of Smad7, thereby enhancing TGF-β1/Smad3-mediated fibrogenesis. Erbb4-IR may represent a precision therapeutic target for chronic kidney disease.
It is known that ethylene signaling is involved in the regulation of the salt stress response. However, the molecular mechanism of ethylene‐regulated salt stress tolerance remains largely unclear. In ...this study, an apple NAM ATAF CUC transcription factor, MdNAC047, was isolated and functionally characterized to be involved in ethylene‐modulated salt tolerance. MdNAC047 gene was significantly induced by salt treatment and its overexpression conferred increased tolerance to salt stress and facilitated the release of ethylene. Quantitative real‐time‐PCR analysis demonstrated that overexpression of MdNAC047 increased the expression of ethylene‐responsive genes. Electrophoretic mobility shift assay, yeast one‐hybrid and dual‐luciferase assays suggested that MdNAC047 directly binds to the MdERF3 (ETHYLENE RESPONSE FACTOR) promoter and activates its transcription. In addition, genetic analysis assays indicated that MdNAC047 regulates ethylene production at least partially in an MdERF3‐dependent pathway. Overall, we found a novel ‘MdNAC047‐MdERF3‐ethylene‐salt tolerance’ regulatory pathway, which provide new insight into the link between ethylene and salt stress.
LAG3 is the most promising immune checkpoint next to PD-1 and CTLA-4. High LAG3 and FGL1 expression boosts tumor growth by inhibiting the immune microenvironment. This review comprises four sections ...presenting the structure/expression, interaction, biological effects, and clinical application of LAG3/FGL1. D1 and D2 of LAG3 and FD of FGL1 are the LAG3-FGL1 interaction domains. LAG3 accumulates on the surface of lymphocytes in various tumors, but is also found in the cytoplasm in non-small cell lung cancer (NSCLC) cells. FGL1 is found in the cytoplasm in NSCLC cells and on the surface of breast cancer cells. The LAG3-FGL1 interaction mechanism remains unclear, and the intracellular signals require elucidation. LAG3/FGL1 activity is associated with immune cell infiltration, proliferation, and secretion. Cytokine production is enhanced when LAG3/FGL1 are co-expressed with PD-1. IMP321 and relatlimab are promising monoclonal antibodies targeting LAG3 in melanoma. The clinical use of anti-FGL1 antibodies has not been reported. Finally, high FGL1 and LAG3 expression induces EGFR-TKI and gefitinib resistance, and anti-PD-1 therapy resistance, respectively. We present a comprehensive overview of the role of LAG3/FGL1 in cancer, suggesting novel anti-tumor therapy strategies.
Au‐BP7@SP nanohybrids with active motion under NIR laser irradiation can effectively enhance the temperature of tumor potentially by converting the kinetic energy to thermal energy, enhancing the ...killing efficiency of the tumor cells compared with Au@SP. The study provides an insight of nanohybrids' effect on photothermal treatment and opens a new avenue to cancer treatment by using self‐propulsion Janus nanohybrids.
AIM： To evaluate the effect of perioperative parenteral nutrition on serum immunoglobulin, weight change, and post-operative outcome in severely malnourished patients with Crohn＇s disease. METHODS： ...Thirty-two severely malnourished patients with Crohn＇s disease who had undergone surgery in our hospital were reviewed. Sixteen patients who received perioperative parenteral nutrition were enrolled in the study group, and the other 16 patients who did not receive parenteral nutrition were enrolled in the control group. Serum immunoglobulin, body mass index （BMI）, liver function, weight change, and postoperative complications were evaluated. RESULTS： Serum IgM levels elevated 1 wk before surgery in both groups, and decreased to normal value （from 139±41 to 105±29 mg/dL, P = 0.04） 4 wk after operation in the study group, while no significant changes was noted in the control group （from 133±16 to 129±13 mg/dL, P = 0.34）. There were no significant changes in concentrations of IgG and IgA. The BMI of the study group increased from 13.9±0.6 to 15.3±0.7 kg/m^2 （P = 0.02） with no significant change in the control group （14.1±0.7 and 14.5±0.5, respectively, P = 0.81）. The percentage of resuming work was higher in the study group than in the control group. CONCLUSION： Perioperative parenteral nutrition possibly ameliorates the humoral immunity, reverses malnutrition, and facilitates rehabilitation. 2005 The WJG Press and Elsevier Inc. All rights reserved
EUS is considered one of the most sensitive modalities for pancreatic cancer detection, but it is highly operator-dependent and the learning curve is steep. In this study, we constructed a system ...named BP MASTER (pancreaticobiliary master) for EUS training and quality control.
The standard procedure of pancreatic EUS was divided into 6 stations. We developed a station classification model and a pancreas/abdominal aorta/portal confluence segmentation model with 19,486 images and 2207 images, respectively. Then, we used 1920 images and 700 images for classification and segmentation internal validation, respectively. To test station recognition we used 396 videos clips. An independent data set containing 180 images was applied for comparing the performance between models and EUS experts. Seven hundred sixty-eight images from 2 other hospitals were used for external validation. A crossover study was conducted to test the system effect on reducing difficulty in ultrasonographics interpretation among trainees.
The models achieved 94.2% accuracy in station classification and .836 dice in segmentation at internal validation. At external validation, the models achieved 82.4% accuracy in station classification and .715 dice in segmentation. For the video test, the station classification model achieved a per-frame accuracy of 86.2%. Compared with EUS experts, the models achieved 90.0% accuracy in classification and .77 and .813 dice in blood vessel and pancreas segmentation, which is comparable with that of experts. In the crossover study, trainee station recognition accuracy improved from 67.2% to 78.4% (95% confidence interval, .058-1.663; P < .01).
The BP MASTER system has the potential to play an important role in shortening the pancreatic EUS learning curve and improving EUS quality control in the future.
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The purpose of image composition is to combine the visual elements of different natural images to produce a natural image. The performance of most existing image composition methods drops ...significantly when they solve multiple issues, such as image harmonization, image blending, shadow generation, object placement, and spatial transformation. To address this problem, we propose a multitask GAN for image compositing based on spatial features, aiming to simultaneously address the geometric and appearance inconsistency. We use three related learning objective functions to train the network. Moreover, a new dataset including 7756 images with RoI region annotations is contributed to help evaluate the multitask image compositing results. Extensive experiments demonstrate that our proposed method is effective on our dataset.
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