MicroRNA-141-3p mediates epithelial cell proliferation, apoptosis, and epithelial-mesenchymal transition and alleviates pulmonary fibrosis in mice via Spred2

Objective. This study probed the mechanism of microRNA (miR)-141-3p in the progression of pulmonary fibrosis (PF). Methods. Mice were intratracheally administered with bleomycin (BLM) to establish a PF mouse model. To investigate the effects of miR-141-3p/Spred2 on PF in mice, PF mice received tail vein injections with agomir-141-3p and/or adenovirus vectors overexpressing Spred2 one week after BLM treatment. Then, the pathological changes of lung tissues were analyzed with H&E and Masson’s trichrome staining, and hydroxyproline contents in lung tissues were measured. For cell experiments, after loss- and gain-of-function assays, the role of miR-141-3p/Spred2 in the apoptosis and viability of TGF-β1-stimulated MLE-12 cells was examined by flow cytometry and CCK-8 assay, respectively. miR-141-3p, Spred2, COl 1, and α-SMA expression was determined in cells and mice. Then, the binding of miR-141-3p to Spred2 was tested with a dualluciferase reporter assay. Results. There were abnormally upregulated Spred2 and downregulated miR-141-3p in lung tissues of PF mice. TGF-β1 decelerated viability and augmented apoptosis and COl 1 and α-SMA expression in MLE-12 cells. Spred2 knockdown diminished apoptosis and αSMA and COl 1 expression while enhancing proliferation in TGF-β1-treated MLE-12 cells. Mechanistically, Spred2 was a target gene of miR-1413p. miR-141-3p upregulation accelerated proliferation and repressed apoptosis and α-SMA and COl 1 expression in TGF-β1-treated MLE-12 cells, which was nullified by further overexpressing Spred2. miR-141-3p alleviated PF in mice by targeting Spred2. Conclusion. miR-141-3p negatively modulates Spred2 to promote proliferation and repress epithelialmesenchymal transition and apoptosis of epithelial cells, as well as ameliorating PF in mic

Ferroptosis of CD163+ tissue-infiltrating macrophages and CD10+ PC+ epithelial cells in lupus nephritis

BackgroundDysregulation of cell death and defective clearance of dying cells are closely related to the pathogenesis of lupus nephritis (LN). However, the contribution of a recently discovered form of programmed cell death (PCD) called ferroptosis to LN has not been explored in detail. The purpose of this study was to investigate the role of ferroptosis and its associated metabolic pathways in the pathogenesis of LN.MethodsThe composite gene expression scores were calculated by averaging the z-scored transformed log2 expressed genes within each form of PCD and pathway. Immunohistochemistry and immunofluorescence assays were used to verify the bioinformatics results.ResultsWe determined that ferroptosis is prominently and specifically elevated in the glomerular compartment of LN patients compared to other forms of PCD and kidney disease. This finding was then verified by immunohistochemical staining of 4-HNE (a key indicator for ferroptosis) expression in our own cohort (P < 0.0001). Intercorrelation networks were observed between 4-HNE and blood urea nitrogen, SLE disease activity index, serum creatinine, and complement 4, and negatively correlated with glomerular filtration rate in our own LN cohort (P < 0.05). Furthermore, enhanced iron metabolism and reduced fatty acid synthesis may be the most important factors for ferroptosis within the glomerulus. Through analysis of a single cell sequencing dataset and verification of immunohistochemical and immunofluorescence staining, aberrantly activated lipid peroxidation in CD163+ macrophages and CD10+ PC+ (pyruvate carboxylase) epithelial cells indicated that they may be undergoing ferroptosis in the glomerular compartment.ConclusionsTwo dysregulated genes, CD163 and PC, were identified and verified that were significantly associated with lipid peroxidation. Targeting ferroptosis in CD163+ macrophages and CD10+ PC+ epithelial cells may provide novel therapeutic approaches in LN

Leakage current simulations of Low Gain Avalanche Diode with improved Radiation Damage Modeling

We report precise TCAD simulations of IHEP-IME-v1 Low Gain Avalanche Diode (LGAD) calibrated by secondary ion mass spectroscopy (SIMS). Our setup allows us to evaluate the leakage current, capacitance, and breakdown voltage of LGAD, which agree with measurements' results before irradiation. And we propose an improved LGAD Radiation Damage Model (LRDM) which combines local acceptor removal with global deep energy levels. The LRDM is applied to the IHEP-IME-v1 LGAD and able to predict the leakage current well at -30 $^{\circ}$C after an irradiation fluence of $\Phi_{eq}=2.5 \times 10^{15} ~n_{eq}/cm^{2}$. The charge collection efficiency (CCE) is under development

CEPTM: A Cross-Edge Model for Diverse Personalization Service and Topic Migration in MEC

For several reasons, the cloud computing paradigm, e.g., mobile edge computing (MEC), is suffering from the problem of privacy issues. MEC servers provide personalization services to mobile users for better QoE qualities, but the ongoing migrated data from the source edge server to the destination edge server cause users to have privacy concerns and unwillingness of self-disclosure, which further leads to a sparsity problem. As a result, personalization services ignore valuable user profiles across edges where users have accounts in and tend to predict users’ potential purchases with insufficient sources, thereby limiting further improvement of QoE through personalization of the contents. This paper proposes a novel model, called CEPTM, which (1) collects mobile user data across multiple MEC edge servers, (2) improves the users’ experience in personalization services by loading collected diverse data, and (3) lowers their privacy concern with the improved personalization. This model also reveals that famous topics in one edge server can migrate into several other edge servers with users’ favorite content tags and that the diverse types of items could increase the possibility of users accepting the personalization service. In the experiment section, we use exploratory factor analysis to mathematically evaluate the correlations among those factors that influence users’ information disclosure in the MEC network, and the results indicate that CEPTM (1) achieves a high rate of personalization acceptance due to the availability of more data as input and highly diverse personalization as output and (2) gains the users’ trust because it collects user data while respecting individual privacy concerns and providing better personalization. It outperforms a traditional personalization service that runs on a single-edge server. This paper provides new insights into MEC diverse personalization services and privacy problems, and researchers and personalization providers can apply this model to merge popular users’ like trends throughout the MEC edge servers and generate better data management strategies

A Heuristic Model for Supporting Users’ Decision-Making in Privacy Disclosure for Recommendation

Privacy issues have become a major concern in the web of resource sharing, and users often have difficulty managing their information disclosure in the context of high-quality experiences from social media and Internet of Things. Recent studies have shown that users’ disclosure decisions may be influenced by heuristics from the crowds, leading to inconsistency in the disclosure volumes and reduction of the prediction accuracy. Therefore, an analysis of why this influence occurs and how to optimize the user experience is highly important. We propose a novel heuristic model that defines the data structures of items and participants in social media, utilizes a modified decision-tree classifier that can predict participants’ disclosures, and puts forward a correlation analysis for detecting disclosure inconsistences. The heuristic model is applied to real-time dataset to evaluate the behavioral effects. Decision-tree classifier and correlation analysis indeed prove that some participants’ behaviors in information disclosures became decreasingly correlated during item requesting. Participants can be “persuaded” to change their disclosure behaviors, and the users’ answers to the mildly sensitive items tend to be more variable and less predictable. Using this approach, recommender systems in social media can thus know the users better and provide service with higher prediction accuracy

The Impact of Ambient Temperature on Electrothermal Characteristics in Stacked Nanosheet Transistors with Multiple Lateral Stacks

With characteristic size scaling down to the nanoscale range, the confined geometry exacerbates the self-heating effect (SHE) in nanoscale devices. In this paper, the impact of ambient temperature (Tamb) on the SHE in stacked nanosheet transistors is investigated. As the number of lateral stacks (Nstack) increases, the nanoscale devices show more severe thermal crosstalk issues, and the current performance between n- and p-type nanoscale transistors exhibits different degradation trends. To compare the effect of different Tamb ranges, the temperature coefficients of current per stack and threshold voltage are analyzed. As the Nstack increases from 4 to 32, it is verified that the zero-temperature coefficient bias point (VZTC) decreases significantly in p-type nanoscale devices when Tamb is above room temperature. This can be explained by the enhanced thermal crosstalk. Then, the gate length-dependent electrothermal characteristics with different Nstacks are investigated at various Tambs. To explore the origin of drain current variation, the temperature-dependent backscattering model is utilized to explain the variation. At last, the simulation results verify the impact of Tamb on the SHE. The study provides an effective design guide for stacked nanosheet transistors when considering multiple stacks in circuit applications

Progressive bilateral lipoma arborescens of the knee complicated by juvenile spondyloarthropathy: a case report and review of the literature

OBJECTIVES: To report an unusual case of lipoma aborescens (LA) presented in a patient with treatment-responsive juvenile spondyloarthropathy (JSPA) and to summarize the clinical manifestations, therapy and prognosis of LA by literature review. METHODS: We report an atypical case of a 17-year-old patient with an initial presentation of juvenile spondyloarthropathy, whose inflammatory condition was improved successfully by traditional anti-rheumatic drugs and an anti-TNF alpha agent but developed progressive swelling of bilateral knees. Lipoma arborescens were diagnosed in each knee by synovial biopsy obtained by arthroscopic surgery. Fifty-one cases of LA have been reported and are reviewed in detail. RESULTS: Clinically, LA could present as monoarthritis or oligoarthritis. The lateral compartment of the knee is the most common site of involvement. Several cases were reported as a comorbidity of inflammatory diseases, but were not improved by anti-inflammatory therapy. Most patients were diagnosed by classic MRI and biopsy findings. The lesions can be managed by open or arthroscopic surgery, but a minority of the cases may have reoccurrence in the same or opposite joint. CONCLUSIONS: LA is a very rare lesion of the synovial and bursal tissue with an unknown etiology. It is considered to be a benign proliferation of the synovial fat associated with trauma, degenerative or inflammatory conditions. LA should be considered as a secondary or comorbid condition in inflammatory arthropathies if other joints respond well to intensive therapy and one or more do not