Exploring galectin-3’s role in predicting mild cognitive impairment in type 2 diabetes and its regulation by miRNAs

ObjectiveThis study aimed to investigate the role of galectin-3 (Gal-3; coded by LGALS3 gene), as a biomarker for MCI in T2DM patients and to develop and validate a predictive nomogram integrating galectin-3 with clinical risk factors for MCI prediction. Additionally, microRNA regulation of LGALS3 was explored.MethodsThe study employed a cross-sectional design. A total of 329 hospitalized T2DM patients were recruited and randomly allocated into a training cohort (n = 231) and a validation cohort (n = 98) using 7:3 ratio. Demographic data and neuropsychological assessments were recorded for all participants. Plasma levels of galectin-3 were measured using ELISA assay. We employed Spearman’s correlation and multivariable linear regression to analyze the relationship between galectin-3 levels and cognitive performance. Furthermore, univariate and multivariate logistic regression analyses were conducted to identify independent risk factors for MCI in T2DM patients. Based on these analyses, a predictive nomogram incorporating galectin-3 and clinical predictors was developed. The model’s performance was evaluated in terms of discrimination, calibration, and clinical utility. Regulatory miRNAs were identified using bioinformatics and their interactions with LGALS3 were confirmed through qRT-PCR and luciferase reporter assays.ResultsGalectin-3 was identified as an independent risk factor for MCI, with significant correlations to cognitive decline in T2DM patients. The developed nomogram, incorporating Gal-3, age, and education levels, demonstrated excellent predictive performance with an AUC of 0.813 in the training cohort and 0.775 in the validation cohort. The model outperformed the baseline galectin-3 model and showed a higher net benefit in clinical decision-making. Hsa-miR-128-3p was significantly downregulated in MCI patients, correlating with increased Gal-3 levels, while Luciferase assays confirmed miR-128-3p’s specific binding and influence on LGALS3.ConclusionOur findings emphasize the utility of Gal-3 as a viable biomarker for early detection of MCI in T2DM patients. The validated nomogram offers a practical tool for clinical decision-making, facilitating early interventions to potentially delay the progression of cognitive impairment. Additionally, further research on miRNA128’s regulation of Gal-3 levels is essential to substantiate our results

Expression and distribution of PPP2R5C gene in leukemia

<p>Abstract</p> <p>Background</p> <p>Recently, we clarified at the molecular level novel chromosomal translocation t(14;14)(q11;q32) in a case of Sézary syndrome, which caused a rearrangement from TRAJ7 to the <it>PPP2R5C </it>gene. <it>PPP2R5C </it>is one of the regulatory B subunits of protein phosphatase 2A (PP2A). It plays a crucial role in cell proliferation, differentiation, and transformation. To characterize the expression and distribution of five different transcript variants of the <it>PPP2R5C </it>gene in leukemia, we analyzed the expression level of <it>PPP2R5C </it>in peripheral blood mononuclear cells from 77 patients with <it>de novo </it>leukemia, 26 patients with leukemia in complete remission (CR), and 20 healthy individuals by real-time PCR and identified the different variants of <it>PPP2R5C </it>by RT-PCR.</p> <p>Findings</p> <p>Significantly higher expression of <it>PPP2R5C </it>was found in AML, CML, T-ALL, and B-CLL groups in comparison with healthy controls. High expression of <it>PPP2R5C </it>was detected in the B-ALL group; however, no significant difference was found compared with the healthy group. The expression level of <it>PPP2R5C </it>in the CML-CR group decreased significantly compared with that in the <it>de novo </it>CML group and was not significantly different from the level in the healthy group. By using different primer pairs that covered different exons, five transcript variants of <it>PPP2R5C </it>could be identified. All variants could be detected in healthy samples as well as in all the leukemia samples, and similar frequencies and distributions of <it>PPP2R5C </it>were indicated.</p> <p>Conclusions</p> <p>Overexpression of <it>PPP2R5C </it>in T-cell malignancy as well as in myeloid leukemia cells might relate to its proliferation and differentiation. Investigation of the effect of target inhibition of this gene might be beneficial to further characterization of molecular mechanisms and targeted therapy in leukemia.</p

Altered expression of the TCR signaling related genes CD3 and FcεRIγ in patients with aplastic anemia

<p>Abstract</p> <p>Background</p> <p>Aplastic anemia (AA) is characterized by pancytopenia and bone marrow hypoplasia, which results from immune-mediated hematopoiesis suppression. Understanding the pathophysiology of the immune system, particularly T cells immunity, has led to improved AA treatment over the past decades. However, primary and secondary failure after immunosuppressive therapy is frequent. Thus, knowledge of the immune mechanisms leading to AA is crucial to fundamentally understand the disease.</p> <p>Findings</p> <p>To elucidate the T cell receptor (TCR) signal transduction features in AA, the expression levels of CD3γ, δ, ε and ζ chain and FcεRIγ genes, which are involved in TCR signal transduction, and the negative correlation of the expression levels between the CD3ζ and FcεRIγ genes in T cells from peripheral blood mononuclear cells (PBMCs) were analyzed. Real-time RT-PCR using the SYBR Green method was used to detect the expression level of these genes in PBMCs from 18 patients with AA and 14 healthy individuals. The β2microglobulin gene (β2M) was used as an endogenous reference. The expression levels of the CD3γ, CD3δ, CD3ε and CD3ζ genes in patients with AA were significantly increased compared to a healthy control group, whereas the FcεRIγ gene expression level was significantly decreased in patients with AA in comparison with the healthy control group. Moreover, the negative correlation of the expression levels between the CD3ζ and FcεRIγ genes was lost.</p> <p>Conclusions</p> <p>To our knowledge, this is the first report of the CD3γ, CD3δ, CD3ε, CD3ζ and FcεRIγ gene expression in patients with AA. The abnormally expressed TCR signaling related genes may relate to T cells dysfunction in AA.</p

Mobile Edge Computing Task Offloading Strategy Based on Parking Cooperation in the Internet of Vehicles

Due to the limited computing capacity of onboard devices, they can no longer meet a large number of computing requirements. Therefore, mobile edge computing (MEC) provides more computing and storage capabilities for vehicles. Inspired by a large number of roadside parking vehicles, this paper takes the roadside parking vehicles with idle computing resources as the task offloading platform and proposes a mobile edge computing task offloading strategy based on roadside parking cooperation. The resource sharing and mutual utilization among roadside vehicles, roadside units (RSU), and cloud servers (cloud servers) were established, and the collaborative offloading problem of computing tasks was transformed into a constraint problem. The hybrid genetic algorithm (HHGA) with a mountain-climbing operator was used to solve the multi-constraint problem, to reduce the delay and energy consumption of computing tasks. The simulation results show that when the number of tasks is 25, the delay and energy consumption of the HHGA algorithm is improved by 24.1% and 11.9%, respectively, compared with Tradition. When the task size is 1.0 MB, the HHGA algorithm reduces the system overhead by 7.9% compared with Tradition. Therefore, the proposed scheme can effectively reduce the total system cost during task offloading

Attacks and Comments on Several Recently Proposed Key Management Schemes

Abstract. In this paper, we review three problematic key management (KM) schemes recently proposed, including Kayam’s scheme for groups with hierarchy [10], Piao’s group KM scheme [14], Purushothama’s group KM schemes [17]. We point out the problems in each scheme. Kayam’s scheme is not secure to collusion attack. Piao’s group KM scheme is not secure. The hard problem it bases is not really hard. Purushothama’s scheme has a redundant design that costs lots of resources and doesn’t give an advantage to the security level and dynamic efficiency of it. We also briefly analyze the underlying reasons why these problem emerge

Yet Another Attack On the Chinese Remainder Theorem Based Hierarchical Access Control Scheme

Abstract. The hierarchical access control scheme based on Chinese Reminder Theorem [49] (CRTHACS) was supposed to be capable of hiding hierarchical structure, but Geiselmann et al. [18] showed practical attacks on CRTHACS to reveal the hierarchies it hides. Then, Zou et al. modified it, and gave a new CRTHACS [50] to resist those attacks. Nevertheless, we find that the modified version is still defective if it permits changes of structure, i.e. the scheme works in a dynamic scenario. In this paper, we describe our attack on the modified version of CRTHACS. We extend the description of the CRTHACS in a more proper form making it easier for us to look into the problem it has. We find the key character of the vulnerability which we name as double-invariance. We generalize our attack in an algebraic form and apply it to a series of hierarchical cryptographic access control schemes that share the same vulnerability with CRTHACS. We also give the countermeasure to fix this vulnerability